Multiple myeloma (MM) typically afflicts elderly patients with a median age of 65 years. However, while recently shown to provide superior outcome to standard treatment, high-dose therapy (HDT) has usually been limited to patients up to 65 years. Among 550 patients with MM and a minimum follow-up of 18 months, 49 aged >/=65 years were identified (median age, 67; range, 65 to 76 years). Their outcome was compared with 49 younger pair mates (median, 52; range, 37 to 64 years) selected among the remaining 501 younger patients (<65 years) matched for five previously recognized critical prognostic factors (cytogenetics, beta2-microglobulin, C-reactive protein, albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All patients received high-dose melphalan-based therapy; 76% of the younger and 65% of the older group completed a second transplant (P =.3). Sufficient peripheral blood stem cells to support two HDT cycles (CD34 > 5 x 10(6)/kg) were available in 83% of younger and 73% of older patients (P =.2). After HDT, hematopoietic recovery to critical levels of granulocytes (>500/microL) and of platelets (>50,000/microL) proceeded at comparable rates among younger and older subjects with both first and second HDT. The frequency of extramedullary toxicities was comparable. Treatment-related mortality with the first HDT cycle was 2% in younger and 8% among older subjects, whereas no mortality was encountered with the second transplant procedure. Comparing younger/older subjects, median durations of event-free and overall survival were 2.8/1.5 years (P =.2) and 4.8/3.3 years (P =.4). Multivariate analysis showed pretransplant cytogenetics and beta2-microglobulin levels as critical prognostic features for both event-free and overall survival, whereas age was insignificant for both endpoints (P =.2/.8). Thus, age is not a biologically adverse parameter for patients with MM receiving high-dose melphalan-based therapy with peripheral blood stem cell support and, hence, should not constitute an exclusion criterion for participation in what appears to be superior therapy for symptomatic MM.
"Thereafter, elderly patients, if in a fit medical condition, have been considered to be eligible for ASCT irrespective of the chronological age in most institutions [21, 22]. Several single institution studies have reported the experience of ASCT in elderly patients as well as in younger patients (Table 2) [23–30]. As conditioning regimen before ASCT, reduced dose of melphalan to 100–140 mg/m2 has been used in the elderly patients. "
[Show abstract][Hide abstract] ABSTRACT: High-dose melphalan (200 mg/m(2)) as conditioning regimen followed by autologous stem cell transplantation (ASCT) rescue has been established as a standard treatment for patients with multiple myeloma (MM) younger than 65 years of age. However, the role of ASCT in elderly patients older than 65 years remains controversial in the era of novel agents such as thalidomide, bortezomib, and lenalidomide. The efficacy and feasibility of ASCT have been shown in elderly patients by reducing the dose of melphalan to 100-140 mg/m(2). Although the clinical benefit of reduced-intensity ASCT in elderly patients has not been clearly established in comparison with that of novel agent-based induction therapy, recent studies have demonstrated that sequential strategies of novel agent-based induction therapy and reduced-intensity ASCT followed by consolidation/maintenance with novel agents translate into better outcome in the management of elderly patients. Thus, ASCT could also be a mainstay in the initial treatment of elderly MM patients, and its indication should be evaluated based on performance status and the presence of complications and/or comorbidities of each elderly patient with MM.
"It is obvious that no single factor can explain the difference in outcome between the age groups; our data indicate that both higher vulnerability to intensive therapy and more aggressive disease resulting in inferior disease control contribute to the difference found. Our finding that age above 60 years is an adverse prognostic factor for patients undergoing intensive therapy is in contrast to other published results (Siegel et al, 1999; Sirohi et al, 2000; Reece et al, 2003). However, in contrast to our study, these were all retrospective comparisons on a selected group of patients who actually underwent autologous transplantation and survival was calculated from time of transplantation and not from initiation of therapy. "
[Show abstract][Hide abstract] ABSTRACT: The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months; P = 0.001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60-64 years but with less superiority than in younger patients.
British Journal of Haematology 06/2006; 133(4):389-96. DOI:10.1111/j.1365-2141.2006.06042.x · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although outcome in multiple myeloma (MM) patients has improved significantly with the introduction of autotransplants (AT), the curability of this approach remained to be demonstrated. Therefore, we analysed outcome and prognostic factors using a logistic regression model in 515 consecutive newly diagnosed and previously treated patients intended to receive melphalan-based tandem transplants with follow up of > or = 5 years. One quarter of patients had event-free survivals (EFS) > or = 5 years with no further relapses seen after 7 years (46 patients on plateau). On multivariate analysis, factors associated with EFS > or = 5 years were absence of chromosome 11 and 13 abnormalities (odds ratio: 6.1), < or = 12 months of preceding standard-dose therapy (SDT) (OR: 2.6) and beta-2 microglobulin (B2M) level < or = 2.5 mg/l at time of first AT (OR: 1.7). Patients with only favourable variables (25%) had a 7-year EFS in excess of 35%, compared with 15% and 10%, respectively, with one (43%) or two unfavourable variables (27%), and 0% for 5% of patients with three unfavourable variables (P < 0.0001). Using a 1-year landmark analysis to allow for guaranteed time and thereby excluding early treatment failures, attaining a complete remission (CR) had no significant effect on long-term survival. Our data are consistent with cure in MM patients with a CR duration . or = 7 years and re-establishment of a monoclonal gammopathy of undetermined significance (MGUS) phase in those with persistent evidence of disease post transplantation, but without disease progression > or = 7 years.
British Journal of Haematology 02/2002; 116(1):211-7. DOI:10.1046/j.1365-2141.2002.03231.x · 4.71 Impact Factor
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