Early viral reactivation despite excellent immune reconstitution following haploidentical Bone marrow transplant with post-transplant cytoxan for sickle cell disease

Dilan A. Patel, Nathalie Dhedin, Heidi Chen, Leena Karnik, Katie Gatwood, Katie Culos, Sanjay Mohan, Brian G. Engelhardt, Carrie Kitko, Jim Connelly, Gowri Satyanarayana, Madan Jagasia, Josu De La Fuente, Adetola Kassim

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4 Scopus citations

Abstract

Background: Haploidentical bone marrow transplant (haplo-BMT) offers near universal donor availability as a curative modality for individuals with severe sickle cell disease (SCD). However, the required intense immunodepletion is associated with increased infectious complications. A paucity of data exists on immune reconstitution following haplo-BMT for SCD. Methods: A multi-institution learning collaborative was developed in the context of a phase II clinical trial of a non-myeloablative, related haplo-BMT with post-transplant cyclophosphamide for SCD. We report results from a cohort of 23 patients for whom immune reconstitution data up to one year were available. Results: Median age was 14.8 years. Out of 23, 18 participants received pre-conditioning with azathioprine, hydroxyurea, and hypertransfusions. 70% (16/23) of participants had multiple indications for haplo-BMT. We observed excellent immune reconstitution of CD4, CD8, CD19, and CD56 cellular subsets by 6 months post transplant. Engraftment rate and event-free survival in this cohort were 100% and 96%, respectively. 70% (16/23) of patients had at least one viral reactivation or infection, including CMV 35% (8/23), HHV-6 22% (5/23), and polyoma virus 17% (4/23), with no cases of post-transplant lymphoproliferative disease. Conclusion: Further prospective studies are needed to better characterize immune reconstitution and the immunologic basis for increased viral reactivation following haplo-BMT with post-transplant cyclophosphamide for SCD.

Original languageEnglish
Article numbere13222
JournalTransplant Infectious Disease
Volume22
Issue number1
DOIs
StatePublished - Feb 1 2020

Keywords

  • haploidentical bone marrow transplant
  • immune reconstitution
  • sickle cell disease
  • viral reactivation

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