Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Childhood MDS comprises a group of heterogeneous clinical disorders with overlapping features and many similarities to adult MDS. Environmental factors, genetic predisposition, certain viral infections, and impairment of the developing immune system perhaps play a major role in the genesis of the most common disease forms, such as JCMMoL and the monosomy 7 syndrome. One intriguing finding in these disorders is the striking male predominance. Diagnostic difficulties occur because dysplastic manifestations of the hematopoetic systems are usually not as impressive as in adults and because myelodysplastic and myeloproliferative disease forms overlap considerably. Despite these problems, we believe that pediatric cases of MDS should also be classified according to the established FAB classification for MDS. However, as has already been proposed earlier by others, JCMMol clearly should be considered as a specific entity different from the adult form of CMMoL. As has been shown by cell culture studies, JCMMoL is characterized by the presence of neoplastic macrophage/monocyte progenitor cells. These cells produce several factors that result in autostimulation and suppression of normal hematopoiesis. MDS is a highly malignant disease in children and evolves to acute leukemia after a short period. During the early phase of the disease, supportive care is sufficient. If a compatible donor is available, BMT is the treatment of choice and should be performed during the early stage of disease progression after clinical remission is obtained with chemotherapy. If BMT is not feasible, intensive chemotherapy may improve the clinical condition and prolong survival. Preliminary data suggest that the incorporation of hematopoietic growth and/or differentiation factors in chemotherapy and BMT protocols may have some beneficial effects. The only way to accumulate sufficient data on MDS in children with respect to clinical features, prognosis, and efficacy of treatment is to follow a uniform diagnostic and treatment program. To achieve substantial improvements in the management of childhood MDS, multicenter trials will be essential.
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PMID:Experience in pediatric myelodysplastic syndromes. 161 11

It is important to make the correct diagnosis of MDS and to exclude very carefully all other disorders that may induce dysplastic features in the bone marrow. In patients without excess of bone marrow blasts, cytogenetics and in vitro bone marrow cultures may aid in making the correct diagnosis. MDS patients without excess of bone marrow blasts or symptomatic cytopenia or cytogenetic abnormalities associated with poor prognosis should be followed on a regular basis with sequential examinations of blood counts and bone marrow specimens. In the absence of obvious disease progression, ie, increasing cytopenia or increasing percentage of marrow blasts, patients should only receive supportive care. An increase in RBC requirements alone is insufficient reason to start cytotoxic therapy. Once progression of the disease has been well documented, cytotoxic treatment is indicated. There is no reason to delay treatment until these patients have progressed to overt AML. In patients over the age of 50, the best available therapy is low-dose cytarabine with a 30% probability of a good response; this therapy requires careful supervision and the availability of intensive supportive care. In patients under 50 years with progressive disease, or with clear evidence of a poor prognosis, allogeneic BMT is the therapy of choice if a HLA-identical sibling can be identified. In those patients who lack a HLA-identical sibling, intensive combination therapy is the treatment of choice and should preferably include high-dose cytarabine. Intensive consolidation therapy will be necessary for a durable remission. Trials with inducers of differentiation remain experimental. Results to date have been disappointing.
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PMID:Management of the myelodysplastic syndromes. 282 13

We conducted a prospective, multicenter pilot study of remission induction therapy in patients with poor prognosis MDS and AML evolving from a preceding phase of MDS. Fifty evaluable patients from 15 institutions were treated with one or two remission-induction courses consisting of i.v. idarubicin 12 mg/m2/day on days 1, 2, and 3 combined with a continuous i.v. infusion of cytarabine of 200 mg/m2/day on days 1 to 7. Of the 27 complete remitters (54%), 23 received a consolidation course which was identical to the remission-induction course except for the idarubicin 12 mg/m2 which was given on day 1 only. Fifteen patients received maintenance therapy consisting of six courses of cytarabine 10 mg/m2, s.c. twice daily, for 14 days. Two complete remitters were allografted and five patients received an ABMT. The median survival of all 50 treated patients was 14 months. The median duration of disease-free survival was 11 months with two patients in CR more than 2 years after entering CR. Twenty-four of the 27 remitters have relapsed. Four patients died during remission-induction therapy, but no patient died as a result of persisting hypoplasia. No fatal complications occurred during the consolidation and maintenance courses. Age and stage of disease had no significant impact on CR rate nor on remission duration. The CR rate was significantly (P = 0.03) higher in patients with only normal metaphases compared to patients with cytogenetic abnormalities. The DFS at 2 years was 33 vs 8%, respectively, for patients without or with cytogenetic abnormalities (P = 0.02). This study shows that patients below the age of 60 years with poor risk features are candidates for treatment with combination chemotherapy. A complete remission rate of more than 50% may be expected. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT may be treated with intensive post-remission chemotherapy or autologous BMT.
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PMID:Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG). 747 66

Administration of G- and GM-CSF increases the neutrophil counts in a number of clinical situations. GM-CSF shows the additional effect of increasing the number of monocytes and eosinophil granulocytes. Both G- and GM-CSF affect of neutrophil functions, in the case of GM-CSF there are some potentially negative effects on neutrophil migration and adhesiveness. The clinical relevance of the various effects on mature haematopoietic cells is not fully understood. Clinical data with G-CSF treatment indicate that increased levels of neutrophil granulocytes following cytotoxic chemotherapy may translate into clinical benefit such as a decreased rate of neutropenic infection and an increased cytotoxic chemotherapy dose even though the data are conflicting and the risk of "laboratory cosmetics" is apparent. Regarding treatment with GM-CSF following chemotherapy, the clinical benefit is unclear. The clinical benefit of GM-CSF-induced monocytes and eosinophils is unknown. G- and GM-CSF accelerates neutrophil recovery following autologous or allogeneic BMT. The influence on neutropenic infections is, however, less impressive. Pretreatment with G- or GM-CSF increases the yield of peripheral stem cell harvest, thereby reducing the number of leukaphereses needed. Transplantation of G- and GM-CSF primed autologous peripheral stem cells tends to reduce the period of post-transplant cytopenia, particularly thrombocytopenia, in comparison with traditional ABMT. In patients with MDS, G- and GM-CSF appear to increase the number of neutrophil granulocytes and there is some evidence that patients with severe infectious problems will benefit from this treatment. However, little influence was seen on the main clinical problems with these patients, which are anaemia and thrombocytopenia. In conclusion, G- and GM-CSF are two different proteins with different properties in vivo and in vitro. GM-CSF has, compared with G-CSF, more complex pharmacological effects and a more trouble-some side-effect profile. Early clinical development indicates that both compounds have a substantial influence on the levels of certain blood cells. Whether the increases in different blood cells translate into long-term clinical benefit for greater patient groups is the focus of ongoing research. The effects of G- and GM-CSF may be potentiated by other cytokines, an area which is presently being explored.
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PMID:G- and GM-CSF in oncology and oncological haematology. 751 79

TNF alpha levels were determined by ELISA in serum from 112 BMT patients during pre-transplant conditioning. Patients who developed post-transplant complications had significantly higher TNF alpha levels than those without complications (mean 620 pg/ml vs 440 pg/ml, P = 0.04). In particular this effect is associated with patients who developed grade II-IV acute GVHD (mean 960 pg/ml, P < 0.001) and chronic GVHD (mean 724 pg/ml, P = 0.001). High TNF alpha levels were the only statistically significant risk factor for acute GVHD. IL-1 beta and IL-6 levels were not correlated with TNF alpha levels or posttransplantation complications. In multivariate analysis of chronic GVHD, patient age > 17 years and CMV disease were the only statistically significant risk factors. Relapse was associated with low levels of TNF alpha during conditioning (mean 318 pg/ml, P = 0.02). In multivariate analysis, high risk disease was the only factor that correlated with relapse. Low risk patients had significantly higher levels than high risk patients (551 vs 377, P= 0.04). CML and MDS patients had higher TNF alpha levels than acute leukemia patients. There was no difference in TNF alpha levels between patients conditioned with BU/CY and CY/TBI. We conclude that determination of TNF alpha levels during conditioning may be useful in the prediction of acute GVHD.
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PMID:TNF alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. 774 64

Allogeneic BMT is the treatment of choice for patients with MDS or sAML, offering a good chance of long-term disease-free survival if the transplant is performed in an early stage of disease or if the patient receives the transplant in complete remission after polychemotherapy. The transplant is limited to a minority of relatively young patients (aged below 55 years) with an HLA-identical sibling. Allogeneic BMT may also be considered when a closely- or fully-matched unrelated donor has been identified for a young and fit patient. All patients, including those without an excess of blasts, should be conditioned with bone marrow ablative therapy rather than an immune suppressive regime, such as cyclophosphamide alone. For the majority of patients there is no standard therapy other than appropriate supportive care. Relatively young patients below the age of 60 years with poor risk features can be considered for treatment with combination chemotherapy. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT could be treated with post-remission chemotherapy or autologous BMT in the framework of prospective studies. Older patients can be considered for treatment with haematopoietic growth factors alone or in combination with differentiating agents such as low-dose Ara-C. This treatment should be delivered within the context of carefully designed and conducted trials.
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PMID:New treatment approaches for myelodysplastic syndrome and secondary leukaemias. 807 47

Case 1: A 26-year-old female was admitted because of leukocytosis with 43.6% myeloblasts and 33.6% monocytes, and trilineage myelodysplasia (T-MDS) was detected on bone marrow (BM) smear. She was diagnosed as having acute myeloid leukemia (AML) (M4) with T-MDS and was treated with the Japan Adult Leukemia Study Group (JALSG) AML87 protocol. After completion of chemotherapy, leukemic myeloblasts remained minimally and myelodysplastic changes were still detected on BM smear. She underwent allo-BMT from an HLA-identical sibling. The conditioning regimen consisted of busulfan and cyclophosphamide. Cyclosporine A and short term methotrexate were administered prophylactically for graft-versus-host disease (GVHD). She developed slight veno-occlusive disease and pancytopenia, which improved soon. She is surviving free of disease for 37 months from BMT. Case 2: A 41-year-old male was diagnosed as having T-MDS AML (M2) and achieved complete remission with the AML89 protocol, but relapsed soon. He underwent allo-BMT from an HLA-identical sibling. The conditioning regimen and prophylaxis against GVHD were the same as in case 1. He developed mild acute GVHD, pleural effusion and later mild chronic GVHD. These improved soon. He is surviving free of disease for 21 months from BMT. Some reports suggest that intensive chemotherapy can induce CR in 40%-70% of patients with T-MDS AML, but most of them tend to relapse and rarely survive long. We consider that the best strategy for treatment of T-MDS AML is allo-BMT at present, if suitable donors are available.
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PMID:[Allogeneic bone marrow transplantation for two patients with acute myeloid leukemia with trilineage myelodysplasia (T-MDS)]. 813 16

We report the case of a 14-year-old boy with myelodysplastic syndrome (MDS/RAEB) which developed following Fanconi anemia. The patient received BMT from an HLA-identical sister. Based on the in vitro CY-sensitivity test, 100 mg/kg of CY was administered for conditioning combined with 6 Gy TBI. Mucosal symptoms such as stomatitis, diarrhea and hematuria were severe, but manageable, and engraftment was successful. The patient has maintained normal trilineage hematopoiesis with > 90% Karnofsky score for 30 months with disappearance of a clonal chromosomal abnormality (47,XY, +i(lq)) which was detected before BMT.
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PMID:Successful allogeneic bone marrow transplantation in a case with myelodysplastic syndrome which developed following Fanconi anemia. 852 82

A 49-year-old man with myelodysplastic syndrome (MDS, RAEB in T) who relapsed following allogeneic bone marrow transplantation (allo BMT) was treated with infusions of donor buffy coat leukocytes. He sustained hematologic and cytogenetic remission, but severe graft-versus-host disease (GVHD) developed for which cyclosporin A and prednisolone were required. This therapeutic approach appears to be valuable for relapsed MDS following allo BMT as well as for chronic myelogenous leukemia (CML).
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PMID:Donor buffy coat infusions for a patient with myelodysplastic syndrome who relapsed following allogeneic bone marrow transplantation. 853 26

These two issues of the Seminars in Hematology will provide the physician the necessary knowledge to help make sense of this somewhat confusing array of diseases. The subdivisions of MDS reflect the precision of our techniques of dissection, with morphological and histochemical analyses forming the foundation to identify and subdivide MDS. Although steady refinement has occurred over the last half-century, the basic morphologic technique is unchanged. Cytogenetic analysis, which has been possible since the 1960s and 1970s, should be done at least at initial presentation in all patients to provide refinement of diagnosis and prognosis. FISH is not, at this time, useful as a screening technique. Although the 1990s is an era of rapidly growing knowledge and technical abilities in molecular biology, the use of these techniques in MDS is in its infancy. Very few genes have been identified which are altered in MDS, although many must exist. The molecular assays continue to be cumbersome and impractical to use in the clinical laboratory and remain the domain of the research scientist. Nevertheless, in the future, molecular biology will enable the internist to give each individual a clearer diagnosis and prognosis and may even provide targetted therapies of patients with MDS. At this time the center of management is good supportive care. Some patients, however, will benefit from special interventions, which include the use of growth factors, BMT, and in selected patients, aggressive chemotherapy. Induction of differentiation of the abnormal hematopoietic clone remains only a dream, although some of the differentiation agents may have applicability for their ability to induce apoptosis and prevent growth of the MDS clone of cells. Many of the major advances in our knowledge of cancer developed through the study of hematopoietic malignancy. A lot of these advances are due to the ease of obtaining the abnormal cells. MDS provides an excellent model for studying the progression of cells from their normal to preneoplastic and fully transformed states. A lucid understanding of this progression can form the paradigm for basic science to study neoplastic progression, and the molecular biology techniques used for these studies will be the basic tools used by hematologists and oncologists in the future.
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PMID:Myelodysplastic syndromes. 872 80


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