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Journal of Clinical Immunology

, Volume 39, Issue 2, pp 182–187 | Cite as

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

  • Ramya UppuluriEmail author
  • Meena Sivasankaran
  • Shivani Patel
  • Venkateswaran Vellaichamy Swaminathan
  • Kesavan Melarcode Ramanan
  • Nikila Ravichandran
  • Balasubramaniam Ramakrishnan
  • Indira Jayakumar
  • Lakshman Vaidhyanathan
  • Revathi Raj
Original Article
  • 118 Downloads

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.

Keywords

Haploidentical stem cell transplantation primary immune deficiency post-transplant cyclophosphamide 

Abbreviations

CRS

Cytokine release syndrome

PID

Primary immune deficiency disorders

HSCT

Hematopoietic stem cell transplantation

Haplo SCT

Haploidentical stem cell transplantation

IL6

Interleukin 6

CMV

Cytomegalovirus

PTCy

Post-transplant cyclophosphamide

TCR

T cell receptor

USD

United states dollar

PBSC

Peripheral blood stem cells

MRD

Matched related donor

HLH

Hemophagocytic lymphohistiocytosis

WAS

Wiskott-Aldrich syndrome

MSMD

Mendelian susceptibility to mycobacterial diseases

Notes

Acknowledgements

We would like to acknowledge the immense support provided by the pediatric critical care team, the infectious disease specialists Dr. Abdul Ghafur and Dr. Vidyalakshmi, and the stem cell pheresis team in the management of these children.

Authors’ Contributions

All co-authors have reviewed the manuscript and have contributed in a substantive and intellectual manner to the work described.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ramya Uppuluri
    • 1
    Email author
  • Meena Sivasankaran
    • 1
  • Shivani Patel
    • 1
  • Venkateswaran Vellaichamy Swaminathan
    • 1
  • Kesavan Melarcode Ramanan
    • 1
  • Nikila Ravichandran
    • 1
  • Balasubramaniam Ramakrishnan
    • 1
  • Indira Jayakumar
    • 2
  • Lakshman Vaidhyanathan
    • 3
  • Revathi Raj
    • 1
  1. 1.Department of Pediatric Hematology, Oncology, Blood and Marrow TransplantationApollo HospitalsChennaiIndia
  2. 2.Department of Pediatric Critical CareApollo HospitalsChennaiIndia
  3. 3.Department of Stem Cell PheresisApollo HospitalsChennaiIndia

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