Allogeneic stem cell transplantation following relapse post autologous stem cell transplantation in adult patients with acute myeloid leukemia: A retrospective analysis of 537 patients from the Acute Leukemia Working Party of the EBMT

Patients with acute myeloid leukemia (AML) who relapse after autologous stem cell transplantation (ASCT) can be rescued by allogeneic SCT. We identified 537 adult patients with AML allografted in second complete remission (CR2) or first relapse after ASCT in the European Society for Blood and Marrow Transplantation (EBMT) registry. At 3 years post allograft, leukemia free survival (LFS) was 31.4% [95%CI 27.3‐35.6], overall survival (OS) 39.5% [95%CI 35.1‐43.9], relapse incidence (RI) 34.6% [95%CI 30.4‐38.8], and nonrelapse mortality (NRM) 33.7% [95%CI 29.6‐37.9]. RI was higher in patients transplanted in relapse in comparison to those transplanted in CR2 (HR 1.76, P = .004) and in patients who relapsed later after ASCT (HR 0.97 per month, P < 10−3), both translating into better LFS/ OS. Relapse was also lower in patients undergoing allogeneic stem cell transplantation (allo‐HSCT) from an unrelated donor (UD) in comparison to those transplanted from a matched sibling donor (MSD) (HR 0.49, P < 10−3). NRM was increased in patients who received total body irradiation (TBI) pre‐ASCT (HR 2.43; P < 10‐4), translating into worse LFS/OS. LFS/OS did not differ between patients allotransplanted with reduced intensity (RIC) or myeloablative (MAC) conditioning. In conclusion, one third of adult patients with AML relapsing post ASCT can be rescued with allo‐HSCT, with better LFS/OS in patients who relapsed later post ASCT, those transplanted in CR2 and those who had not received TBI pre‐ASCT.

[1]  M. Labopin,et al.  Optimizing the Pretransplant Regimen for Autologous Stem Cell Transplantation in Acute Myelogenous Leukemia : Better Outcomes with Busulfan and Melphalan Compared with Busulfan and Cyclophosphamide in High Risk Patients Autografted in First Complete Remission , 2017 .

[2]  H. Döhner,et al.  Midostaurin in FLT3-Mutated Acute Myeloid Leukemia. , 2017, The New England journal of medicine.

[3]  M. Labopin,et al.  Unrelated matched versus autologous transplantation in adult patients with good and intermediate risk acute myelogenous leukemia in first molecular remission , 2017, American journal of hematology.

[4]  A. Vekhoff,et al.  Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms‐like tyrosine kinase 3‐mutated acute myeloid leukemia , 2017, Cancer.

[5]  B. Quesnel,et al.  Impact of Wilms' tumor 1 expression on outcome of patients undergoing allogeneic stem cell transplantation for AML , 2017, Bone Marrow Transplantation.

[6]  J. Esteve,et al.  Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT , 2016, Bone Marrow Transplantation.

[7]  A. Ganser,et al.  Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study , 2016, Journal of Hematology & Oncology.

[8]  M. Labopin,et al.  Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP–EBMT analysis on patients with AML in remission , 2016, Bone Marrow Transplantation.

[9]  K. Ohashi,et al.  Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR , 2016, Bone Marrow Transplantation.

[10]  M. Labopin,et al.  Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects , 2015, Bone Marrow Transplantation.

[11]  E. Estey,et al.  Sorafenib treatment following hematopoietic stem cell transplant in pediatric FLT3/ITD acute myeloid leukemia , 2015, Pediatric blood & cancer.

[12]  E. Vellenga,et al.  Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years , 2014, Leukemia.

[13]  R. Berger,et al.  Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation , 2014, Haematologica.

[14]  V. V. D. van der Velden,et al.  High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  J. Szer,et al.  Unrelated donor allogeneic transplantation after failure of autologous transplantation for acute myelogenous leukemia: a study from the center for international blood and marrow transplantation research. , 2013, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[16]  J. Szer,et al.  Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research , 2013, Haematologica.

[17]  E. Vellenga,et al.  Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. , 2011, Blood.

[18]  L. Robison,et al.  Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. , 2010, Blood.

[19]  R. Hills,et al.  Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. , 2010, Blood.

[20]  B. Sandmaier,et al.  Defining the intensity of conditioning regimens: working definitions. , 2009, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[21]  G. Vogelsang,et al.  Chronic graft versus host disease , 2004, British journal of haematology.

[22]  S. Rives,et al.  Allogenic stem cell transplantation as salvage therapy for patients relapsing after autologous transplantation: experience from a single institution. , 2001, Leukemia research.

[23]  M. Slovak,et al.  Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study , 2000 .

[24]  M. Labopin,et al.  The dismal outcome in patients with acute leukaemia who relapse after an autograft is improved if a second autograft or a matched allograft is performed , 2000, Bone Marrow Transplantation.

[25]  T. Barbui,et al.  Allogeneic bone marrow transplant or second autograft in patients with acute leukemia who relapse after an autograft , 1999, Bone Marrow Transplantation.

[26]  J P Klein,et al.  Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. , 1999, Statistics in medicine.

[27]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[28]  J Crowley,et al.  Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. , 1999, Statistics in medicine.

[29]  N. Gorin Autologous stem cell transplantation in acute myelocytic leukemia. , 1998, Blood.

[30]  N. Callander,et al.  Allogeneic bone marrow transplantation in patients who relapse after autologous transplantation , 1997, Bone Marrow Transplantation.

[31]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[32]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[33]  M. Kiehl,et al.  Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant , 2000, Bone Marrow Transplantation.

[34]  P. Hougaard,et al.  Frailty models for survival data , 1995, Lifetime data analysis.

[35]  D.,et al.  Regression Models and Life-Tables , 2022 .