UMLS:C0026986 - FACTA Search

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Query: UMLS:C0026986 (myelodysplastic syndrome)
14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we review the cumulative international experience with allo-CT used to treat 163 patients, 105 with CML and 58 with other hematologic diseases, who relapsed following allogeneic BMT. The first patient treated by allo-CT was diagnosed with acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic and extramedullary relapse shortly after BMT. He was given infusions of donor (sister) PBL in multiple increments. Subsequently, he developed mild, reversible graft-vs-host disease (GVHD) in parallel with regression of all hematologic and cytogenetic disease manifestations. More than 8 years after allo-CT, he is disease-free with Karnofsky score 100% and no evidence of residual male cells by PCR. International data show that relapse after BMT was successfully reversed by donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete response after allo-CT was obtained in recipients of both TCD-BMT and unmodified BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100 (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha-interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of patients with other diseases. The cumulative experience shows that allo-CT can successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and even more effectively of chronic leukemia independently of alpha-interferon therapy. Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.
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PMID:Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. 854 46

The option of bone marrow transplantation (BMT) significantly improved prognosis of adult patients with hematologic malignancies aged less than 50 years. Allogeneic BMT using the marrow of an HLA-identical family member still provides the most effective method of BMT. Conventional indications for this form of BMT are chronic myeloid leukemia (CML), acute leukemias presenting with adverse risk factors, myelodysplastic syndromes and severe aplastic anemia. If performed early in the disease course (e.g. during the chronic phase of CML or first remission of acute leukemia and MDS) allogeneic BMT cures 50 to 60% of patients. About 20% die of therapy related complications, e.g. graft versus host disease (GvHD), fatal infections or venoocclusive disease of the liver (VOD) and about 20% of patients succumb to relapse of their hematologic disorder. 80% presenting with severe aplastic anemia can be cured, if allogeneic BMT is performed soon after diagnosis without previous immunosuppressive therapy and blood transfusions. BMT with the marrow of a matched unrelated donor or autologous BMT are increasingly used as alternative procedures. A rate of lethal complications as high as 50% hinders rapid extension of BMT with unrelated donors. Therefore, this form of BMT should be restricted to young patients with leukemias, who cannot achieve long-term remission with conventional chemotherapy (in case of acute leukemias) or alpha-interferon (in case of CML). Reconstitution of hematopoiesis is more rapid after peripheral blood stem cell transplantation (PBSCT) compared with autologous BMT. Therefore, PBSCT will replace autologous BMT in most cases. Most favourable results of PBSCT have been reported in patients with malignant lymphomas after relapse or inferior response to primary induction therapy. Due to the higher relapse rate autologous BMT is inferior to allogeneic BMT in leukemia patients. Trials are required to clarify the potential role of myeloablative therapy with stem cell support in the treatment of patients with solid tumors. Many of the preliminary results already published are unsatisfactory and data of larger trials are still lacking. Therefore, BMT or PBSCT cannot be recommended generally for the therapy of patients with solid tumors.
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PMID:[Indications, technique and risks in bone marrow transplantation in adulthood]. 864 1

The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients.
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PMID:Erythropoietin and the anemia of cancer. 866 61

We report six cases of trisomy 15 in patients with hematological malignancy. In four cases trisomy 15 was the sole abnormality and in two cases it was associated with sex chromosome loss. The patient age range was 6-91 years, and three patients were male. Four patients had myelodysplasia (refractory anemia), one patient each had acute myeloid leukemia and acute lymphoblastic leukemia. A literature review identified ten other cases of trisomy 15 as the sole abnormality in hematological malignancies. Trisomy 15 as the sole autosomal abnormality in hematological malignancy is uncommon, but can occur in both myeloid and lymphoid malignancies. It appears to occur most frequently in myelodysplasia.
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PMID:Trisomy 15 in hematological malignancies: six cases and review of the literature. 868 5

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

The occurrence of multiple malignancy was studied in 674 patients with hematologic malignancies who were admitted to this department during the past 10 years. Of the 674 patients, 205 were aged 65 years or older, and 56 (8.3%) had another cancer. The frequency of multiple malignancy was significantly higher in older patients than in younger patients: 44 (21.5%) vs. 12 (2.6%). The major hematologic conditions in patients with multiple malignancy were multiple myeloma, myelodysplastic syndromes, non-Hodgkin's lymphoma, and chronic myelogenous leukemia. The major sites of cancers other than hematological malignancies were the stomach, colon, breast, and esophagus. Many of the older patients had gastric cancer or colon cancer, and gastric cancer was common in the younger patients. The multiple malignant neoplasms were synchronous in as many as 20 of the 44 older patients. There was only one such case among the younger patients. Of the 56 patients, nine had received alkylating agents, and one has received etoposide. In brief, elderly patients with hematologic malignancies are likely to have multiple malignant neoplasms. If they are synchronous, the patient's prognosis may be adversely affected, because simultaneous management of multiple malignant neoplasms is not easy.
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PMID:[Double cancer in elderly patients with hematologic malignancies]. 875 14

A 28-year-old man developed Crohn's disease and myelodysplastic syndrome concurrently. Chromosomal analysis of the bone marrow revealed a normal male karyotype. Subsequently, the myelodysplastic syndrome progressed to acute myelocytic leukemia. Several causes, including the medical treatment for Crohn's disease, chromosomal abnormalities, and a common underlying immune dysfunction, have been proposed as pathogenetic factors in the association with Crohn's disease of hematologic malignancies. This case suggests that neither medical treatment for Crohn's disease nor chromosomal abnormalities are inevitable causes of the development of hematologic malignancies associated with Crohn's disease. At present, the cause of the association remains unclear, although the idea of a common immune dysfunction is attractive.
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PMID:Simultaneous development of Crohn's disease and myelodysplastic syndrome progressing to acute myelocytic leukemia in a patient with a normal karyotype. 884 86

Transcription factors play a key role in controlling the cellular differentiation of hematopoietic cells. Among the known transcription factors, both GATA-1 and SCL play roles in the cellular differentiation of erythrocytic and megakaryocytic lineages, while GATA-2 is thought to maintain and promote the proliferation of early hematopoietic progenitors. In this review, the clinical implications of expression of the GATA family, SCL, and EVI1 gene in various types of human leukemia are discussed. De novo acute myeloid leukemia (AML) patients may be subdivided into three categories depending on the expression pattern of transcription factors, i.e., GATA-1(+)SCL(+), GATA-1(+)SCL(-), and GATA-1(-)SCL(-). AML patients with both GATA-1 and SCL expression have a poor prognosis and have some characteristic clinical and hematologic features. The EVI1 gene may be expressed through at least two pathways in hematologic malignancies; one is related to chromosomal changes at 3q26, while the other is related to myelodysplasia regardless of chromosomal changes at 3q26 region. These findings suggest that the pattern of expression in transcription factors in abnormal hematopoietic cells is reflected in the malignant phenotype and play a role in the pathogenesis of the disease.
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PMID:Pattern of expression and their clinical implications of the GATA family, stem cell leukemia gene, and EVI1 in leukemia and myelodysplastic syndromes. 903 Oct 72

In a double-blind, randomized study performed between 1988 and 1990, 40 patients undergoing allogeneic BMT from HLA-identical siblings for hematologic malignancies received 8 mg/kg/d rHuGM-CSF (molgramostim, n = 20) for 14 days. The median neutrophil count on day 14 was significantly higher in the GM-CSF group (1.90 vs 0.46 yen 10(9)/L, P < .0001). The incidence of acute GVHD and transplant-related mortality were comparable. Only two deaths occurred after 6 months; one due to pulmonary fibrosis in the GM-CSF group on day 1591, and one due to relapse on day 1590 in the placebo group. The Karnofsky score of the 10 survivors, 3 in the placebo group and 7 in the GM-CSF group, is 90-100% (median 100%), and none has chronic GVHD requiring therapy. There was no evidence of increased relapse in the GM-CSF group with only two relapses occurring; both in the placebo group. With a follow-up of 4.5-6.8 years (median 5.5 years), these patients are amongst the longest surviving patients to have received a recombinant growth factor post-allograft. We conclude that the administration of GM-CSF after allogeneic BMT does not appear to be associated with an increased incidence of chronic GVHD or relapse, or of other adverse effects such as the development of myelodysplasia.
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PMID:Long-term safety of GM-CSF (molgramostim) administration after allogeneic bone marrow transplantation for hematologic malignancies: five-year follow-up of a double-blind randomized placebo-controlled study. 915 59

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56. Patients with CD56+ blast cells were selected, and morphologic review was performed. Clinical information was obtained, and cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of the mixed lineage leukemia (MLL) gene was performed when possible. The samples from 23 of 114 patients studied demonstrated anomalous expression of CD56 on myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients with CD56+ AML demonstrated at least partial monocytic differentiation. Dysplastic features were displayed in the samples of 12 patients. Correlation with specific cytogenetic abnormalities was not found. The MLL gene was rearranged in five of 18 patients. Seventeen patients have died, with a median survival of 4.6 months for patients with AML. Three have sustained a complete remission. One has findings of high-grade myelodysplastic syndrome. Two were unavailable for follow-up. Expression of CD56 was found in 20% of patients with increased myeloblasts, including patients with high-grade MDS, chronic myelogenous leukemia in blast crisis, and AML. This phenotype was associated with dysplasia, monocytic differentiation, and rearrangement of the MLL gene.
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PMID:Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes. 916 61

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