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

• Published in: Bone marrow transplantation (Basingstoke) 2024-11, Vol.59 (11), p.1513-1524
• Main Authors: Shanmugasundaram, Krithika, Napier, Scott, Dimitrova, Dimana, Stokes, Anita, Wilder, Jennifer, Chai, Amy, Lisco, Andrea, Anderson, Megan V., Sereti, Irini, Uzel, Gulbu, Freeman, Alexandra F., McKeown, Christi, Sponaugle, Jennifer, Sabina, Ruby, Rechache, Kamil, Hyder, Mustafa A., Kanakry, Jennifer A., Kanakry, Christopher G.
• Format: Article
• Language: English
• Subjects: 692/699/1541/1990; 692/699/67/1059/2325; Adolescent; Adult; Aged; Allografts; Cancer immunotherapy; Cell Biology; Cell therapy; Conditioning; Cyclophosphamide; Cyclophosphamide - therapeutic use; Effectiveness; Female; Graft versus host disease; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Internal Medicine; Lymphocyte Transfusion; Lymphocytes; Male; Medicine; Medicine & Public Health; Middle Aged; Public Health; Stem cell transplantation; Stem Cells; Tissue Donors; Toxicity; Transplantation; Transplantation Conditioning - methods; Transplants; Transplants & implants; Young Adult
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-024-02312-4

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.