Vander Lugt et al, Reduced-intensity single-unit unrelated cord blood transplantSee Umbilical Cord Blood Transplant (UCBT). with optional immune boost for nonmalignant disorders. Blood Advances 2020; 4 (13): 3041-3052 Click here to view publication
Background
Historically, treatment-related morbidity and mortality rates have limited referrals for patients who may benefit from allogeneic hematopoietic stem cell transplantation (HSCTHematopoietic stem cell transplantation (HSCT), a type of transplantation using multipotent hematopoietic stem cells typically derived from bone marrow, peripheral blood, or that from umbilical cord b). 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.
Summary
- The first 44 consecutive patients with 20 genetically distinct non-malignant disorders (NMD) had a umbilical cord blood transplant (UCBTAn umbilical cord blood transplant utilizes blood from the umbilical cord for transplantation purposes. Like bone marrow and peripheral blood, the umbilical cord is also a rich source of stem cells) 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 trialA clinical trial is research designed to understand the safety and efficacy of a drug, biologic or device. There are 4 phases to most clinical trials from Phase 1 that seeks to answer safety concern 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
Conclusion
In summary, this article describes a highly effective rational RIC regimen that can be used in a number of inheritedThe way genes are passed down from one generation to the next. There are many different types of inheritance patterns. Krabbe disease is inherited in an autosomal recessive pattern of inheritance. disorders including Krabbe disease for unrelated UCB grafts in whom HSCT is indicated. The favorable outcome described may help serve emerging gene therapyA type of therapy that offers hope and promise for a cure for many genetic disorders. A working copy of the gene replaces the non-working copy of the gene. Gene therapy is at the forefront of many strategies in the near future.