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

In order to examine the effect of hematopoietic stem cell transplantation (HSCT) on cardiac systolic function, we measured left ventricular ejection fraction (LVEF) by radioventriculography (RVG) before and after the transplantation procedure. One hundred and forty-eight patients were examined, 96 undergoing allogeneic grafting and 52 autologous. Fifty patients had CML, 48 AML, 21 ALL, 18 multiple myeloma and 11 breast cancer. The second RVG examination was performed 22 to 227 days (median 60 days) after HSCT. The mean LVEF value in the whole patient group was 60.2% (range 39-81%) before and 61.1% (35-86%) after transplantation. Patients with CML had significantly higher LVEF before transplantation than patients with acute leukemia (P = 0.007) and multiple myeloma (P = 0.005). No significant changes in mean LVEF between the pre- and post-transplant measurements were seen in any of the diagnostic subgroups or in allogeneic or autologous recipients. None of the 148 patients in the study has shown any signs of clinical heart failure at 2, 5 to 10 years follow-up. Patients who had received anthracyclines in the previous treatment had significantly lower LVEF before transplantation but showed no increased risk of decline in cardiac function. In conclusion, the HSCT procedure does not seem to affect myocardial function 1-7 months after transplantation.
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PMID:Cardiac systolic function before and after hematopoietic stem cell transplantation. 1091 29

Interleukin-2 (IL-2) has proven to be able to generate an effective anticancer immunity against both solid and hematologic malignancies. Moreover, recent advances in the knowledge of psychoneuroimmunology have demonstrated that anticancer immunity is under neuroendocrine control and that the pineal hormone melatonin (MLT) may stimulate the IL-2-dependent anticancer reaction. Finally, preliminary clinical studies have already shown that the concommitant administration of MLT may amplify the efficacy of IL-2 in the treatment of advanced solid neoplasms, whereas there are no data about MLT influence on IL-2 activity in hematologic malignancies. The aim of the present study was to evaluate the efficacy and tolerability of a neuroimmunotherapeutic combination of low-dose IL-2 plus MLT in advanced hematologic malignancies which did not respond to previous standard therapies. The study included 12 evaluable patients. Tumor histotypes were as follows: non-Hodgkin's lymphoma (NHL) 6; Hodgkin's disease (HD), 2; multiple myeloma, 2; acute myelogenous leukemia (ALM), 1 and chronic myelomonocytic leukemia (CMML), 1. IL-2 was injected subcutaneously at a dose of 3 million IU/day for 6 days per week for 4 weeks, corresponding to one cycle. MLT was given orally at 20 mg/day in the evening, without interruption. In non-progressing patients, a second IL-2 cycle was planned after a 3 week-rest period. A partial response was achieved in one patient with multiple myeloma. Stable disease occurred in 7 other patients (NHL, 3; HD, 1; AML, 1; CLLM, 1; multiple myeloma, 1), whereas the other 4 patients progressed. Therefore, lack of progression was obtained in 8 out of 12 (67%) patients, with a median duration of 21+ months (14-30+ months). The treatment was well tolerated in all patients. These preliminary results would suggest that the concomitant administration of low-dose IL-2 plus the pineal hormone MLT may prolong the survival time in untreatable advanced hematologic malignancies, with results comparable to those previously reported using a more toxic immunotherapy, consisting of high-dose IL-2 alone.
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PMID:A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal hormone melatonin in untreatable advanced hematologic malignancies. 1092 60

We evaluated 443 outpatients and inpatients in Keio University Hospital between 1994 and 1999. Morphologic features from peripheral blood and bone marrow aspiration were evaluated in our hematology laboratory, using Wright-Giemsa, peroxidase staining films and other cytochemistry. Immunophenotype was determined by cell surface antigen analysis by laser flow cytometry, FACscan, using various monoclonal antibodies. Information on cytogenetic and molecular genetic characteristics can be also integrated for diagnosis. One hundred fifty patients were diagnosed with acute leukemia, in which 59 cases were ALL and 91 cases were AML. Seventy-four cases were MDS, 76 cases were myeloproliferative disorders, 21 cases were CLL related disorders, 104 patients were malignant lymphoma, and 18 cases were multiple myeloma. The ratio of male to female was 1.7. The probability of diagnostic rate by Immunophenotyping was estimated by Discriminant analysis in 189 patients, using multivariate analysis of immunophenotype compared to morphology. The average probability by immunophenotypic analysis for diagnostic rate was 91.7%, in which the probability for NHL was very high of 97.1%. Thus, morphologic and immunophenotypic analysis is most essential and basic approach in laboratory hematology, from the perspective of rapid and precise diagnostic methods. Recent advance appreciates the rapid contribution for diagnosis by immunophenotypic analysis. Furthermore, Tele-hematology would contribute the standardization for morphologic method in the near future.
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PMID:[Morphology and immunophenotyping in hematological malignancies]. 1106 91

Single-agent topotecan is an active drug in chemotherapy-naive MDS and CMML and, to a lesser degree, in refractory/relapsed acute leukemias, low-/intermediate-grade lymphoma, and myeloma. Its combination with cytosine arabinoside induces complete remissions in high-risk MDS/CMML. A triple-combination regimen of cyclophosphamide, cytosine arabinoside, and topotecan (CAT) was extensively tested in refractory/relapsed as well as in untreated AML. By proving effective in inducing complete remission in newly diagnosed AML at rates comparable to those achieved by anthracycline-cytosine arabinoside regimens, for example, CAT offers a useful treatment alternative. Topotecan combined with paclitaxel is promising in low-/intermediate-grade lymphomas. The activity of topotecan justifies further evaluation of topotecan-containing combination regimens, particularly in MDS/CMML and acute leukemias.
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PMID:Topotecan (hycamptin) and topotecan-containing regimens in the treatment of hematologic malignancies. 1119

We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear.
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PMID:Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease. 1124 40

We have examined the in vitro anticancer activity of METVAN [bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV); VO(SO(4))(Me(2)-Phen)(2)] against acute lymphoblastic leukemia (ALL; NALM-6 and MOLT-3), acute myeloid leukemia (AML; HL-60), Hodgkin's disease (HS445), and multiple myeloma (ARH-77, U266BL, and HS-SULTAN) cell lines as well as primary leukemic cells from patients with ALL, AML, and chronic acute myeloid leukemia (CML). METVAN induced apoptosis in NALM-6, MOLT-3, and HL-60 cells in a concentration-dependent fashion with EC(50) values of 0.19 +/- 0.03 microM, 0.19 +/- 0.01 microM, and 1.1 +/- 0.2 microM, respectively. METVAN induced apoptosis at low micromolar concentrations in primary leukemic cells from patients with ALL, AML, and CML. METVAN inhibited the constitutive expression of matrix metalloproteinase (MMP)-9 protein and its gelatinolytic activity in HL-60 cells and MMP-2 as well as MMP-9 gelatinolytic activities in leukemic cells from ALL, AML, and CML patients. Furthermore, METVAN inhibited the leukemic cell adhesion to the extracellular matrix proteins laminin, type IV collagen, vitronectin, and fibronectin and the invasion through Matrigel matrix. Further preclinical development of METVAN may provide the basis for the development of more effective chemotherapy programs.
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PMID:Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(I.V.) as a novel antileukemic agent with matrix metalloproteinase inhibitory activity. 1130 62

The epithelial mucin MUC1 is overexpressed on the cell surface of many epithelial malignancies as well as on some B-cell lymphomas and multiple myelomas. Recently, we identified two HLA-A2-restricted T-cell epitopes derived from the MUC1 protein. To further extend the potential application of these peptides, we analyzed the expression of MUC1 on blast cells from patients with acute myelogenous leukemia (AML; n = 43) and several other hematological malignancies including acute lymphoblastic leukemia (n = 24), chronic lymphocytic leukemia (n = 36), hairy cell leukemia (n = 9), follicular lymphoma (n = 7), and multiple myeloma (n = 12). Using reverse transcription-PCR and MUC1-specific monoclonal antibodies, MUC1 expression was found in 67% of AML samples and 92% of myeloma samples. To analyze the presentation of MUC1 peptides by primary AML blasts, we induced MUC1-specific CTLs in vitro using peptide-pulsed dendritic cells from HLA-A2+ healthy donors as antigen-presenting cells. These CTLs efficiently lysed in an antigen-specific and HLA-A2-restricted manner not only target cells pulsed with the antigenic peptide but also tumor cell lines including multiple myeloma cells and primary AML blasts that constitutively expressed both MUC1 and HLA-A2. The specificity of the CTLs was confirmed in a cold target inhibition assay. Our data demonstrate that MUC1-derived peptides are tumor antigens in AML and several other hematological malignancies that could potentially be used for immunotherapeutic approaches.
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PMID:The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. 1155 60

It is yet undetermined whether patients with different hematological malignancies have different propensities to infectious complications after high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 136 cycles of HDC and autologous HSCT in 114 patients with acute myeloid leukemia (AML, 24 cycles), non-Hodgkin's lymphoma/Hodgkin's disease (NHL/HD, 55 cycles), and multiple myeloma (MM, 57 cycles) with respect to early infectious complications. Median duration of neutropenia was longer in patients with AML and NHL/HD than in patients with MM (11 days vs 8 days) and after conditioning including total body irradiation (TBI) compared with chemotherapy only preparative regimens (11 days vs 7 days). Fever requiring antimicrobial therapy was observed in 88 percent of cycles, with fever of unknown origin (FUO) accounting for 60 percent of febrile episodes. There was no proven fungal infection, but one case of probable invasive pulmonary aspergillosis. Microbiologically documented infections were seen in 29 percent and clinically documented infections in 11 percent. Response to first-line empirical antibiotic therapy was better for FUO than for documented infections (70 percent vs 40 percent). Patients with TBI as part of their conditioning regimen had more overall infections than patients without TBI (96 percent vs 82 percent). There were no differences with respect to the type or incidence of infections between patients with AML, NHL/HD, and MM. Patients with different hematological malignancies have similar rates of early infectious complications after HDC and autologous HSCT. TBI may be associated with an increased risk for infections in the early post-transplant period.
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PMID:Infectious complications after autologous hematopoietic stem cell transplantation: comparison of patients with acute myeloid leukemia, malignant lymphoma, and multiple myeloma. 1218 6

We describe the toxicity and efficacy of donor lymphocyte infusions (DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations performed at 16 centers in the United Kingdom. The diseases treated included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia (CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9). Eighty-eight percent received stem cells from sibling donors. The patients received 130 infusions (median, 1; range, 1-4). Indications for DLI were unsatisfactory response/disease progression in 51 patients, mixed chimerism in 18, preemptive in 10, and other in 2. Graft hypoplasia was uncommon (11%). Grade II to IV graft-versus-host disease (GVHD) occurred in 23 of 81 patients (28%) and limited and extensive chronic GVHD in 5 of 69 and 18 of 69 evaluable patients (total incidence 33%). Conversion from mixed to full donor chimerism occurred in 19 of 55 evaluable patients (35%) at a median of 48 days after the DLI; partial responses occurred in 6 patients (total response rate 45%). Eighteen of 51 (35%) patients with measurable disease after stem cell transplantation had a complete response (2 molecular), and 5 a partial response (total response rate 45%). Eleven of 17 evaluable complete responders had full donor chimerism. Eight of 13 patients with follicular NHL had complete responses as did 4 of 12 patients with CML. Clinical and chimeric responses correlated strongly with acute and chronic GVHD. Forty-seven patients (58%) survive at a median of 508 days after transplantation (range, 155-1171 days) with a median Karnofsky score of 90. Thirty-four patients (42%) died at a median of 211 days after transplantation with the major causes being progressive disease (26%) and GVHD (9%). Further systematic studies are required to determine the efficacy and optimum use of DLI for patients with each disease treated by nonmyeloablative stem cell transplantation.
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PMID:The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. 1238 6

Factors influencing the collection of autologous peripheral blood stem cells (PBSCs) were studied in 182 mobilization procedures performed on 145 consecutive patients with acute myeloblastic leukemia (AML; n=67) and with various non-myeloid malignancies (NMM; n=78). PBSC were collected following mobilization with chemotherapy, treatment with granulocyte colony-stimulating factor (G-CSF) or chemotherapy plus G-CSF. Fewer colony-forming unit granulocyte-macrophages (CFU-GMs) were collected from patients with AML than from patients with NMM (P<0.0001), although there were no differences in the numbers of CD34+ cells collected between both groups. Multiple regression analysis showed that chemotherapy alone was predictive of a low CD34+ yield in patients with NMM (regression coefficient (RC)=-2.1; P=0.003). In addition, the interactions "diagnosis mutliple myeloma (MM)xmobilization with chemotherapy" (RC=2.9; P=0.004) and "diagnosis MMxmobilization with chemotherapy plus G-CSF" (RC=2.1; P=0.04) also remained in the model, both showing a favorable influence. In AML, mobilization with chemotherapy plus G-CSF was associated with higher CD34+ yields (P=0.003). In this subgroup of patients, multiple regression analysis identified the number of cycles of previous chemotherapy (< or =2 cycles; RC=1.3; P=0.03) and peripheral blood counts (WBC > or =1.5 x 10(9)/l and monocytes >20%; RC=0.8; P=0.02) as the factors most predictive of CD34+ cell yield. These findings emphasize the need to optimize harvesting technique to enhance safety and minimize morbidity and costs of this valuable procedure.
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PMID:Factors influencing the collection of peripheral blood stem cells in patients with acute myeloblastic leukemia and non-myeloid malignancies. 1247 46


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