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High-dose therapy for refractory multiple myeloma: improved prognosis with
better supportive care and double transplants
DH Vesole, B Barlogie, S Jagannath, B Cheson, G Tricot, R Alexanian and J Crowley
Division of Hematology/Oncology, University of Arkansas for Medical
Sciences, Little Rock 72205.
One hundred and thirty-five patients with advanced and refractory myeloma
received one of three high-dose therapy regimens: melphalan at doses of 90
to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body
irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750
mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma
cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both
peripheral blood stem cells (PBSC) and ABMT plus GM- CSF intended as a
double-transplant program (67 patients; 42 have completed and 3 are still
awaiting a second autotransplant; 5 additional patients received an
allograft for their second transplant). Mortality within 2 months of
therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with
MEL 200, mainly because severe neutropenia (< 500/microL) was shortened
to less than 1 week due to infusion of PBSC and use of growth factor
therapy. Low beta 2- microglobulin (beta 2M) levels < or = 2.5 mg/L and
MEL 200 therapy were identified as the two most important independent
favorable variables associated with prolonged event-free survival (EFS) and
overall survival (OS). On the basis of these two parameters, three risk
groups were defined: 29 good-risk patients with low beta 2M receiving MEL
200 had the best outcome, with median durations of EFS of 37 months and
projected OS of > or = 43 months; 54 intermediate-risk patients
displaying one of the two favorable parameters had EFS and OS durations of
16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M
not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS
of 5 months (all P < .0001). Further analysis that excluded treatment as
a variable identified high beta 2M and resistant relapse as the two major
adverse prognostic factors, one of which was present in 80% of the 135
patients. Among these 108 high-risk patients, prognosis was improved
markedly with MEL 200 because of both better supportive care (PBSC and
hematopoietic growth factors) and more intensive therapy using the
double-transplant approach. This study supports the concept that safer and
potentially more-effective therapies can be developed in the setting of
advanced and resistant disease.
Volume 84,
Issue 3,
pp. 950-956,
08/01/1994
Copyright © 1994 by The American Society of Hematology
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