High-dose melphalan-based autotransplants for multiple myeloma - The Arkansas experience since 1989 in 3077 patients

Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Cancer (Impact Factor: 4.89). 05/2008; 112(8):1754-64. DOI: 10.1002/cncr.23327
Source: PubMed


In this report, the authors describe their collective experience with melphalan-based autotransplants since the inception of their program at the University of Arkansas for Medical Sciences in 1989.
The authors evaluated the clinical outcomes of 3077 successive patients with multiple myeloma (MM) who underwent at least 1 melphalan-based autotransplantation at the University of Arkansas. Of these, 1078 patients were enrolled on front-line Total Therapy (TT) protocols (TT-P) TT1, TT2, and TT3; 1104 patients were entered on protocols for newly diagnosed or previously treated patients (non-TT-P); and 895 patients were treated off protocol (non-P).
The 10-year overall survival (OS) rates after first transplantation were 41%, 19%, and 11% (P< .001) for the TT-P, non-TT-P, and non-P groups, respectively. In the TT-P group, the median OS was 72 months on TT1, was not reached at >or= 7 years on TT2, and was 88% at 2 years on TT3. Among 2683 patients with complete baseline data, absence of hypodiploidy/chromosome 13 deletion, beta-(2)-microglobulin <3.0 mg/L, C-reactive protein <6 mg/L, albumin >or= 3.0 g/dL, and platelet count >or= 100,000/microL all were associated independently with superior OS (P< .001), event-free survival (P< .001), and duration of complete remission (P< .001).
The results from this large, single-institution experience demonstrated that >10-year OS was accomplished in >40% of all patients enrolled on TT-P, whereas such success was observed in only 15% of the remaining patients (including 25% in the presence of all 5 good-risk features). Superior outcomes with protocol-based, primary transplant regimens such as TT-P draw attention to the importance of applying the best available therapies upfront.

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Available from: Guido Tricot, Sep 30, 2015
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    ABSTRACT: This chapter gives an account of the experience of the Arkansas myeloma program since 1989 with transplant-supported high-dose melphalan, novel agents, and prognostic factors as they relate to standard laboratory features, gene expression profiling, and magnetic resonance imaging (MRI). Incorporation of novel agents and new concepts, such as post-tandem transplant consolidation therapy, has improved the rate and duration of complete response and prolonged event-free and overall survival rates. With Total Therapy 2, median survival exceeds 8 years, while Total Therapy 3 with added bortezomib has sustained complete remissions in more than 90% of patients at 2 years which, when used as a survival surrogate in Total Therapy 2, assured a high 6-year survival rate of 75%. Gene expression profiling identified 15% of patients with very short survival. MRI-defined focal lesions are associated with poor outcome, while their resolution - although slower than the time course of attaining clinical complete remission - conferred superior survival. Representing a frequent source of recurrence, with genetic profiles (in both plasma and stromal cells) distinct from those in random bone-marrow samples, therapeutic efforts are directed at hastening onset and increasing frequency of focal lesion resolution.
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    ABSTRACT: Cytogenetic studies were performed as part of all diagnostic and surveillance bone marrow examinations in 956 newly diagnosed patients with multiple myeloma (MM) receiving total therapy (TT) protocols and in 1085 previously treated patients enrolled in non-TT protocols. In both groups, cytogenetic abnormalities (CA) were present in one-third at baseline and persisted in 14% prior to first and 10% prior to second transplant (TT, 5%; non-TT, 15%); post-transplant detection rates increased progressively with time, from 7% within 6 months to 21% within 24 months to 28% at relapse. According to multivariate analyses, overall survival was adversely affected by the presence of CA at baseline (hazard ratio (HR)=7.20, P<0.001) and the development of CA both prior to (HR=3.28, P<0.001) and after first transplant (HR=6.24, P<0.001), whereas suppression of CA pretransplant was favorable (HR=0.38, P<0.001). The presence of CA at relapse further distinguished patients with a short median post-relapse survival of only 11 versus 47 months in those without CA (P<0.0001). Post-relapse survival was independently adversely affected by the detection of CA both at baseline (HR=1.35, P=0.044) and relapse (HR=2.47, P<0.001). Collectively, these results underscore the importance of monitoring for CA and attest to the favorable prognostic consequences of CA suppression with effective therapy.
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