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

• Published in: Journal of clinical immunology Vol. 39; no. 2; pp. 182 - 187
• Main Authors: Uppuluri, Ramya, Sivasankaran, Meena, Patel, Shivani, Swaminathan, Venkateswaran Vellaichamy, Ramanan, Kesavan Melarcode, Ravichandran, Nikila, Ramakrishnan, Balasubramaniam, Jayakumar, Indira, Vaidhyanathan, Lakshman, Raj, Revathi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2019; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Bone marrow; Chediak-Higashi syndrome; Child; Child, Preschool; Children; Chimerism; Congenital diseases; Cyclophosphamide; Cyclophosphamide - therapeutic use; Cytomegalovirus; Deficiency diseases; Female; Graft-versus-host reaction; Griscelli syndrome; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histiocytosis; Humans; Immunoglobulin M; Immunology; Immunosuppressive Agents - therapeutic use; India; Infant; Infectious Diseases; Internal Medicine; Lymphocytes T; Lymphocytosis; Male; Medical Microbiology; Original; Original Article; Peripheral Blood Stem Cell Transplantation; Primary Immunodeficiency Diseases - therapy; Stem cell transplantation; Stem cells; Tertiary Care Centers; Transplantation, Haploidentical; Transplants & implants; Treatment Outcome; Wiskott-Aldrich syndrome; India; primary immune deficiency; post-transplant cyclophosphamide; Haploidentical stem cell transplantation
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-019-00600-z

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.