T-cell depleted, immunoregulatory-enriched grafts with RIC

Current understanding

Reduced intensity conditioning (RIC) paired with ex vivo T-cell depletion of donor grafts — engineered to enrich immunoregulatory populations — is being explored as a strategy to enable allo-HCT in older or unfit patients with advanced hematologic malignancies, including MPNs. The approach aims to preserve immune reconstitution and graft-versus-tumor activity while reducing GVHD, and is applicable to both matched and haploidentical donor settings. Evidence is currently early-trial stage.

Evidence log

• 2026-07-20 — Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis: cross-connection with ric-haplo-hct-myelofibrosis: Two parallel GVHD-mitigation strategies for RIC allo-HCT in MF: peri-transplant pharmacologic JAK inhibition vs T-cell depleted / immunoregulatory-enriched graft engineering. (novelty: 3)
• 2026-07-01 — CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene: CASPALLO (iCasp9 suicide-gene allodepleted donor T cells + AP1903 dimerizer) offers a complementary lever within the T-cell-depleted graft paradigm: rather than only depleting/enriching populations ex vivo, engineered add-back T cells can be pharmacologically eliminated if GvHD emerges, potentially permitting higher T-cell doses to accelerate immune reconstitution. (novelty: 4)
• 2026-04-08 — Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft: cross-connection with peritransplant-ruxolitinib-gvhd: Both target GVHD reduction in MPN/advanced hematologic malignancy transplant — graft engineering vs. pharmacologic JAK inhibition represent complementary GVHD-prevention axes that could be combined or compared. (novelty: 3)

Open questions

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