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Safety but limited efficacy of donor lymphocyte infusion for post-transplantation cyclophosphamide-treated patients

  • Krithika Shanmugasundaram,
  • Scott Napier,
  • Dimana Dimitrova,
  • Anita Stokes,
  • Jennifer Wilder,
  • Amy Chai,
  • Andrea Lisco,
  • Megan V. Anderson,
  • Irini Sereti,
  • Gulbu Uzel,
  • Alexandra F. Freeman,
  • Christi McKeown,
  • Jennifer Sponaugle,
  • Ruby Sabina,
  • Kamil Rechache,
  • Mustafa A. Hyder,
  • Jennifer A. Kanakry,
  • Christopher G. Kanakry

摘要

The therapeutic efficacy of donor lymphocyte infusions (DLIs) given after allogeneic hematopoietic cell transplantation (HCT) is limited by risk of graft-versus-host disease (GVHD). Post-transplantation cyclophosphamide (PTCy) effectively prevents severe GVHD, but there are limited data on outcomes of DLIs given to PTCy-treated patients. We reviewed 162 consecutive PTCy-treated patients transplanted between 2015–2022 within the Center for Immuno-Oncology at the National Cancer Institute. Of 38 DLIs given to 21 patients after 22 HCTs, few DLIs were associated with toxicities of acute GVHD (7.8%), cytokine release syndrome (CRS, 7.8%), or chronic GVHD (2.6%), and all occurred in those receiving serotherapy-containing pre-HCT conditioning (50% of HCTs). Seven DLIs resulted in complete response (18.4%), with 5 of these given after HCTs using serotherapy-containing conditioning. Excluding infectious indications, complete response to DLIs given after transplants with versus without serotherapy-containing pre-HCT conditioning were 30% and 4.3%, respectively. Two patients received DLI for infection and experienced complete resolution without GVHD or CRS, although the efficacy cannot be definitively attributable to the DLI. DLIs given to PTCy-treated patients had low toxicity but limited efficacy, although pre-HCT serotherapy may modulate both toxicity and response. Novel strategies are needed to enhance the therapeutic efficacy of post-transplant cellular therapies without aggravating GVHD.