Phase 2 cord blood transplantation (allogeneic hematopoietic stem-cell graft) after myeloablative conditioning in pediatric/AYA blood cancers

This Memorial Sloan Kettering Cancer Center, multi-cohort Phase 2 study tests whether umbilical cord blood transplantation (CBT)—used as a first allogeneic transplant in high-risk remission patients or as a second allogeneic transplant in very high-risk relapse settings—can deliver acceptable engraftment, relapse control, and safety. The intervention is a CBT graft plus intensive conditioning built from total body irradiation (DNA damage via ionizing radiation) and alkylator/antimetabolite chemotherapy: cyclophosphamide (DNA crosslinking alkylator), busulfan (DNA alkylator), thiotepa (DNA alkylator), fludarabine (purine analog inhibiting DNA synthesis), and clofarabine (purine nucleoside analog inhibiting DNA synthesis), followed by graft-versus-host disease prophylaxis with tacrolimus or cyclosporine (calcineurin inhibitors) plus mycophenolate mofetil (IMPDH inhibitor). Eligible diseases span ALL (MRD-negative CR1–CR2), AML (CR1–CR2), MDS, other acute leukemias, CML with prior accelerated/blast phase, Hodgkin lymphoma post-salvage without progression, and aggressive/indolent NHL, plus very high-risk cohorts including post–prior alloSCT relapse and R/R AML/ALL/MDS with MRD+ or up to ~30% blasts. The angle is operational and access-driven: cord blood can be available when matched related/unrelated donors cannot be secured quickly (here, within ~4 weeks), potentially reducing delays for patients whose window to transplant is narrow. Today’s care for these pediatric/AYA high-risk leukemias/lymphomas is multi-agent induction/consolidation (plus targeted agents when indicated), then allogeneic transplant in selected high-risk or relapsed settings—typically using matched related/unrelated donors or haploidentical donors—so this study asks whether optimized CBT can be a reliable alternative for both first and “salvage” second transplants.