title: Pretransplant immunosuppression followed by reduced-toxicity conditioning and stem cell transplantation in high-risk thalassemia: a safe approach to disease control.
abstract: Patients with class 3 thalassemia with high-risk features for adverse events after high-dose chemotherapy with hematopoietic stem cell transplantation (HSCT) are difficult to treat, tending to either suffer serious toxicity or fail to establish stable graft function. We performed HSCT in 18 such patients age ≥7 years and hepatomegaly using a novel approach with pretransplant immunosuppression followed by a myeloablative reduced-toxicity conditioning regimen (fludarabine and i.v. busulfan [Flu-IV Bu]) and then HSCT. The median patient age was 14 years (range, 10 to 18 years). Before the Flu-IV Bu + antithymocyte globulin conditioning regimen, all patients received 1 to 2 cycles of pretransplant immunosuppression with fludarabine and dexamethasone. Thirteen patients received a related donor graft, and 5 received an unrelated donor graft. An initial prompt engraftment of donor cells with full donor chimerism was observed in all 18 patients, but 2 patients developed secondary mixed chimerism that necessitated withdrawal of immunosuppression to achieve full donor chimerism. Two patients (11%) had acute grade III-IV graft-versus-host disease, and 5 patients had limited chronic graft-versus-host disease. The only treatment-related mortality was from infection, and with a median follow-up of 42 months (range, 4 to 75), the 5-year overall survival and thalassemia-free survival were 89%. We conclude that this novel sequential immunoablative pretransplantation conditioning program is safe and effective for patients with high-risk class 3 thalassemia exhibiting additional comorbidities.
authors: Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Usanarat
authors: U
authors: Anurathapan
authors: Samart
authors: S
authors: Pakakasama
authors: Piya
authors: P
authors: Rujkijyanont
authors: Nongnuch
authors: N
authors: Sirachainan
authors: Duantida
authors: D
authors: Songdej
authors: Ampaiwan
authors: A
authors: Chuansumrit
authors: Somtawin
authors: S
authors: Sirireung
authors: Pimlak
authors: P
authors: Charoenkwan
authors: Arunee
authors: A
authors: Jetsrisuparb
authors: Surapol
authors: S
authors: Issaragrisil
authors: Artit
authors: A
authors: Ungkanont
authors: Rosarin
authors: R
authors: Sruamsiri
authors: Supanart
authors: S
authors: Srisala
authors: Borje S
authors: BS
authors: Andersson
authors: Suradej
authors: S
authors: Hongeng
mesh_terms: D000293:Adolescent; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D012307:Risk Factors; D013789:Thalassemia / Q000188:drug therapy* / Q000601:surgery*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Class 3 high-risk thalassemia; Reduced-toxicity conditioning; Transplantation
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