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)

The projected outcome of allogeneic BMT for myeloma based on the EBMT data is as follows: for patients transplanted after first line therapy there is a 30% risk of transplant related death, a 55% chance of being alive at 5 years and a 35% chance of being alive in complete remission at 5 years. If BMT is performed later in the course of the disease, the risk of transplant related death is increased and the chance of long term relapse-free survival correspondingly reduced. Conversely, ABMT has a low mortality risk, but there is currently no evidence that ABMT using unpurged marrow can produce long term cure as no series has shown any evidence of a plateau in remission duration. The early results of maintenance interferon are encouraging but longer follow-up is needed to determine whether the proportion of patients in continuing remission at 5 years will approach that seen after allogeneic BMT. Early results of peripheral blood stem cell transplantation are also encouraging but longer follow-up is required. It remains extremely important when comparing results of ABMT with chemotherapy alone to compare similar patient groups, bearing in mind that patients who have autologous transplantation in first response are by definition responders with good performance status and without significant renal failure. In order to address this problem in a prospective manner, a randomised study has been planned by the EORTC in collaboration with the EBMT. In this study, patients with adequate renal function will be randomised at diagnosis to chemotherapy followed by either autologous BMT or continuing chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The current position of allogeneic and autologous BMT in multiple myeloma. 128 47

The use of high-dose chemoradiotherapy with allogeneic hemopoietic stem cell support for the treatment of MM began about a decade ago. Because this procedure has been performed increasingly and because larger numbers of patients are being followed for longer periods of time, the proper role of allogeneic BMT in this setting is becoming clearer. Data available thus far indicate that such an approach results in a complete remission rate of at least 50% to 60%, and even higher if applied as consolidation treatment in the remission phase, a transplant-related mortality reported as 40% to 50% and a long-term survival plateau at around 40%. The 40% 5-year probability of relapse-free survival is considerably higher than that observed following autologous BMT and may result from an allogeneic graft-versus-tumor effect (graft versus myeloma) similar to the well-recognized graft-versus-leukemia effect. Although follow-up is still too short to clearly identify the likelihood of cure for MM allotransplant recipients, a certain number of them are currently long-term, disease-free survivors and--we hope--cured. These promising results and the incurability of MM with conventional chemotherapy should, therefore, encourage further application of allogeneic BMT to selected patients with unfavorable prognostic features. Continued efforts to reduce the morbidity and mortality related to the procedure, as well as to design effective pretransplant regimens with lower extramedullary toxicity and to identify those patients most likely to benefit from BMT, will improve the value of allogeneic BMT in MM.
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PMID:Allogeneic bone marrow transplantation in multiple myeloma. 158 83

Modifications of standard therapy with melphalan and prednisone have not improved the prognosis of patients with multiple myeloma. Encouraging results with high doses of intravenously administered melphalan have generated interest in marrow-ablative therapy with hemopoietic stem cell support. Experience in about 400 patients receiving alkylating agents, sometimes with added total body irradiation, demonstrates partial remissions in virtually all patients with advanced and refractory myeloma, but complete remissions (CR) in less than one-half, even when transplants were performed for responsive disease with low tumor burden. Despite patient and disease heterogeneity, different sources of hemopoietic stem cells (allogeneic or autologous, bone marrow or blood), ex vivo purging of autografts, and different preparative regimens, some general recommendations can be made: (1) Allogeneic BMT should be reserved for patients under age 50, where transplant-related mortality can be expected not to exceed 30%; 40% will achieve CR with a 3-year relapse-free survival expectation of 70%, and (2) With autologous transplantation, low mortality under 10% and marked therapeutic benefit (greater than 30% CR, 80% overall survival at greater than 3 years) seem to be achievable mainly if performed when tumor bulk is low and standard doses of therapy are still effective. Because of the encouraging results even in patients older than 60 years, hemopoietic stem cell grafting should be seriously considered as part of an overall treatment strategy, in order to avoid irreversible normal hemopoietic stem cell damage from nitrosoureas and radiation to marrow-containing bones.
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PMID:Bone marrow transplantation in multiple myeloma. 204 63

Thirty patients with malignant hematological disease underwent allogeneic bone marrow transplantation following Busulphan (Bu) and Cyclophosphamide (Cy). The diseases were chronic myelogenous leukemia, acute lymphoblastic and non lymphoblastic leukemia, myelofibrosis and multiple myeloma in complete remission and in relapse. A sustained disease-free survival (DFS) was achieved in 0/5 acute leukemia patients transplanted in relapse, in 5/7 acute leukemia patients transplanted in remission (600-1550 days) and in 6/9 CML patients transplanted in the chronic phase of the disease (500-950 days). A sustained DFS was also achieved in one 2nd BMT for relapsed CML. The data suggest that the Bu-Cy protocol combines high tumor ablative capability with toxicity comparable to previously described conditioning regimens for allogeneic BMT, particularly in diseases involving a great expansion of the bone marrow.
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PMID:Allogeneic bone marrow transplantation for hematological malignancies following therapy with high doses of busulphan and cyclophosphamide. 251 Nov 15

On July 7h, 1988 all Italian groups practicing allogeneic bone marrow transplantation (AlloBMT) convened with the objectives of performing an analysis of their clinical material and designing some cooperative retrospective and prospective studies. It was felt that, although the great majority of the Institutions performing AlloBMT contribute data to the International Bone Marrow Transplant Registry (IBMTR) and to the European Group for Bone Marrow Transplantation (EBMT), it might still be of interest to pursue specific regional studies, establish a National Registry, and program workshops and educational meetings. The Italian Group for Bone Marrow Transplantation (GITMO) was accordingly founded. It has been determined that by December 31st, 1988, 1390 AlloBMTs have been performed in Italy by 19 Centres. Fourteen have been involved in BMT for adults and children, and 5 exclusively for children. The chief indication for AlloBMT in this clinical material was chronic myelogenous leukaemia, followed by homozygous beta thalassaemia and by the acute leukaemias; severe aplastic anaemia, malignant lymphomas and multiple myeloma have also been important indications. Overall crude survival was 58.3%; this was reduced to 50% for patients over 20, while it reached 62.5% for those under 20. Other studies are in preparation, and a similar survey for Auto BMT has been presented at the GITMO Meeting of June 28, 1989, which is currently in press.
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PMID:[Allogenic bone marrow transplant in Italy]. 269 Feb 21

We have begun an autologous bone marrow transplantation (ABMT) treatment protocol for patients with myeloma who achieve a minimal disease (less than 10% marrow plasma cells) status. Sites of bony disease are irradiated before BMT. Melphalan 70 mg/m2 on days 1 and 2 is followed by 1200 rads total-body irradiation administered in fractionated doses over 3 d. Autologous marrow which has been previously treated with anti-CALLA, B1, and PCA-1 monoclonal antibodies is then thawed and reinfused. 4 males and 2 females with median age of 46 yr (41-56) have been treated. Granulocytes greater than 500/mm3 and platelets greater than 20,000/mm3 were noted at 21 (12-46) and 23 (12-53) d post-transplant (PT), respectively. Acute mucositis and dermatomal Herpes zoster developed in 3 patients each; all patients are clinically well at 233 (30-807) d PT. All patients achieved pathologically normal marrows, but monoclonal plasma cells and marrow myelofibrosis were each noted in a single patient at 486 and 272 d PT, respectively. A single patient has responded to alpha 2 interferon therapy PT; all others have received no therapy. AMBT offers an exciting new treatment for myeloma; however, relapses post-ABMT suggest that improved ablative regimens and/or marrow purging methods may be required.
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PMID:Autologous bone marrow transplantation therapy for multiple myeloma. 269 88

17 patients with multiple myeloma (MM) received marrow transplants from their HLA-matched, MLC-negative sibling donors. 9 patients had progressive disease not responding to conventional treatments, while the other 8 patients were rated as responders. The most frequently used conditioning regimen consisted of total body irradiation and high-dose, multi-agent chemotherapy with cyclophosphamide plus either oral melphalan (5 cases) or BCNU (1 case) on both these drugs (7 cases). 12 patients were evaluable for response to BTM: 7 of them (6 responders and 1 with advanced refractory MM) entered complete remission, while 5 had a sustained decrease in tumor mass that ranged between 72% and 93%. 11 patients died of transplant-related causes, 1 of them with signs of progressive disease. The remaining 6 patients are alive and 5 of them maintain a complete remission status 4 to 67 (median 36) months after BMT. It is concluded that therapeutic benefits of transplantation in MM are still offset by the high mortality related to the procedure. A more accurate selection of patients who would most benefit from BMT and performing transplant at an earlier phase of the disease are warranted before major advances can be made in the cure of these patients.
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PMID:High-dose chemoradiotherapy and allogenic bone marrow transplantation in multiple myeloma. 269 91

Organ toxicity in BMT may in part be due to free radical damage. Therefore the 'Total Radical-trapping Antioxidant Parameter of plasma' (TRAP), individual plasma antioxidants, serum iron and linoleic acid, a main substrate of lipid peroxidation, were monitored before and after BMT, and they were compared with values obtained from healthy controls. Seven patients (3 AML, 3 CML, 1 multiple myeloma) receiving 16 mg/kg busulfan, 30-45 mg VP-16 and 120 mg/kg cyclophosphamide were investigated. TRAP values declined during chemotherapy by about 40% (day -9: 1019 +/- 245 mumol/l, mean +/- s.d.; day 0: 660 +/- 164 mumol/l; P < 0.05). The concentration of uric acid, one of the main antioxidants in plasma, decreased markedly (day -9: 339 +/- 108 mumol/l, day 0: 148 +/- 61 mumol/l; P < 0.05) and paralleled TRAP values. Vitamin E and bilirubin did not change from day -9 to 0 whereas vitamin C increased (day -9: 46 +/- 16 mumol/l, day 0: 89 +/- 44 mumol/l; P < 0.05). Serum iron rapidly increased within the pre-transplantation period, reaching values normally seen only in iron overload (day -9: 11.8 +/- 5.2 mumol/l, day 0: 40.6 +/- 6.5 mumol/l; P < 0.05). Linoleic acid levels were normal at the start and decreased substantially (27.0 +/- 1.6 wt% at day -9; 15.7 +/- 4.9 wt% at day 0; P < 0.05), indicating possible lipid peroxidation during high-dose chemotherapy. In conclusion, complex monitoring of the antioxidant status before and after BMT revealed a breakdown of plasma antioxidant defence and of radical-vulnerable lipids, which was associated with high circulating levels of iron.
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PMID:Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation. 767 Apr 3

Over a 5-year period we evaluated 65 myeloma patients aged < or = 55 years as potential candidates for intensive therapy and allogeneic BMT. Twenty six (40%) patients were transplanted; the median duration of disease was 4 months (range 2-58 months) and median number of prior regimens was 1 (range 1-5); all but five patients had chemosensitive disease. Conditioning regimens included combinations of BU+CY+MEL in 14 patients, BUCY2 in eight and CY+TBI in four. Donors were HLA-matched siblings in 19 cases, one antigen mismatched siblings in three and unrelated donors in four. All patients received CsA, plus either methylprednisolone (n = 5) or MTX with or without other agents (n = 19). Grade III or IV regimen-related toxicity (RRT) was relatively infrequent (3 patients) and was not seen in nine patients conditioned with BU (total dose 12 mg/kg) + MEL (100 mg/m2) + CY (90 mg/m2). Grade II-IV acute GVHD occurred in 20 patients, and was the cause of death in three. Chronic GVHD also caused three deaths. Thirteen of 21 evaluable patients (62%) achieved a CR and six achieved a PR. Actuarial progression-free survival (PFS) was 40% (95% confidence interval (CI) 19-61%) at a median follow-up of 14 months (range 3-56 months); the PFS was 52% (95% CI 24-74%) in chemoresponsive patients, compared with 0% in chemoresistant patients (P = 0.0066).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of myeloma using intensive therapy and allogeneic bone marrow transplantation. 774 43

Serial blood and marrow specimens from eight adult recipients of sex-mismatched transplants (BMT) for chronic myeloid leukemia (CML, n = 3), Ewing sarcoma (n = 1), acute myeloid leukemia (AML) in second remission (n = 1), acute lymphatic leukemia (ALL, n = 1) and multiple myeloma (n = 2) were analyzed by the simultaneous immunophenotypic CD3, CD4, CD8, CD20, CD34, CD10 and genotypic analysis (for X and Y chromosomes). This combined technique of moAb/APAAP staining for cell surface and cytoplasmic antigens and fluorescence in situ hybridization (FISH) for the detection of sex chromosomes allowed the qualitative and quantitative evaluation of mixed chimerism and/or relapse. Using the same slides for moAb/APAAP and FISH allowed the simultaneous identification of the cell lineage, the lymphocyte subpopulation and the genotype (XX or YX) in every blood or BM specimen analyzed. A mixed chimerism in the T cell (CD4, CD8+: median 26% host cells, range 5-44%) and in the myelomonocytic cell population (CD14+ median 16% host cells, range 5-50%) was observed at day +7 after BMT. By days +14 to +18 this mixed chimerism was reduced to 18% host T cells (range 5-50%) and 7% host myelomonocytic cells (range 0-20%). Beyond days +21 to +28 a stable donor chimerism for T cells, myelomonocytic cells and granulocytes was observed in seven of eight patients. Still 0.5-1% host cells of different lineages were detectable in five from the eight patients at later time points (> day + 100). In three patients with CML these cells were CD13 or CD13, CD34 positive and in one was CD4, CD8 positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of mixed chimerism and leukemic relapse after allogeneic bone marrow transplantation in subpopulations of leucocytes by fluorescent in situ hybridization in combination with the simultaneous immunophenotypic analysis of interphase cells. 774 54


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