Fludarabine vs cladribine plus busulfan and low-dose TBI as reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation: a prospective randomized trial.
Purine analogs are often used for conditioning preceding allogeneic hematopoietic stem cell transplantation (HCT). We prospectively tested fludarabine (Flu) 40 mg/m(2)/day x 5 days vs cladribine (Clad) 10 mg/m(2)/day x 5 days plus oral busulfan (1 mg/kg q6 h x 2 days) and total body irradiation 200 cGy in 32 recipients of matched sibling and unrelated donor (URD) HCT. Patients were similar in age (median 52 years), diagnosis, extensive pre-HCT therapy (56 vs 63%), and high-risk disease status (81 vs 93%). Neutrophil engraftment was prompt (median 11 vs 12 days), but early graft failure using Clad halted randomization. Platelet recovery was prompt (median Flu 18 vs Clad 24 days). Graft-versus-host disease (GVHD) after Flu vs Clad was similar; (acute grade II/IV 56 vs 69%, P=0.26; chronic 50 vs 31%, P=0.27). Nonrelapse mortality (Flu 25 vs Clad 38%, P=0.47) and progression-free survival at 3 years were similar as well. Multivariate analyses showed slightly, but not significantly lower relative risk (RR) of neutrophil engraftment with Clad (RR 0.6 (95% CI 0.2-1.3) P=0.16) and with URD RR 0.4 (0.2-1.0) P=0.04). Older patients with advanced hematologic malignancies achieve satisfactory outcomes using either of these reduced intensity conditioning regimens.
Markova
M
M
Blood and Marrow Transplantation Program, University of Minnesota, Minneapolis, MN, USA.
Barker
J N
JN
Miller
J S
JS
Arora
M
M
Wagner
J E
JE
Burns
L J
LJ
MacMillan
M L
ML
Douek
D
D
DeFor
T
T
Tan
Y
Y
Repka
T
T
Blazar
B R
BR
Weisdorf
D J
DJ
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D016026:Bone Marrow Transplantation / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage*; D017338:Cladribine / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
D019653:Myeloablative Agonists; D017338:Cladribine; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine