Selection of the type of transplantation for a patient, autologous or allogeneic, depends on the type of malignancy, age of the recipient, availability of a suitable donor, the ability to collect a tumor-free autograft, the stage and status of disease (bone marrow involvement, bulk of disease, chemosensitivity to conventional chemotherapy), and the malignancy's susceptibility to GVM effects.

Autologous transplantation is readily available, and there is no need to identify an HLA-matched donor. Autologous transplants have a lower risk of life-threatening complications; there is no risk of GVHD and no need for immunosuppressive therapy to prevent GVHD and graft rejection. Immune reconstitution is more rapid than after an allogeneic transplant and there is a lower risk of opportunistic infections. Graft failure occurs rarely. Treatment-related mortality is lower than 5% in most studies, and elderly patients can tolerate treatment relatively well.^97,98

However, autologous transplants have several drawbacks. Since malignant cells may involve the blood and bone marrow, the autograft may be contaminated with clonogenic tumor cells that can contribute to relapse. Autologous transplantation relies solely on the effect of high-dose cytoreductive treatment and lacks the immune-mediated graft-versus malignancy effect resulting after allogeneic transplantation. In most malignancies, relapse rates are higher after autologous transplants than after allogeneic transplantation, although this is often offset by a lower rate of treatment-related mortality. Prior therapy, especially with multiple courses of alkylating agents or purine analogs, produce cumulative myelosuppression and may result in poor stem cell collection and persistent pancytopenia after transplant.⁹⁹ Patients with extensive prior therapy are at high risk for developing myelodysplasia and secondary acute leukemia after autologous hematopoietic transplantation.^100,101

Allogeneic transplantation has the advantage that the graft is free of contaminating tumor cells. The graft also includes donor-derived immunocompetent cells which may produce an immune graft-versus-malignancy effect. There is generally a lower risk for disease recurrence after allogeneic transplants compared to autologous transplantation. However, allogeneic transplants may be associated with a number of potentially fatal complications such as regimen-related organ toxicity, graft failure, and graft-versus-host disease. Immune reconstitution is slower after allogeneic transplantation and opportunistic infections are more frequent. Treatment-related mortality is significantly higher than with autologous transplantation and is increased with mismatched or unrelated allogeneic transplants compared to transplantation from an HLA-identical sibling donor.

Allogeneic hematopoietic transplantation has usually been restricted to younger patients in good general condition because of the increased risk of regimen-related toxicity and GVHD with advanced age. Most malignancies that are effectively treated by allogeneic transplantation are more common in elderly patients. The development of nonablative preparative regimens, as well as improvement in supportive care, infection control, and immunosuppressive therapy enable many centers to treat older patients, ≥ 65 years of age.^48,51,102

In general, allogeneic transplants have been used predominantly in the treatment of leukemias and myelodysplastic syndromes. Autologous transplants have been used more often in solid tumors, lymphoma, and myeloma, although nonablative allogeneic transplants are under evaluation in these disorders as a means to induce graft-versus-malignancy effects.

The outcome of transplantation relates to the selection of patients and timing of transplant during the natural history of the malignancy. The best results occur when the transplant is performed early in the disease course, when the malignancy is still sensitive to chemoradiotherapy treatment, and when the tumor burden is low. Conversely, transplants done as a last resort are associated with high rates of both relapse and treatment-related toxicity. The malignancy may also be complicated by development of infections, organ toxicity, or poor performance status over time which markedly increases the risk of transplant-related complications. Many malignancies can be initially controlled with relatively nontoxic standard forms of chemotherapy, and transplants are best employed after failure of initial treatment. In general, transplantation should be offered early in the course to patients with diseases that are at high risk for relapse or transformation to aggressive form, or to patients with early disease recurrence. The possibility of future transplant should be considered early in the course of appropriate malignancies, and early identification of a potential donor is advisable so that a transplant can be promptly performed should the disease recur.

Responsiveness to conventional-dose chemo- therapy is a major predictive factor for the outcome of hematopoietic transplant. The best results have been achieved in patients with chemosensitive relapse or when transplant was performed in high-risk patients as consolidation of response, particularly in patients with minimal disease at the time of transplant. Patients with partial response to initial chemotherapy are also good candidates. Primary resistance can sometimes be overcome by dose-intense treatment, such as in patients with acute leukemia, Hodgkin disease, or multiple myeloma which has failed to achieve an initial remission. However, patients with bulky disease, refractory relapse, or multiple relapses of their malignancy have a poor prognosis.