Vander Lugt et al, Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders. Blood Advances 2020; 4 (13): 3041-3052
Historically, treatment-related morbidity and mortality rates have limited referrals for patients who may benefit from allogeneic hematopoietic stem cell transplantation (HSCT). A novel chemotherapy-based reduced-intensive conditioning (RIC) transplant regimen resulted in outstanding survival rates and was very effective in permitting successful engraftment for single-unit umbilical cord blood grafts in a broad range of disorders, including Krabbe disease.
- The first 44 consecutive patients with 20 genetically distinct non-malignant disorders (NMD) had a umbilical cord blood transplant (UCBT) at UPMC Children’s Hospital of Pittsburgh between September 2011 and December 2018 (www.clinicaltrials.gov: #NCT01962415).
- The median follow-up of surviving patients is 49.5 months (range, 13.3-98.4 months).
- Overall survival at 1 and 5 years posttransplantation is 95% (95% CI, 83-99) and 85% (95% CI, 67-94), respectively.
- There are several reasons this “Pitt-RIC” regimen could be transformative for children with Krabbe disease and other NMDs.
- First, the graft failure rate of <5% seen in this trial is the lowest ever reported for unmanipulated cord blood grafts in malignant or nonmalignant diseases, even when myeloablative conditioning regimens are included.
- Second, this reduced-intensive conditioning regimen was associated with a very low 1-year treatment-related mortality of 5%, resulting in >90% event-free survival at 1 year.
- Third, a single-unit cord blood graft could be identified for all 44 eligible children regardless of ethnicity, showing the unique and unparalleled suitability of cord blood grafts even with HLA allele mismatches.
- Lastly, and perhaps most importantly, this regimen is adaptable to less resource-rich countries.
- Although this is a single-center dataset, all patients had at least 12 months follow-up, and it is the largest prospective clinical trial to report on cord blood transplantation for non-malignant disorders.
- Nevertheless, due to mortality related to adenovirus and cytomegalovirus (CMV) infections, this trial failed to show superiority compared with MAC regimens
In summary, this article describes a highly effective rational RIC regimen that can be used in a number of inherited disorders including Krabbe disease for unrelated UCB grafts in whom HSCT is indicated. The favorable outcome described may help serve emerging gene therapy strategies in the near future.