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)

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

Myelodysplastic syndromes are a heterogeneous group of acquired primary and secondary alterations of hematopoietic stem cells that result in cytopenias in blood and cytologic features of dysplasia in blood and/or bone marrow. To better understand the cytologic features that would permit differentiation of primary and secondary forms of myelodysplasia, we reviewed 267 consecutive bone marrow reports from dogs. These reports indicated that 34 dogs (12.7%) had dysgranulopoiesis, dyserythropoiesis, and/or dysthrombopoiesis in >10% of granulopoietic cells, erythroid cells, and/or megakaryocytes, respectively. Thirteen dogs had primary myelodysplastic syndromes, and 21 had secondary myelodysplastic syndromes. Of the 13 dogs with primary myelodysplasia, 4 were subclassified as myelodysplastic syndrome with refractory anemia (MDS-RA), and 9 were subclassified as myelodysplastic syndrome with excess blasts (MDS-EB). Secondary conditions associated with dysplasia in the bone marrow included malignant lymphoma (n = 5), myelofibrosis (n = 3), immune-mediated thrombocytopenia (n = 4), immune-mediated hemolytic anemia (n = 5), multiple myeloma with melphalan administration (n = 1), pyometra with estrogen administration (n = 1), polycythemia vera (n = 1), and thrombopathia (n = 1). MDS-RA was characterized by <5% myeloblasts in bone marrow, normal granulocyte maturation ratio, increased erythroid maturation ratio, and dysplastic changes in >15% of erythroid cells. MSD-EB was characterized by >/=5% myeloblasts in bone marrow, high granulocyte maturation and erythroid maturation ratios, >/=32% dysplastic granulocytes, and the presence of small atypical immature myeloid cells. Secondary myelodysplastic syndromes were characterized by <5% myeloblasts in bone marrow, variable granulocyte maturation and erythroid maturation ratios, and variable dysplastic features. These results indicate that morphology alone cannot be used to distinguish primary and secondary myelodysplastic syndromes in dogs.
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PMID:Cytologic evaluation of primary and secondary myelodysplastic syndromes in the dog. 1202 19

Secondary myelodysplastic syndrome (sMDS) and secondary acute leukemia (sAL) are hematologic neoplasms occurring a few years following another primary malignancy, and are believed to be related to the chemotherapy used for the primary disease. Alkylating agents are considered to be more leukemogenic than other chemotherapeutic agents. Hodgkin's disease and multiple myeloma, among the hematologic neoplasms, and breast cancer among the solid tumors, are associated with this late complication more than other malignancies. The clinical picture is similar to primary MDS. However, the course is rapid, with early leukemic transformation and poor prognosis. since many sMDS patients are relatively young, it is reasonable to suggest an aggressive approach, i.e. bone-marrow transplantation (BMT) or antileukemic chemotherapy. The older patients may be offered low dose ara-c (LDAC), differentiating agents or clinical trials with growth factors. Even the responders survive no more than a few months.
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PMID:Secondary myelodysplastic syndromes and acute leukemias. 1205 Dec 92

We present five cases of concomitant relapsed multiple myeloma and therapy related myelodysplasia (t-MDS). After treatment with thalidomide marked anti-myeloma activity was observed, but it was associated with rapid progression of the MDS clone to acute myeloid leukemia (AML). This paradoxical effect of thalidomide is concerning because there is increasing use of thalidomide in relapsed, heavily treated multiple myeloma patients who already have a higher propensity to develop MDS. The leukemic transformation in our cases most probably reflects the natural progression of MDS, though it clearly demonstrates that thalidomide is ineffective in controlling blast proliferation in t-MDS. More concerning, however, is the possibility that thalidomide, while suppressing the myeloma clone, eliminates inhibitory signals and subsequently stimulates the proliferation of the leukemic clone. The use of thalidomide should be carefully assessed in relapsed multiple myeloma patients with clinical and cytogenetic evidence of t-MDS.
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PMID:Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia. 1215 95

The best strategies for non-myeloablative stem cell transplants (NST) are not known. We hypothesized that a high stem cell dose and post-transplant donor lymphocyte infusions (DLI) in a T cell-depleted NST setting may result in stable engraftment without severe GvHD. We used conditioning with 200 mg/kg cyclophosphamide, and ATG, a high peripheral stem cell dose of >10 x 10(6) CD34(+) cells/kg, T cell-depleted to <1 x 10(5) CD3(+) cells/kg followed by incremental DLI. Ten patients, 53 (42-61) years of age with hematological malignancy (CML in 3, MDS in 2, myeloma in 3 and CLL in 2) were included. All patients achieved initial engraftment, at a median 13.5 (10-20) days. Three patients achieved complete chimerism, four achieved a complete hematologic remission. In seven patients the graft ultimately failed. Acute GvHD grade II was seen in three patients after DLI. At a median follow-up of 28 months (range 15-35), eight patients are alive, none died of treatment-related complications. NST with T cell depletion to prevent GVHD results in a high graft failure rate. High stem cell dose (> or =10 x 10(6) CD34(+)cells/kg) and post-transplant DLI will not compensate for the lack of T cells to ensure stable engraftment.
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PMID:High stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation. 1279

The concept of utilizing enhanced immunosuppression rather than myeloablative cytotoxic conditioning has allowed the engraftment of allogeneic stem cells from related and unrelated donors with lower early transplant-related mortality (TRM) and morbidity. This approach shifts tumor eradication to the graft-vs-host immune response directed against minor histocompatibility antigens expressed on tumor cells. This is not without risk, as the long-term effects of graft-versus-host disease (GVHD), it's treatment, or resulting complications and immunodeficiency may be life threatening. However, this approach does allow the application of a potentially curative procedure to elderly or medically infirm patients who would not tolerate high-dose conditioning regimens. Section I, by Dr. Sandmaier, describes the current use of nonmyeloablative regimens and matched related or unrelated donors for the treatment of patients with CLL, CML, acute leukemia, MDS, lymphoma, and myeloma. In Section II, Dr. Maloney discusses the use of cytoreductive autologous followed by planned non-myeloablative allografts as treatment for patients with myeloma or NHL. This tandem transplant approach has a lower TRM than conventional high dose allografting. The nonmyeloablative allograft may allow the graft-versus-tumor (GVT) immune response to eradicate the minimal residual disease that causes nearly all patients with low-grade NHL or myeloma to relapse following autologous transplantation. In Section III, Dr. Mackinnon discusses the risks and benefits of T cell depletion strategies to prevent acute GVHD, while retaining GVT activity by planned donor lymphocyte infusions. Finally, in Section IV, Dr. Shizuru discusses the relationship between GVHD and GVT activity. Future studies, employing a greater understanding of these issues and the separation of GVHD from GVT activity by immunization or T cell cloning, may allow nonmyeloablative allogeneic transplantation to be safer and more effective.
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PMID:Non-myeloablative transplantation. 1244 34

Hematopoietic stem cell transplants (HSCTs) are considered the best treatment option for many hematological malignancies, and transplant numbers have increased five-fold during the last decade. Only a few controlled prospective studies are available, and different opinions prevail. Data from 118 167 HSCT (36% allogeneic, 64% autologous) collected within the EBMT activity survey from 1990 to 2001 were used to assess trends over time, transplant rates and coefficient of variation (CV) of transplant rates among European countries for acute myeloid leukemia (AML; 18.5%), acute lymphocytic leukemia (ALL; 12%), chronic myeloid leukemia (CML; 11.5%), myelodysplastic syndromes (MDS; 3%), lymphoproliferative disorders (LPS; 36.3%) and multiple myeloma (MM; 18.7%). Transplant rates increased in all countries and for all indications from 1990 to 2001 from 1.7-fold (CML) to 24.8-fold (MM). Transplant rates have declined for CML since 1999. Autologous HSCT are the preferred choice for LPS and MM, allogeneic HSCT for ALL and myeloid malignancies. CVs of less than 50% suggest consensus for allogeneic HSCT in AML, ALL, CML, MDS and NHL, for autologous HSCT in LPS and MM. These data give an overview of the current status of HSCT for hematological malignancies in Europe and provide objective information for health-care providers and patient counselling.
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PMID:Hematopoietic stem cell transplantation for hematological malignancies in Europe. 1275 Jul 9

Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high-dose therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan-based tandem autotransplants (median follow-up, 5 years). Negative consequences for both overall survival (OS) and event-free survival (EFS) in the presence of any CA were confirmed, especially when detected within 3 months of HDT. In the context of standard prognostic factors (SPF), 'MM-MDS' (MM karyotype that contains, in addition, CA typical of MDS) imparted a poor OS and EFS, after adjusting for any CA and all individual CA. One-year mortality was also high, especially for the MM-MDS subgroup with trisomy 8 within a MM signature karyotype (87%vs 34% in its absence, P < 0.001). No patient remained event free 5 years post transplant in the presence of these baseline high-risk CA. However, certain trisomies (e.g. chromosomes 7 and 9) and del 20 had favourable clinical consequences. The higher risk that is associated with CA compared with SPF justifies routine cytogenetic studies in all patients with MM at diagnosis and whenever additional treatment decisions are considered, such as in planning HDT either for initial response consolidation, at the time of primary unresponsiveness to induction therapy, or at relapse.
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PMID:MDS-type abnormalities within myeloma signature karyotype (MM-MDS): only 13% 1-year survival despite tandem transplants. 1287 70

Mini-transplantations in leukemia or MDS in the elder patients are reported to have almost the same results as of the young patients. On the other hand, multiple myeloma is considered that no conventional chemotherapy is curable. Here are some reports of short term of observations at our hospital. We tried pre-conditioning with ATG(2.5/kg x 2), TBI(1 Gy x 2), L-PAM (70 mg x 2), M-Pred(700 mg/m2 x 5) to ten progressive multiple myeloma cases, 40% became mixed chimera and they all became completely donor type with DLI. In almost 4 years of observations, over all survival rate is 68% that it is worth while to continue this treatment.
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PMID:[Multiple myeloma]. 1451 28

Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n=24) or allogeneic (n=35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 micromol/g dry weight (7.7 mg/g; range 31-631 micromol/g). In total, 4/32 (12%) patients with HIC <150 micromol/g and 10/27 (37%) with hepatic iron > or =150 micromol/g showed invasive aspergillosis at autopsy (P=0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P=0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.
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PMID:Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis. 1528 93


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