Article

Prognostic factor analyses of myeloma survival with intergroup trial S9321 (INT 0141): examining whether different variables govern different time segments of survival

Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham #816, Little Rock, AR 72205, USA.
Annals of Hematology (Impact Factor: 2.4). 12/2010; 90(4):423-8. DOI: 10.1007/s00277-010-1130-y
Source: PubMed

ABSTRACT Multiple myeloma (MM) survival plots usually display steeper initial and shallower subsequent slopes reflecting differences in disease biology and likely prognostic factors (PF). S9321 trial was selected to determine PF operative at baseline and subsequent 3, 4, 5, and 7-year landmarks (LM-0, LM-3, LM-4, LM-5, and LM-7). With a median follow-up of 8.2 years, survival was similar in transplant and standard therapy arms, justifying data pooling. Median survival for 775 eligible patients is 48 months. According to proportional hazards models, seven of 12 investigated baseline variables retained independent significance for LM-0, of which only two (beta-2-microglobulin and age) extended out to LM-7; the remaining five comprised features of disease aggressiveness (lactate dehydrogenase, calcium, platelet count, C-reactive protein) and host co-morbidity (performance status). Our observations of LM dependency of PF can be exploited toward advancing myeloma therapy by stratifying patients according to whether early or late portions of the survival history are being targeted.

Download full-text

Full-text

Available from: Vanessa Bolejack, Jul 14, 2014
0 Followers
 · 
130 Views
  • Source
    • "conventional karyotyping, fluorescent in situ hybridisation, and/or gene expression profiling (Fermand et al, 2005; Greipp et al, 2005; Rajkumar and Kyle, 2005; Kyle and Rajkumar, 2009; Chang et al, 2010; Hose et al, 2011; Munshi et al, 2011). High-dose chemotherapy followed by autologous stem cell transplantation is a cornerstone within the current standard treatment for symptomatic myeloma patients fit for intensive treatment (Child et al, 2003; Terpos et al, 2003; Barlogie et al, 2004; Blade et al, 2005; Fermand et al, 2005; Rajkumar and Kyle, 2005; Wang et al, 2007; Palumbo et al, 2009; Rajkumar, 2009; Lonial, 2010; Cavo et al, 2011). In fact, a number of studies have established the benefit of autologous transplantation for myeloma patients in prolonging the time to progression and, at least in some of them, also in improving overall survival (Attal et al, 1996; Child et al, 2003; Barlogie et al, 2004; Blade et al, 2005; Cavo et al, 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: High-dose chemotherapy with autologous stem cell transplantation is a cornerstone in the first-line treatment of multiple myeloma patients. However, only few factors have been identified affecting the outcome in such patients. We hypothesised that varying levels of mobilised CD34+ cells confer prognostic information in myeloma patients undergoing high-dose chemotherapy. We determined circulating CD34+ cells at the day of peripheral stem cell collection in 158 consecutive myeloma patients between January 2001 and August 2010. Patients were stratified into two groups (super vs normal mobilisers) with a cutoff of 100,000 peripheral CD34+ cells per ml. We found that patients with more than 100,000 peripheral CD34+ cells per ml had a better overall survival (P=0.005) and a prolonged time to progression (P=0.0398) than patients with CD34+ cell counts below 100,000 CD34+ cells per ml. High levels of CD34+ cells were an independent marker for better overall survival and time to progression in a multivariate analysis that included disease stage, response at transplant, light-chain subtype, age, sex, and height. Our results suggest that high levels of mobilised peripheral CD34+ cells are associated with favourable outcome in myeloma patients undergoing autologous transplantation.
    British Journal of Cancer 08/2011; 105(7):970-4. DOI:10.1038/bjc.2011.329 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In patients who have symptomatic multiple myeloma (MM), a high serum lactate dehydrogenase (LDH) level is associated with features of advanced disease, adds prognostic value to the international staging system (ISS) and predicts for inferior survival. However, it has not been clearly defined what the impact of this abnormality is for patients treated upfront with novel agent-based regimens. To address this issue we analyzed 203 consecutive unselected patients with symptomatic MM who received upfront treatment with novel agents in a single center. The median overall survival for patients with normal LDH was 54 months but in patients with increased LDH levels it was 21 months (P = .003), whereas increased serum LDH was associated with a higher probability of early death. Multivariate analysis confirmed that an increased LDH level is independently associated with poor survival. Furthermore, increased LDH levels could identify subgroups of patients within ISS-2 and ISS-3 with even worse outcome. We conclude that serum LDH is a simple, inexpensive, and readily available blood test that may be included among the variables that define very-high-risk MM.
    Clinical lymphoma, myeloma & leukemia 09/2011; 11(5):409-13. DOI:10.1016/j.clml.2011.07.001 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the effectiveness of the iterative decomposition of water and fat with echo asymmetric and least-squares estimation (IDEAL) MRI to quantify tumour infiltration into the lumbar vertebrae in myeloma patients without visible focal lesions. The lumbar spine was examined with 3 T MRI in 24 patients with multiple myeloma and in 26 controls. The fat-signal fraction was calculated as the mean value from three vertebral bodies. A post hoc test was used to compare the fat-signal fraction in controls and patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma or symptomatic myeloma. Differences were considered significant at P < 0.05. The fat-signal fraction and β(2)-microglobulin-to-albumin ratio were entered into the discriminant analysis. Fat-signal fractions were significantly lower in patients with symptomatic myelomas (43.9 ±19.7%, P < 0.01) than in the other three groups. Discriminant analysis showed that 22 of the 24 patients (92%) were correctly classified into symptomatic or non-symptomatic myeloma groups. Fat quantification using the IDEAL sequence in MRI was significantly different when comparing patients with symptomatic myeloma and those with asymptomatic myeloma. The fat-signal fraction and β(2)-microglobulin-to-albumin ratio facilitated discrimination of symptomatic myeloma from non-symptomatic myeloma in patients without focal bone lesions. KEY POINTS : • A new magnetic resonance technique (IDEAL) offers new insights in multiple myeloma. • Fat-signal fractions were lower in patients with symptomatic myelomas than in those with asymptomatic myelomas. • The β2-microglobulin-to-albumin ratio also aided discrimination of symptomatic myeloma. • The fat-signal fraction may provide information about the myeloma cell mass.
    European Radiology 12/2011; 22(5):1114-21. DOI:10.1007/s00330-011-2351-8 · 4.34 Impact Factor

Similar Publications