Allogeneic hematopoietic cell transplantation for partial RAG deficiency in children and adults: Excellent outcomes with a reduced-intensity posttransplantation cyclophosphamide-based approach.
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История · было → стало
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Dimitrova Dimana, Bosticardo Marita, Delmonte Ottavia M, Kenney Heather, An Annie, Pala Francesca, Magro Gloria, Myint-Hpu Katherine, Kang Esther, Santangeli Enrico, Angelova Angelina, Vujkovic-Cvijin Ivan, Schwarz Benjamin, Campos Jessenia, Chai Amy, Cusmano Alison, Flomerfelt Francis A, Hyder Mustafa A, Mangusan Ralph, Rechache Kamil, Sabina Ruby, Telford William, Kong Heidi H, Nagao Keisuke, Agharahimi Anahita, Bergerson Jenna R E, Freeman Alexandra F, Holland Steven M, Ale Hanadys, El-Marsafy Aisha, Pasic Srdjan, Verbsky James, Walter Jolan, Kanakry Christopher G, Notarangelo Luigi D, Kanakry Jennifer A
Аннотация
OBJECTIVE: Our study evaluated low-toxicity approaches to HCT for pRD.
METHODS: Thirteen children and adults with pRD received radiation-free, predominantly reduced-intensity conditioning (pentostatin/cyclophosphamide/busulfan) HCT with posttransplantation cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis at median (range) age 20 (4-46) years.
RESULTS: With median 2.6 years' follow-up, overall survival for the entire cohort was estimated at 92% and 83% at 1 and 2 years and 100% and 90% for reduced-intensity conditioning recipients (n = 12), with 2 deaths attributed to sepsis. Reversal of clinical manifestations was associated with immune reconstitution, with minimal de novo autoimmunity, 15% 1-year cumulative incidence of grade III-IV acute GVHD, and no chronic GVHD. Vα7.2-positive T-cell proportion increased rapidly after HCT, while mucosa-associated invariant T-cell reconstitution lagged. Dysreactive CD19hiCD21lo and 9G4+ B cells decreased after HCT, along with clinically relevant autoantibodies. However, baseline elevated anti-type I interferon antibodies, potentially predisposing to severe viral infections, decreased slowly, although neutralizing activity was reduced at last follow-up. Outcomes did not differ by donor carrier status or HLA matching. Bronchiectasis exacerbations incurred rehospitalizations in long-term follow-up of patients who entered HCT with irreversible lung disease.
CONCLUSION: Reduced-intensity conditioning HCT with posttransplantation cyclophosphamide-based GVHD prophylaxis is safe and effectively reverses immune dysfunction in patients with pRD.