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


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 primary immune deficiency post-transplant cyclophosphamide 



Cytokine release syndrome


Primary immune deficiency disorders


Hematopoietic stem cell transplantation

Haplo SCT

Haploidentical stem cell transplantation


Interleukin 6




Post-transplant cyclophosphamide


T cell receptor


United states dollar


Peripheral blood stem cells


Matched related donor


Hemophagocytic lymphohistiocytosis


Wiskott-Aldrich syndrome


Mendelian susceptibility to mycobacterial diseases



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.


  1. 1.
    Picard C, Al-Herz W, Bousfiha A, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696–726.CrossRefGoogle Scholar
  2. 2.
    Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186–1205.e78.CrossRefGoogle Scholar
  3. 3.
    Luznik L, O’Donnell PV, Ephraim JF. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical BMT. Semin Oncol. 2012;39(6).
  4. 4.
    Al-Homsi AS, Roy TS, Cole K, Feng Y, Duffner U. Post-transplant high dose cyclophosphamide for the prevention of graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(4):604–11.CrossRefGoogle Scholar
  5. 5.
    Madkaikar M, Aluri J, Gupta S. Guidelines for screening, early diagnosis, and management of severe combined immunodeficiency (SCID) in India. Indian J Pediatr. 2016;83(5):455–62.CrossRefGoogle Scholar
  6. 6.
    Gupta S, Madkaikar M, Singh S, Sehgal S. Primary immunodeficiencies in India: a perspective. Ann N Y Acad Sci. 2012;1250:73–9.CrossRefGoogle Scholar
  7. 7.
    Jindal AK, Pilania RK, Rawat A, Singh S. Primary immunodeficiency disorders in India—a situational review. Front Immunol. 2017;8:714. Scholar
  8. 8.
    Uppuluri R, Jayaraman D, Sivasankaran M, Patel S, Swaminathan VV, Vaidhyanathan L, et al. Hematopoeitic stem cell transplantation for primary immunodeficiency disorders: experience from a referral center in India. Indian Pediatr. 2018;55(8):661–4.CrossRefGoogle Scholar
  9. 9.
    Rastogi N, Katewa S, Thakkar D, Kohli S, Nivargi S, Yadav SP. Reduced-toxicity alternate-donor stem cell transplantation with posttransplant cyclophosphamide for primary immunodeficiency disorders. Pediatr Blood Cancer. 2018;65.
  10. 10.
    Shah RM, Elfeky R, Nademi Z, Qasim W, Amrolia P, Chiesa R, et al. T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. J Allergy Clin Immunol. 2018;141(4):1417–1426.e1.CrossRefGoogle Scholar
  11. 11.
    Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, et al. Single-center experience of unrelated and Haploidentical stem cell transplantation with TCRαβ and CD19 depletion in children with primary immunodeficiency syndromes. Biol Blood Marrow Transplant. 2015;21(11):1955–62.CrossRefGoogle Scholar
  12. 12.
    Pai S, Cowan MJ. Stem cell transplantation for primary immunodeficiency diseases: the North American experience. Curr Opin Allergy Clin Immunol. 2014;14(6):521–6.CrossRefGoogle Scholar
  13. 13.
    Teachey DT, Grupp SA. Cytokine release syndrome after haploidentical stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:1735–7.CrossRefGoogle Scholar
  14. 14.
    Raj RV, Hamadani M, Szabo A, Pasquini MC, Shah NN, Drobyski WR, et al. Peripheral blood grafts for T cell-replete haploidentical transplantation increase the incidence and severity of cytokine release syndrome. Biol Blood Marrow Transplant. 2018;24(8):1664–70. Scholar
  15. 15.
    Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, et al. Severe cytokine-release syndrome after T cell–replete peripheral blood haploidentical donor transplantation is associated with poor survival and anti–IL-6 therapy is safe and well tolerated. Biol Blood Marrow Transplant. 2016;22:1851–60.CrossRefGoogle Scholar

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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