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Ferrata Storti Foundation
Haematologica 2019 Volume 104(9):1798-1803
Acute Myeloid Leukemia
Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience
Ron Ram,1 Christof Scheid,2 Odelia Amit,1 Jens Markus Chemnitz,2 Yakir Moshe,1 Michael Hallek,2 Dominik Wolf,3 Irit Avivi1 and Udo Holtick2
1Bone Marrow Transplantation Unit, Tel Aviv Medical Center and Sackler Faculty of
2
Medicine, Tel Aviv University, Tel Aviv, Israel; Department I of Internal Medicine, University
of Cologne, Cologne, Germany and 3UKIM5, Medical University Innsbruck, Innsbruck, Austria
ABSTRACT
Primary refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The FLAMSA-reduced intensity conditioning protocol (total body irradiation or treosulfan-based) has been described as an effective approach in patients with refractory leukemia undergoing allogeneic hematopoietic cell transplantation. A modified protocol (without amsacrine) has also recently been used. We retrospec- tively analyzed the transplantation characteristics and outcomes of all consecutive patients between the years 2003 and 2017 (n=51) diagnosed with primary refractory AML who underwent transplantation at the University of Cologne and the Tel Aviv Medical Center. Median age was 54 years and median follow up was 37 months. Median time to neu- trophil and platelet engraftment was 13 (range, 8-19) and 13 (range, 7-30) days, respectively. None of the patients had primary graft failure. Incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GvHD), overall and moderate-severe chronic GvHD were 50% (95%CI: 41-67%), 12% (95%CI: 3-25%), 61% (95%CI: 47-72%), and 42% (95%CI: 34-51%), respectively. Anti-thymocyte globulin administration was associated with lower incidence of acute GvHD (HR: 0.327; P=0.02). Non-relapse mortality at three months and three years were 6% and 16%, respectively. Relapse incidences were 6% and 29%, respectively. Overall survival rates at three months, three and five years were 90%, 61%, and 53%, respectively. Chronic GvHD disease was associated with a decreased mortality rate (HR: 0.397; P=0.045). We conclude that sequential therapy in patients with primary refractory acute myeloid leukemia is safe and provides a remarkable anti-leukemic effect with durable survival and should be considered for every patient with primary refractory disease.
Introduction
Primary refractory acute myeloid leukemia (AML) occurs in approximately 30% of AML patients and is a significant challenge in disease management.1,2 Prognosis is poor and the decision as to how to treat these patients depends on performance status, baseline and concomitant comorbidities, disease characteristics, and patient preference. Salvage chemotherapy, including protocols based on novel agents, results in a dismal median overall survival (OS) of 12.5 months.3
While attempts to reduce the rate of induction failure were seen to have only a modest impact,4-8 the only treatment option shown to prolong survival in patients with primary refractory disease is allogeneic hematopoietic cell transplantation (HCT).9,10 In contrast, a second conventional chemotherapy option offers almost no chance of cure for these patients.11,12 However, outcome after allogeneic HCT remains unfavorable if no response is achieved prior to transplant.10 Moreover, a substantial number of patients will never be able to undergo transplantation.
Correspondence:
RON RAM
ronram73@gmail.com
Received: August 5, 2018. Accepted: January 28, 2019. Pre-published: February 7, 2019.
doi:10.3324/haematol.2018.203869
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/9/1798
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