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)

A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.
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PMID:Early and fatal immune haemolysis after so-called 'minor' ABO-incompatible peripheral blood stem cell allotransplantation. 919 61

Immunomagnetic separation with anti-CD34 monoclonal antibodies and paramagnetic microbeads has been used to enrich hematopoietic stem cells from human bone marrow (BM) or mobilized peripheral blood mononuclear cells (PBMNC). The introduction of this technique also constitutes a new principle of tumor cell purging. The efficiency in terms of purging tumor cells from PBMNC was evaluated in seven different experiments. Mobilized (chemotherapy and G-CSF) PBMNC were collected from patients with solid tumors (n = 6) and multiple myeloma (n = 1) by leukapheresis using an automated MNC separation system and contaminated with 1% (n = 5) or 10% (n = 2) tumor cells from different epithelial cell lines being CD34-negative. The cell mixture was sensitized with anti-CD34 (9C5) antibodies and sheep anti-mouse IgG1 paramagnetic microspheres and enriched for CD34+ cells using an Isolex 50 magnetic separator. Purify of CD34+ cells was studied by flow cytometry (FACScan) and tumor cell depletion was evaluated by comparative human tumor cloning assays (HTCA) containing methylcellulose and agar. We achieved a median purity of CD34+ cells of 85.9% (range 69.8-92.9%) and a median yield of 48.1% (range 21.0-85.2%). From these data in each case the estimated log depletion of tumor cells was calculated and compared with the experimentally achieved (HTCA) log depletion (log delta depletion = log experimental depletion--log calculated depletion). In our experiments we achieved a median depletion of 2.75 log (range 1.55-3.69 log). When corrected for CD34+ cell yield of each experiment we observed a median 'yield corrected depletion' of 2.38 log (range 1.48-3.15 log). The following delta depletion values were obtained: +0.32 log (HTB 129, breast), +0.21 log (HTB 26, breast), +0.04 log (HTB 26) for experiments with higher experimental depletion, and -0.23 log (HTB 26), -0.9 log (HTB 26, PBMNC from patient with multiple myeloma), -0.82 log (HTB 131, breast) and -1.66 log (HTB 131) for lower depletion efficacy than calculated. These data suggest that depletion may depend on specific cell surface characteristics of tumor cells. Moreover, plasma factors (eg paraprotein) may also have some impact. In summary, the Isolex 50 provides a high purity of CD34+ cells and depletion of tumor cells was efficient. However, calculated and experimental purging efficiencies are not necessarily identical.
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PMID:The efficiency of tumor cell purging using immunomagnetic CD34+ cell separation systems. 920 19

The best method for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma (MM) remains controversial. We report the results of two different methods of PBPC collection for autologous transplantation in 40 patients with stage II or III MM. In group I (n = 18), HD-CY, 4 g/m2 i.v., was administered followed by GM-CSF, 8 microg/kg/day s.c., until the end of collection, starting the leukaphereses after hematological recovery (>1 x 10(9)/l WBC). In group II (n = 22), G-CSF, 10 microg/kg/day s.c., was used alone until the last day of collection, starting consecutive aphereses on the 5th day. A minimum of two aphereses were performed to collect at least 2 x 10(6)/kg CD34+ cells. Both patient groups were comparable for age, sex and clinical prognostic features as well as previous therapies. In group I, the median yields per pheresis were: MNC 1.47 (1.38-2.32) x 10(8)/kg, CFU-GM 0.82 (0.18-13.2) x 10(4)/kg and CD34+ cells 1.98 (0.96-6.96) x 10(6)/kg. In group II these results were: MNC 2.44 (2.06-3.6 x 10(8)/kg) (P = 0.03), CFU-GM 0.75 (0.16-7.8) x 10(4)/kg and CD34+ 1.05 (0.32-3.4) x 10(6)/kg (P = 0.02). The median number of aphereses performed in each group was 5 (4-12) with a median of 5.24 +/- 2.51 in group I and 3 (2-6) with a median of 3.1 (+/- 0.91) in group II (P = NS). Hospitalization for PBPC mobilization was required in all patients in group I and the treatment-related toxicity was greater in this group: 12 patients (66%) developed fever requiring antibiotics during the neutropenic period after HD-CY and six (33%) patients required transfusion support. After receiving busulfan 12 mg/kg p.o. and melphalan 140 mg/m2 i.v., as the conditioning regimen, the median periods to reach granulocytes (>0.5 x 10(9)/l) and platelet (>20 x 10(9)/l) engraftment were 12 and 11 days respectively (ranges 8-20 and 10-16) in group I (HD-CY plus GM-CSF group), and 11 and 13 days respectively (ranges 7-42 and 10-38) in group II (G-CSF group) (P = NS). In conclusion, these data suggest that although HD-CY plus GM-CSF is superior to G-CSF alone based on mean CD34+ cell yield per pheresis, adequate CD34+ cell collections can be achieved with G-CSF alone in most MM patients with less toxicity and with simplification of the procedure.
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PMID:Comparison of peripheral blood progenitor cell mobilization in patients with multiple myeloma: high-dose cyclophosphamide plus GM-CSF vs G-CSF alone. 925 89

The objective of our study was to evaluate the efficacy and toxicity of a high-dose melphalan-based therapy with or without total body irradiation (TBI) followed by peripheral blood progenitor cell (PBPC) transplantation in patients with multiple myeloma. Between June 1992 and June 1996, 104 patients (71 male, 33 female) with a median age of 51 years (range 30-65 years) underwent transplantation at our center. PBPC were mobilized using high-dose chemotherapy followed by treatment with G-CSF. Fifty patients were treated with TBI+melphalan 140 mg/m2 while 54 patients received melphalan 200 mg/m2. Following PBPC autografting, the median time to attainment of platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l was 11 and 14 days, with no difference between the treatment groups. In the TBI group significantly longer periods of total parenteral nutrition were required due to the occurrence of severe mucositis. Two patients from the TBI group died of transplantation-related complications. Following high-dose treatment, remission state improved in 43 out of 102 patients. No statistically significant advantage in reaching complete or partial remission was observed with TBI+high-dose melphalan compared to the treatment with high-dose melphalan alone. The optimal high-dose treatment, with particular reference to the inclusion or omission of TBI, should be prospectively investigated.
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PMID:Peripheral blood progenitor cell transplantation in multiple myeloma following high-dose melphalan-based therapy. 930 4

The use of primed peripheral blood progenitor cells (PBPC) has improved platelet engraftment following autologous bone marrow/PBPC transplantation (ABMT). The thrombocytopenia associated with ABMT generally lasts 14-18 days, and is associated with variable platelet transfusion requirements. Little, if any, data exist examining prognostic parameters for platelet transfusion requirements during autologous transplantation. We retrospectively examined 286 consecutive patients undergoing autologous transplantation from 1 January 1994 to 1 June 1996 with respect to platelet engraftment and platelet transfusion requirements. One hundred and fifty four patients were transplanted for breast cancer (54%), 72 for non-Hodgkin's lymphoma (25%), 35 for Hodgkin's disease (12%), 13 for acute leukemia (5%), eight for myeloma (3%), and four for other malignancy (1%). The median age was 44. All patients received cytokine priming, usually with G-CSF, for the procurement of PBPC. The median number of CD34+ cells collected was 4.3 x 10(6)/kg. All patients received a chemotherapeutic preparative regimen and all received an autologous transplant using PBPC alone. The median time to a platelet count of 20 x 10(9)/l was 13 days. Patients beginning the transplant with a less than normal platelet count (less than 150 x 10(9)/l) engrafted in 17 days, and received a median number of seven platelet transfusions, as compared with platelet engraftment of 12 days, and four platelet transfusions, for patients beginning the transplant with a normal platelet count (P = 0.001). Both groups of patients received an equivalent dose of CD34+ cells. We conclude that thrombocytopenia at the initiation of autologous transplantation is associated with increased platelet transfusion requirements, independent of the dose of CD34+ cells infused.
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PMID:Platelet transfusion requirements during autologous peripheral blood progenitor cell transplantation correlate with the pretransplant platelet count. 931 78

Prolonged thrombocytopenia resulting from inadequate megakaryocyte (MK) progenitor cell reconstitution is a serious complication of hematopoietic cell-supported high-dose chemotherapy (HDC). In this situation, the infusion of MK progenitors that are expanded ex vivo could be clinically beneficial. In this study we investigated the ability of various growth factor combinations to generate MK progenitors. CD34+ cells derived from bone marrow (BM) and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) from 17 patients with breast cancer, lymphoma, or myeloma were cultured unpertubed for 10 days in a serum-free liquid culture system that contained recombinant growth factors. Five different growth factors combinations were evaluated: Stem cell factor (SCF), interleukin (IL)-3, IL-6 + G-CSF (combination 1); SCF, megakaryocyte growth and development factor (MGDF) + G-CSF (combination 2); SCF + MGDF (combination 3); MGDF alone (combination 4); and SCF, IL-3, IL-6, G-CSF + MGDF (combination 5). PB CD34+ cells yielded significantly higher numbers of CD41+ MK progenitors than BM CD34+ cells with any of the growth factor regimens assayed. PB CD34+ cells (2x10[5]) at day 0 generated 1.2 to 1.3x10(6) CD41+ cells by day 10 when cultured in the presence of growth factor combinations 1, 2, or 3. In contrast, 2x10(5) BM CD34+ cells produced 5x10(5) CD41+ cells after 9 days in the presence of combination 1, whereas lower numbers of CD41+ cells were generated in cultures with combinations 2 and 3 (2.3x10[5] and 4.2x10[4], respectively). The addition of MGDF to cultures that were grown with combination 1 for 5 days increased the number of CD41+ cells (1.7-fold increase in PB-derived cultures, 1.6-fold increase in BM-derived cultures). Treatment with MGDF alone resulted in higher frequencies of MK progenitors than those obtained in cultures with combined growth factors (79% in PB-derived cultures, 25% in BM-derived cultures), but because total cell growth was attenuated, absolute numbers of MK progenitors were lower (7x10(5) in PB-derived cultures, 7x10(4) in BM). Morphological analysis of immunocytochemically identified megakaryocytic cells revealed mononuclear cells as the predominant cell type in all of the cultures. During the 10-day culture period, PB-derived MK progenitors did not show notable maturation, even under the influence of MGDF, whereas in BM-derived cultures MGDF induced a significant shift to binuclear cells and stage I MK after day 5. Phenotypic analysis of cell surface markers showed that the majority of cultured megakaryocytic cells coexpressed CD34 and platelet glycoproteins (GPs), also indicating an immature stage of development. The ex vivo proliferative activity of CD34+ cells and their potential to develop into the megakaryocytic lineage demonstrated considerably high interpatient variations. There was no correlation between platelet recovery following HDC with hematopoietic cell support and the magnitude of GP+ cell expansion ex vivo, suggesting the feasibilty of MK expansion ex vivo in patients with prolonged thrombocytopenia posttransplantation. In summary, these data indicate that GCSF-mobilized CD34+ PBPCs are more effectively expanded ex vivo into the megakaryocytic lineage than are CD34+ BMPCs. CD34+/GP+ MK progenitors may be an appropiate cell population for transplantion as prophylaxis or treatment of prolonged thrombocytopenia. The efficacy of this procedure will be tested prospectively in a clinical trial.
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PMID:Ex vivo expansion of megakaryocyte progenitors: effect of various growth factor combinations on CD34+ progenitor cells from bone marrow and G-CSF-mobilized peripheral blood. 932 49

We treated 103 multiple myeloma (MM) patients with 7 g/m2 cyclophosphamide (Cy) followed by 300 micrograms G-CSF/d to harvest peripheral blood progenitor cells (PBPC). PBPC autografts containing > 2.0 x 10(6) CD34+ cells per kg body weight were obtained at the first attempt from 90/100 evaluable patients. The most significant factor predicting impairment of PBPC collection was the duration of previous melphalan treatment (P < 0.0001). In multivariate discriminate analysis, treatment with melphalan during the most recent chemotherapy cycles prior to mobilization (P = 0.0727) and previous radiotherapy (P = 0.0628) had a marginally significant negative influence on the efficacy of PBPC collection. We found no reduced functional capacity of CD34+ cells to restore haemopoiesis after myeloablative treatment related to the duration of melphalan exposure. At the time of best response to conventional treatment, a median paraprotein reduction of 21% was achieved following high-dose cyclophosphamide (HD-Cy). Two heavily pretreated patients died and one patient developed pulmonary toxicity W.H.O. grade IV following HD-Cy. Potential transplant candidates should undergo mobilization and harvesting of PBPC before melphalan-containing treatment. Combinations of haemopoietic growth factors and their dose-modifications should be investigated to improve PBPC collection, to allow a dosage reduction of the mobilization chemotherapy.
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PMID:Factors influencing collection of peripheral blood progenitor cells following high-dose cyclophosphamide and granulocyte colony-stimulating factor in patients with multiple myeloma. 933 33

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.
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PMID:Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation. 933 54

We sought to determine factors that impact on the recovery of platelets after blood cell transplantation in patients with multiple myeloma. We performed retrospective analyses in 51 patients undergoing blood cell transplantation for multiple myeloma. The proportional-hazards model was applied to determine significant risk factors. Of 51 transplants, 14 patients failed to achieve a platelet count of 50 x 10(9)/l. Median time to a neutrophil count of 0.5 x 10(9)/l was 10.5 days. Median time to achieve a platelet count of 50 x 10(9)/l was 32 days. Multivariate analysis revealed that cyclophosphamide and G-CSF priming before collection of hematopoietic precursors (P < 0.001) was a positive predictor of rapid engraftment and prior exposure to melphalan given orally (P = 0.02) was a negative predictor of subsequent platelet engraftment. The number of mononuclear cells collected, the patient's disease status at the time of transplant and the presence of circulating plasma cells in the harvested product did not have a significant impact on time to platelet engraftment. We conclude that cyclophosphamide and G-CSF priming shortened the time to achieve platelet engraftment compared with G-CSF alone. Prior exposure to melphalan delayed platelet engraftment and can lead to complete failure of platelet recovery. Stem cells should be collected before melphalan administration in patients with multiple myeloma who are candidates for possible blood cell transplantation.
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PMID:Factors influencing platelet recovery after blood cell transplantation in multiple myeloma. 933 52

We describe a patient with multiple myeloma (MM), whose bone marrow (BM) cells were capable of spontaneous paraprotein isotype secretion, which could be strongly stimulated by hematopoietic growth factors (GFs), such as interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF and IL-3. Ig production by BM cells from another five MM patients and four control patients with non-malignant hematological diseases could not be stimulated by these GFs. The results indicate that GFs, at least in some instances, can activate tumoral plasma cells in patients with MM. This possibility should be taken into account when the utility and effectiveness of GFs in the treatment of MM is evaluated.
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PMID:Hematopoietic growth factors stimulate paraprotein isotype production by bone marrow mononuclear cells in an aggressive case of multiple myeloma. 936 91


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