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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.
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PMID:In vitro excess ammonia production in human myeloma cell lines. 966 3

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.
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PMID:Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation. 975 47

Autologous peripheral blood stem cell (PBSC) transplantation results in rapid hematologic recovery when sufficient numbers of CD34+ cells/kg are infused. Recent studies suggest that filgrastim (G-CSF) administration following transplantation leads to more rapid neutrophil recovery and lower total transplant costs. This study compares the use of G-CSF (5 microg/kg/day) with sargramostim (GM-CSF) 500 microg/day from day 0 until neutrophil recovery (ANC >1500/mm3) in patients with breast cancer or myeloma who had PBSC mobilized with the combination of cyclophosphamide, etoposide, and G-CSF. Twenty patients (13 breast cancer and seven myeloma) received GM-CSF and 26 patients (14 breast cancer and 12 myeloma) received G-CSF. The patients were comparable for age and stage of disease, and received stem cell grafts that were not significantly different (CD34+ x 10(6)/kg was 12.5 +/- 11.1 (mean +/- s.d.) for GM-CSF and 19.8 +/- 18.5 for G-CSF; P = 0.10). The use of red cells (2.8 vs 2.3 units), and platelet transfusions (2.5 vs 3.1) was similar for the two groups, as was the use of intravenous antibiotics (4.3 vs 4.6 days) and the number of days with temperature >38.3 degrees C (2.3 vs 1.8). Platelet recovery was also similar in both groups (platelets >50,000/mm3 reached after 11.8 vs 14.9 days). The recovery of neutrophils, however, was faster using G-CSF. ANC >500/mm3 and >1000/mm3 were reached in the GM-CSF group at 10.5 +/- 1.5 and 11.0 +/- 1.7 days, respectively, whereas with G-CSF only 8.8 +/- 1.2 and 8.9 +/- 2.2 days were required (P < 0.001). As a result, patients given G-CSF received fewer injections than the GM-CSF patients (10.9 vs 12.3). Resource utilization immediately attributable to the use of growth factors and the duration of pancytopenia, excluding hospitalization, were similar for the two groups. This study suggests that neutrophil recovery occurs more quickly following autologous PBSC transplant using G-CSF in comparison to GM-CSF, but the difference is not extensive enough to result in lower total cost.
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PMID:Hematopoietic growth factor after autologous peripheral blood transplantation: comparison of G-CSF and GM-CSF. 1041 11

Pericardial involvement is a rare complication of multiple myeloma, caused by amyloidosis, infections, or plasmacell infiltration, usually at late or terminal disease stage. We report a patient with pericarditis coming from a department of Cardiology where a preceding (15 years before) diagnosis of breast cancer and present bloody pericardial effusion with probably malignant cells permitted at first to orientate towards metastatic pericardial involvement in breast cancer. Laboratory findings (pancytopenia, hypogammaglobulinemia, proteinuria) suggested to perform bone marrow aspirate, serum and concentrated urine immunoelectrophoresis, measurement of 24-h urine protein excretion, and further cytologic and immunocytochemical assay of pericardial fluid. Acquired data allowed to diagnose light chain multiple myeloma with pericardial involvement caused by plasmacell infiltration. We diagnosed this complication, representing first and main clinical feature of multiple myeloma, owing to a complete clinical and laboratory evaluation and repetition of cytologic and immunocytochemical assay of pericardial fluid.
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PMID:[Pericardial involvement as initial manifestation of multiple myeloma]. 1042 20

Plasmacytic ascites is an infrequent complication of multiple myeloma. To date, only few cases have been reported with a very rapidly fatal course unresponsive to therapy. We describe a patient with plasmacytic ascites and quiescent multiple myeloma of 8 years of duration. Disease progression became apparent due to myelomatous ascites, unexplained fever, pancytopenia and bone marrow infiltration. This case showed a complete and long-lasting response after VAD chemotherapy followed by autologous PBSC transplantation. Ascites in association with MM may respond for lengthy periods to high-dose chemotherapy and ASCT.
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PMID:Massive myelomatous ascites responsive to VAD chemotherapy and autologous stem cell transplantation. 1045 78

A 70-year-old woman presented with monoclonal gammopathy, pancytopenia, and renal insufficiency, which were initially refractory to combination chemotherapy by VMMD (vincristine, ranimustine, melphalan, and dexamethasone) and MP (melphalan and prednisolone) regimens. The myeloma cells, which consisted of 73% of bone marrow nucleated cells, expressed CD38(+), CD19(+), CD56(-), CD45(-), CD49e(-), and MPC-1(+) phenotypes by flow cytometric analysis and showed the rearranged immunoglobulin heavy chain (IgH) gene by Southern blotting. By immunostaining, the myeloma cells were positive for cytoplasmic immunoglobulin light chain kappa. These results suggest that myeloma cells can express CD19(+)CD56(-), the phenotype considered to be expressed on only normal plasma cells.
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PMID:Multiple myeloma expressing CD19(+)CD56(-) phenotype. 1091 86

Donor leukocyte infusion (DLI) has well-documented activity in CML, but the role of DLI in other diseases is less well defined. To evaluate the strategy in multiple myeloma (MM) we evaluated 25 MM patients from 15 centers who were treated with DLI. Patients with persistent or recurrent disease after allogeneic BMT received DLI from the original marrow donor (23 matched related, one mismatched family, and one matched unrelated). Chemotherapy was given before DLI in three patients. Two of 22 patients responded completely to DLI alone and three patients responded to the combination of DLI and chemotherapy. Nine patients who had not had sufficient disease control after DLI were given additional DLIs; five of these patients had either complete (two) or partial (three) responses. Thirteen of 25 evaluable patients developed acute GVHD and 11 of 21 evaluable patients developed chronic GVHD; all responders developed GVHD. No patients developed post-DLI pancytopenia. Four patients had responses which lasted >1 year after DLI, three patients had responses which lasted <1 year, and three patients had ongoing responses but with follow-up <1 year. In conclusion, DLI has anti-myeloma activity but the strategy is limited by no response or short duration of response in a significant percentage of patients and by significant GVHD in the majority of the responders.
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PMID:Donor leukocyte infusions for multiple myeloma. 1114 28

The myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by pancytopenia, dysplastic hematopoiesis, and a propensity to leukemic transformation. Increased apoptosis has been noted in MDS as a possible explanation for ineffective hematopoiesis, with lower levels in progression to and in de novo acute leukemia. Apoptosis can be measured by binding of Annexin V to exposed membrane phosphatidylserine. We postulated that the apoptotic index would aid in the differential diagnosis of MDS versus other hematopoietic diseases. We examined 33 bone marrow aspirates suspected of hematopoietic malignancy for apoptotic index by Annexin V analysis using a Becton Dickinson FACStar+ flow cytometer. The apoptotic index was expressed as the percentage of Annexin V-positive cells divided by total mononuclear cells in the gate. By standard morphologic analysis, 16 cases were diagnosed as MDS (9 refractory anemia [RA], 2 refractory anemia with ringed sideroblasts [RARS], 1 refractory anemia with excess of blasts [RAEB], 3 chronic myelomonocytic leukemia [CMML], and 1 unclassified), 11 as acute leukemia (AL), 6 as myeloproliferative disorders (MPD). Eight cases (uninvolved marrow of five patients with lymphoproliferative disorders [LPD], one patient with multiple myeloma, and two patients with anemia of chronic disease) served as nonneoplastic controls. A higher degree of apoptosis was observed in MDS (mean = 44.7%; range = 29.5--60%) compared with MPD (mean = 8.2%; range = 2.3--15.4%), AL (mean = 16.1%; range = 5.1--29.4%), and control marrow samples (mean = 11.6%; range = 1.5--21%). Additionally, the apoptotic index was significantly higher in MDS compared with MPD (P < 0.0001). In conclusion, a high apoptotic index occurs in MDS, supporting previous reports and suggesting that Annexin V analysis can be used as an adjunct in the diagnosis of MDS versus MPD. This would be particularly useful for the often-difficult distinction between early MDS and early MPD cases with equivocal morphology.
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PMID:Apoptotic index by Annexin V flow cytometry: adjunct to morphologic and cytogenetic diagnosis of myelodysplastic syndromes. 1124 4

Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.
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PMID:Massive plasmocytosis due to methimazole-induced bone marrow toxicity. 1144 40

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.
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PMID:Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma. 1150 31


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