NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

AHCPR Health Technology Assessments. Rockville (MD): Agency for Health Care Policy and Research (US); 1990-1999.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of AHCPR Health Technology Assessments

AHCPR Health Technology Assessments.

Show details

Autologous Peripheral Stem-Cell Transplantation

Health Technology Assessment, Number 5

, D. O.

Created: .

Foreword

The Office of Health Technology Assessment (OHTA) evaluates the risks, benefits, and clinical effectiveness of new or unestablished medical technologies. In most instances, assessments address technologies that are being reviewed for purposes of coverage by federally funded the health programs.

OHTA's assessment process includes a comprehensive review of the medical literature and emphasizes broad and open participation from within and outside the Federal Government. A range of expert advice is obtained by widely publicizing the plans for conducting the assessment through publication of an announcement in the Federal Register and solicitation of input from Federal agencies, medical specialty societies, insurers, and manufacturers. The involvement these experts helps ensure inclusion of the experienced and varying viewpoints needed to round out the data derived from individual scientific studies in the medical literature.

OHTA analyzed and synthesized data and information received from experts and the scientific literature. The results are reported in this assessment. Each assessment represents a detailed analysis of the risks, clinical effectiveness, and uses of new or unestablished medical technologies. If an assessment has been prepared from the basis for a coverage decision by a federally financed health care program, it serves as the Public Health Service's recommendation to that program and is disseminated widely.

OHTA is one component of the Agency for Health Care Policy and Research (AHCPR), Public Health Service, Department of Health and Human Services.

  • Thomas V. Holohan, M.D., FACP
  • Director
  • Office of Health Technology Assessment
  • Clifton R. Gaus, Sc.D.
  • Administrator
  • Agency for Health Care Policy and Research
  • Question regarding this Assessment should be directed to:
  • Office of Health Technology Assessment
  • AHCPR
  • Willco Building, Suite 309
  • 6000 Executive Boulevard
  • Rockville, MD 20852
  • Telephone: (302) 594-4023

Introduction

Autologous peripheral stem-cell transplantation (APSCT) is a process in which autologous progenitor cells are harvested from a patient's circulating blood via leukapheresis techniques and commonly cryopreserved (with or without enrichment) for subsequent intravenous infusion to effect hematopoietic reconstitution (HR) of the bone marrow (BM) after severe cytopenia associated with high-dose chemotherapy (HDCT) and/or radiotherapy regimens used to treat various malignancies.(1,2) Pluripotent stem cells (capable of multilineage differentiation) cannot be distinguished by morphologic criteria. However, they can be characterized as being CD34+ cells possessing indefinite self-renewal capacity in situ and long-term self-renewal capacity demonstrated in cell cultures.(3-7)

Although the literature commonly treats stem cells as being synonymous with progenitor cells, pluripotent stem cells are in fact the primitive precursors of more committed progenitor cells, which in turn are precursors of all the mature blood cell lineages.(7-9).

Bone marrow transplantation (BMT) associated with HDCT, which has achieved the status of an accepted therapy in the treatment of some malignancies, e.g., leukemia and lymphoma, is also being proposed as a treatment of choice for some selected subsets of patients with other tumors, e.g., breast cancer and multiple (1,10). Stem cells are administered as supportive care to circumvent the morbidity and mortality associated with high-dose treatment regimens which are used in attempts to effect a cure or prolonged survival in patients at high risk for treatment failure or recurrent cancer using conventional therapy.(1-13) Both BM and peripheral blood are currently common sources of autologous progenitor cells, and to date, BM has been the primary source.(14-15) In the future, cultured stem cells derived from fetal liver or obtained from umbilical cord blood may provide a reliable source of stem cells as an alternative to autologous cells for transplants.(16-23)

Hematopoietic stem cells usually reside within BM sinusoids.(24) However, smaller numbers (1/10-1/100 of that present in BM) normally circulate in the peripheral blood.(25-30) These can be harvested by multiple leukaphereses (during a 1-to 2-week period) either in an unperturbed (steady) state, during the transient phase of blood count overshoot occurring during recovery from chemotherapy-or radiotherapy-induced myelosuppression, and/or enhanced by mobilization using cytokines (commonly the recombinant growth factors granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage-colony stimulating factor (GM-CSF).(14,27,30-35) This mobilization results in a substantial (albeit transient) rise in the number of circulating progenitor cells; however, the mechanism(s) by which this is accomplished remains poorly understood.(36-39) The use of cytokine mobilization may be problematic because of the possibility of stimulating the proliferation of residual malignant cells, forcing such cells from marrow into the peripheral circulation (comobilization), and inducing differentiation of pluripotent stem cells to more committed progenitor cells.(40)

In a recent report, current techniques to identify and separate CD34+ cells for use in APSCT resulted in fewer tumor cells being infused than if unseparated peripheral stem cells (PSC) were transplanted, with no differences noted in the resultant HR.(41)

Although optimal methods and appropriate timing of harvesting remain uncertain (as do the quantity and quality of the cells), PSC are commonly collected during outpatient leukapheresis using a continuous-flow blood cell separator.(42-44) Approximately 9-14 L of blood are processed over a 2-to 4-hour period. The majority of the blood cells and plasma are returned to the patient, and a final volume of approximately 200 mL is collected and cryopreserved (although occasionally stored unfrozen for short-term use) (45)

The relatively few progenitors seen in peripheral blood require an average of 6-10 phereses over period of 5-7 days to obtain sufficient numbers of cells for engraftment.(46,47) Chemotherapy-induced mobilization results in a 10-to 20-fold increase in the number of progenitors, and another 10-to 100-fold increase may be seen after the administration of cytokines.(38,46,48) These increases of progenitor cells (in both percentage and number) in the peripheral blood serve to reduce the number of phereses required to obtain adequate numbers of cells for successful engraftment to 1-5.(38,41,46,48) However, such yields are not obtainable in heavily pretreated patients.(35,44,49-52) Peripheral stem cells have been commonly measured as colony-forming-unit granulocyte-macrophage progenitor cells (CFU-GM), or CD34+ cells.(53-55 Although the definition of anadequate harvest is uncertain,at least one million purified progenitor cells,20 x10(4) CFU-GM, or 2 x 10(7). CD34+ cells/kg body weight or approximately 3-6 x 10(9). mononuclear cells/kg body weight are thought to be potentially adequate for successful transplants in adults(28,41,56,57,58). and 3 x 10(5). cells/kg in children.(27,36,49) A recent report indicated effective HR using unprocessed whole blood after progenitor cell mobilization using cytokines alone.(59)

The primary issues addressed in this assessment (prepared for the Office of Civilian Health and Medical Program of the Uniformed Services) are the safety and effectiveness of PSC for promoting HR and improving patient outcome and the indications and patient selection criteria for the use of APSCT.

Background

The use of autologous bone marrow transplantation (ABMT) has been extensively applied as a technique to support patients after HDCT that would otherwise be associated with unacceptable morbidity and mortality related to infection and bleeding as a consequence of prolonged or irreversible myelosuppression.(46,60) This has occurred without convincing evidence derived from randomized clinical trials (RCTs) (61) The benefits of such support therapies include reduced severity and duration of blood count nadirs, fewer infection and bleeding episodes, reduced requirements for red cell or platelet transfusions, fewer treatment delays, and shorter hospitalizations.(11,62,63) However, despite such support (commonly requiring several weeks of hospitalization), treatment-related mortality is in the range of 5 percent to 25 percent, with the lower rates reported in more recent trials.(39,46,64-69)

The initial rationale for HDCT is based primarily on preclinical chemotherapy trials demonstrating a steep dose-response curve (correlation between chemotherapy dosage and tumor response) and the hypothesis that dose-intensive therapy is associated with increased tumor responses and survival rates.(70,71) Data from some clinical trials and retrospective clinical reviews attempting to confirm the hypothesis surrounding the dose-response curve have been regarded as "promising"(72,73). and "suggestive"(66). but continue to be debated and are not yet proven as conclusive, especially with respect to long-term benefit.(12,38,54,63,65,72-80) It has been suggested that improved durability of responses and survival advantage both appear to be mostly dependent on such prognostic factors as tumor stage and patients' performance status before therapy.(81-84)

A recent metaanalysis of 60 published studies of dose-intensive regimens used in treating small-cell lung cancer failed to demonstrate a positive correlation between dose intensity and outcome.(85) Excepting some lymphomas and leukemias in which randomized trials have been performed, RCTs will continue to be required to determine the extent to which dose intensity determines outcome.(78,86-89)

The use of BM rescue after myelotoxic therapy does not solve the problems of nonhematologic toxicity, which continue to be a dose-limiting barrier to full exploitation of high-dose escalation regimens applied to patients with advanced or refractory malignancies.(1,90-92)

High-dose chemotherapy usually compromises most of the stem cells capable of providing HR, which has been defined as recovery of neutrophils to greater than 500/micro-L, platelets greater than 20,000/micro-L, and hematocrit greater than 25 percent.(43). Questions concerning the necessity of stem-cell rescue for achieving permanent hematopoietic recovery have not been completely resolved and will require prospective RCTs.(81,85) Recent reports have documented the feasibility of subablative HDCT regimens with intensive supportive care (including the use of cytokines) without the need of stem-cell transplants and achieved results comparable to outcomes seen with autologous stem-cell transplants.(80,93-97) Cytokines alone have been shown to accelerate neutrophil recovery, but those in current clinical use do not affect platelet recovery.(98) The nature of the stem cells providing long-term hematopoiesis has not been established, and the specific circulating pluripotent stem cell has not been identified and may exist only in the early stages of embroyogenesis (although other progenitor cells appear to be able to differentiate into the various blood cell lineages) (1,9,44,99) It is possible that some autochthonous progenitor cells are resistant to the effects of chemotherapy or radiotherapy and are the ultimate source of marrow recovery and long-term engraftment, whereas transplanted stem cells provide only short-term rescue.(14,26,100,101) Primitive CD34+ stem cell can be separated from more mature stem cells, and their presence and quantitation are useful as a surrogate marker of the progenitor cells responsible for HR.(3,87,99,102,103) The CD34+ cells mobilized after chemotheraphy are predominantly myeloid in phenotype and contain few proliferating cells.(104) In some patients, in vitro purging of tumor cells has produced a marked reduction and often a total absence of detectable progenitors without significant loss of HR capability.(105) Currently, in humans, it is usually not possible to identify the origin of the stem cells that engraft.(28,87,106) Such positive identification will probably require chromosomal or genetic marking of transplanted cells.(1,99,106-109.)

Hematopoietic reconstitution by cells in the peripheral blood has been amply demonstrated by numerous animal experiments, beginning with Cavins et al in 1964.(110) The presence of hemopoietic progenitor cells in peripheral blood was demonstrated by McCredie et al in 1971.(111) A 1971 report by Richman et al., (33) hypothesizing that the increased number of circulating CFU-GM cells seen after chemotheraphy in humans might be a practical source of autologous stem cells used to support patients receiving intensive chemotheraphy, was the initial suggestion for trials of PSC as an alternative to BM in the study of HDCT as a means of improving tumor response rates.(33)

The presence of BM metastases was initially thought to inhibit the potential of PSC harvest; however, chemotheraphy-induced mobilization was shown to be capable of stimulating the release of stem cells into the peripheral blood even in the face of extensive marrow involvement.(112)

By 1990, it became clear from a number of published studies that PSC were indeed capable of sustained HR in a manner similar to that of BM in patients treated for a variety of malignancies; initially those having lymphoma, myeloma, or other tumors associated with BM metastases or treatment-related marrow hypocellularity.(26,34,35,113-116). In some studies, PC were added to BM for the purpose of accelerating HR, (30,47,100,117-119). and more recently, satisfactory HR has been achieved using PSC alone.(47,67,114,115)

Although the presence of progenitor cells in the peripheral blood has been amply documented, many of these cells may already be "committed" to specific lineages (and therefore have finite renewal capacity), raising questions concerning sustained long-term engraftment.(14,28,120-122) Early preclinical studies concluded that PSC has limited potential for self-renewal compared with stem cell from BM.(123) However, the fact that long-term engraftment has been observed in humans given PSC suggests that sufficient numbers of pluripotent stem cells are also present in circulating blood.(124,126) It has been suggested that initial engraftment probably derives from committed stem cells, whereas later phases of engraftment derive from pluripotent stem cells, both of which are present in peripheral blood.(36,47 126,127)

Rationale

The basic rationale for APSCT is based on its purported enhanced HR.(27,48,51,100,119,129,129) Proponents of APSCT suggest that the more rapid HR (especially for platelets) (46). and the reduced morbidity, mortality, and requirements for supportive care seen with APSCT is in contrast to the situation associated with prolonged treatment-related myelosuppression often seen with BMT (particularly after pharmacologic purging) (49,54,63,119,130,131) In addition, suggested advantages of APSCT include the avoidance of general or spinal anesthesia, cell harvesting and providing PSC infusions to outpatients, and use when marrow is deemed unsuitable (tumor infiltration, prior treatment, or age) (14,29,32,36,38,44,132-136). or in circumstances in which sequential cycles of HDCT are contemplated.(4,61,67,75,87,137,138)

A recent report indicated that the immunosuppression seen with HDCT and BMT, sometimes persisting for years, may be shorter and less severe with HDCT and APSCT.(139). The potential advantages of a more rapid immunologic reconstitution of using PSC (possibly related to infusion of T-lymphocytes) has not been fully evaluated, and conflicting evidence exists regarding immune recovery.(31,140)

Proponents also hypothesize that, because some of the failures of HDCT strategies may be related to reinfusion of malignant cells during BMT, better results might be obtained using PSC, which may be less contaminated by malignant cells than BM.(34,131,141-147)

Review of Available Information

The literature search encompassed all journal articles and textbooks (English and non-English) published between 1975 and December 1994 available through MEDLINE and ancillary search capabilities of the National Library of Medicine. The key words used in the search were "peripheral blood stem-cell transplantation," "hematopoietic stem cells," and "autologous stem-cell rescue." Titles and abstracts from the peer-reviewed literature numbered 447, from which 25 papers were identified for further review using APSCT in 20 or more patients alone or compared with BMT. The search was expanded to include additional references cited in the reviewed articles and textbooks. Additional information was obtained via a Federal Register announcement of this assessment;(148). solicitation of information from professional societies, government agencies, and organizations having interest and/or experience with this technology; preprints of papers submitted for publication; and published abstracts.

Autologous peripheral stem-cell transplantation has been proposed as a safe, reliable, and well-tolerated procedure with associated morbidity less than that seen with BMT.(132,149,150) However, the procedures associated with harvesting the cells and their subsequent infusion are not completely benign, albeit with acceptable and manageable toxicity.

The risks and morbidity associated with apheresis have been well described.(150,151). In a report of 215 aphereses in 61 children (age 17 months to 17 years) with various refractory malignancies, three children experienced marked and persistent cytopenia for longer than 1 week, and all patients required reinfusion of the platelet-rich plasma to treat thrombocytopenia.(37) Reversible cyanosis or hypotension developed in two children, and one had an allergic reaction to the red cells used in the priming of the extracorporeal tubing. Eight aphereses were interrupted because of thrombus formation in the catheters.

In a review of the "safety and efficiency" of apheresis in 125 normal donors and 101 patients after interleukin-2 pretreatment or chemotherapy for malignancy, significant anemia and thrombocytopenia (requiring transfusions) were seen in 20 percent of patients but not in the donor.(151) No other serious procedure-related events were noted.

In a study of 27 lymphoma and leukemia patients undergoing a single apheresis, mild bone pain was noted as the only side effect.(49) In another study, nine lymphoma patients underwent a median of 10 aphereses and, excepting transient cytopenias, tolerated the procedure well.(14) Four patients required 0-1 units of red cells, and five others required 4-8 units.

There is a small but definite risk associated with chemotherapy-induced mobilization. In a study of 15 patients with advanced breast cancer undergoing cyclophosphamide mobilization of PSC, 56 percent of patients given a dose of 4 g/m(2) and all patients who received a 7 g/m(2) dose of cyclophosphamide required hospitalization for the treatment of febrile neutropenia, and one patient died of sepsis.(91) This issue may be moot in view of the fact that the use of cytokines has largely displaced cytoxic drugs for stem-cell mobilization.(22)

Side effects associated with PSC infusions have been attributed to the cryoprotectant (dimethyl sulfoxide) content of the infusate and its volume of red cells.(2,152,153) These transient and nondisabling effects seen in the majority of patients include hemoglobinuria, chills, fever, nausea, headache, vomiting, and hypertension. Abnormal signs and symptoms seen less frequently include tachypnea, cough, flushing, diarrhea, and elevated serum creatinine and/or bilirubin.

Recent literature has emphasized the reported increase in myelodysplastic syndrome associated with HDCT and autologous stem-cell transplantation.(154) Included in these reports is a study by Miller et al(155). indicating a significantly greater actuarial risk with PSC than if BM was used (31 +/-33 percent, vs. 10.5 +/-12 percent).

The use of APSCT has dramatically increased during the past 5 years, with the majority of procedures performed in patients having lymphomas associated with hypoplastic or tumor-involved marrow, leukemia, or poor-prognosis breast cancer.(156) A report from the European Bone Marrow Transplant Group indicated that 3,399 autologous stem-cell transplants were performed in 1992, of which 644 involved PSC alone and 261 were PSC combined with BM.(157)

In data obtained from the Statistical Center of the North American Autologous Bone Marrow Transplant Registry (which represents approximately one-half of the transplants performed in the United States and Canada), peripheral blood represented the source of stem cells in 15 percent of transplants for breast cancer in 1989, 26 percent in 1992, and 45 percent in 1993 (incomplete 1993 data).(15). The numbers of breast cancer patients receiving stem-cell transplants in those years were 123, 616, and 431, respectively.

There have been no completed prospective RCTs comparing the effectiveness of APSCT in HDCT regimens compared with ABMT or conventional therapy. As of September 1994, the Physician Data Query (PDQ) registry listed 17 currently active protocols involving the use of PSC. Two protocols were phase I, one was phase I/II, 12 were phase II, and the only phase III study was one involving the use of combined BM plus PSC.

The clinical experience published to date, involving APSCT in 20 or more patients, is summarized in Tables 1 and 2.

Table 1. Clinical experience involving APSCT.

Table

Table 1. Clinical experience involving APSCT.

Table 2. Comparison of median HR and hospital stay.

Table

Table 2. Comparison of median HR and hospital stay.

Discussion

The proposed advantages of APSCT over ABMT relating to the more rapid HR seen with PSC, the avoidance of general or spinal anesthesia, and its application in patients with unsuitable marrow have been suggested in numerous case series, leading a number of investigators to predict that APSCT may soon replace the use of ABMT in studies involving HDCT, especially in patients with a high risk of the marrow graft harboring malignant cells or in circumstances involving sequential HDCT regimens.(22,32,43,82,131,172-179)

Questions concerning the permanence of HR using PSC await longer followup of currently treated patients and further study using chromosomal and genetic markers.

Despite the absence of an RCT directly comparing the use of PSC vs. BM, the recent existing literature and information obtained from BM transplant registries in both the United States and Europe confirm the increased use of APSCT.(15,180)

The heterogeneity of regimens involving scheduling for priming harvesting, and infusion, plus the use of various cytokines, has as yet not led to agreement as to the optimum use of PSC.(38,42,44,131,169,174,181.) This continued lack of standardization presents difficulties in comparing results from different institutions.(182) In addition, the absolute necessity of any stem-cell rescue for therapy-induced myelotoxicity continues to be questioned.(66,93-97,183)

Although PSC harvests appear to contain fewer malignant cells than are seen in BM harvests, (142,145,146). issues surrounding the significance of such stem-cell contamination to the risk of relapse have not been resolved, and in the absence of a clinical trial it is impossible to determine the relative benefit of purged marrow vs. PSC.(57,131,149,184) Recent data suggest that, in patients with solid tumors without evidence of marrow involvement, mobilization regimens result in recruitment ot tumor cells into the peripheral blood.(144,185,186) However, the ability to detect small numbers of cancer cells in a steam-cell harvest continues to be poor, and questions concerning the need for purging remain unanswered.(32,66)

There has been a complete lack of uniform reporting of patient selection criteria in all the published reports on the use of stem cells for HR, as well as their impact on response rates or survival. The available data from Table 2 and other reports to suggest but do not confirm the hypothesis that patients given PSC transplant experience shorter periods of neutropenia and thrombocytopenia and have reduced treatment-related morbidity (as reflected in the duration of hospitalization) than "comparable" patients receiving BMT.(127,187) Mechanisms responsible for a potentially more rapid HR using PSC have not been elucidated. However, suggested explanations include the fact that approximately 10-fold more cells are infused than are commonly contained in a marrow autograft, and peripheral blood contains more mature ("committed") stem cells that require less time for maturation.(128). Long-term engraftment does not appear to be dependent on the source of the stem cells.(156) Whether long-term engraftment will be sustained over a period of years has yet to be established.(4,22,139,182,188)

Although investigators have commented on the reduced costs associated with APSCT, (62,189,190). the only published data of the relative costs of using PSC vs. BMT appeared as a letter to the editor, (191). a brief comment in one report, (159). one editorial, (179). and one abstract.(192) The letter noted that the major impact of the use of PSC was on posttransplant hospitalization, which was reduced from 26 days using BM in 19 patients to 14 days using PSC in 4 patients (patient selection criteria were not stated). There was also a reduction in the use of antibiotics; blood product support; and pathology, radiology, and microbiology costs. The total cost of using PSC was 25 percent less than the cost of BMT.

The report (from the France Autograft Group) indicated that the shortened hospitalization and reduced need for antibiotic and transfusion support, plus the lack of need for purging resulted in a 50 percent reduction in total cost of transplantation using PSC. The editorial stated that the use of PSC rather than BM has almost halved the cost of an autograft for Hodgkin's disease (details were not provided).

The abstract reported that the addition of G-CSF primed PSC to autologous marrow plus G-CSF resulted in significantly lower hospital charges than those incurred with the use of G-CSF plus autologous marrow without PSC (median $77,530 vs. $100,319).

Multiple HDCT trials with stem-cell support (albeit nonrandomized) have demonstrated conflicting outcomes in various tumor types, and the role of HDCT in such treatment continues to be undefined and is the subject of a number of ongoing clinical trials.(74,82,193,194). In addition, questions concerning issues of event-free survival and patient outcome using PSC (that appear to be at least comparable to that achieved using BM(69,195). ) cannot be answered in the absence of prospective RCTs comparing APSCT vs. ABMT or with HDCT alone.(12,14,196)

The consensus panel of an international conference held in France in June 1993, to consider which diseases are or are not likely to benefit from HDCT trials with stem-cell rescue, suggested that adult acute myelocytic leukemia (AML) and acute lymphocytic leukemia (ALL), adult lymphomas, and adult solid tumors are diseases that should be evaluated in prospective RCTs to determine patient benefits in terms of risk and impact on survival.(180) This same panel also stated that, despite a good theoretic basis for HDCT plus stem-cell rescue, it has not been established as being superior to conventional therapy for any stage of any adult solid tumor.

A 1994 textbook on BMT stated that PSC may be used in patients in whom marrow harvest is not feasible, but questions of its preference to marrow and its cost benefit remain unanswered.(196)

In response to the Federal Register notice of this assessment(148). and the solicitation of information from organizations and institutions involved with stem-cell transplantation, the Office of Health Technology Assessment has received the following input.

Institutional Comments

The Cleveland Clinic Foundation (December 1993) stated that the indications for APSCT are essentially the same as those for AMBT. The advantages of using PSC are that their engraftment may be more rapid and may have less risk of contamination with tumor cells than autologous marrow. The use of PSC was also associated with a decreased incidence of infections and a decrease in the hospital length of stay compared with that for ABMT.

The Ohio Bone Marrow Transplantation Consortium (December 1993) provided a summary of their experience in the treatment of a variety of malignancies with APSCT during an 18-month period beginning in January 1992. A total of 99 patients were given transplants; the average hospital length of stay was 29 days and the average hospital charges were $94,220. This was compared with 111 patients treated with ABMT for whom the average hospital length of stay was 38 days and average hospital charges were $127,692.

Disease indications for which autologous stem-cell transplantation is approved by the consortium are Hodgkin's and non-Hodgkin's lymphoma, CML, AML, ALL, neuroblastoma, breast cancer, testicular tumors, Wilm's tumor, Ewing's sarcoma, and rhabdomyosarcoma.

The Fox Chase Cancer Center (January 1994) members have commenced an APSCT program with studies involving ovarian cancer and non-small-cell lung cancer. As part of the Philadelphia Bone Marrow Transplantation Group, they will also participate in studies using PSC in breast cancer, and non-Hodgkin's lymphoma protocols.

The University of Nebraska Medical Center (January 1994) listed the following indications and contraindications for the use of PSC.

Indications:

  1. Candidates for marrow ablative theraphy and autologous transplant who have BM unsuitable for autografting because of too few cells, pelvic bone mestastases, or marrow containing tumor cells not readily removable by purging techniques.
  2. Candidates for marrow ablative theraphy and an autologous transplant whose marrow cannot be harvested for technical reasons.
  3. A less well-established (but potential) advantage of APSCT over ABMT may be that the patient is more likely to experience long-term, event-free Postulated reasons for this include:
    1. PSC harvests are less likely to contain malignant cells than are BM harvests.
    2. The cytotoxicity of mononuclear and other cells collected with apheresis but not present in BM autografts may provide a direct therapeutic effect.
    3. Immune reconstitution (related to lymphocytes present in PSC harvests and absent from BM harvests) may allow for a more rapid immune surveillance and decrease the incidence of late infections.

Contraindications:

Candidates for HDCT who have evidence of circulating tumor cells on a routine blood smear or have too few progenitor cells in the circulation to provide a usable graft product.

The Washington University School of Medicine (January 1994) states that PSC wered initially used in preference to BM in patients with hypocellular or fibrotic marrow due to prior theraphy. Subsequent indications for APSCT included patients having tumor-involved marrow or metastatic lesions at the usual sites of harvests, or those unable to tolerate general or spinal anesthesia. In addition, PSC harvests engraft reliably, at a significantly faster rate than BM; usually contain fewer tumor cells than BM harvests; and may provide better immunologic reconstitution than BM.

Contraindications the use of APSCT would be the inability to mobilize sufficient numbers of nucleated cells or the inability to tolerate apheresis.

There is decreased cost of APSCT compared with ABMT, related to the shorter engraftment times, fewer days in hospital, and fewer infectious days. Costs of APSCT range from $60,000 to $12,000 on average around transplant centers in the United States.

Public Health Service Comments

The Food and Drug Administration (FDA; January 1994) stated that use of PSC is not currently a fully accepted therapy but is being actively explored as a substitute or comparable to use of BM in transplantation after myeloablative HDCT regimens. Other possible applications of PSC include support of, or faster, HR when BM is damaged but not ablated (myelosuppression), combined with BM to enhance engraftment after BM damage, use in patients in whom marrow is difficult to harvest because of fibrosis or other destructive processes, and us in patients whose marrow contains a heavy tumor burden not seen in peripheral blood. The FDA is currently collecting clinical data on the use of all hematopoietic stem cells with the view of developing standards and regulations for their clinical application.

The National Institutes of Health (December 1993) has provided the following information: Suggested advantages of PSC over the use of BM include easier collection and less contamination with tumor cells. Claims of more rapid HR using PSC have not been tested in a properly controlled trial, and limited studies comparing marrow with or without PSC have shown no significant difference. Disadvantages of using PSC include the monitoring of the timing of mobilization and harvesting and toxicities associated with cytokine mobilization.

Autologous peripheral stem-cell transplant may be used in situations in which ABMT is indicated. Diseases for which long-term, disease-free survival ("cure") is the goal commonly include refractory lymphomas, certain stages of breast cancer, AML in first relapse or later, neuroblastoma, and Wilm's tumor. For most other tumors, the use of autologous stem cells in HDCT regimens is more likely to be palliative, and its use outside of clinical trials is questionable. A possible exception is chromic myelogenous leukemia when an allogeneic donor is not available.

Summary and Conclusions

Circulating PSC cn be obtained from patient's blood for subsequent infusion after HDCT used to treat a variety of malignancies. This procedure, termed APSCT, is an effort to circumvent the morbidity and mortality associated with therapy-induced myelosuppression.

Initially, such supportive therapy was accomplished by stem cells obtained from BM. However, abundant clinical experience during the past 5 years has demonstrated that PSC may serve as a functionally equivalent alternative to BM in providing satisfactory HR. This is based, in part, on the perception that PSC harvests produce less morbidity than BM harvests, and that the purportedly more rapid HR will be as durable as that achieved using BM. Despite the absence of RCT proving its benefit, the use of APSCT has dramatically increased and already replaced BMT in many settings at many centers, and has generated predictions that it will soon replace BMT for most, if not all, clinical indications.

Suggested advantages offered by the use of PSC compared with BMT include accelerated HR, thereby reducing morbidity, mortality, and resources for supportive care; avoidance of general or spinal anesthesia for stem-cell harvests; use as an outpatient procedure; use in patients whose marrow is unsuitable for harvesting; and use in sequential HDCT regimens. In general, despite its widespread application, the therapeutic benefit of HDCT and PSC support has yet to be firmly established and it is the subject of a number of ongoing clinical trials.

In the absence of appropriate RCTs, the current available data do not generate answers to questions concerning the efficacy and cost effectiveness of HDCT regimens, and additional studies are required to determine the optimum dosage and collection regimens for APSCT and whether disease-free survival rates are comparable to those achieved with ABMT. There continues to be lack of standardization on the definition of a PSC autograft that will provide a satisfactory and timely HR.

In vitro PSC assays have not been defined, which makes for difficulties in comparing results from different institutions and promoting the diffusion of this technology beyond research centers. In the absence of negative or conflicting data, the existing evidence suggests that PSC can provide satisfactory HR. However, the rate of HR with PSC does not appear to be consistently different from that using BM. The clinical importance of HR continues to be secondary to the primary issue of the benefits of HDCT in terms of antitumor response, palliation, or survival.

References

1.
Gulati SC, Yahalon Yahalom J, Portlock C. Autologous bone marrow transplantation Curr Probl Cancer 1991. 15: 1–57. [PubMed: 2001627]
2.
Kessinger A, Schmit-Pokorny K, Smith D, et al. Cryopreservation and infusion of autologous peripheral blood stem cells Bone Marrow Transplant 1990. 5 (Suppl 1) 25–27. [PubMed: 1969303]
3.
Ogawa M. Differentation Differentiation and proliferation of hematopoietic sten stem cells Blood 1993. 81: 2844–2853. [PubMed: 8499622]
4.
Chopra R. The Third UCH high dose meeting Bone Morrow Transplant 1994. 13: 317–319. [PubMed: 7911049]
5.
Uchida N, Weissman IL. Searching for hematopoietic stem cellcells: evidence that Thy-1.1lo LIN-Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone morrow J Exp Med 1992. 175: 175–184. [PMC free article: PMC2119064] [PubMed: 1346154]
6.
Schofield R. Assessment of cytotoxic injury to bone morrowmarrow Br J Cancer 1986. 7: 115–125. [PMC free article: PMC2149748] [PubMed: 3521698]
7.
Orlic D, Bodine DM. What defines a pluripotent hematopoietic stem cell (PHSC): will the real PHSC please stand up! [editorial; comment] Blood 1994. 84: 3991–3994. [PubMed: 7994018]
8.
Metcalf D. Hematopoietic regulators: redundancy or subtlety? Blood 1993. 82: 3515–3523. [PubMed: 8260692]
9.
Uchida N, Aguila HL, Fleming WH, et al. Rapid and sustained hematopoietic recovery in lethally irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ hemotopoietic sten cells Blood 1994. 83: 3758–3779. [PubMed: 7911343]
10.
Bierman PJ, Vose JM, Armitage JO. Autologous transplantation for Hodgkin's disease: coming of age? [editorial; comment] Blood 1994. 83: 1161–1164. [PubMed: 8118020]
11.
Neidhart JA. Hematopoietic colony-stimulating factors. Uses in combination with standard chemotherapeutic regimes and in support of dose intensification Cancer 1992. 70 (Suppl 4) 913–920. [PubMed: 1379115]
12.
Freedman AS, Nadler LM. Which patients with relapsed non-Hodgkin's lymphoma benefit from high-dose therapy and hemopoietic stem-cell transplantation? [editorial; comment] J Clin Oncol 1993. 11: 1841–1843. [PubMed: 8105033]
13.
Advani R, Chao NJ, Horning SJ, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to autologous hemopoietic stem cell transplantation for lymphoma Ann Intern Med 1992. 116: 183–189. [PubMed: 1345803]
14.
Rapoport AP, Rowe JM, Heal JM. Treatment of relapsed or refractory Hodgkin's disease and non-Hodgkin's lymphoma with high-dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue Am J Hematol 1992. 40: 86–92. [PubMed: 1585923]
15.
Horowitz, MM. Personal communication, Aug 1994. North American Autologous Bone Marrow Transplant Registry .
16.
Broxmeyer HE, Hangoc G, Cooper S, et al. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults Proc Nat Acad Sci USA 1992. 89: 4109–4113. [PMC free article: PMC525642] [PubMed: 1373894]
17.
Gale RP. Meeting report, autotransplants: now and in the future in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Morrow Transplantation. Proceedings of the Fifth International Symposium. , University of Nebraska Medical Center, 1990. pp. 905–909.
18.
Naughton BA, Jacob L, Naughton GA. A three-dimensional culture system for the growth of hematopoietic cells, in Gross S, Gee AP, Worthington-White DA (Eds) Bone Morrow Purging and Processing. , New York: Wiley Liss, 1990. pp. 435–445.
19.
Gross S. Perspectives in marrow purging in Gross S, Gee AP, Worthington-White DA (Eds): Bone Marrow Purging and Processing., New York: Wiley Liss, 1990. pp. XXIX–XXXIV.
20.
Tocci A, Rezzoug F, Aitouche A, et al. Comparison of fresh, cryopreserved and cultured haematopoietic stem cells from fetal liver Bone Marrow Transplant 1994. 13: 641–648. [PubMed: 7914448]
21.
Harris DT, Schumacher MJ, Rychlik S, et al. ColectionCollection, separation, and cryopreservation of umbilical cord blood for use in transplantation Bone Morrow Marrow Transplant 1994. 13: 135–143. [PubMed: 8205082]
22.
Goldman J. Blood and morrow marrow transplantation: a message from the editor Bone Morrow Marrow Transplant 1994. 14:–. [PubMed: 7951096]
23.
Gluckman E. Current knowledge about the properties of umbilical cord blood hematopoietic stem cells Bone Morrow Marrow Transplant [editorial] 1994; . 14:–. [PubMed: 7994230]
24.
Anderson JR. The blood and bone morrow marrow in Murr's Textbook of Pathology, 12th Edition (chapter 17), Baltimore: Edward Arnold, 1993, . –.
25.
Areman EM, Sacher RA, Deeg HJ. Processing and storage of human bone marrow: a survey of current practices in North America Bone Morrow Marrow Transplant 1990. 6: 203–209. [PubMed: 2252961]
26.
Korbling M, Holle R, Hass R. et al. Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site J Clin Oncol 1990. 8; 978–985. [PubMed: 1971851]
27.
Takaue Y, Watanabe T, Abe T, et al. Experience with peripheral blood stem cell collection for autograft in children with active cancer Bone Morrow Marrow Transplant 1992. 10: 241–248. [PubMed: 1358378]
28.
Henon PR, Butturini A, Gale RP. Blood-derived haematopoietic cell transplant transplants: blood to blood? Lancet 1991. 337: 961–963. [PubMed: 1678042]
29.
Haas R, Ho AD, Bredthauer U, et al. Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte-macrophage colony-stimulating factor Exp Hematol 1990. 18: 94–98. [PubMed: 1968009]
30.
Kessinger A, Armitage JO. The use of peripheral stem cell support of high-dose chemotherapy in De Vita VT, Hellman S, Rosenberg SA (Eds): Important Advances in Oncology., Philadelphia: JB Lippincott, 1993. pp. 167–175.
31.
Magrin S, Gentile S, Santoro A, et al. Collection, processing and storage of peripheral blood stem cells (PBSC) Haematologica 1991; . 76 (Suppl 1) 55–57. [PubMed: 1677912]
32.
Gulati SC, Acaba L. Improving the role of hematopoietic support for high-dose cytotoxic therapy Cancer Invest 1993. 11: 319–326. [PubMed: 8097959]
33.
Richman CM, Weiner RS, Yankee RA. Increase in circulating stem cells following chemotherapy in man Blood 1976. 47: 1031–1039. [PubMed: 1276467]
34.
Kessinger A, Armitage JO, Smith DM, et al. High-dose therapy and autologous peripheral blood stem-cell transplantation for patients with lymphoma Blood 1989. 74: 1260–1265. [PubMed: 2569900]
35.
Bishop MR, Anderson JR, Jackson JD, et al. High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft Blood 1994. 83: 610–616. [PubMed: 7904489]
36.
Patti C, Majolino I, Scime R, et al. High-dose cyclophosphamide, etoposide and BCNU (CVB) with autologous stem cell rescue in malignant lymphomas Eur J Haematol 1993. 51: 18–24. [PubMed: 8348940]
37.
Nagasu M, Aizawa S, Hojo H, et al. Detecting of the minimal residual disease contaminated in peripheral blood stem-cell transplantation in the B-cell malignant lymphoma patients Am J Hematol 1992. 41: 107–112. [PubMed: 1384313]
38.
Elias AD, Ayash L, Anderson KC, et al. Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer Blood 1992. 79: 3036–3044. [PubMed: 1350229]
39.
Champlin R. The technology of blood and marrow transplantation Clinical and Society Issues in Marrow Transplantation. , Meeting, Bethesda, MD, Mar 24-25, 1994. pp. 24–27.
40.
Brugger W, Bross KJ, Glatt M, et al. Mobilization of tumor cells and hematopoietic progenitor cells into peripherall blood of patients with solid tumors Blood 1994. 83: 636–640. [PubMed: 7507729]
41.
Brugger W, Henschler R, Heimfeld S, et al. Positively selected autologous blood CD 34+cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose V16, ifosfamide, carboplatin, and epirubicin Blood 1994. 84: 1421–1426. [PubMed: 7520769]
42.
Peters WP, Rosner G, Ross M, et al. Comparative effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on primary peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy Blood 1993; . 81: 1709–1719. [PubMed: 7681699]
43.
Shpall EJ, Jones RB. Mobilizations and collection of peripheral blood progenitor cells for support of high-dose cancer therapy in Forman SJ, Blume KG, Thomas ED (Eds): Bone Marrow Transplantation., Boston, Blackwell Scientific, 1994. pp. 913–918.
44.
Siena S, Bregni M, Brando B, et al. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients Blood 1991. 77: 400–409. [PubMed: 1702334]
45.
Gulati S, Nath BA, Whitmarsh KG, et al. Cryopreserving stem cells without controlled rate freezing in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transportation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 259–265.
46.
Elias A, Mazanet R, Wheeler C, et al. Peripheral blood progenitor cells (PBPC): two protocols using GM-CSF potentiated progenitor cell collection in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transportation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 875–879.
47.
Bensinger W, Singer K, Appelbaum F, et al. Autologous transportation transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor Blood 1993. 81: 3158–3163. [PubMed: 7684625]
48.
Juttner CA, To LB, Haylock DN, et al. Autologous blood stem-cell transplantation Transplant Proc 1989. 21 (1 Pt 3): 2929–2931. [PubMed: 2565063]
49.
Pettengell R, Morgenstern GR, Woll PJ, et al. Peripheral blood progenitor cell transportation transplantation in lymphoma and leukemia using a single apheresis Blood 1993. 82: 3770–3777. [PubMed: 7505124]
50.
Tarella C, Ferrero D, Siena S, et al. Conditions influencing the expansion of the circulating hemopoietic progenitor cell compartment Hematologica 1990. 75 (Suppl 1) 11–14. [PubMed: 2351338]
51.
Stoppa AM, Blaise D, Viens P, et al. Phase 1 study of in vivo lenograstim (rHuG-CSF) for stem cell collection demonstrates improved neutrophil recovery after autologous bone marrow transplantation Bone Marrow Transplant 1994. 13: 541–547. [PubMed: 7519936]
52.
Sacher R. Where are we going? Bone marrow and stem-cell transplantation. Bone marrow and stem-cell transplantation—Where are we going? Sem Hematol 1993; . 30: 130–133.
53.
Wunder E, Sowala H, Liang H, et al. The role of monocytes in the stimulation of progenitor cells in high-risk myeloma in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 881–892.
54.
Reiffers J, Merit G, Rice A, et al. Peripheral blood stem-cell transplantation in patients with acute myeloid leukemia in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transportation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 823–827.
55.
Juttner CA, To LB, Haylock DN, et al. Peripheral blood stem cell selection, collection and autotransplantation in Gross S, Gee AP, Worthington-White DA (Eds): Bone Marrow Purging and Processing., New York: Wiley Liss, 1990. pp. 447–460.
56.
Korbling M, Drach J, Champlain RE, et al. Large-scale preparation of highly purified, frozen/thawed CD34+, HLA-DR-hematopoietic progenitor cells by sequential immunoadsorption (CEPRATE-SC) and flourescence-activated cell sorting: implications for gene transduction and/or transplantation Bone Marrow Transplant 1994. 13: 469–654. [PubMed: 7519938]
57.
Myers SE, Mick R, Williams SF. High-dose chemotherapy with autologous stem-cell rescue in women with metastatic breast cancer with involved bone marrow: a role for peripheral blood progenitor transplant Bone Marrow Transplant 1994. 13: 449–454. [PubMed: 8019470]
58.
Bender JG, To LB, Williams S, et al. Defining a therapeutic dose of peripheral blood stem cells J Hematother 1992. 1: 329–341. [PubMed: 1285382]
59.
Ossenkoppele GJ, Jonkhoff AR, Huijgens PC, et al. Peripheral blood progenitors mobilized mobilised by G-CSF (filgrastim) and reinfused as unprocessed autologous whole blood shorten the pancytopenic period following high-dose melphalan in multiple myeloma Bone Marrow Transplant 1994. 13: 37–41. [PubMed: 7517255]
60.
Gianni AM, Siena S, Bregni M, et al. Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation Lancet 1989. 2: 580–585. [PubMed: 2570283]
61.
Goldstone AH, McMillan AK. The place of high-dose therapy with haemopoietic stem-cell transplantation in relapsed and refractory Hodgkin's disease Ann Oncol 1993. 4: 21–27. [PubMed: 8101726]
62.
Richel DJ, Baars JW, Wijngaarden MJGJ, et al. Favorable effect of hemapoietic hematopoietic stem cells isolated from blood on hematologic recovery following high-dose chemotherapy Ned Tijdschr Geneeskd 1993. 137: 245–250. [PubMed: 7679478]
63.
Peters WP. Use of CSF-primed peripheral blood progenitor cells in high-dose chemotherapy studies for metastatic and primary breast cancer Ann Oncology 1992. 3:–.
64.
Peters WP. High-dose chemotherapy and autologous bone marrow support for breast cancer, in DeVita VT, Hellman S, Rosenberg SA (Eds) Important Advances in Oncology, 1991. , Philadelphia: JB Lippincott, 1991. pp. 135–150.
65.
Hortobagyi GN. Potential indications for high-dose chemotherapy programs in high risk primary breast cancer in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 363–369.
66.
Livingston RB. Dose intensity and high-dose therapy. Two different concepts Cancer 1994. 74 (Suppl 3) 1177–1183. [PubMed: 8039154]
67.
Reece DE, Connors JM, Spinelli JJ, et al. Intensive therapy with cyclophosphamide, carmustine, etoposide, ± cisplatine, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy Blood 1994. 83: 1193–1199. [PubMed: 8118023]
68.
Bishop MR, Anderson JR, Jackson JD, et al. High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte -macrophage colony-stimulating factor on the autograft Blood 1994; . 83: 610–616. [PubMed: 7904489]
69.
Liberti G, Pearce R, Taghipour G, et al. Comparison of peripheral blood stem cell and autologous bone marrow transplantation fro for lymphoma patients: a case-controlled analysis of the EBMT Registry data Ann Oncol 1994. 5 (Suppl 2) 151–153. [PubMed: 7911318]
70.
O'Shaughnessy JA, Cowan KH. Dose-intensive therapy for breast cancer JAMA 1993. 270: 2089–2092. [PubMed: 8411576]
71.
Frei EJ III, Canellos GP. Dose: a critical factor in cancer chemotherapy Am J Med 1980. 69: 585–594. [PubMed: 6999898]
72.
Goldstone AH, Chopra R. Autografting in lymphoma: prospects for the future in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 551–561.
73.
Henderson IC, Hayes DF, Gelman R. Dose-response in the treatment of breast cancer: a critical review J Clin Oncol 1988. 6: 1501–1515. [PubMed: 3047340]
74.
Antman KH, Elias A, Fine HA. Dose-intensive therapy with autologous bone marrow transplantation in solid tumors in Forman SJ, Blume KG, Thomas ED (Eds): Bone Marrow Transplantation., Boston, Blackwell Scientific, 1994. pp. 767–788.
75.
Tepler I, Cannistra SA, Frei E III, et al. Use of peripheral blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy J Clin Oncol 1993; . 11: 1583–1591. [PubMed: 8101563]
76.
Shpall EJ, Jones RB, Bearman SI, et al. Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment J Clin Oncol 1994. 12: 28–36. [PubMed: 7505806]
77.
Armitage JO. Bone marrow transplantation N Engl J Med 1994. 330: 827–838. [PubMed: 8114836]
78.
Hryniuk WM, Goodyear M. The calculation of received dose intensity [editorial; comment] J Clin Oncol 1990; . 8: 1935–1937. [PubMed: 2230885]
79.
Simon R, Korn EL. Selecting drug combinations based on total equivalent dose (dose intensity) J Natl Cancer Inst 1990. 82: 1469–1476. [PubMed: 2118188]
80.
Peters WP, Ross M, Vredenburgh JJ, et al. High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer J Clin Oncol 1993. 11: 1132–1143. [PubMed: 8501500]
81.
Schmitz N, Glass B, Dreger P, et al. High-dose chemotherapy and hematopoietic stem-cell rescue in patients with relapsed Hodgkin's disease Ann Hematol 1993. 66: 251–256. [PubMed: 8099502]
82.
Vose JM, Anderson JR, Kessinger A, et al. High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma J Clin Oncol 1993. 11: 1146–1151. [PubMed: 8105034]
83.
Dunphy FR, Spitzer G, Fornoff JE, et al. Factors predicting long-term survival for metastatic breast cancer patients treated with high-dose chemotherapy and bone marrow support Cancer 1994. 73: 2157–2167. [PubMed: 8156520]
84.
Cohen MH, Ahuja N, Nguyen D, et al. Prognostic factors may account for the increased survival of advanced ovarian cancer patients receiving high-dose-intensity chemotherapy [abstr] Proc Am Soc Clin Oncol 1990. 9:–.
85.
Klasa RJ, Murray N, Coldman AJ. Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung J Clin Oncol 1991. 9: 499–508. [PubMed: 1847968]
86.
Nesbit ME Jr., Buckley JD, Feig SA, et al. Chemotherapy for induction of remission of childhood acute myeloid leukemia followed by marrow transplantation or multiagent chemotherapy: a report from the Children's Cancer Study Group J Clin Oncol 1994. 12: 127–135. [PubMed: 8270968]
87.
Chao NJ, Blume KG. Bone marrow transplantation. Part II -autologous West J Med 1990; . 152: 46–51. [PMC free article: PMC1002253] [PubMed: 2408234]
88.
O'Reilly RJ. The role of marrow transplantation in the treatment of acute lymphocytic leukemia Clinical and Society Issues in Marrow Transplantation, Meeting, Bethesda, MD, March 24-25, 1994, [abstr] pp. 9–10.
89.
Bronchud M. Can hematopoietic growth factors be used to improve the success of cytotoxic chemotherapy? Anticancer Drugs 1993. 4: 127–139. [PubMed: 8490192]
90.
Press OW, Eary JF, Applebaum FR, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support N Engl J Med 1993. 329: 1219–1224. [PubMed: 7692295]
91.
Pittman KB, To LB, Bayly JL, et al. Non-haematological toxicity limiting the application of sequential high-dose chemotherapy in patients with advanced breast cancer Bone Marrow Transplant 1992. 10: 535–540. [PubMed: 1362687]
92.
Bearman SI, Mori M, Petersen FB. Regimen-related toxicity after marrow transplantation for acute leukemia in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 189–198.
93.
Laporte JP, Fouillard L, Douay L, et al. GM-CSF instead of autologous bone-marrow transplantation after the BEAM regimen Lancet 1991; . 338: 601–602. [PubMed: 1679155]
94.
Neidhart JA, Kohler W, Stidley C, et al. Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation J Clin Oncol 1990. 8: 1728–1738. [PubMed: 2213108]
95.
Neidhart JA. Hematopoietic cytokines. Current use in cancer therapy Cancer 1993. 72 (Suppl 11) 3381–3386. [PubMed: 8242571]
96.
Huan SD, Yau JC, Dunphy FR, et al. Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin J Clin Oncol 1991. 9: 1609–1617. [PubMed: 1875221]
97.
Tourani JM, Levy R, Colonna P, et al. High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease J Clin Oncol 1992. 10: 1086–1094. [PubMed: 1607915]
98.
Bregni M, Siena S, Bonadonna G, et al. Clinical utilizationutilisation of human haematopoietic progenitors elicited in the peripheral blood by recombinant human granulocyte colony-stimulating factor (rHuG-CSF) Eur J Cancer 1994. 30A: 235–238. [PubMed: 7512358]
99.
Berenson RJ, Bensinger WI, Hill R, et al. Stem cell selection-clinical experience in Gross S, Gee AP, Worthington-White DA (Eds): Bone Marrow Purging and Processing., New York: Wiley Liss, 1990. pp. 403–413.
100.
Sheridan WP, Begley CG, Juttner CA, et al. Effect of peripheral blood progenitor cells mobilized by filgrastim (GCSF) on platelet recovery after high-dose chemotheraphy Bone Marrow Transplant 1993. 11 (Suppl 2) 23–29. [PubMed: 8334435]
101.
Bostom B. Can maximal-dose chemotherapy with marrow growth factors replace autologous bone marrow transplantation? in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 861–867.
102.
Applebaum Apppelbaum FR. The use of colony-stimulating factors in marrow transplantation Cancer 1993. 72: 3387–3392. [PubMed: 8242572]
103.
Berenson R. Human stem-cell transplantation Leuk-Lymphoma 1993. 11 (Suppl 2) 137–139. [PubMed: 7510193]
104.
Bender JG, Williams SF, Myers S, et al. Characterization of chemotherapy-mobilized peripheral blood progenitor cells for use in autologous stem-cell transplantation Bone Marrow Transplant 1992. 10: 281–285. [PubMed: 1384900]
105.
Rowley SD, Colvin OM, Stuart RK. Human multilineage progenitor cell sensitivity to 4-hydroperoxy- cyclophosphamide Exp Hematol 1985. 13: 295–298. [PubMed: 3987832]
106.
O'Shaugnessy JA, Cowan KH, Wilson W, et al. Pilot study of high-dose ICE (ifosfamide, carboplatin, etoposide) chemotherapy and autologous bone marrow transplant (ABMT) with neoR-transduced bone marrow and peripheral blood stem cells in patients with metastatic breast cancer Hum Gene Ther 1993. 4: 331–354. [PubMed: 8338880]
107.
Brenner MK, Rill DR, Holladay MS, et al. Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients Lancet 1993. 342: 1134–1137. [PubMed: 7901474]
108.
Brenner MK, Rill DR, Moen RC et al. Gene-marking to trace origin of relapse after autologous bone marrow transplantation Lancet 1993. 341: 85–86. [PubMed: 8093407]
109.
Kessinger A, Smith DM, Strandjord SE, et al. Allogeneic transplantation of blood-derived, T cell-depleted hemopoietic stem cells after myeloablative treatment in a patient with acute lymphoblastic leukemia Bone Marrow Transplant 1989; . 4: 643–646. [PubMed: 2573397]
110.
Cavins JA, Scheer SC, Thomas ED, et al. The recovery of lethally irradiated dogs give infusion of autologous leukocytes preserved at-80C Blood 1964; . 23: 38–43. [PubMed: 14113471]
111.
McCredie KB, Hersh EM, Freireich EJ. Cells capable of colony formation in the peripheral of blood in man Science 1971. 171: 293–294. [PubMed: 5538844]
112.
Kotasek D, Shepherd KM, Sage RE, et al. Factors affecting blood stem-cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma, and solid tumors Bone Marrow Transplant 1992. 9: 11–17. [PubMed: 1347478]
113.
Korbling M, Cayeux S, Baumann M, et al. Hemopoietic reconstitution and disease-free survival in a series of 45 patients with AML in first complete remission: a comparison between ABSCT and ABMT Bone Marrow Transplant 1989. 4 (Suppl 2)–.
114.
To LB, Juttner CA. Peripheral blood stem-cell a new therapeutic option for AML? Br J Hematol 1987; . 66:–. [PubMed: 2887196]
115.
Kessinger A, Armitage JO, Landmark JD, et al. Autologous peripheral hematopoietic stem-cell transplantation restores hematopoietic function following marrow ablative therapy Blood 1988. 71: 723–727. [PubMed: 2894230]
116.
Lowry PA, Tabbara IA. Peripheral hematopoietic stem-cell transplantation: current concepts Exp Hematol 1992. 20: 937–942. [PubMed: 1354619]
117.
Hermann Herrmann RP, O'Reilly J, Meyer BF, et al. Prompt haemopoietic reconstitution following hyperthermia-purged autologous marrow and peripheral blood stem-cell transplantation in acute myeloid leukemia Bone Marrow Transplant 1992. 10: 293–295. [PubMed: 1358379]
118.
Carella AM, Pollicardo N, Raffo MR, et al. Intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and acute lymphoblastic leukemia Leukemia 1992. 6 (Suppl 4) 120–123. [PubMed: 1359202]
119.
Juttner CA, To LB, Ho JQK, et al. Early lympho-hemopoietic recovery after autografting using peripheral blood stem cells in acute non-lymphoblastic leukemia Transplant Proc 1988. 20: 40–43. [PubMed: 2894085]
120.
Zander AR, Lyding J, Bielack S. Transplantation with blood stem cells Blood Cells 1991. 17: 301–309. [PubMed: 1680500]
121.
Brito-Babapulle F, Bocock SJ, Marcus RE, et al. Autografting for patients with chronic myeloid leukemia in chronic phase: peripheral blood stem cells may have a finite capacity for maintaining haemopoiesis Br J Haematol 1989. 73: 76–81. [PubMed: 2572271]
122.
Russell NH, Hunter AE. Peripheral blood stem cells for allogeneic transplantation Bone Marrow Transplant 1994. 13: 353–355. [PubMed: 7517257]
123.
Micklem HS, Anderson N, Ross E. Limited potential of circulating haemopoietic stem cells Nature 1975. 256: 41–43. [PubMed: 237239]
124.
Takaue Y, Watanabe T, Kawano Y, et al. Recovery kinetics of hematopoiesis after peripheral blood stem-cell autotransplantation Jpn J Cancer Chemother 1989. 16: 781–786. [PubMed: 2565703]
125.
Baumann I, Testa NG, Lange C, et al. Haemopoietic cells mobilized mobilised into the circulation by lenograstim as alternative to bone marrow for allogeneic transplants [letter] Lancet 1993: . 341:–. [PubMed: 7679177]
126.
Juttner CA, to LB. Peripheral stem cells: mobilization by myelosuppressive chemotherapy in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 783–790.
127.
Siena S, Bregni M, Bonsi L, et al. Clinical implications of the heterogeneity of hematopoietic progenitors elicited in peripheral blood by anticancer therapy with cyclophosphamide and cytokine(s) Stem Cells Dayt 1993. 11 (Suppl 2) 72–75. [PubMed: 8104618]
128.
Korbling M. The role of stem-cell mobilization in autologous blood stem-cell transplantation (ABSCT) in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 791–799.
129.
Elias AD, Mazanet R, Wheeler C, et al. GM-CSF potentiated peripheral blood progenitor cell (PBPC) collection with or without bone marrow as hematologic support of high-dose chemotherapy: two protocols Breast Can Res Treat 1991. 20: (Suppl) S25–S29. [PubMed: 1687204]
130.
Kawano Y, Takaue Y, Saito S, et al. GranulocuteGranulocyte colony-stimulating factor (CSF), macrophage-CSF, granulocute-macrophage CSF, interleukin-3, and interleukin-6 levels in sera from children undergoing blood stem-cell autografts Blood 1993. 81: 856–860. [PubMed: 7679001]
131.
Reiffers J, Marit G, Vezon G, et al. Autologous blood stem cell grafting in hematological malignancies. Present status and future directions Transfus Sci 1992; . 13: 399–405. [PubMed: 10147738]
132.
Menichella G, Pierelli L, Foddai ML. Autologous blood stem cell harvesting and transplantation in patients with advanced ovarian cancer Br J Haematol 1991. 79: 444–450. [PubMed: 1684283]
133.
To LB, Haylock DN, Dyson PG, et al. An unusual pattern of hemopoietic reconstitution in patients with acute myeloid leukemia transplanted with autologous recovery phase peripheral blood Bone Marrow Transplant 1990; . 6: 109–114. [PubMed: 1976398]
134.
Shap JG, Vaughan WP, Kessinger A, et al. Significance of detection of tumor cells in hematopoietic stem-cells harvests of patients with breast cancer in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 385–391.
135.
Williams SF, Bitran JD, Richards JM, et al. Peripheral blood-derived stem-cell collections for use in autologous transplantation after high-dose chemotherapy: an alternative approach in Gross S, Gee AP, Worthington-White DA (Eds): Bone Marrow Purging and Processing., New York: Wiley Liss, 1990. pp. 461–469.
136.
Dreyfus F, Leblond V, Belanger C, et al. Peripheral blood stem-cell collection and autografting in high-risk lymphomas Bone Marrow Transplant 1992; . 10: 409–413. [PubMed: 1464001]
137.
Shea TC, Mason JR, Storniolo AM, et al. Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy J Clin Oncol 1992. 10: 464–473. [PubMed: 1740685]
138.
Takamatsu Y, Teshima T, Akaski K, et al. Successful second autologous blood stem-cell transplantation after G-CSF-combined conditioning for the treatment of high-risk acute myelogenous leukemia Bone Marrow Transplant 1994. 13: 325–327. [PubMed: 7515302]
139.
Ashihara E, Shimazaki C, Yamagata N, et al. Reconstitution of lymphocyte subsets after peripheral blood stem-cell transplantation: two-color flow cytometric analysis Bone Marrow Transplant 1994. 13: 377–381. [PubMed: 7912603]
140.
Henon PR, Liang H, Beck-Wirt G, et al. Comparison of hematopoietic and immune recovery after autologous bone marrow or blood stem-cell Bone Marrow Transplant 1992. 9: 285–291. [PubMed: 1376185]
141.
Samson D. The current position of allogeneic and autologous BMT in multiple myeloma Leuk-Lymphoma 1992. 7 (Suppl) 33–38. [PubMed: 1283547]
142.
Sharp JG, Kessinger MA, Pirruccello SJ, et al. Frequency of detection of suspected lymphoma cells in peripheral stem-cell collections in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 801–810.
143.
Brugger W, Boss Bross KJ, Glatt M, et al. Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors Blood 1994. 83: 636–640. [PubMed: 7507729]
144.
Lopez M, Mortel O, Pouillart P, et al. Acceleration of hemopoietic recovery after autologous bone marrow transplantation by low doses of peripheral blood stem cells Bone Marrow Transplant 1991. 7: 173–181. [PubMed: 1676321]
145.
Moss TJ, Sanders DG, Lasky LC, et al. Contamination of peripheral blood stem-cell harvests by circulating neuroblastoma cells Blood 1990. 76: 1879–1883. [PubMed: 2224136]
146.
Ross AA, Cooper BW, Lazarus HM, et al. Detection and viability of tumor cells in peripheral blood stem-cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques Blood 1993. 82: 2605–2610. [PubMed: 8219214]
147.
Douer D, Chaiwum B, Glaspy J, et al. Analysis of peripheral blood progenitor cell harvests for occult breast cancer micrometastasis using a sensitive immunohistochemical method [abstr no. 51] Proc Am Soc Clin Oncol 1993. 12:62.
148.
[no authors listed] Federal Register, October 5, 1993. 58:51827.
149.
Malachowski ME, Comenzo RL, Hillyer CD, et al. Large-volume leukapheresis for peripheral blood stem-cell collection in patients with hematologic malignancies Transfusion 1992. 32: 732–735. [PubMed: 1357789]
150.
English PA, Desmith VL, Yancey EP, et al. The safety and utility of leukapheresis of normal donors for obtaining products for immunologic research [letter; comment] J Immunol Methods 1990. 135: 285–288. [PubMed: 2273264]
151.
Keilholz V, Klein HG, Korbling M, et al. Peripheral blood mononuclear cell collection from patients undergoing adoptive immunotheraphy or peripheral blood-derived stem-cell transplantation and from healthy donors J Clin Apheresis 1991. 6: 131–136. [PubMed: 1686264]
152.
Davis J, Rowley SD, Santos GW. Toxicity of autologous bone marrow graft infusion in Gross S, Gee AP, Worthington-White DA (Eds): Bone Marrow Purging and Processing., New York: Wiley Liss, 1990. pp. 531–540.
153.
Okamoto Y, Takaue Y, Saito S, et al. Toxicities associated with cryopreserved and thawed peripheral blood stem-cell autografts in children with active cancer Transfusion 1993. 33: 578–581. [PubMed: 8101399]
154.
Stone RM. Myelodysplastic syndrome after autologous transplantation for lymphoma: the price of progress? [editorial] Blood 1994. 83: 3437–3440. [PubMed: 8204870]
155.
Miller JS, Arthur DC, Litz CE, et. [al] Myelodysplastic syndome syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy Blood 1994. 83: 3780–3786. [PubMed: 8204897]
156.
Vose JM, Armitage JO. Role of autologous bone marrow transplantation in non-Hodgkin's lymphoma Hematol Oncol Clin North Am 1993. 7: 577–590. [PubMed: 8102135]
157.
Gratwohl A, Hermans J. Bone marrow transplantation activity in Europe 1992: report from the European Group for Bone Marrow Transplantation (EBMT) Bone Marrow Transplant 1994. 13: 5–10. [PubMed: 8019452]
158.
Reiffers J, Levenger G, Marit G, et al. Haematopoietic reconstitution in Gale RP, Champlin R, (Eds): Bone Marrow Transplantation: Current Controversies., New York: AR Liss, 1989. pp. 313–320.
159.
Henon PR. Blood stem-cell autografts in malignant blood disease: the French experience with a special focus on myeloma Haematologica 1990. 75 (Suppl 1) 53–59. [PubMed: 1972129]
160.
Iacone A, Dragani A, Fioritoni G, et al. Autologous blood stem-cell transplantation in hematological malignancies. The Italian experience Bone Marrow Transplant 1990. 5 (Suppl 1) 46–47. [PubMed: 1969311]
161.
Takaue Y, Hoshi Y, Abe T, et al. Treatment of childhood acute leukemias and lymphoma with high-dose chemotherapy and peripheral blood stem-cell autografts in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 811–821.
162.
Kessinger A, Vose JM, Bierman PJ, et al. High-dose therapy and autologous peripheral stem-cell transplantation for patients with bone marrow metastases and relapsed lymphoma: an alternative to bone marrow purging Exp Hematol 1991. 19: 1013–1016. [PubMed: 1680733]
163.
Brice P, Marolleau JP, Dombret H, et al. Autologous peripheral stem-cell transplantation after high-dose therapy in patients with advanced lymphomas Bone Marrow Transplant 1992. 9: 337–342. [PubMed: 1352162]
164.
Juttner CA, To LB, Roberts MM, et al. Comparison of haematologic recovery, toxicity and supportive care of autologous PBSC, autologous BM, and allogeneic BM transplants [abstr] Int J Cell Cloning 1992. 10:160.
165.
Rowlings PA, Rawling CM, To LB, et al. A comparison of peripheral blood stem-cell mobilization after chemotherapy with cyclophosplamide as a single agent in doses of 4 g/2 or 7 g/m2 in patients with advanced cancer Aust NZ J Med 1992. 22: 660–664. [PubMed: 1489289]
166.
Fermand JP, Chevret S, Ravaud P, et al. High-dose chemoradiotherapy and autologous blood stem-cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients Blood 1993. 82: 2005–2009. [PubMed: 8104534]
167.
Kawano Y, Takaue Y, Watanabe T, et al. Effect of progenitor cell dose and preleukapheresis use of recombinant granulocyte colony-stimulating factor on the recovery of hematopoiesis after blood stem-cell autografting in children Exp Hematol 1993. 21: 103–108. [PubMed: 7678082]
168.
Schwartzberg L, Birch R, Blanco R, et al. Rapid and sustained hematopoietic reconstitution by peripheral blood stem-cell infusion alone following high-dose chemotherapy Bone Marrow Transplant 1993. 11: 369–374. [PubMed: 8099300]
169.
Ayash LJ, Elias A, Wheeler C, et al. Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study J Clin Oncol 1994. 12: 37–44. [PubMed: 7505807]
170.
Brice P, Divine M, Marolleau Jp, et al. Comparison of autografting using mobilized peripheral blood stem cells with and without granulocyte colony-stimulating factor in malignant lymphomas Bone Marrow Transplant 1994. 14: 5–55. [PubMed: 7524907]
171.
Sheridan WP, Begley CG, To LB, et al. Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies Bone Marrow Transplant 1994. 14: 105–111. [PubMed: 7524904]
172.
Comenzo RL, Malachowski ME, Miller KB, et al. Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma Transfusion 1992. 32: 729–731. [PubMed: 1357788]
173.
Henon P, Beck-Wirth G, Eisenmann JC, et al. Autologous blood stem-cell transplantation (ABSCT) in high-risk myeloma in Dicke KA, Armitage JO, Dicke-Evinger MJ (Eds): Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. University of Nebraska Medical Center, 1990. pp. 841–849.
174.
Kessinger A, Armitage JO. The evolving role of autologous peripheral stem-cell transplantation following high-dose therapy for malignancies [editorial] Blood 1991. 77: 211–213. [PubMed: 1670758]
175.
Beuther Beutler E. Bone marrow transplantation beyond treatment of aplasia and neoplasia West J Med 1994. 160: 129–132. [PMC free article: PMC1022317] [PubMed: 8160463]
176.
Applelbaum FR. Hematopoietic growth factors play an important role in marrow transplantation Clinical and Society Issues in Marrow Transplantation, Meeting, Bethesda, MD, Mar 24-25, 1994. pp. 22–23.
177.
Fermand JP, Chevret S, Levy Y, et al. The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma Hematol Oncol Clin North Am 1992. 6: 451–462. [PubMed: 1349886]
178.
Jagannath S, Barlogie B. Autologous bone marrow transplantation for multiple myeloma Hematol Oncol Clin North Am 1992. 6: 437–449. [PubMed: 1582984]
179.
Holyoake TL, Franklin IM. Bone marrow transplants from peripheral blood [editorial] BMJ 1994. 309: 4–5. [PMC free article: PMC2542633] [PubMed: 7913849]
180.
Coiffier B, Philip T, Burnet AK, et al. Consensus conference on intensive chemotherapy plus hematopoietic stem-cell transplantation in malignancies, Lyon, France, Jun 4-6, 1993 Ann Oncol 1994. 5: 19–23. [PubMed: 7909684]
181.
Morse EE, Tuck D, Ascensao J, et al. Factors affecting recovery after peripheral blood stem-cell transplantation Ann Clin Lab Sci 1993. 23: 89–96. [PubMed: 7681274]
182.
Rosenfeld CS, Cullis H, Tarosky T, et al. Peripheral blood stem-cell collection using the small volume collection chamber in the Fenwal CS-3000 Plus blood cell separator Bone Marrow Transplant 1994. 13: 131–134. [PubMed: 8205081]
183.
Laporte JP, Fouillard L, Douay L, et al. GM-CSF instead of autologous bone marrow transplantation after the BEAM regimen Lancet 1991. 338: 601–602. [PubMed: 1679155]
184.
Bishop MR, Bierman PJ, Vose JM, et al. The role of high dose therapy with hematopoietic stem-cell rescue in low-grade non-Hodgkin's lymphoma Ann Oncol 1993. 4 (Suppl 1) 1–6. [PubMed: 8101723]
185.
Shpall EJ, Jones RB. Release of tumor cells from bone marrow [editorial, comment] Blood 1994. 83: 623–625. [PubMed: 7905297]
186.
Brugger W, Bross KJ, Glatt M, et al. Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors Blood 1994. 83: 636–640. [PubMed: 7507729]
187.
To LB, Roberts MM, Haylock DN, et al. Comparison of hematological haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem-cell transplants, autologous bone marrow transplants, and allogeneic bone marrow transplants Bone Marrow Transplant 1992. 9: 277–284. [PubMed: 1350938]
188.
Colombat P, Donadio D, Fouillard L, et al. Value of autologous bone marrow transplantation in follicular lymphoma: a France autogreffe retrospective study of 42 patients Bone Marrow Transplant 1994. 13: 157–162. [PubMed: 8205084]
189.
Ayash LJ. High-dose chemotherapy with autologous stem-cell support for the treatment of metastatic breast cancer Cancer 1994. 74 (Suppl 1) 532–535. [PubMed: 8004629]
190.
Van Hoef MEHM, Ranson M, Morgenstern GR, et al. Rapid haematological recovery after high-dose consolidation chemotheraphy with peripheral blood progenitor cells (PBPC) as sole source of support collected at a single apheresis Bone Marrow Transplant 1994. 13: 834–840. [PubMed: 7920325]
191.
Russell NH, Pacey S. Economic evaluation of peripheral blood stem-cell transplantation for lymphoma [letter] Lancet 1992. 340:1290. [PubMed: 1359344]
192.
Peters WP, Rosner G. A bottom line analysis of the financial impact of hematopoietic colony-stimulating factors and CSF-primed peripheral blood progenitor cells [abstr no. 14] Proc Am Soc Hematol 1991. 78:6a.
193.
Anderson JE, Litzow MR, Applelbaum FR, et al. Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease. The 21-year Seattle experience J Clin Oncol 1993. 11: 2342–2350. [PubMed: 8246023]
194.
Liberti G, Pearce R, Taghipour G, et al. Comparison of peripheral blood and autologous bone marrow transplantation for lymphoma patients: a case controlled analysis of the EBMT Registry data. Ann Oncol (in press). . [PubMed: 7911318]
195.
Bierman PJ, Armitage JO. Autologous bone marrow transplantation for non-Hodgkin's lymphoma in Forman SJ, Blume KG, Thomas ED (Eds): Bone Marrow Transplantation., Oxford: Blackwell, 1994. pp. 683–695.
196.
Phillips GL. Transplantation for Hodgkin's disease in Forman SJ, Blume KG, Thomas ED (Eds): Bone Marrow Transplantation., Oxford: Blackwell, 1994. pp. 696–708.

AHCPR Pub. No. 95-0074

PubReader format: click here to try

Views

  • PubReader
  • Print View
  • Cite this Page

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...