Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience

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 retrospectively 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 neutrophil 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-v ersus -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.

Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD

“…However, a poor response to salvage therapy in patients with relapsed or refractory FLT3 -ITD acute myeloid leukemia often prevents them from being bridged to hemopoietic stem-cell transplantation, and according to a previous publication, the best timing of allogeneic hematopoietic cell transplantation is after salvage chemotherapy if CR is achieved [ 6 , 7 ]. This is further supported by data of an extended Cox regression model combining the time-dependent covariables response to salvage therapy ( P <0.0001) and possibility to perform an allo-HCT ( P <0.0001) [ 7 , 40 ].…”

ULK2 Is a Key Pro-Autophagy Protein That Contributes to the High Chemoresistance and Disease Relapse in FLT3-Mutated Acute Myeloid Leukemia

“…Chemoresistance, which contributes to the development of refractory and relapsed diseases, is a significant challenge in the treatment of AML patients. Refractory disease, typically defined by a failure to induce complete remission, occurs in approximately 30% of patients who are treated with a curative intent [ 2 ]. Relapsed disease, typically defined by disease recurrence after a period of complete remission, occurs in approximately 50% of patients treated with a curative intent [ 3 ].…”

An In Vitro Model for Acute Myeloid Leukemia Relapse Using the SORE6 Reporter

“…Despite recent therapeutic advances, the five-year survival rate for AML patients receiving treatment with a curative intent is approximately 30% [ 1 ]. Refractory disease, defined as a failure to achieve complete remission, occurs in approximately 30% of all treated AML patients [ 2 ]. In patients who achieve complete remission after the initial treatment, disease relapses develop in 40–50% of those who are aged <65 years and in the vast majority of patients who are aged ≥65 years [ 3 , 4 ].…”