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Autologous bone marrow transplantation in multiple myeloma: identification
of prognostic factors
S Jagannath, B Barlogie, K Dicke, R Alexanian, G Zagars, B Cheson, FC Lemaistre, L Smallwood, K Pruitt and DO Dixon
Division of Hematology-Oncology, University of Arkansas for Medical
Sciences, Little Rock, AR 72205.
Multiple myeloma remains a universally fatal malignancy with a median
survival time not exceeding 3 years. A clinical trial was undertaken to
determine feasibility and efficacy of marrow-ablative chemoradiotherapy
supported by unpurged autologous bone marrow (ABMT) and to define
prognostic variables. Total body irradiation and either melphalan or
thiotepa were administered to 55 patients (median age 53 years; range 20 to
66 years). The group of 21 patients with resistance to standard
melphalan-prednisone and to continuous infusions of vincristine and
Adriamycin with high dose dexamethasone (VAD) included 7 with primary
unresponsive disease and 14 with resistant relapse; among the 34 patients
achieving remission with the VAD regimen, 14 were in first and 20 in a
subsequent remission. Marked cytoreduction by greater than or equal to 75%
was observed among all 21 patients with refractory myeloma, whereas further
cytoreduction of this magnitude was noted in only 56% of the 34 patients
already in remission after VAD. Five of the 6 early deaths among all 55
patients occurred in the 14 patients with resistant relapse, none of whom
achieved complete remission and who, as a group, had median durations of
relapse-free and overall survival of only 8 and 7 months, respectively.
Among the 41 remaining patients, there was only one early death, and 27%
achieved complete remission including a 36% incidence among the 14 patients
treated in first remission; their projected 4-year survival rate was 82%
regardless of their disease status (first or later remission or primary
resistance). When information about sensitivity to prior therapy is
unavailable, the presence before ABMT of both high beta-2-microglobulin
levels (greater than 3 mg/L) and non-IgG isotype helped identify 9 among
the 55 patients with a very poor prognosis: all 8 responders relapsed
within 9 months, and 8 patients died within 15 months. By contrast, a
4-year projected survival rate of over 70% for the other patients (about
80% of this series) justifies further investigation of this novel treatment
approach in comparison with standard dose regimens. Our results indicate
that marrow-ablative therapy cannot be recommended for myeloma patients
with resistant relapse or those with a combination of risk factors
(advanced tumor burden, absence of IgG isotype). The apparent lack of an
adverse effect of even marked plasmacytosis in autografts (up to 30%)
emphasizes the need for better cytoreduction rather than bone marrow
purging.
Volume 76,
Issue 9,
pp. 1860-1866,
11/01/1990
Copyright © 1990 by The American Society of Hematology
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