Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.
A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m(2) daily for 5 days in combination with melphalan 180 mg/m(2) (n = 66) or 140 mg/m(2) (n = 12). Eight patients received cladribine 12 mg/m(2) continuous infusion for 5 days with melphalan 180 mg/m(2). The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Nonrelapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95% CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control can be achieved with reduced-intensity conditioning in this population.
Giralt
S
S
Department of Blood and Bone Marrow Transplantation and Biomathematics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. sgiralt@notes.mdacc.tmc.edu
Thall
P F
PF
Khouri
I
I
Wang
X
X
Braunschweig
I
I
Ippolitti
C
C
Claxton
D
D
Donato
M
M
Bruton
J
J
Cohen
A
A
Davis
M
M
Andersson
B S
BS
Anderlini
P
P
Gajewski
J
J
Kornblau
S
S
Andreeff
M
M
Przepiorka
D
D
Ueno
N T
NT
Molldrem
J
J
Champlin
R
R
D000208:Acute Disease; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D017338:Cladribine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015996:Survival Rate; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D017338:Cladribine; D014740:Vidarabine; D000241:Adenosine; C024352:fludarabine; D008558:Melphalan