Hematopoietic Stem Cell Transplant for a New Primary Immunodeficiency Disorder: A Voyage Where No Transplant Physician Has Gone Before

Connelly, James

doi:10.1016/j.bbmt.2017.04.008

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…However, the landscape of PIDs has expanded markedly since the first PID transplants were performed, with >350 PIDs genetically and phenotypically now recognized and many characterized by immune dysregulation rather than solely immune deficiency [1]. Increasingly, patients with PIDs of variable natural history, hypomorphic variants, or somatic reversion are diagnosed later in life and only considered for BMT after incurring significant comorbidities or refractory disease sequelae [2][3][4]. Family members may also be affected, limiting donor options [5].…”

Section: Introductionmentioning

confidence: 99%

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

Dimitrova

Gea‐Banacloche

Steinberg

et al. 2020

Biology of Blood and Marrow Transplantation

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Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.

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