title: Fludarabine-based conditioning chemotherapy for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia.
abstract: Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m(2)/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 10(8)/kg (range, 0.60-6.7 × 10(8)/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.
authors.affiliation: Adult HSCT Program, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hazzaa
authors.initials: H
authors.lastname: Al-Zahrani
authors.forename: Amr
authors.initials: A
authors.lastname: Nassar
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Mohareb
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Sharif
authors.forename: Said
authors.initials: S
authors.lastname: Mohamed
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Anazi
authors.forename: Moosa
authors.initials: M
authors.lastname: Patel
authors.forename: Walid
authors.initials: W
authors.lastname: Rasheed
authors.forename: Abu Jafar Mohammed
authors.initials: AJ
authors.lastname: Saleh
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Bakr
authors.forename: Shad
authors.initials: S
authors.lastname: Ahmed
authors.forename: Khalid
authors.initials: K
authors.lastname: Ibrahim
authors.forename: Fazal
authors.initials: F
authors.lastname: Hussain
authors.forename: Naser
authors.initials: N
authors.lastname: Elkum
authors.forename: Tusneem
authors.initials: T
authors.lastname: Elhassan
authors.forename: Zubeir
authors.initials: Z
authors.lastname: Nurgat
authors.forename: Naeem
authors.initials: N
authors.lastname: Chaudhri
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001792:Blood Platelets / Q000166:cytology; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009504:Neutrophils / Q000166:cytology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008727:Methotrexate