Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI “preemptively,” in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML.
Highlights
Allogeneic hematopoietic stem cell transplantation is an effective, potentially curative treatment in patients with a range of acute and chronic leukemias, based on a potent graft-versus-leukemia (GvL) immune effect [1]
A total of 342 adult patients with acute myeloid leukemia (AML) were treated with a first allo-HSCT at our unit between January 1, 2009, and December 31, 2017
Of the primary study cohort with first allo-HSCT, 292 of 342 patients (85%) met the combined day-100 landmark (CR on day +30; being alive without re-transplant on day +100) as the clinical setting most likely to qualify for future donor lymphocyte infusions (DLI) use (Online Resource 1a)
Summary
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective, potentially curative treatment in patients with a range of acute and chronic leukemias, based on a potent graft-versus-leukemia (GvL) immune effect [1]. The timing of mixed chimerism and genetic analyses was determined by routine clinical follow-up schedules, including bone marrow and peripheral blood analysis on day +30 post-transplant for remission assessment. The retrospective analysis of our single-center alloHSCT database for adult AML patients included three hierarchically ordered steps for mutually exclusive and collectively exhaustive cohort partitioning (Online Resource 1a): (i) selection of first-time allo-HSCT only, since re-transplantation in AML is associated with a very different outcome [15]; (ii) selection of alloHSCT meeting a combined landmark of CR on day +30 after transplantation and being alive without retransplantation on day +100 vs those not meeting this landmark; and (iii) stratification of allo-HSCT meeting the combined day-100 landmark by DLI use, distinguishing between first-dose DLI given prior to any hematological relapse (preDLI), first-dose DLI given after relapse (relDLI), and no DLI during follow-up. Data were analyzed using GraphPad Prism version 8.3.0 (GraphPad Software, San Diego, CA, USA), accepting p
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