Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Sixteen patients with relapse after allogeneic BMT were treated with donor leukocyte infusions (DLI) from the original donor. The diagnoses at relapse were: CML in chronic phase (CP) (two patients), CML in accelerated phase (AP) (four patients), AML (four patients), MDS (one patient), ALL (four patients) and relapse of Hodgkin's disease (one patient). The patients received a mean of 5.2 x 10(8) leukocytes/kg with a range of 1.4-12.3 x 10(8) leukocytes/kg. Six patients obtained complete remission (CR), one with CML in CP, three with CML in AP, one MDS and one ALL. Partial remission (PR) was seen in three patients, one patient with CML in AP, one with AML and one with Hodgkin's disease. Seven patients had no response (NR) to the infusions, including one patient with CML in CP transplanted with a syngeneic donor. Four patients developed marrow hypoplasia after DLI (three CR and one PR) and two patients (ALL with CR and MDS with CR) were hypoplastic at relapse and marrow hypoplasia continued after DLI. GVHD occurred without GVL, but GVL only occurred in one patient with absence of GVHD. Eleven patients died of leukemia, six patients are alive. Three patients with CML are in CR 12, 12 and 32 months after DLI and one patient with ALL is in CR 15 months after DLI.
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PMID:Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients. 886 54

Fluorescence in situ hybridization in combination with morphology (MGG/FISH) was used to detect minimal residual disease (MRD) in complete remission (CR) in 12 cases of acute leukaemia (six MDS-AML, five de novo AML, one pre-B ALL) with numerical chromosomal aberrations at diagnosis. Residual leukaemic cells could be detected in the remission bone marrows by MGG/FISH in five patients, whereas the other seven showed no abnormalities. All five patients with signs of MRD at CR relapsed in the bone marrow with 2-9 months, in contrast to two of seven with a normal finding by MGG/FISH at CR. In both these patients a second MGG/FISH analysis showed that a subpopulation of leukaemic blasts had reappeared, 4 and 5 months prior to the leukaemia becoming clinically overt. One patient suffered a CNS relapse, but without any evidence of bone marrow involvement. The remaining four patients with no evidence of MRD at CR were still in haematological remission at follow-up after 4, 11, 12 and 13 months, respectively. We conclude that MGG/FISH seems to be a clinically useful method to detect MRD in acute leukaemia and to predict relapses, particularly when repeat studies are performed during CR.
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PMID:Fluorescence in situ hybridization in combination with morphology detects minimal residual disease in remission and heralds relapse in acute leukaemia. 898 43

To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.
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PMID:Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. 905 12

A quantitative analysis of expression levels of GM-CSF receptors was performed by flow cytometry in different disease categories, ie AML (n = 72), ALL (n = 18), and MDS (n = 12), as well as 12 healthy volunteers, using three different unconjugated GM-CSF/R monoclonal antibodies (McAbs) (HGM-CSFR (CD116), M5D12, 4B5F5), and appropriate standards. By using the reference HGM-CSFR McAb, in healthy subjects we found detectable levels of GM-CSF/R on blood monocytes (mean MESF (molecules of equivalent soluble fluorochrome)/cell: 36.1 x 10[3]), neutrophils (mean MESF/cell: 7.4 x 10[3]), bone marrow (BM) myelo-monocytic precursors (MESF range for the myeloid component, ie promyelocytes, myelocytes, metamyelocytes: 11.7-40.5 x 10[3], and for the monocytic lineage: 25.7-69.2 x 10[3]), and in two distinct subsets of BM CD34+ progenitor cells (GM-CSF/R dim: 2.5 x 10[3] MESF/cell, GM-CSF/R bright (10% of the total number of CD34 cells: 22.0 x 10[3] MESF/cell). In these subjects, there was no correlation between the expression levels of GM-CSF/R and CFU (CFU-GM, CFU-GEMM, BFU-E) colony production. Among the AML samples, M5D12 McAb was positive in 33%, 4B5F5 McAb in 90%, and HGM-CSF/R McAb in 78% of the cases examined (range of MESF/cell for the HGM-CSFR McAb: 0.9 x 10[3]-106.7 x 10[3]). The highest MESF values were seen in the M5 FAB subvariety (mean: 39.4 x 10[3]), where all the patients tested (n = 20) showed a strong positivity for the HGM-CSFR McAb. On the contrary, all ALL samples were GM-CSF/R negative except in two patients, who displayed a dim GM-CSF/R positivity (My+ALL: 1.3 x 10[3] MESF/cell; pro-B ALL: 1.0 x 10[3] MESF/cell). In most (>70%) M1 FAB subtypes, GM-CSF/R+ blasts co-expressed CD34low, HLA-DRhigh, CD33, CD38 antigens, and had little or no capacity to form CFU-GM colonies. GM-CSF/R+ blasts from the M5 FAB category were also positive for CD14, CD11c, CD33 and CD87. Furthermore, the number of GM-CSF/R expressed by leukemic cells from five out of 72 (7%) AML patients was above the highest values seen in normal samples (>69.2 x 10[3] MESF/cell), allowing the possibility of using this marker for the monitoring of the minimal residual disease (MRD) in a subset of AML. Cell culture studies aimed at evaluating GM-CSF receptor modulation following AML blast exposure to rhGM-CSF showed two distinct patterns of response; in the first group (6/10 cases) rhGM-CSF down-modulated GM-CSF receptors, whereas in the second group (4/10 cases), rhGM-CSF treatment was associated with either an increase or no change in the number of GM-CSF/R. In conclusion, cellular GM-CSF/R expression was variable and ranged from undetectable (ALL and a minority of AML) to very high intensities in M5 AML, and were also documented in some M0 AML, thus suggesting the concept that GM-CSF/R detection may be of help in lineage assignment of undifferentiated forms. Since the number of GM-CSF/R on AML blasts may be modulated after GM-CSF treatment, it can be postulated that the clinical use of GM-CSF in this disease may be optimized by a dynamic analysis of the number and the affinity status of GM-CSF-R in blasts and normal hemopoietic cells.
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PMID:Flow cytometry measurement of GM-CSF receptors in acute leukemic blasts, and normal hemopoietic cells. 932 92

The incidence of aplastic anemia appears to be relatively high in some parts of the world, including Pakistan. Since some of the etiological factors are shared by aplastic anemia and the preleukemic syndrome, there is a strong possibility that a proportion of cases of aplastic anemia may in fact be preleukemia. The study of chromosomes offers a relatively easy method of detecting cases of preleukemia, because some chromosomal abnormalities are frequently observed in this condition. Chromosomal studies were carried out in peripheral blood cell cultures of 31 patients with otherwise typical aplastic anemia. Chromosomal abnormalities were detected in 7 (22.5%) cases. The most common chromosomal abnormality detected was trisomy 8, seen in four cases. Other abnormalities detected were 22q-, t(14;22) and t(15;21), in one case each. These abnormalities have been found to be associated with AML, MDS, ALL, and NHL as well. We hypothesize that a proportion of cases of otherwise typical aplastic anemia may in fact be due to a leukemic process in evolution.
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PMID:Aplastic anemia or aplastic preleukemic syndrome? 943 74

Cytogenetic analysis was performed in 86 cases of hematologic malignancy, using conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) analysis at two university hospitals in Korea between 1993 and 1995. In addition to well-known anomalies, some unusual abnormalities were found, such as t(17;22), trisomy 9 combined with t(14;17), (2;7) and Philadelphia chromosome in CML; t(1;12), t(11;22), t(9;17), and t(12;21) in AML; trisomy 11 in MDS; t(2;9) and complex t(8;8;13;14) in ALL. The results of FISH analysis in interphase nuclei using a translocation probe for CML and APL showed more than 85% positive cells in CML, and 75% positive cells in APL.
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PMID:Cytogenetic and fluorescence in situ hybridization analyses of hematologic malignancies in Korea. 946 Apr 92

Within a prospective study we analyzed hematopoietic chimerism in serial peripheral blood samples taken from 55 patients with acute leukemias (ALL 21, AML 20, MDS 14) with a median age of 13.5 years at very short time intervals following allogeneic bone marrow transplantation (allo-BMT). The investigation was performed to determine the implications of mixed hematopoietic chimerism (MC) with regard to the clinical outcome in patients with acute leukemias after allo-BMT. Analysis of chimerism was performed by PCR of variable number of tandem repeat (VNTR) sequences with a maximum sensitivity of 0.8%. Thirteen male patients transplanted with the marrow of a female donor were also studied by amplification of a Y-chromosome-specific alphoid repeat (0.1-0.01% sensitivity). VNTR analysis in 55 patients revealed complete chimerism (CC) in 36 cases, MC in 18 follow-ups and autologous recovery in one patient. Quantitative analysis of MC identified 10/18 patients with increasing autologous patterns in whom 9/10 subsequently relapsed. The patient with autologous recovery relapsed as well. Eight of 18 patients with MC showed decreasing amounts of autologous DNA and became CC upon further follow-up. In contrast, only 7/36 patients with CC in the prior analysis of chimerism status relapsed. However, in 4/7 patients the interval between last CC confirmation and relapse was more than 4 months. In 2/7 patients autologous DNA was not detectable in peripheral blood but in bone marrow aspirates. One of these seven patients developed a fulminant relapse within 3 weeks. The probability of relapse-free survival for patients with CC is 0.67 (n = 36), for patients with decreasing MC 1.0 (n = 8) and for patients with increasing MC 0.1 (n = 10). In summary, the results demonstrate that serial and quantitative chimerism analysis at short time intervals by PCR provides a reliable and rapid screening method for the early detection of recurrence of underlying disease and is therefore a prognostic tool to identify patients at highest risk of relapse.
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PMID:Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. 953 41

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.
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PMID:Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients. 957 Jun 80

The telomerase activity of various hematologic disorders, including malignant and non-malignant ones is discussed in this paper. In total of 137 cases, each positivity of telomerase activity was MDS = 17/51, overt leukemia from MDS = 6/15, AML = 17/21, ALL = 4/6, CML-CP (chronic phase) = 0/10, CML-BC (blastic crisis) = 4/4, MPD (myeloproliferative disease)-BC = 3/3, CLL = 1/10, MM (multiple myeloma) = 0/6, aplastic anemia = 3/5, essential thrombocytosis = 0/3, and polycythemia vera = 1/3. The MPD-BC showed very high level of telomerase activity as well as CML-BC cases. From the analysis for 18 cases of AML and/or malignant lymphoma patients, significant results showed that the expression of cyclin D/E was not related to telomerase activity in these hematologic disease, as was not the case with breast cancer which was reported formerly.
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PMID:[Analysis for telomerase activity in various hematologic disorders]. 961 44

Mitoxantrone (Mito) is presently used in an increasing number of malignancies including leukemias, breast carcinomas and solid tumors. With it has come increased incidence of post remission cytopenias and delayed engraftment following autologous bone marrow transplantation (ABMT). We evaluated engraftment in 18 patients who underwent allogeneic BMT (allo-BMT) following a preparative regimen that included high dose Mito (60 mg m2). Sixteen patients with malignant disease (AML 10, ALL 3, CML 2, MDS 1) and two with non-malignant disease (SCID 1, osteopetrosis 1) underwent non-T cell depleted allo-BMT. Fourteen patients with malignancies were transplanted at an advanced stage of disease while only two patients were standard risk patients. Of the 18 patients, 12 were females and six males, with a median age of 30.5 (0.3-48) years. Nine patients, (breast cancer 3, malignant lymphoma 4 and AML 2), who underwent ABMT following preparative regimens with comparable doses of Mito, served as controls. Engraftment following allo-BMT was normal and not statistically different from engraftment following ABMT. Five patients, who underwent allo-BMT, developed >grade II acute graft versus host disease (GVHD) and two developed chronic GVHD. After a median follow up of 28 (6-42) months, five patients are alive (one with disease). In summary, engraftment following high dose Mito and allo-BMT is not statistically different from engraftment following ABMT. Controlled studies with a larger group of standard risk patients are needed to elucidate the role of Mito in conditioning regimens pre-BMT.
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PMID:Engraftment following mitoxantrone (Mito) based conditioning for allogeneic bone marrow transplantation (allo-BMT). 961 12


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