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Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia.

ABSTRACT: Donor lymphocyte infusion (DLI) is commonly used to treat leukemia relapse following stem cell transplantation. In florid relapse, however, the efficacy of DLI is limited with substantial risk of severe graft-versus-host disease (GvHD). Here, we develop a novel risk-adapted strategy characterized by pre-emptive DLI initiated at the time of mixed chimerism, a small starting dose based on donor source, dose-escalation guided by real-time chimerism monitoring and withholding of DLI immediately in patients achieving full donor chimerism. A total of 178 DLIs were given to 38 patients with mixed chimerism; thereafter, 33 patients (86.8%) had donor chimerism successfully increased, including 30 (78.9%) who had chimerism fully converted back to 100% donor. Cumulative incidence of relapse was significantly lower (P=0.00004) and overall survival higher (P=0.0003) in patients with chimerism fully corrected as compared with those of patients whose chimerism remained mixed. Only 13.2% of the patients developed acute grade III-IV GvHD with no associated mortality. In conclusion, the risk-adapted DLI strategy is useful in minimizing the risk of childhood leukemia relapse, GvHD and death.

SUBMITTER: Rujkijyanont P

PROVIDER: S-EPMC3763390 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia.

Rujkijyanont P P Morris C C Kang G G Gan K K Hartford C C Triplett B B Dallas M M Srinivasan A A Shook D D Pillai A A Pui C-H CH Leung W W

Blood cancer journal 20130830

Donor lymphocyte infusion (DLI) is commonly used to treat leukemia relapse following stem cell transplantation. In florid relapse, however, the efficacy of DLI is limited with substantial risk of severe graft-versus-host disease (GvHD). Here, we develop a novel risk-adapted strategy characterized by pre-emptive DLI initiated at the time of mixed chimerism, a small starting dose based on donor source, dose-escalation guided by real-time chimerism monitoring and withholding of DLI immediately in p ...[more]

PMID: 23995046

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Project description:ImportanceThe 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.ObjectiveTo compare overall survival (OS) after an allo-HCT2 or DLI in relapsed AML after a first allo-HCT.Design, setting, and participantsA 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 measuresNumber of patients with relapsed AML who are alive after 2 years and 5 years from receiving an allo-HCT2 or DLI.ResultsOf 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 relevanceHeterogeneity 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.

Dataset Information

Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia.

Publications

Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia.

Similar Datasets

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