Optimized Cord Blood Transplantation for the Treatment of Patients With High-risk Hematologic Malignancies Who Have Relapsed After First Allogeneic Stem Cell Transplantation

Researchers with the Department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center are currently recruiting patients for a trial of optimized cord blood transplantation (CBT) for second transplantation of patients with acute leukemia or myelodysplastic syndrome (MDS) who relapsed after first allogeneic stem cell transplantation (https://clinicaltrials.gov NCT06807606).  

CBT is associated with robust graft-versus-leukemia effect. Data from multiple centers in North America (e.g. at Fred Hutch Sloan Kettering), Europe (UK/Ireland), and Asia (Japan, China) have shown lower relapse with CBT compared with matched related and matched or mismatched unrelated donor transplants. Multiple series have shown decreased risk of relapse in patients with measurable residual disease and/or high-risk molecular mutations prior to transplant. CBT has also been used in the second/ third transplantation setting for pediatric patients with a recently published Sloan Kettering study of 26 patients with hematologic malignancies (median age at first HCT 11.5 years, median time from 1st HCT to relapse of 1.1 years) showing encouraging overall survival (3-year overall survival rate 69.2%) and remarkable low relapse rate (15.9% at 3 years; Lucas et al., Front. Onc. 2023). Multiple potential mechanisms explain the unique cord blood graft-versus-leukemia biology, with translational data supporting potential roles of increased mismatch with cord blood grafts over other graft sources, unique immune properties of cord blood-derived immune cells or immune reconstitution following CBT, maternal micro-chimerism’s/ shared inherited paternal antigens, reduced likelihood of HLA-loss as a mechanism of relapse, and, for double cord blood grafts, graft-versus-graft interactions.  

On the background of these clinical and translational data, MD Anderson launched a phase II clinical trial studying cord blood transplantation in the second transplant setting for patients with acute leukemia or myelodysplastic syndrome who relapsed after first allogeneic stem cell transplantation. Adult and pediatric patients are eligible if ≤60 years, with acute leukemia or MDS/chronic myelomonocytic leukemia which relapsed >100 days after first allogeneic transplantation. Patients receive conditioning with the medium dose intensity conditioning regimen pioneered by Dr. Juliet Barker et al. with the Cord Blood Transplantation Program at Memorial Sloan Kettering Cancer Center, including Fludarabine 150mg/m2, Cyclophosphamide 50mg/kg, Thiotepa 5-10mg/kg, and 400 cGy of Total Body Irradiation. Patients receive graft-versus-host disease prophylaxis with tacrolimus and mycophenolate mofetil (MMF). For more information or to refer a patient, please contact the study PI Dr. Warren Fingrut at [email protected].

Submitted by Dr. Warren Fingrut, MD Anderson