Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders

Abstract

<jats:title>Abstract</jats:title> <jats:p>Children with many inherited nonmalignant disorders can be cured or their condition alleviated by hematopoietic stem cell transplantation (HSCT). Umbilical cord blood (UCB) units are a rapidly available stem cell source and offer great flexibility in HLA matching, allowing nearly uniform access to HSCT. Although reduced-intensity conditioning (RIC) regimens promise decreased treatment-related morbidity and mortality, graft failure and infections have limited their use in chemotherapy-naive patients. We prospectively evaluated a novel RIC regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa with a single-unit UCB graft in 44 consecutive patients with inborn errors of metabolism, immunity, or hematopoiesis. In addition, 5% of the UCB graft was re-cryopreserved and reserved for cord donor leukocyte infusion (cDLI) posttransplant. All patients engrafted at a median of 15 days posttransplant, and chimerism was &amp;gt;90% donor in the majority of patients at 1-year posttransplant with only 1 secondary graft failure. The incidence of grade II to IV graft-versus-host disease (GVHD) was 27% (95% confidence interval [CI], 17-43) with no extensive chronic GVHD. Overall survival was 95% (95% CI, 83-99) and 85% (95% CI, 64-93) at 1 and 5 years posttransplant, respectively. No significant end-organ toxicities were observed. The use of cDLI did not affect GVHD and showed signals of efficacy for infection control or donor chimerism. This RIC transplant regimen using single-unit UCB graft resulted in outstanding survival and remarkably low rates of graft failure. Implementation of the protocol not requiring pharmacokinetic monitoring would be feasible and applicable worldwide for children with inherited disorders of metabolism, immunity, or hematopoiesis. This trial was registered at www.clinicaltrials.gov as #NCT01962415.</jats:p>

Human placenta/umbilical cord derivatives in regenerative medicine – Prospects and challenges

“…Since 1989, when UCB was first successfully used for hematopoietic cell transplant, there have been more than 40 000 such transplants for malignant and non-malignant conditions 152 like bone marrow failure syndromes, primary immunodeficiency disorders and hemoglobinopathies such as sickle cell disease and thalassemia. 153–156 An upsurge in the utilization of perinatal tissues for clinical studies followed the advent of the clinical trial registries and biobanks that ensured safer storage and faster and timely availability of tissues and respective stem cells for rapidly progressing metabolic disorders and high-risk malignancies. Even unrelated donor cord blood stem cells can be rapidly procured within a short duration of two weeks.…”

The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy

“…The MPS patients consisted of one with Hurler syndrome, who underwent transplant at 22 months of age and two children with Hunter syndrome who underwent transplant at 10 months and 1.25 years of age, respectively. They continued to achieve and improve skills, but showed mild developmental delay (Vander Lugt et al, 2020). The high molecular weight (MW) of monoclonal antibodies indicates a low CNS bioavailability, but analog to MS, effects on the peripheral immune system might secondarily impact CNS inflammation.…”

Haematopoietic stem cell transplantation for severe autoimmune diseases in children: A review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

“…Use of MUD can also remove some concerns of inherent genetic components of ADs within families. If fully matched donors are not available, umbilical cord blood (CB) has been used as a rapidly available source of haematopoietic stem cells 22–24 . However, GvHD prophylaxis remains decisive to success, in particular in non‐malignant diseases where no graft‐versus‐leukaemia (GvL) effect is required.…”

“…If fully matched donors are not available, umbilical cord blood (CB) has been used as a rapidly available source of haematopoietic stem cells. [22][23][24] However, GvHD prophylaxis remains decisive to success, in particular in non-malignant diseases where no graft-versus-leukaemia (GvL) effect is required. Furthermore, CB lackS antigen-experienced T cells, and IS associated with increased infection risk post transplant.…”