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Blood, 1 February 2001, Vol. 97, No. 3, pp. 631-637
CLINICAL OBSERVATONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Melphalan and purine analog-containing preparative regimens:
reduced-intensity conditioning for patients with hematologic
malignancies undergoing allogeneic progenitor cell
transplantation
Sergio Giralt,
Peter F. Thall,
Issa Khouri,
Xuemei Wang,
Ira Braunschweig,
Cindy Ippolitti,
David Claxton,
Michele Donato,
Jill Bruton,
Agueda Cohen,
Marilyn Davis,
Borje S. Andersson,
Paolo Anderlini,
James Gajewski,
Steven Kornblau,
Michael Andreeff,
Donna Przepiorka,
Naoto T. Ueno,
Jeff Molldrem, and
Richard Champlin
From the Department of Blood and Bone Marrow
Transplantation and Biomathematics, University of Texas MD Anderson
Cancer Center, Houston, TX.
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/m2 daily for 5 days in
combination with melphalan 180 mg/m2 (n = 66) or 140 mg/m2 (n = 12). Eight patients received
cladribine 12 mg/m2 continuous infusion for 5 days with
melphalan 180 mg/m2. 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.
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