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 combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.
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PMID:Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2). 834 74

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

Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were selected on the basis of informative IgG allotype (Gm) differences between the BM donor and the recipient. To investigate the kinetics of the appearance of IgG of donor origin and the disappearance of IgG of recipient origin, G1m and G2m allotype levels were quantified in sera obtained at regular intervals between 3 months and 5 years after BM transplantation (BMT). For this quantification, a dot immunobinding assay (DIBA) has been developed. In 19 of 22 informative recipients, the Gm allotype distribution had reached the range of values expected on the basis of the Gm phenotype of the donor within 6 months after BMT. Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients until last follow up, ie, for several years after BMT. In addition to the origin of total IgG production, the origin of homogeneous IgG components (H-IgG) appearing after BMT was investigated. H-IgG of donor origin could be detected as early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8 of 13 informative recipients for a period of up to 1 year after BMT. We conclude that host-type IgG-producing cells were not eradicated by the (myeloablative) conditioning regimen and persisted in a high number of graft recipients. It is our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of these recipients results in the persistence of IgG-producing cells of host origin. These observations may be relevant for the evaluation of patients who received allogeneic BMT for the treatment of multiple myeloma.
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PMID:The origin of IgG production and homogeneous IgG components after allogeneic bone marrow transplantation. 855 8

The presence of a graft-versus-tumor effect has been well established in leukemia but not in multiple myeloma. A 40-year-old patient with myeloma refractory to standard chemotherapy and autologous transplantation received a matched unrelated T-cell-depleted transplant after conditioning with fractionated total-body irradiation, thiotepa, and cyclophosphamide. This procedure resulted in a transient and incomplete response with evidence of rapidly progressive disease within 2.5 months posttransplantation. The patient then received a small number of donor peripheral blood (PB) mononuclear cells (CD3 cells 1.2 x 10(6)/kg) without any further cytotoxic therapy. A complete remission was attained, lasting now for more than 14 months. The procedure was associated with severe acute and subsequently limited chronic graft-versus-host disease (GVHD). This report provides the first direct evidence of a graft-versus-myeloma effect after allogenic transplantation.
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PMID:Graft-versus-myeloma effect: proof of principle. 856 47

A 29-year-old male underwent allogeneic bone marrow transplantation for progressive multiple myeloma. His post-transplant course was complicated by severe chronic pulmonary graft-versus-host disease (GVHD) resistant to cyclosporin A, corticosteroids and azathioprine. The introduction of thalidomide resulted in a dramatic improvement in his lung function which has been maintained even after cessation of thalidomide. He remains well 40 months after transplantation.
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PMID:Thalidomide responsive chronic pulmonary GVHD. 901 41

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.
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PMID:Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. 870 95

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

Between September 1987 and December 1994, 80 patients with multiple myeloma (MM) received high-dose busulfan and cyclophosphamide without (n = 57) or with modified total body irradiation (n = 23) followed by marrow from allogeneic donors. At transplant, 71% of the patients had disease that was refractory to chemotherapy. Thirty-five patients died of transplant-related causes within 100 days and 11 deaths occurred later. The actuarial probabilities of survival and progression-free survival were .24 +/- 0.17 and .20 +/- 0.10 at 4.5 years. Complete remissions were obtained in 36% of patients who had actuarial probabilities of survival and event-free survival of .50 +/- 0.21 and .43 +/- 0.17 at 4.5 years. In a multivariate analysis, adverse risk factors for outcome endpoints included: transplantation greater than 1 year from diagnosis; beta-2 microglobulin > 2.5 at transplant; female patients transplanted from male donors; patients who had received greater than eight cycles of chemotherapy before transplant and Durie stage 3 disease at the time of transplant. These results indicate that allografting for patients with MM can result in long-term disease-free survival for a minority of patients. Efforts to reduce transplant-related mortality should focus on earlier transplantation, less toxic treatment regimens, better supportive care, and improved prevention and treatment of graft-versus-host disease (GVHD).
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PMID:Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. 883 77

Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.
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PMID:Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation. 893 45

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, I have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines, in this review. IFN-alpha has been approved for chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN-alpha is one of the most useful and wide-ranging antitumor agents in hematological malignancies. Most striking effects have been studied in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the category of treatment is difficult to choose in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been made to prime leukemic cells by CSFs to make them more susceptible to chemotherapy, but no convincing evidence has been obtained.
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PMID:Cytokine therapy for hematological malignancies. 899 Jun 22


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