Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia.
Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2-3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0.001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44-58) months and 16 (3-52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.
The Bone Marrow Transplantation Center at the University of Parana, Curitiba, PA, Brazil.
J
J
Zanis-Neto
M E D
ME
Flowers
C R
CR
Medeiros
M A
MA
Bitencourt
C M
CM
Bonfim
D C
DC
Setúbal
V
V
Funke
J
J
Sanders
H J
HJ
Deeg
H P
HP
Kiem
P
P
Martin
W
W
Leisenring
R
R
Storb
R
R
Pasquini
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005199:Fanconi Anemia / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide