Allogeneic hematopoietic stem cell transplantation improves long-term outcome for relapsed AML patients across all ages: results from two East German Study Group Hematology and Oncology (OSHO) trials

Abstract

Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Of the non-refractory patients, 48.4% with a median age of 63 (range 17-85) years relapsed. Relapses occurred within 6 months after CR in 46.5%, between 7 and 18 months in 38.7%, and after 18 months in 14.8% of patients. Relapse treatment resulted in CR2 in 39% of patients depending upon age (54.5% of ≤ 60 and 28.6% of > 60 years), duration of CR1, and treatment of relapse. Overall survival (OS) was 10.9 (7.4-16.2) %, but OS after HCT ± intensive chemotherapy (ICT) was 39.3% (31.8-48.6) at 5 years and not different in younger and older patients. Donor lymphocyte infusion ± chemotherapy and ICT alone resulted only in OS of 15.4% and of 5%, respectively. Independent favorable factors for OS were long CR1 duration, and HCT, while non-monosomal disease was beneficial for OS in elderly patients. Leukemia-free survival [LFS; 24.9 (19.5-31.7) % at 10 years] was affected by similar risk factors. In a competing risk model, the relapse incidence at 5 years was 53.5 ± 3.5% and the non-relapse mortality rate 21.7 ± 2.9%. Lower relapse incidence was observed in patents with HCT, long CR1 duration, and female gender. Risk factors for non-relapse mortality were HCT in younger and type of AML in elderly patients. In conclusion, allogeneic HCT ± IC improved the results in relapsed AML in younger and elderly patients. Increasing CR2 rates and HCT frequency will be the challenge for the next years. Relapse of the disease remains the major problem.

Keywords: Allogeneic stem cell transplantation; Prognostic factors; Relapsed acute myeloid leukemia.

Fig. 1

(Newly diagnosed patients). A Overall survival for newly diagnosed AML patients (n = 1621), for younger (≤ 60 years; n = 740), and for elderly (> 60 years; n = 881) patients entered in the OSHO studies. B Overall survival for all patients, for younger (≤ 60 years), and for elderly (> 60 years) patients (n = 1621) according to remission status. Abbreviations: CR1 ind., after one induction; CR1 after 2 ind., CR1 after two inductions; PR, partial remission; NR, nonresponse (2 circles in Fig. 1B are showing younger and elderly patients in CR and CRi). C Leukemia-free survival (LFS) of patients with AML (all n = 1144) according to age. D Non-relapse mortality (NRM) and relapse incidence (RI) for newly diagnosed AML patients according to age (all ages, patients ≤ 60 years and > 60 years)

Fig. 2

(Relapsed patients). A Overall survival (OS) of patients with AML after first relapse according to age. B Overall survival (OS) of patients with AML after first relapse according to de novo, secondary, and therapy-related AML. C Overall survival (OS) of patients with AML after first relapse according to favorable, intermediate, and unfavorable cytogenetics. D Overall survival (OS) of patients with AML after first relapse according to time interval CR1 and relapse in months

Fig. 3

A Overall survival (OS) of patients with AML after first relapse according to age and therapy. Patients were treated with HCT ± induction chemotherapy (ICT), ICT alone, and palliative/supportive treatment. B Relapse incidence (RI) and non-relapse mortality (NRM) in patients with AML after first relapse (all ages, patients ≤ 60 years and > 60 years)