Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study.

Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; P = .03), LFS (HR, 1.43; P = .01), and OS (HR, 1.55; P < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; P = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; P < .05), LFS (HR, 1.43; P = .02), and OS (HR, 1.53; P = .005) with no difference in NRM (HR, 1; P = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML.

[1]  M. Konopleva,et al.  Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. , 2017, Blood advances.

[2]  R. Geffers,et al.  Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation , 2017, Annals of Hematology.

[3]  S. Miyano,et al.  Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. , 2017, Blood.

[4]  E. Leifer,et al.  Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  L. Möllgård,et al.  Characterization and prognostic features of secondary acute myeloid leukemia in a population‐based setting: A report from the Swedish Acute Leukemia Registry , 2015, American journal of hematology.

[6]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[7]  R. Gale,et al.  SIMILAR OUTCOMES USING MYELOABLATIVE VERSUS REDUCED INTENSITY ALLOGENEIC TRANSPLANT PREPARATIVE REGIMENS FOR AML OR MDS , 2011, Bone Marrow Transplantation.

[8]  A. Groselj‐Strele,et al.  Reduced-intensity allografting in patients with therapy-related myeloid neoplasms and active primary malignancies , 2011, Bone Marrow Transplantation.

[9]  Elias Campo,et al.  The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. , 2011, Blood.

[10]  K. Döhner,et al.  The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. , 2011, Blood.

[11]  O. Gadeberg,et al.  Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML. , 2010, Cancer genetics and cytogenetics.

[12]  K. Bendix,et al.  Reasons for treating secondary AML as de novo AML , 2010, European journal of haematology.

[13]  M. Maris,et al.  Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  J. Sierra,et al.  Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  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.

[16]  G. Pond,et al.  Outcome of patients who develop acute leukemia or myelodysplasia as a second malignancy after solid tumors treated surgically or with strategies that include chemotherapy and/or radiation , 2008, Cancer.

[17]  S. Brunet,et al.  Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission , 2008, Bone Marrow Transplantation.

[18]  R. Storb,et al.  Outcomes among patients with recurrent high-risk hematologic malignancies after allogeneic hematopoietic cell transplantation. , 2007, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[19]  J. Wagner,et al.  Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis , 2007, American journal of hematology.

[20]  J. Ritz,et al.  Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[21]  G. Mufti,et al.  Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. , 2006, Blood.

[22]  Yi Ning,et al.  Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. , 2006, Blood.

[23]  A. Nagler,et al.  Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity , 2006, Leukemia.

[24]  H. Deeg,et al.  Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis , 2006, Leukemia.

[25]  J. Esteve,et al.  Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) , 2005, Leukemia.

[26]  C. Flowers,et al.  Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. , 2004, Blood.

[27]  W. Hiddemann,et al.  Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML , 2004, Leukemia.

[28]  S. Chevret,et al.  Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  R. Storb,et al.  Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy. , 1997, Blood.