Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary hematopoietic disease manifesting as acute myeloid leukemia, myelodysplastic syndrome or clonal karyotypic abnormalities, has been recently recognized as a relatively frequent and potentially serious complication of autologous bone marrow transplantation for both Hodgkin's disease and non-Hodgkin's lymphoma. The available evidence suggests the disease results primarily from repeated exposure of the host stem cells to therapeutic agents before the time of transplant, but a conspiratory role for the transplantation procedure itself cannot be entirely excluded. Strategies to decrease the incidence of secondary hematopoietic disease include earlier stem cell harvest and/or transplantation, and the performance of screening karyotypic studies on the bone marrow prior to autologous grafting.
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PMID:Myelodysplasia and acute myeloid leukemia occurring after autologous bone marrow transplantation for lymphoma. 883 91

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

The patient was initially diagnosed as having non-Hodgkin's lymphoma and was cured following treatment with prednisolone, vincristine, daunorubicin, 1-asparaginase, and cyclophosphamide. Seven years and two months later, he developed osteosarcoma in his right femur. He received chemotherapy consisting of methotrexate, carboplatin, etoposide, and ifosfamide and again obtained remission. After 2 years and 7 months, however, he was found to have pancytopenia with morphological abnormalities in the erythroid and myeloid series. Diagnosis of myelodysplastic syndrome (MDS) was made. Cytogenetic analysis of bone marrow cells revealed -5 and -7, which is typical for secondary MDS. This is a rare case of third malignancy presumably caused by alkylating agents.
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PMID:Myelodysplastic syndrome presenting as third malignancy after non-Hodgkin's lymphoma and osteosarcoma. 906 80

We studied four patients with inv(11)(p15q22) associated with malignant myeloid diseases by using fluorescence in situ hybridization (FISH) with phage and cosmid probes mapped and ordered on 11q22-24. Two of the four patients had non-Hodgkin's lymphoma or acute lymphoblastic leukemia as the primary malignancy and had received cytotoxic chemotherapy, including topoisomerase II inhibitors. The other two had de novo acute myeloid leukemia or myelodysplastic syndrome. FISH analysis showed that all 11q breakpoints were located centromeric to the MLL gene and between cosmids CN2900 and CN1323. We identified a yeast artificial chromosome (YAC) clone that spanned the inv(11) breakpoints on 11q. From this YAC, we identified a P1 clone, which included the breakpoints in at least three of the four patients. It is highly likely that the same gene on the P1 clone is rearranged in leukemic cells of each patient. This gene may be one of the targets for topoisomerase II inhibitors.
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PMID:Inversion of chromosome 11 inv(11)(p15q22), as a recurring chromosomal aberration associated with de novo and secondary myeloid malignancies: identification of a P1 clone spanning the 11q22 breakpoint. 921 95

We conducted a multicenter study to improve the treatment of B-cell non-Hodgkin's lymphoma and acute lymphoblastic leukemia (NHL/ALL) in Japanese children. The subjects were a total of 57 untreated patients with the B-cell type of either NHL (27 Burkitt's and 9 diffuse large) or ALL between 2 and 15 years old (median: 8 years) seen between 1988 and 1994. All patients received the same cytoreductive therapy (half doses of vincristine and prednisolone) and the same first and second induction courses (vincristine, prednisolone, high-dose methotrexate, repetitive high-dose cyclophosphamide, and adriamycin). Three cycles of consolidation blocks A and B (consisting of reduced doses of similar agents used in the second induction course) followed for patients with stage III or IV NHL or B-ALL, while only one cycle was given for stage I or II disease. Fifty-three patients (93.0%) achieved complete remission. Eight patients had relapse all occurring within 1 year. Another patient had secondary myelodysplastic syndrome. The median follow-up period was 48 months (range: 24-94 months). The overall survival and event-free survival (EFS) rates for all patients were, respectively, 75.9% (S.E.: 5.9) and 70.1 (S.E.: 6.1). The relapse-free interval rate of the 53 patients who achieved CR was 83.5% (S.E.: 5.3). EFS was 75.0% (S.E.: 21.7) in stage I, 84.6% (S.E.: 10.0) in stage II, 78.63% (S.E.: 11.0) in stage III, 80.0% (S.E.: 17.9) in stage IV, and 52.4% (S.E.: 10.9) in ALL. Among the stage IV NHL and ALL patients, EFS was significantly worse in patients with initial CNS involvement than in those without it (14.3% (S.E.: 13.2) vs. 73.7% (S.E.: 10.1); P = 0.0025). In conclusion, our regimen (AT-B88) produced a more than 70% cure-rate for children with any stage of B-cell NHL/ALL without initial CNS involvement. However, a new regimen is needed for patients with initial CNS involvement.
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PMID:Treatment outcome of AT-B88 regimen for B-cell non-Hodgkin's lymphoma and surface immunoglobulin-positive acute lymphoblastic leukemia in children. 922 Jun 64

Idarubicin is an anthracycline agent available as both oral and intravenous formulations. The oral formulation has demonstrated efficacy in the treatment of advanced breast cancer, low-grade non-Hodgkin's lymphoma, myelodysplastic syndromes and as first-line induction therapy of acute myelogenous leukaemia where intravenous anthracycline treatment is precluded. It also has potential in ameliorating blast crisis of chronic myelogenous leukaemia and in multiple myeloma. The most frequent adverse effects associated with oral idarubicin are those commonly found with anthracyclines, namely myelosuppression, nausea and vomiting, diarrhoea and mucositis. There appears to be minimal significant cardiotoxicity with oral idarubicia. In summary; available data concerning oral idarubicin in haematological malignancies and advanced breast cancer are sufficiently encouraging to warrant further research. To maximise the use of oral idarubicin, future studies should define the optimal dose for elderly patients, its comparative efficacy with other available regimens and address quality-of-life and pharmacoeconomic issues associated with the substitution of oral for intravenous chemotherapy.
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PMID:Oral idarubicin. A review of its pharmacological properties and clinical efficacy in the treatment of haematological malignancies and advanced breast cancer. 923 41

The incidence of secondary myelodysplastic syndromes (MDS) are rarely reported in an homogeneous patient population treated for non-Hodgkin's lymphoma (NHL). Less than 10 per cent of secondary MDS are usually observed in patients treated for Hodgkin's disease and NHL. Data on the incidence of secondary MDS induced by modern chemotherapeutic regimens is needed. Between January 1985 and January 1989, 20 patients with localized gastric non-Hodgkin's lymphomas (stage I to IIE) were prospectively treated at the Institut Gustave-Roussy with PROMACE-MOPP multi-agent chemotherapy and involved-field irradiation. The mean age was 54 years (range 23 to 69 years). Seven patients died while on therapy or relapsed 2 to 28 months after therapy. Thirteen patients were followed up for at least 5 years. Three of the 13 long-term survivors (23 per cent) developed a myelodysplastic syndrome (MDS) 48, 62 and 72 months after the end of therapy. Cytogenetic analysis was performed in two cases and showed-7 and 18q- in one case, t(9;21)(q13;q22), 21q+, i17q in the other case. PROMACE-MOPP plus radiotherapy should not be recommended in patients with localized gastric non-Hodgkin's lymphoma due to the high risk of developing secondary myelodysplastic syndromes.
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PMID:High incidence of secondary myelodysplastic syndromes following PROMACE-MOPP and involved field radiotherapy for localized gastric non-Hodgkin's lymphomas. 926 61

In the Netherlands, childhood leukaemia is recorded by the Dutch Childhood Leukaemia Study Group (DCLSG, set up in 1972) and by nine regional cancer registries which together form the Netherlands Cancer Registry (NCR, set up in 1989). The data files from the incidence years 1989-1992 of the two registries were linked in order to evaluate accuracy and completeness and to calculate and equalise the incidence rates for childhood leukaemia in The Netherlands. Unlinked records or records with disagreements (birth date, sex, type of leukaemia and incidence date) were checked by the DCLSG and by the regional cancer registries. The DCLSG recorded 431 cases of childhood leukaemia, while the NCR recorded 434 cases. After record linkage and review of the cases, it was concluded the 445 records should have been recorded as childhood leukaemia. The NCR had recorded 425 of the 445 correct cases (95.5%), but had missed 20 cases (4.5%). The DCLSG had recorded 431 of the 445 correct cases (96.9%) and had missed 14 cases (3.1%). In addition, the NCR had recorded 9 cases incorrectly as childhood leukaemia. Part of the disagreement was caused by differences in coding rules (definition of non-Hodgkin's lymphoma (NHL) and the myelodysplastic syndrome versus leukaemia). It could be concluded that the quality and completeness of the two registries was very high. Regular comparison of the recorded data will help to reveal the inherently problematic disagreement between definitions and coding.
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PMID:Accuracy and completeness of the registration of childhood leukaemia in The Netherlands, 1989-1992. 929 11

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are being reported with increasing frequency as a complication of ABMT for Hodgkin's disease and non-Hodgkin's lymphoma. At present there is no method available to predict who is at risk or is destined to develop this nearly universally fatal disorder. We therefore investigated whether clonal growth of cells is predictive of the development of t-AML/MDS. In a patient who developed secondary AML/MDS 18 months after ABMT, X-linked clonality analysis at the human androgen receptor locus was performed on serial banked samples, and documented transition from polyclonal to clonal hematopoiesis. Clonal cells could be identified 6 months after transplant (1 year prior to the diagnosis of t-AML/MDS), at a time when there was no morphologic or clinical evidence of disease. Clonality analysis can be predictive of the development of t-AML/MDS after ABMT and may offer important insights into associated risk factors and strategies to minimize the risk of t-AML/MDS.
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PMID:Prediction of therapy-related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma. 929 68

In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.
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PMID:Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. 932 77


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