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Original Investigation
September 2018

Association of Second Allogeneic Hematopoietic Cell Transplant vs Donor Lymphocyte Infusion With Overall Survival in Patients With Acute Myeloid Leukemia Relapse

Author Affiliations
  • 1Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida
  • 2Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation, Paris Study Office, Paris, France
  • 3Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
  • 4Section of Hematology-Oncology and Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
  • 5Department of Medicine, Hematology-Oncology, University of Freiburg, Freiburg, Germany
  • 6Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
  • 7Division of Hematology, Department of Internal Medicine, Dresden University Hospital, Dresden, Germany
  • 8Department of Hematology and Stem Cell Transplantation, University Hospital, Strasbourg, France
  • 9Radboud University Medical Centre Nijmegen, Nijmegen, the Netherlands
  • 10First State Pavlov Medical University of St. Petersburg Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St. Petersburg, Russia
  • 11Hematology and BMT Department, Beilinson Hospital, Petach Tikva, Israel
  • 12Department of Hematology, Umeå University Hospital, Umeå, Sweden
  • 13Department of Microbiology and Immunology, Laboratory of Clinical Bacteriology and Mycology, Catholic University Leuven, University Hospitals Leuven, Leuven, Belgium
  • 14Division of Hematology, University of Geneva Hospitals and University of Geneva Medical School, Geneva, Switzerland
  • 15Section for Stem Cell Transplantation, Klinikum Augsburg, University of Munich, Munich, Germany
  • 16Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
  • 17Hopital Saint-Antoine, Université Pierre and Marie Curie, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche U938, Paris, France
JAMA Oncol. 2018;4(9):1245-1253. doi:10.1001/jamaoncol.2018.2091
Key Points

Question  Does a treatment approach using a second allogeneic hematopoietic cell transplant compared with donor lymphocyte infusion yield superior overall survival for acute myeloid leukemia relapse after a first allogeneic hematopoietic cell transplant?

Findings  In this registry-based study of 418 adults, comparable overall survival was achieved with both allogeneic hematopoietic cell transplant and donor lymphocyte infusion at 2 years (26% vs 25%) and 5 years (19% vs 15%). A shorter time from the first allogeneic hematopoietic cell transplant to relapse and presence of active disease at the time of allogeneic hematopoietic cell transplant or donor lymphocyte infusion were adverse prognostic factors for overall survival.

Meaning  Allogeneic hematopoietic cell transplant or donor lymphocyte infusion appear to offer the best results in patients relapsing after 6 months from allogeneic hematopoietic cell transplant or those who attain complete remission beforehand.

Abstract

Importance  The optimal treatment approach to patients with acute myeloid leukemia (AML) who relapse after an allogeneic hematopoietic cell transplant (allo-HCT) remains elusive. No randomized clinical trial comparing survival outcomes of a second allo-HCT (allo-HCT2) vs donor lymphocyte infusion (DLI) has been conducted to date.

Objective  To compare overall survival (OS) after an allo-HCT2 or DLI in relapsed AML after a first allo-HCT.

Design, Setting, and Participants  A retrospective registry study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation involving 418 adults who received an allo-HCT2 (n = 137) or DLI (n = 281) for postallograft-relapsed AML. Analysis was assessed on the principle of intent-to-first received intervention. The data were collected from November 21, 2015, to May 15, 2017, and analysis was performed June 1, 2017.

Main Outcomes and Measures  Number of patients with relapsed AML who are alive after 2 years and 5 years from receiving an allo-HCT2 or DLI.

Results  Of the 418 patients, 228 (54.5%) were men; mean age was 46.2 years (interquartile range, 36.5-56.9 years). There was no apparent difference in OS whether an allo-HCT2 or DLI was prescribed (2-year OS with allo-HCT2, 26%; 5-year OS with allo-HCT2, 19%; 2-year OS with DLI, 25%; 5-year OS with DLI, 15%; P = .86). Overall survival was better if either of these procedures was offered when the patient was in complete remission (hazard ratio, 0.55; 95% CI, 0.41-0.74; P < .001). Conversely, OS was low for patients relapsing within less than 6 months after an allo-HCT1, regardless of the treatment prescribed (5-year OS: allo-HCT2, 9%; 95% CI, 1%-17% vs DLI, 4%; 95% CI, 1%-8%; P = .86).

Conclusion and Relevance  Heterogeneity of the patient-, disease-, and treatment-related characteristics limit the ability to recommend one approach over another. Findings of this study highlight that best outcomes seem to be achieved in patients relapsing 6 or more months from an allo-HCT1 or those in complete remission at the time of either allo-HCT2 or DLI.

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