Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D03343 (MDS)
 2,225 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37) were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven patients (2, class 1) in the BM group had one HLA locus mismatch donor, respectively. The following factors were matched: HLA-compatibility, diagnosis, disease stage, age and gender. The median age in the PBSC group was 37 years (19-56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM group consisted of 12 females and 25 males, 17 females and 20 males were in the PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four (14/20) of the 74 patients (45%) were considered as high risk patients. The conditioning regimen was BU/CY for standard risk patients with myeloid diseases (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients received intensified conditioning with VP16 (2 patients), thiotepa (2 patients) or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days, in PBSC and BM transplants, respectively. The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26 days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly between the groups. The incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05, log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and 27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a significantly faster leukocyte engraftment. The significant increase with regard to the incidence and shorter time of onset of severe aGVHD in PBSC patients, compared to marrow transplant patients, need to be confirmed in a randomised trial.
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PMID:A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study. 1093 83

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

We diagnosed a probable fludarabine-induced secondary MDS approximately 18 months after treatment of a low grade non-Hodgkin's lymphoma. After diagnosis of a B-cell lymphoma composed of relatively small cells, fludarabine was administered between May and October, 1997, to a 64-year-old female patient. In December 1998, a mild bicytopenia was present with a leukocyte count of 3800/microl and platelets of 142000/microl. The white cell differential count was normal. The hemoglobin level was normal, but MCV was elevated. Bone marrow cytology revealed normal cellularity with dyserythropoiesis and dysmegakaryocytopoiesis. PAS staining showed scattered positivity in early erythroid cells. In 12 of 20 mitoses, the karyotype showed complex rearrangements, described as 46,XX,t(4;11)(q23?24;q13),del(5q),del(7)(q22),+mar[8]/45,-3. A diagnosis of treatment-related MDS was made. While there was no evidence of bone marrow infiltration by the lymphoma, CT scans demonstrated paraaortic lymph nodes up to 10 cm in diameter. After one course of CHOP chemotherapy, prolonged bone marrow aplasia and septic complications occurred. Chemotherapy was abandoned and Rituximab was administered. In July and November, 1999, bilateral pneumonia and urinary tract infection, respectively, were treated with antibiotics. NHL was in complete remission, but peripheral blood counts deteriorated markedly, and transfusions of packed red cells had to be started in November, 1999. The suspicion of leukemic transformation could not be confirmed because the patient declined further bone marrow biopsies. In December, 1999, the patient died from pneumonia.
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PMID:Secondary myelodysplastic syndrome after fludarabine therapy of a low-grade non-Hodgkin's lymphoma. 1113 66

Using red cell phenotyping (RCP) and/or cytogenetics (CYT) we identified 19 patients with persisting mixed chimerism (MC) among 231 patients transplanted with partially T cell-depleted stem cell grafts from HLA-identical siblings. Persisting MC is defined as MC for more than 2 years in patients without any evidence of relapse. Median leukemia-free survival in these patients was 150 (range, 50-218) months. Diagnoses were ALL (n= 10); AML (n = 2); CML (n = 2); NHL (n = 2); MDS (n= 1); MM (n = 1) and SAA (n = 1). Purpose of this study was the long-term follow-up of MC and definition of patterns of chimerism in the various subsets of PBMCs and granulocytes. Using a PCR-STR technique CD3(+)/CD4(+) (T4 lymphocytes), CD3(+)/CD8(+) (T8 lymphocytes), CD45(+)/CD19(+) (B lymphocytes), CD45(+)/CD14(+) (monocytes), CD45(+)/CD15(+) (granulocytes) and CD3(-)/CD56(+) (NK-cells) were analyzed. The majority of patients with persisting MC were conditioned with a less intensive conditioning regimen and had little GVHD. Sequential monitoring of the chimerism resulted in a group of patients (n = 7) with very slow transient mixed chimerism that resulted in complete DC after median 7 years. Another nine patients had a relatively high percentage of persisting autologous cells for a median of 12 years and in three patients we observed a stable low percentage of autologous cells. Only two out of 19 patients (AML-CR1, CML-CP1) relapsed during follow-up. Both patients had a relatively high percentage of autologous cells. Chimerism in granulocytes and PBMC subsets was analyzed at a median of 8 years after SCT in nine patients. In five patients mixed chimerism simultaneously detected by RCP and CYT was associated with MC in all subsets. Within each individual patient the percentages of donor and recipient cells were very different between the different subsets. Two CML-CP1 patients were mixed chimera in only two subsets and in one patient these subsets represented pending relapse. In another two patients mixed chimerism with a very low number of autologous red cells was not found in the PBMCs because of the different sensitivity level of the RCP and the PCR-STR technique. We conclude that in patients with persisting mixed chimerism after partially T cell-depleted SCT a remarkable number of patients had lymphoid malignancies, the majority of the patients were conditioned with less intensive conditioning regimens and the mixed chimerism was not correlated with relapse. Chimerism in granulocytes and PBMC subsets did show great intra-individual differences in the subsets and these data correlated well with RCP and CYT data with the exception of the NK cells.
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PMID:Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation. 1184 Feb 58

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

Age >or=50 years has been reported to be an adverse risk factor for allogeneic BMT, and consequently many of these patients are either not transplanted or treated on nonmyeloablative protocols. To study if older patients perform poorly relative to younger adults following myeloablative allogeneic transplants, we compared the outcomes of consecutive adults aged >or=50 years (n=51) to those <50 years (n=262) who received BU, CY+/-etoposide and allogeneic transplantation for AML, CML, MDS and NHL from 1984 to 2000. Median ages were 53 (range 50-66) and 35 (range 18-49) years for older and younger patients, respectively. Patients were low-risk if they had AML in CR1, CML in first chronic phase, refractory anemia, or NHL in remission or sensitive relapse at the time of transplantation. All others were high-risk. In patients with low-risk disease, there was no significant difference in overall survival (OS) between older and younger adults (P=0.64), while older patients tended to have a shorter OS among high-risk patients (P=0.06). The 3-year OS was 53% (95% CI, 29-77%) compared to 60% (95% CI, 50-69%) for older and younger patients with low-risk disease, respectively. The corresponding 3-year OS were 27% (95% CI, 11-43%) and 37% (95% CI, 25-45%) for high-risk patients. In low-risk patients, the incidence of acute and chronic graft-versus-host disease, and treatment-related mortality were similar in older and younger patients, while older patients experienced more treatment-related deaths by day 100. On multivariable analysis, age >or=50 years was a significant adverse factor only when high-risk patients were considered. We conclude that when radiation-free conditioning is used, age >or=50 years is not a significant adverse risk factor for allogeneic BMT in patients with low-risk disease, and that such patients should not be excluded from conventional myeloablative approaches until the efficacy of nonmyeloablative transplantation is better established.
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PMID:Radiation-free regimens result in similar outcomes of allogeneic hematopoietic progenitor cell transplantation in patients aged >or=50 years compared to younger adults with low-risk disease. 1262 88

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

We assessed the prognostic importance of the platelet count 100 days post transplant of 107 consecutive patients receiving ablative allogeneic bone marrow transplant (BMT) between 7/96 and 12/00 who survived at least 100 days. Diagnoses included AML (n=36), chronic myelogenous leukemia (n=27), NHL (n=14), ALL (n=16), MDS (n=9), aplastic anemia (n=3), and one Hodgkin's disease and myelofibrosis each. In total, 64% were in remission or in chronic phase or had aplastic anemia (good risk), and 36% had active disease at the time of transplant (bad risk). In all, 70% were matched sibling transplants and 30% were matched unrelated donor transplants. The mean follow-up for the patients remaining alive is 48 months. Survival was powerfully influenced by the 100-day platelet count: 4-year survival was 19% for patients with a platelet count <30 x 10(9)/l; 41% for patients with a platelet count of 30-50; and 72% for those with a platelet count >50 (P<0.001; log-rank test). In a multivariable analysis, the most powerful risk factors for mortality after allogeneic BMT were low 100-day platelet count (P<0.001) and bad risk disease (P=0.009). We conclude that the platelet count 100 days post transplant is a powerful predictor of overall survival.
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PMID:Prognostic importance of the platelet count 100 days post allogeneic bone marrow transplant. 1468 14

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated three patients with severe aGVHD refractory to steroids with infliximab. Patients (MDS 1, NHL 1, ALL 1) developed grade II-IV GVHD at a median of 13 days (range 9-17) after non-myeloablative PBSCT (HLA mismatched). All patients had received treatment with high-dose steroids for a median of 7 days (range 7-10) in addition to mycophenolate mofetil (MMF) (one). Infliximab was given in 3 weekly doses of 5 mg/kg. In one of three patients a partial resolution of diarrhea and minor improvement of skin were observed. One patient died with refractory GVHD. Infliximab is apparently an effective drug for the treatment of aGVHD, but can be more effective at doses of 5 mg/kg or higher and/or by administering it repeatedly every week.
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PMID:Infliximab for the treatment of severe steroid refractory acute graft-versus-host disease in three patients after allogeneic hematopoietic transplantation. 1495 53

Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant.
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PMID:Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course. 1564 Aug 12


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