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Haematologica. 2016 Jul;101(7):839-45. doi: 10.3324/haematol.2015.141622. Epub 2016 Apr 1.

Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy.

Author information

1
Department of Internal Medicine III, University Hospital Ulm, Germany.
2
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
3
Department of Oncology and Hematology, Klinikum Braunschweig, Germany Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany.
4
Department of Oncology and Hematology, Klinikum Oldenburg, Germany.
5
Department of Internal Medicine II, University Hospital Schleswig-Holstein Campus Kiel, Germany.
6
Department of Internal Medicine III, CIO, University Hospital of Bonn, Germany.
7
Department of Hematology/Oncology, University-hospital Giessen, Germany.
8
Department of Internal Medicine III, Technical University of Munich, Germany.
9
Department of Hematology/Oncology, Hanuschkrankenhaus, Wien, Austria.
10
Department of Medical Oncology and Hematology, Krankenhaus der Barmherzigen Schwestern, Linz, Austria.
11
Department of Hematology/Oncology, Asklepios Klinik Altona, Hamburg, Germany.
12
Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
13
Department of Hematology/Oncology, Krankenhaus der Barmherzigen Brüder, Trier, Germany.
14
Department of Hematology and Oncology, Georg-August-University Hospital of Göttingen, Germany.
15
Department of Hematology/Oncology, Caritas-Krankenhaus, Lebach, Germany.
16
Department of Medicine III, Johannes Gutenberg-University Mainz, Germany.
17
Department of Hematology/Oncology, Caritas-Krankenhaus, Saarbrücken, Germany.
18
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany.
19
Department of Internal Medicine III, University Hospital Ulm, Germany richard.schlenk@uniklinik-ulm.de.

Abstract

Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (3 g/m(2)/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m(2) intravenously on days 2-3) in 93 patients aged 18-60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy. (clinicaltrials.gov identifier: 00143975).

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00143975.

PMID:
27036160
PMCID:
PMC5004463
DOI:
10.3324/haematol.2015.141622
[Indexed for MEDLINE]
Free PMC Article

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