Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide for Primary Immune Deficiency Disorders in Children: Challenges and Outcome from a Tertiary Care Center in South India

Abstract

Haploidentical stem cell transplantation (haplo SCT) has emerged as an acceptable alternative to matched family donor transplantation for children diagnosed to have primary immune deficiency disorders (PIDs). We present data over 4 years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age diagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study. Of the 16 transplants included in the study, 5 children were diagnosed to have Wiskott-Aldrich syndrome, 3 with congenital hemophagocytic lymphohistiocytosis, 2 each with Griscelli syndrome and Mendelian susceptibility to mycobacterial diseases, and one each with Chediak-Higashi syndrome, ORAI 1 mutation immune deficiency, severe combined immune deficiency, and Hyper IgM syndrome. The source of stem cells was PBSC in 62.5% and bone marrow in 32.5%. Engraftment by day 16-21 post hematopoietic stem cell transplantation was achieved in 75% transplants with 91% of these remaining in sustained complete chimerism. Acute skin and gut graft versus host disease of grade 2-3 were noted in 50% transplants and cytomegalovirus (CMV) reactivation in 43.7% transplants. One child with congenital HLH succumbed to refractory CMV, adenovirus, and BK virus infection. Cytokine release syndrome (CRS) was noted in 75% transplants with 2 children succumbing to the illness. Tocilizumab was successfully used early in one child. Overall mortality was found to be 37.5% with overall survival of 62.5% with a median follow-up of 23.3 months. In resource limited settings, PTCy has the potential to provide a cost-effective advantage in terms of accessibility of this curative procedure among children with PIDs.

Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases

“…Recent reports focusing on haploidentical HSCT with PT-Cy in pediatric patients with nonmalignant diseases offer different promising approaches using a variety of conditioning regimens [6][7][8][9][10]. Klein et al reported HSCT of 11 children with nonmalignant disorders showing very good outcomes with limited GvHD, excellent engraftment outcomes and no treatment related mortality using a RIC regimen with fludarabine, melphalan and upfront serotherapy with alemtuzumab [9].…”

“…Our patient did not survive and died 20 days post HSCT from VOD and CMV pneumonitis. However, there are some recent reports with promising results of successful haploidentical transplants with PT-Cy for patients with HLH [8,26].…”

“…The availability, safety profile, effectiveness in reducing GvHD, and low cost of the procedure have contributed to the increasing popularity of this modality all over the world [5]. For pediatric nonmalignant diseases, regimens with PT-Cy for haploidentical HSCT are increasingly adapted as well, and recent reports of haploidentical HSCT with PT-Cy for nonmalignant diseases show feasibility of this approach and promising results [6][7][8][9][10].…”

Haematopoietic stem cell transplantation for inborn errors of immunity: 25‐year experience from University of Malaya Medical Centre, Malaysia

“…The presence of infection at time of HSCT is associated with poorer outcomes and impacts negatively on survival . Infants older than 3 months whose infection had resolved had similar survival to older infants who were never infected or young infants with/without infection, with survival rates of 82, 90 and 94%, respectively, independent of type of transplant .…”

“…HLA-haploidentical transplant for IEI has become an acceptable alternative for patients without matched donors. 11 Historically, haploidentical transplants were associated with high rates of GvHD, graft failure and transplant-related morbidity and mortality. Survival using HLA-HDs was only 66%, significantly inferior to MSD transplants for patients with SCID.…”