Mohamed A Kharfan-Dabaja1, Myriam Labopin2, Emmanuelle Polge2, Taiga Nishihori3, Ali Bazarbachi4, Jürgen Finke5, Michael Stadler6, Gerhard Ehninger7, Bruno Lioure8, Nicolaas Schaap9, Boris Afanasyev10, Moshe Yeshurun11, Cecilia Isaksson12, Johan Maertens13, Yves Chalandon14, Christoph Schmid15, Arnon Nagler2,16, Mohamad Mohty2,17. 1. Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida. 2. Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation, Paris Study Office, Paris, France. 3. Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. 4. Section of Hematology-Oncology and Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon. 5. Department of Medicine, Hematology-Oncology, University of Freiburg, Freiburg, Germany. 6. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 7. Division of Hematology, Department of Internal Medicine, Dresden University Hospital, Dresden, Germany. 8. Department of Hematology and Stem Cell Transplantation, University Hospital, Strasbourg, France. 9. Radboud University Medical Centre Nijmegen, Nijmegen, the Netherlands. 10. First State Pavlov Medical University of St. Petersburg Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St. Petersburg, Russia. 11. Hematology and BMT Department, Beilinson Hospital, Petach Tikva, Israel. 12. Department of Hematology, Umeå University Hospital, Umeå, Sweden. 13. Department of Microbiology and Immunology, Laboratory of Clinical Bacteriology and Mycology, Catholic University Leuven, University Hospitals Leuven, Leuven, Belgium. 14. Division of Hematology, University of Geneva Hospitals and University of Geneva Medical School, Geneva, Switzerland. 15. Section for Stem Cell Transplantation, Klinikum Augsburg, University of Munich, Munich, Germany. 16. Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel. 17. Hopital Saint-Antoine, Université Pierre and Marie Curie, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche U938, Paris, France.
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.
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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