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. 2018 Sep 1;4(9):1245-1253.
doi: 10.1001/jamaoncol.2018.2091.

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

Mohamed A Kharfan-Dabaja  1 , Myriam Labopin  2 , Emmanuelle Polge  2 , Taiga Nishihori  3 , Ali Bazarbachi  4 , Jürgen Finke  5 , Michael Stadler  6 , Gerhard Ehninger  7 , Bruno Lioure  8 , Nicolaas Schaap  9 , Boris Afanasyev  10 , Moshe Yeshurun  11 , Cecilia Isaksson  12 , Johan Maertens  13 , Yves Chalandon  14 , Christoph Schmid  15 , Arnon Nagler  2   16 , Mohamad Mohty  2   17
Affiliations

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

Mohamed A Kharfan-Dabaja et al. JAMA Oncol. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kharfan-Dabaja is a member of the speakers bureau for Seattle Genetics, Incyte Corp, and Alexion Pharmaceuticals and has participated in an advisory board of Pharmacyclics. Dr Nishihori has received research funding from Novartis. Dr Yeshurun owns stock in Kalytera Therapeutics Inc and royalties and other intellectual property in Kalytera Therapeutics Inc. Dr Maertens is a member of the speakers bureau of Astellas Pharma, MSD, Pfizer, Gilead Sciences, and Basilea and received compensation for travel, accommodations, and expenses from Astellas Pharma, MSD, Pfizer, Gilead Sciences, and Basilea. Dr Chalandon has consulting/advisory roles for Novartis, Incyte Corp, Amgen, and Erytech Pharma and received compensation for travel, accommodations, and expenses from Roche, MSD, Jazz Pharmaceuticals, BMS, and Pfizer. Dr Isaksson has consulting and advisory roles for MolMed and Jazz Pharmaceuticals; is a member of the speakers bureau for Celgene, Novartis, and Incyte Corp; and has received research funding from Celgene, Novartis, and Incyte Corp. Dr Mohty has received honoraria from Sanofi, Janssen, Amgen, Celgene, Takeda, Novartis, Jazz Pharmaceuticals, MolMed, and BMS; has consulting/advisory roles for Sanofi, Jazz Pharmaceuticals, and MolMed; is a member of the speakers bureau for Sanofi, Janssen, Amgen, Jazz Pharmaceuticals, and MolMed; has received research funding from Sanofi, Jazz Pharmaceuticals, BMS; and has received compensation for travel, accommodations, and expenses from Sanofi.

Figures

Figure 1.
Figure 1.. Overall Survival (OS) with a Second Allogeneic Hematopoietic Cell Transplant (Allo-HCT2) vs Donor Lymphocyte Infusion (DLI) in All Patients
Two-year OS for allo-HCT2, 26% (95% CI, 19%-33%) and DLI, 25% (95% CI, 20%-30%) (P = .86).
Figure 2.
Figure 2.. Overall Survival (OS) With a Second Allogeneic Hematopoietic Cell Transplant (Allo-HCT2) vs Donor Lymphocyte Infusion (DLI) in Patients With vs Without Complete Remission (CR)
A, Two-year OS with allo-HCT2 in patients with CR (35%; 95% CI, 22%-48%) vs no CR (active disease at the time of intervention) (20%; 95% CI, 11%-29%) (P = .002). B, OS with DLI in patients with CR (51%; 95% CI, 36%-65%) vs no CR (active disease at the time of intervention) (19%; 95% CI, 14%-25%) (P < .001).
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