Sequential Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Intermediate- or High-Risk Acute Myeloid Leukemia in Complete Remission: A Study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
Post-transplant relapse is the leading cause of treatment failure in acute myeloid leukemia (AML) patients after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT). To improve their outcome, we evaluated the outcome of a sequential intermediate-intensity conditioning regimen combining fludarabine, cytosine arabinoside, amsacrine, cyclophosphamide, and either total body irradiation or busulfan (FLAMSA) in patients with intermediate or high-risk AML in first or second complete remission (CR). A total of 265 patients (median age, 55 years; range, 19 to 76) with AML who underwent allo-HSCT using a FLAMSA regimen were included. At the time of transplant, 216 (81.5%) were in CR1 and 49 (18.5%) in CR2. Cytogenetic was intermediate in 114 (43%) and poor in 42 (15.8%) patients, whereas 109 patients (41.1%) had a secondary AML. With a median follow-up of 46 months (range, 1 to 145), the Kaplan-Meier estimate of overall and leukemia-free survival at 2 years were 56.1% (95% CI, 49.7% to 62.6%) and 52.8% (95% CI, 46.4% to 59.2%), respectively. At 2 years, the cumulative incidences of relapse and nonrelapse mortality were 22.8% (95% CI, 17.6% to 28.4%) and 24.0% (95% CI, 18.8% to 29.5%), respectively. In multivariate analysis, patient age and cytogenetics were the only parameters with a significant impact on overall survival. These data suggest that the FLAMSA sequential intermediate conditioning regimen provides an efficient disease control in intermediate- and high-risk AML patients, including those in CR2 and with secondary AML.
Department of Haematology, Saint Antoine Hospital, Paris, France; INSERM UMRs 938, Paris, France; Pierre et Marie Curie University, Paris, France. Electronic address: malardf@yahoo.fr.
Florent
F
Malard
Department of Haematology, Saint Antoine Hospital, Paris, France.
Myriam
M
Labopin
German Diagnostic Clinic, ZMT Center, Wiesbaden, Germany.
Gernot
G
Stuhler
Department of Internal Medicine, BMT Unit, University of Saarland, University Hospital, Homburg, Germany.
Jörg
J
Bittenbring
Department of Haematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Arnold
A
Ganser
Department of Internal Medicine III, BMT Unit, Ludwig-Maximilians-University Hospital of Munich-Campus Grosshadern, Munich, Germany.
Johanna
J
Tischer
Department of Haematology, University Hospital Lyon Sud, Lyon, France.
Mauricette
M
Michallet
Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany.
Nicolaus
N
Kröger
Department of Internal Medicine, Augsburg Hospital, Ausburg, Germany.
Christoph
C
Schmid
Hematology Department, IUCT Oncopole, Toulouse, France.
Anne
A
Huynh
Department of Medicine, University of Cologne, Cologne, Germany.
Michael
M
Hallek
Haematology and Transplantation, Vanderbilt University, Nashville, Tennessee.
Bipin N
BN
Savani
Department of Haematology, Saint Antoine Hospital, Paris, France; INSERM UMRs 938, Paris, France; Pierre et Marie Curie University, Paris, France; EBMT Paris Study Office/CEREST-TC, Paris, France.
Mohamad
M
Mohty
EBMT Paris Study Office/CEREST-TC, Paris, France; Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Arnon
A
Nagler
D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D000677:Amsacrine / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006648:Histocompatibility; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D012306:Risk; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation; D055815:Young Adult
D000677:Amsacrine; D003561:Cytarabine; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Complete remission; Intermediate intensity conditioning regimen; Sequential conditioning regimen