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 influence of the CFU-GM content of donor marrow on the outcome of allogeneic marrow transplantation (BMT) has been debated. We now report 38 patients (25 acute leukemias, 10 chronic myeloid leukemias, two myeloma; 24 in first CR/CP and 14 in more advanced phases of their disease) undergoing unmanipulated HLA-identical sibling BMT following conditioning with cyclophosphamide and total body irradiation (TBI). The median number of nucleated cells infused was 4.3 x 10(8)/kg (range 1.5-8.4); median CFU-GM numbers were 2.4 x 10(4)/kg (range 0.1-46). End-points of the study were (1) speed of neutrophil and platelet engraftment; (2) quality of engraftment beyond day +50 after BMT; and (3) transplant-related mortality in patients stratified according to whether they had received less than (n = 18) or more than (n = 20) 2.4 x 10(4)/kg CFU-GM. These two groups were comparable for diagnosis, disease status, donor sex, donor age, recipient sex, recipient age, CVHD prophylaxis, number of cells infused and CMV serology. Neutrophil counts were comparable at all time intervals. There was also no difference in platelet counts on days +7 to +50. However, patients who had received higher CFU-GM numbers had significantly higher platelet counts on day +80 (149 vs. 75 x 10(9)/L; P = 0.002), day +100 (153 vs. 77 x 10(9)/L; P = 0.0009) and day +150 (179 vs. 95 x 10(9)/L; P = 0.01). The 2-year actuarial transplant-related mortality was 5% vs. 53% (P = 0.007) in patients receiving high or low numbers of CFU-GM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of marrow CFU-GM content on engraftment and survival after allogeneic bone marrow transplantation. 777 10

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
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PMID:Bone marrow transplantation in Iran. 792 Mar 8

Mafosfamide (ASTA-Z) is a chemotherapeutic agent currently in use for in vitro purging of tumor-bearing human BM cells prior to autologous bone marrow transplantation (ABMT). We tested the efficacy of ASTA-Z against mouse plasmacytoma cells MOPC-315 (MOPC), a model of human multiple myeloma. BALB/c mice were injected intraperitoneally with different doses of MOPC preincubated with ASTA-Z. All control mice receiving > or = 10(4) MOPC intraperitoneally (ip) died within 23 days. All recipients of ASTA-Z pretreated MOPC remained healthy for > 180 days. To simulate the clinical situation, BALB/c mice received lethal doses of 10(3) MOPC ip prior to ABMT. Subsequently, mice were treated with cyclophosphamide 200 mg/kg one day prior to syngeneic BMT with 10(7) BMC containing 10(6) MOPC; 90% of the mice receiving unpurged syngeneic BMC died within 45 days whereas all mice transplanted with ASTA-Z-treated BMC/MOPC mixtures remained disease-free for > 100 days. Our results suggest that a similar approach may be successful in patients with multiple myeloma and residual disease prior to cryopreservation of their BM for ABMT. Bone marrow purging with ASTA-Z is effective and under certain conditions could be critical for prevention of relapse following ABMT, provided that effective elimination of residual disease in the host can be achieved by the conditioning regimen prior to ABMT.
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PMID:Successful purging of murine plasmacytoma by mafosfamide (ASTA-Z). 801 50

Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4 myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen males and 11 females, aged 27-53 years (median 39.5 years) received oral busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17 patients and severe mucositis in 22. There was no evidence of cardiotoxicity, nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive disease. Twenty-three patients engrafted with the median duration of neutropenia (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x 10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related complications. Of 15 evaluable patients with active disease at BMT, 9 responded and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months) later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival at 36 months was 64% and 58%, respectively, while for the entire group of 24 patients these values were 39% and 34%. Busulphan and melphalan is a safe and inexpensive conditioning regimen for autologous BMT with acceptable toxicity and substantial antitumour activity particularly against lymphomas.
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PMID:Busulphan and melphalan prior to autologous bone marrow transplantation. 827 31

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.
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PMID:In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT. 840 55

In August 1988 we began a program in which multiple myeloma patients achieving < or = 10% marrow plasma cells and > or = 50% reduction in paraprotein levels after the VAD (vincristine, doxorubicin, dexamethasone) regimen underwent bone marrow harvest, ex vivo marrow purging with 4-hydroperoxycyclophosphamide (4-HC) and marrow cryopreservation. Conditioning with a regimen of high-dose busulfan (total dose 16 mg/kg), cyclophosphamide (120 mg/kg) and melphalan (90 mg/m2) (BU + CY + MEL) followed by autologous BMT was then carried out. Seventeen of the 24 patients who received VAD (71%, 95% confidence interval [CI] 49 to 87%) were eligible for bone marrow harvest. One patient was not harvested because of non-medical reasons; two patients who underwent marrow harvest had gross plasmacytosis present in biopsies performed intraoperatively and did not undergo BMT. Fourteen patients (58%, 95% CI 37 to 78%) received BU + CY + MEL and 4-HC-purged autologous BMT. The median time to recovery of 0.5 x 10(9)/l neutrophils was 19 days (range 14 to 26) while the last platelet transfusion was given on a median of day 32 (range 10 to 46) post-BMT in the evaluable patients. The major non-hematologic toxicity was hepatic; two patients in complete remission died of hepatic veno-occlusive disease. Another patient succumbed to fungal infection despite neutrophil recovery. The remaining 11 patients achieved responses (complete in six and partial in five) associated with a normal performance status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of multiple myeloma with intensive chemotherapy followed by autologous BMT using marrow purged with 4-hydroperoxycyclophosphamide. 843 63

Analysis of prognostic factors has been made in 369 allogeneic transplants for multiple myeloma reported to the registry of the European Group for Blood and Bone Marrow Transplantation (EBMT). Favorable prognostic factors for obtaining a complete remission (CR) were stage I at diagnosis (CR 77%), one line of treatment before conditioning (CR 52%), CR before conditioning (CR 60%), and Ig A or light chain myeloma (CR 43% and 42%). Factors that predicted significantly for favorable survival in a univariate analysis included having received only one line of treatment, female sex, stage I at diagnosis, stage I at conditioning and a beta 2-Microglobulin less than 4 mg/l. Favorable post-BMT factors consisted of obtaining a CR following BMT and not being in graft-versus-host disease stage III or IV. A multivariate analysis of pre-BMT factors showed that the sex of the patient and the number of lines of treatment pretransplant were independent prognostic factors. Allogeneic BMT is a promising treatment method for patients who have received only one line of treatment, particularly if they are of the female sex. BMT late in the course of the disease is usually unsuccessful.
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PMID:An update of prognostic factors for allogeneic bone marrow transplantation in multiple myeloma using matched sibling donors. European Group for Blood and Marrow Transplantation. 852 May

A pilot study was undertaken in order to determine the feasibility and toxicity of rh-alpha-2b-interferon as maintenance therapy after allogeneic BMT for multiple myeloma. The study incorporated planned dose escalation of interferon in successive patient cohorts from an initial dose of 1 MU three times weekly to a target dose of 3 MU three times weekly. No clinical complications were observed in five patients receiving a dose of 1 Mu three times weekly. At a dose of 2 MU three times weekly, one of seven patients developed acute GVHD, which was fatal. At a dose of 3 MU three times weekly, four of five patients developed acute or chronic GVHD, and the study was therefore terminated at this point. We conclude that the use of interferon in myeloma patients early after allogeneic BMT is associated with a significant risk of GVHD, which is dose-related, and that the maximum tolerated dose in the early post-transplant period is 1-2 MU three times weekly.
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PMID:Feasibility and toxicity of interferon maintenance therapy after allogeneic BMT for multiple myeloma: a pilot study of the EBMT. 873 94

Whether or not peripheral stem cells have an unlimited capacity for self renewal is debated. However, everyday haematopoietic requirements are met by progenitors; and it seems that few "real' stem cells are needed. Although we may not yet have identified these "true' stem cells, for practical purposes the long term culture-initiating cells (LTC-ICs) are a close approximation. To date, experience in peripheral blood progenitor cell (PBPC) transplantation is largely confined to non-ablative regimens. It is therefore difficult to determine the number of PBPCs needed to effect long-term reconstitution. The number of tumour cells present among mobilised PBPCs can be reduced using the CD34 affinity column and by positive purging methods. The ex vivo expansion of CD34 cells also has the effect of diluting tumour cell concentration. In clinical use, PBPC transplantation has a proven role in support of high dose chemotherapy in certain haematological and oncological malignancies but the concept of dose intensification is not universally accepted. With the exception of leukaemia, lymphoma, myeloma or relapsed testicular cancer and possibly some subgroups of breast cancer; high dose chemotherapy does not demonstrate a survival benefit. For patients with CML, autografting with Ph- cells appears to become a useful alternative to allogeneic BMT. Allogeneic PBPC transplantation may have potential, though work is preliminary. Cord blood transplantation between matched siblings is viable, but it is not yet clear whether this source will increase the donor pool for adults needing allogeneic transplantation. For gene therapy using haematopoietic cells to be effective, a greatly increased rate of transduction will be needed. Meeting in Paris in September 1995, a European School of Oncology Task Force considered a number of important questions relating to peripheral blood progenitor cell (PBPC) physiology and transplantation. This review is a brief account of their conclusions.
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PMID:Peripheral blood progenitor cell transplantation: where do we stand? Chairman's Summary of the European School of Oncology Task Force meeting Peripheral Blood progenitor cell's held September 29-30, 1995. 880 40

Haematopoietic stem cell-supported myeloablative therapy appears to be a promising treatment modality for MM. It yields increased overall response and CR rates when compared with conventional chemotherapy, and seems to prolong the duration of survival. These conclusions, while encouraging, have mostly been drawn from uncontrolled studies carried out in select groups of patients and, obviously, need to be confirmed in controlled clinical trials. While the results of these studies are still awaited, the wider application of BMT should probably be encouraged. As in other malignancies, the best candidates appear to be those less heavily pre-treated, with chemosensitive disease, low tumour cell mass and other favourable prognostic features, for example low beta 2-microglobulin levels. Under these conditions, the chance of entering CR following BMT, be it autologous or allogeneic, is currently estimated to be of at least 50%, and the long-term probability of survival averages approximately 30%. However, while it appears that a plateau for progression-free survival cannot be ascertained following a single ABMT, reported observations of patients with continued disease-free survivals up to and beyond 10 years after allografting suggest that this latter procedure may be curative. It seems likely therefore that the higher mortality related to allogeneic BMT (which in recent years decreased from 50% to approximately 30% as the results of a better selection of patients and increasing experience in their management) may be offset by more durable control of the disease and cure in a certain proportion of patients. Recurrence of underlying malignant disease remains, however, a major problem and is the most common cause of treatment failure following BMT. For this reason, attempts to improve the impact of transplantation are warranted. Options currently under investigation include the development of more effective conditioning regimens, as applied in double auto-transplant or with targeted therapy using antibody-radionuclide conjugates, as well as post-transplant immunomodulation with either IFN-alpha, interleukin-2 or idiotype vaccines. In addition, many other problems regarding BMT for MM are still unresolved and could be properly addressed only in future clinical trials. The most important of these issues include the choice of the best conditioning regimen and the optimal source of haematopoietic stem cells, the nature of relapse after autografting, the need to purge or not to purge the autologous marrow, the existence of a 'graft-versus-myeloma' effect and its role in prolonging the duration of disease control and, finally, the likelihood of cure, especially for patients with molecularly-defined CR.
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PMID:The role of haematopoietic stem cell-supported myeloablative therapy for the management of multiple myeloma. 884 73


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