Total Therapy With Tandem Transplants for Newly Diagnosed Multiple Myeloma
Author:
Barlogie B.1, Jagannath S.1, Desikan K.R.1, Mattox S.1, Vesole D.1, Siegel D.1, Tricot G.1, Munshi N.1, Fassas A.1, Singhal S.1, Mehta J.1, Anaissie E.1, Dhodapkar D.1, Naucke S.1, Cromer J.1, Sawyer J.1, Epstein J.1, Spoon D.1, Ayers D.1, Cheson B.1, Crowley J.1
Affiliation:
1. From the Myeloma and Transplantation Research Center (MTRC), University of Arkansas for Medical Sciences, Arkansas Cancer Research Center, Little Rock, AR; St Vincent’s Comprehensive Cancer Center, New York, NY; the Medical College of Wisconsin, Milwaukee, WI; the Greenbaum Cancer Center, Baltimore, MD; CTEP, National Cancer Institute, Bethesda, MD; and the Fred Hutchinson Cancer Research Center and Southwest Oncology Group Office, Seattle, WA.
Abstract
Abstract
Between August 1990 and August 1995, 231 patients (median age 51, 53% Durie-Salmon stage III, median serum β-2-microglobulin 3.1 g/L, median C-reactive protein 4 g/L) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy (“Total Therapy”). Remission induction utilized non–cross-resistant regimens (vincristine-doxorubicin-dexamethasone [VAD], high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection, and etoposide-dexamethasone-cytarabine-cisplatin). The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete (CR) or partial (PR) remission was maintained after the first transplant; in case of less than PR, total body irradiation or cyclophosphamide was added. Interferon--2b maintenance was used after the second autotransplant. Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle. Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84% and 71% (the majority within 8 and 15 months, respectively). Eight patients (3%) died of toxicity during induction, and 2 (1%) and 6 (4%) during the two transplants. True CR and at least a PR (PR plus CR) were obtained in 5% (34%) after VAD, 15% (65%) at the end of induction, and 26% (75%) after the first and 41% (83%) after the second transplants (intent-to-treat). Median overall (OS) and event-free (EFS) survival durations were 68 and 43 months, respectively. Actuarial 5-year OS and EFS rates were 58% and 42%, respectively. The median time to disease progression or relapse was 52 months. Among the 94 patients achieving CR, the median CR duration was 50 months. On multivariate analysis, superior EFS and OS were observed in the absence of unfavorable karyotypes (11q breakpoint abnormalities, -13 or 13-q) and with low β-2-microglobulin at diagnosis. CR duration was significantly longer with early onset of CR and favorable karyotypes. Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly, independent of cytogenetics and β-2-microglobulin. Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients, using multi-regimen induction and tandem transplantation followed by interferon maintenance. As a result, the proportion of patients attaining CR increased progressively with continuing therapy. This observation is particularly important because CR is a sine qua non for long-term disease control and, eventually, cure.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
442 articles.
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