Early viral reactivation despite excellent immune reconstitution following haploidentical Bone marrow transplant with post-transplant cytoxan for sickle cell disease.
Adolescent
Adult
Anemia, Sickle Cell
/ complications
Bone Marrow Transplantation
/ adverse effects
Child
Clinical Trials, Phase II as Topic
Cyclophosphamide
/ administration & dosage
Disease-Free Survival
Graft vs Host Disease
Humans
Immune Reconstitution
Immunosuppressive Agents
/ administration & dosage
Prospective Studies
Transplantation Conditioning
/ adverse effects
Transplantation, Haploidentical
/ adverse effects
Virus Activation
Young Adult
haploidentical bone marrow transplant
immune reconstitution
sickle cell disease
viral reactivation
Journal
Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
21
08
2019
revised:
11
11
2019
accepted:
24
11
2019
pubmed:
30
11
2019
medline:
3
10
2020
entrez:
30
11
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31782875
doi: 10.1111/tid.13222
pmc: PMC10260348
mid: NIHMS1902364
doi:
Substances chimiques
Immunosuppressive Agents
0
Cyclophosphamide
8N3DW7272P
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13222Subventions
Organisme : NCI NIH HHS
ID : T32 CA217834
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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