Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the prognostic significance of plasmablastic (PB) multiple myeloma (MM) in Eastern Cooperative Oncology Group Phase III trial E9486. Two reviewers independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85% concordance (P < .0001). These PB cases had significantly lower hemoglobin and serum albumin levels, higher calcium and beta 2-microglobuin levels, and higher percentage BM plasma cells (PC) by immunofluorescence. They had higher bone marrow PC labeling indices, higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan, cyclophosphamide, and prednisone (VBMCP) alone; VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2 (rIFNalpha2). Although the numbers are low, patients with PB had a significantly lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P < .0001]), but not with added rIFNalpha2. Event-free and overall survival of PB MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no survival difference between the patients who were classified as PB by both reviewers versus patients classified as PB by only one reviewer. We conclude that PB MM is a discrete entity associated with more aggressive disease and shortened survival. Tumor cell ras mutations and increased sIL-6R may contribute to a higher proliferation rate and reduced survival. There were significant improvements in response and progression with the addition of HiCy and rIFNalpha2 to VBMCP, but the numbers were small and improved survival could not be shown.
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PMID:Plasmablastic morphology--an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group. 951 51

Multiple myeloma (MM) remains largely incurable, although traditional chemotherapy and new compounds have been shown to produce a clinical response. Clinical studies were performed to determine the effectiveness of interferon-alpha (IFN-alpha) in MM, which has also recently been shown to function as a survival factor for MM cells. The effects of different doses of native human leukocyte interferon-alpha (nhIFN-alpha), recombinant human interferon-alpha2a (rhIFN-alpha2a) and recombinant human interferon-alpha2b (rhIFN-alpha2b) on in vitro P3-X63-Ag8.653 mouse myeloma cell growth were compared. A statistically significant dose-dependent reduction in cell viability following cell culture with nhIFN-alpha was observed. On the other hand, a statistically significant increase in cell viability was observed following cell culture with rhIFN-alpha2a and rhIFN-alpha2b, but only in relation to the control group and seemingly without dose dependency. These results highlight the importance of the type of human IFN-alpha used in the treatment and study of MM, and suggest that nhIFN-alpha may have a role in future personalized therapy approaches.
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PMID:Effects of native human leukocyte interferon-alpha and recombinant human interferon-alpha on P3-X63-Ag8.653 mouse myeloma cell growth. 1993 Aug 65


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