Regimen-related toxicity after fludarabine-melphalan conditioning: a prospective study of 31 patients with hematologic malignancies.
A total of 31 consecutive patients with hematologic malignancies who were considered poor candidates for TBI underwent allogeneic stem cell transplantation after conditioning with fludarabine and melphalan. A total of 25 matched sibling recipients received fludarabine 25 mg/m(2) x 5 days and melphalan 70 mg/m(2) x 2 days. For unrelated and haploidentical donor recipients, fludarabine was increased to 30 mg/m(2) and ATG 30 mg/kg x 4 days was added. Graft-versus-host disease prophylaxis consisted of tacrolimus and mini methotrexate. All patients engrafted. Regimen-related toxicity was considerable and included mainly renal, hepatic and mucosal toxicity. There were seven regimen-related-deaths including two VOD, two pulmonary, one renal, one cardiac and one mucosal toxicity. One case of fatal pulmonary toxicity death could be attributed to pre-existing pulmonary damage. Progression-free survival at 12 months was 44% (90% CI: 30-58%) for recipients of HLA-identical sibling transplants and 33% (90% CI: 21-45%) for all patients. In conclusion, the fludarabine-melphalan regimen leads to consistent engraftment. The regimen-related toxicity is considerable and cannot be explained solely by patient selection. Cardiac toxicity is emerging as a unique toxicity of this regimen. Despite toxicity, fludarabine-melphalan has considerable activity and leads to durable remission in a proportion of patients.
Van Besien
K
K
University of Illinois at Chicago, Chicago, IL 60637, USA.
Devine
S
S
Wickrema
A
A
Jessop
E
E
Amin
K
K
Yassine
M
M
Maynard
V
V
Stock
W
W
Peace
D
D
Ravandi
F
F
Chen
Y-H
YH
Hoffman
R
R
Sossman
J
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D018572:Disease-Free Survival; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D035781:Siblings; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan