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)

Optimal methods of stem cell mobilization in multiple myeloma are undefined, and contaminating clonotypic cells could contribute to disease recurrence. A phase 2 trial of intravenous melphalan (60 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg/d) for mobilization was performed. To enhance reliability, contamination was assessed with 2 sensitive methods, immunoglobulin light and heavy chain variable region patient-specific limiting-dilution polymerase chain reaction (PCR). We evaluated 29 stem cell components (SCCs) from 15 patients; for 9 SCCs, only VL PCR was used because of light chain disease or technical problems with VH primers. For 20 SCCs, VL and VH PCR results were highly correlated (r2 = 0.93, P <.01), with 35% (7 of 20) having identical estimates. VH PCR gave significantly higher estimates for 8-and VL PCR for 5-SCCs, supporting the utility of using 2 methods. Estimated clonotypic contamination per SCC was 0.0009% (range, 0%-0.1%) or 0.5 x 10(4) clonotypic cells per kilogram (range, 0-41.2 x 10(4)/kg), and contamination correlated with CD34+ cells collected (r2 = 0.42, P <.01). Melphalan-mobilized SCCs contain minimal clonotypic contamination.
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PMID:Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination. 1264 34

Mini-transplantations in leukemia or MDS in the elder patients are reported to have almost the same results as of the young patients. On the other hand, multiple myeloma is considered that no conventional chemotherapy is curable. Here are some reports of short term of observations at our hospital. We tried pre-conditioning with ATG(2.5/kg x 2), TBI(1 Gy x 2), L-PAM (70 mg x 2), M-Pred(700 mg/m2 x 5) to ten progressive multiple myeloma cases, 40% became mixed chimera and they all became completely donor type with DLI. In almost 4 years of observations, over all survival rate is 68% that it is worth while to continue this treatment.
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PMID:[Multiple myeloma]. 1451 28

We conducted a phase II multicenter trial to estimate the response and survival of patients with newly diagnosed multiple myeloma to high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation. Eligible patients who had undergone induction with vincristine, adriamycin and dexamethasone (VAD) should have adequate cardiac, pulmonary and renal function (creatinine <2 mg/dL). Melphalan at 200 mg/m2 was used as a conditioning regimen. Eighty patients were enrolled from 13 centers. The median age of the patients was 53 yr (range; 20 to 68 yr). The initial stage was IA/IIA/IIB/IIIA/IIIB in 3/8/1/54/14 patients, respectively. Beta2-microglobulin, CRP and LDH were increased in 74, 42 and 34% of the patients examined. Cytogenetic data were available in 30 patients, and 6 patients showed numeric or structural abnormalities. Two therapy-related mortalities occurred from infection. Among the 78 evaluable patients, CR/PR/MR/NC/PD were achieved in 48/26/2/1/1 patients, respectively. After a median follow-up of 30 months, the median overall and event-free survivals were 66 months (95% CI: 20-112) and 24 months (95% CI: 18-29), respectively. This study verifies the efficacy and feasibility of high dose melphalan therapy with autologous stem cell transplantation in newly diagnosed multiple myeloma.
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PMID:High dose therapy followed by autologous peripheral blood stem cell transplantation as a first line treatment for multiple myeloma: a Korean Multicenter Study. 1455 19

A 70-year-old woman was admitted for anemia, elevated serum total protein and a right axillary mass. Laboratory data showed monoclonal x IgM with a decrease in serum IgG and IgA levels. An occipital punched-out lesion was detected on a cranial X-ray. A tumor lesion was detected on chest X-ray and computed tomography. Biopsy specimen revealed plasmacytoma with cytoplasmic IgM. Bone marrow aspiration revealed an elevated plasma cell count. An immunophenotype analysis of the plasma cells showed positivity of cytoplasmic IgM, x, CD5, CD38, CD11a (LFA-1), CD44 (HCAM), CD49d (VLA-4) and CD54 (ICAM-1). From the above results, we diagnosed the patient as having IgM myeloma associated with plasmacytoma. Melphalan and prednisolone therapy were prescribed, their effect on the myeloma was short term, so we changed the chemotherapy to VAD (vincristine, adriamycin and dexamethasone), but this treatment had little effect. The patient developed bacterial pneumonia and died. IgM myeloma is a rare disease and reports of immunophenotype analysis are also rare. There is no case report of plasmacytoma associated with IgM myeloma.
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PMID:[IgM type multiple myeloma expressing various surface adhesion molecules and demonstrating an aggressive clinical course]. 1457 17

We measured the serum levels of p53 mutant protein (p53M-ELISA) in 65 patients with plasma cell dyscrasia (PCD) and compared them with some conventional laboratory variables. Our aim was to assess, for the first time, the potential of this parameter as a new marker for laboratory management of PCD. Twenthy-tree out of 65 patients had monoclonal gammapathy of undetermined significance (MGUS) and 42 suffered from multiple myeloma (MM). MM patients, with no prior chemotherapy consecutively entered this study. They were treated with standard regimens of Melphalan and Prednisone (MP) and were analyzed for serum p53M level from the time of diagnosis to response to therapy or death. A subgroup of nine patients was regularly monitored for changes occurring in p53M levels during MP therapy. Serum levels of p53M were elevated in MM patients compared with MGUS and healthy controls (p = 0.002). Significantly higher p53M levels were shown by MM patients refractory to chemotherapy than by responding patients (0.38 ng/ml vs 0.22 ng/ml, p = 0.05). The measurement of serum p53M in the nine patients during the course of chemotherapy correlated with disease progression or response to therapy. If confirmed on a larger series of patients, these results suggest a potential role of serum p53 mutant levels in laboratory management of PCD patients.
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PMID:Potential usefulness of serum p53 for laboratory management of plasma cell dyscrasias. 1505 3

A 57-yr-old woman with multiple myeloma received an autologous tandem transplant at a 4-month interval. She was conditioned twice with 225 mg/m2 melphalan. After the second transplant, interstitial pneumonitis (IP) ensued. The clinical course was life threatening and mechanical ventilation was required for 32 d. All attempts to identify an infectious agent failed. A presumptive diagnosis of idiopathic IP, possibly related to melphalan toxicity, was made. High-dose methylprednisolone administration led to rapid and durable improvement. Melphalan was employed for conditioning in the tandem setting with an interval of only 3-4 months between two courses or a dose elevation to 225 instead of 200 mg/m2, may have induced IP which responded favorably to methylprednisolone.
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PMID:A rare case of interstitial pneumonitis after tandem high-dose melphalan conditioning and autologous stem cell transplantation in multiple myeloma. 1524 15

Melphalan-prednisone (MP) has been the gold standard treatment for more than 30 years in elderly multiple myeloma (MM) patients. In order to assess whether the combination of dexamethasone with melphalan (MD) could improve on the efficacy of MP, we have carried out a randomized trial comparing both treatment approaches. A total of 201 patients >/=70 years old were included in the study. The overall response rate was similar after six cycles (MP: 67.9%versus MD: 64.5%) and after 12 cycles (MP: 49.4%versus MD: 46.1%). However, the proportion of complete responses (CR) was higher in the MD arm, particularly after 12 cycles (MD: 22.4%versus MP: 9.1%; P < 0.05). There was no significant difference in event-free survival (MP: 15.9 months versus MD: 23.3 months). The median overall survival in both arms was almost identical (MP: 29.4 months versus MD: 27.2 months; P = 0.63). No significant differences in haematological toxicity were observed, but non-haematological toxicity was significantly higher in the MD arm. According to these results MP remains as the gold standard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents.
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PMID:Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma. 1546 21

Melphalan, a DNA cross-linker, is one of the most widely used and effective drugs in the treatment of multiple myeloma (MM). In this report, we demonstrate that enhanced interstrand cross-link (ICL) repair via the Fanconi anemia (FA)/BRCA pathway contributes to acquired drug resistance in melphalan-resistant myeloma cell lines, and disruption of this pathway reverses drug resistance. Using the alkaline comet assay (single-cell gel electrophoresis), we observed that melphalan-resistant cells have reduced ICL formation and enhanced ICL repair compared with melphalan-sensitive cells. Cell-cycle studies demonstrated that enhanced ICL repair released cells from melphalan-induced cell-cycle delay. Using siRNA to knock down FANCF in 8226/LR5 and U266/LR6 drug-resistant cells demonstrated a direct relationship between ICL repair capacity and drug sensitivity. Overexpression of FANCF in 8226/S and U266/S drug-sensitive cells partially reproduced the drug-resistant phenotype. These data show that enhanced DNA repair via the Fanconi anemia/BRCA pathway is involved in acquired melphalan resistance. Our findings provide for a new target to enhance response to DNA cross-linking agents in cancer treatment.
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PMID:The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells. 1580 32

Multiple myeloma (MM) is a rapidly fatal plasma-cell malignancy that evolves mainly in the bone marrow. Melphalan is widely used to treat patients with MM but as yet its mechanisms of action are poorly documented. In the current study, we demonstrate that melphalan induces a drastic downregulation of Mcl-1L, Bcl-x(L) and BimEL in human melphalan-sensitive myeloma cells while the most potent proapoptotic isoforms, BimL and S, are affected to a lesser extent. Moreover, Mcl-1L and BimEL disappearance is associated with the generation of proapoptotic cleaved forms generated by a caspase cleavage. In myeloma cells, we have previously shown that Mcl-1 neutralizes the proapoptotic function of Bim and therefore, prevents the activation of death effectors. In this study, we demonstrate that melphalan disrupts the Mcl-1/Bim complex whereas the Bcl-2/Bim complex is not modified. The disappearance of full length Mcl-1 allows the release of Bim isoforms, particularly L and S, which can exert their proapoptotic function and leads to Bax activation and cytochrome c release. Thus, we can hypothesize that the cleaved 26 kDa proapoptotic Mcl-1 and the 19 and 12 kDa of Bim, generated during melphalan treatment could contribute to the amplification loop of apoptosis.
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PMID:Melphalan-induced apoptosis in multiple myeloma cells is associated with a cleavage of Mcl-1 and Bim and a decrease in the Mcl-1/Bim complex. 1609 44

Plasma cell leukemia (PCL) is a rare disease and is the least common variant of multiple myeloma accounting for 2-3% of all plasma cell dyscrasias. We report a patient who presented with history of high grade fever, weakness, palpitations, loss of appetite, bone pains and mental confusion for twenty days. Initial evaluation revealed plasmacytosis with blood plasma cell count of 5184/cumm. His hemoglobin (Hb) was 11.3 gm/dl, platelets were 75000/cumm and total leucocyte count (TLC) was 21600/cumm (24% plasma cells). Bone marrow examination revealed >60% plasmablasts. Serum LDH was high at 3117 U/L and serum calcium was also elevated at 13.9 mg/dl. A diagnosis of PCL was made and the patient was started on treatment for hypercalcaemia with Melphalan/Prednisolone regime along with supportive care. Patient deteriorated very rapidly despite treatment and died on the eighth day. A detailed report of this case and a review of PCL is presented here.
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PMID:Plasma cell leukemia: case report of a rare and aggressive variant of multiple myeloma. 1630 56


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