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

• Published in: Annals of hematology Vol. 100; no. 9; pp. 2387 - 2398
• Main Authors: Heinicke, Thomas, Krahl, Rainer, Kahl, Christoph, Cross, Michael, Scholl, Sebastian, Wolf, Hans-Heinrich, Hähling, Detlev, Hegenbart, Ute, Peter, Norma, Schulze, Antje, Florschütz, Axel, Schmidt, Volker, Reifenrath, Kolja, Zojer, Niklas, Junghanss, Christian, Sayer, Herbert G., Maschmeyer, Georg, Späth, Christian, Hochhaus, Andreas, Fischer, Thomas, Al-Ali, Haifa Kathrin, Niederwieser, Dietger
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2021; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Chemotherapy; Female; Germany - epidemiology; Hematology; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Leukemia, Myeloid, Acute - epidemiology; Leukemia, Myeloid, Acute - therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Mortality; Neoplasm Recurrence, Local - therapy; Oncology; Original; Original Article; Prospective Studies; Risk factors; Transplantation, Homologous; Treatment Outcome; Young Adult; Germany; Allogeneic stem cell transplantation; Prognostic factors; Relapsed acute myeloid leukemia
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-021-04565-1

Summary
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.