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)

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases.
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PMID:Therapeutic aspects of myelodysplastic syndromes in chronic phase. 131 Jan 27

We examined the feasibility of maintaining specific plasma concentrations of ara-C and VP-16 in children with AML. Sixty-one children were treated with 6 sequential cycles of intensive chemotherapy consisting of: (1) cytarabine (ara-C)/VP-16, (2) ara-C/daunorubicin (Dauno), (3) VP-16/amsacrine (m-AMSA), (4) VP-16/5-azacytidine (5-Az), (5) ara-C/Dauno, and (6) ara-C/VP-16. Fifty-nine children had de novo AML, and 2 had a previous myelodysplastic syndrome. The number of patients with each specific FAB subtype was: M0-1; M1-7; M2-24; M3-7; M4-5; M5-11; and M7-6. Simultaneous continuous infusions of ara-C and VP-16 (cycle 1) given at individualized doses to achieve drug plasma concentrations of 1 microM and 30 microM, respectively, produced complete remission (CR) in 26 of 61 patients (43%); an additional 17 patients entered CR after Dauno/ara-C (cycle 2), and one patient required 4 cycles of chemotherapy to achieve CR (total CR rate = 72%). The preliminary 2-year event-free survival (EFS) for patients with FAB-M1 and -M2 AML was only 15% versus 40% for those with FAB-M4 and -M5 AML. Overall, 21 of the 61 patients remain in CR (2-yr EFS = 29%). We conclude that intense treatment with ara-C and VP-16 at doses individualized to achieve target plasma concentrations is feasible although severely myelosuppressive. It results in an acceptable CR rate, but does not improve EFS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital. 137 92

The response to treatment with low-dose ara-C was studied in 102 consecutive patients; 79 with myelodysplastic syndrome (MDS) and 23 with acute myelogenous leukaemia (AML) following MDS. The aim was to find variables that could predict the response to treatment. All patients had clinical symptoms related to cytopenia. Peripheral blood values, bone marrow morphology histology and chromosomes were analysed before the start of treatment. The median survival of the patients was 9 months and a poor survival was predicted by advanced age, low platelet counts, the presence of pseudo-Pelger morphology and > or = 2 chromosomal aberrations. Thirty patients (29%) responded with either a complete remission or a significant increase in haemoglobin level. For the remaining 71%, the treatment was ineffective and in some cases hazardous. The factors associated with a poor response to treatment could be divided into two groups: one included low platelet counts and the presence of chromosomal aberrations, both signs of progressive MDS with a short survival, and the other comprised morphological findings, indicating ineffective haemopoiesis. Patients with platelet counts > 150 x 10(9)/l had a response rate of 55% compared to 23.5% in patients with subnormal platelet counts. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and < 2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts < 150 x 10(9)/l. These factors and the platelet count were combined in a predictive model which can divide patients into three groups with different probabilities of response: a favourable group, 38.6% of the patients, with a response rate of > 50%, an intermediate group, 32.7% of the patients, with a response rate of 24%, and an unfavourable group, 28.7% of the patients, with only 3% responses. While low-dose ara-C is an effective treatment for some patients, it is ineffective and hazardous for others. We present a model that can facilitate therapeutic decision making in two-thirds of patients with MDS and MDS-AML by identifying patients who should not be treated with low-dose ara-C as well as patients with a relatively high probability of response.
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PMID:A predictive model for the clinical response to low dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia. 139 Feb 36

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.
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PMID:Short term therapy (STT) for acute myelogenous leukaemia (AML). 157 52

We have prospectively evaluated a regimen of mitozantrone and cytosine arabinoside (Ara-C) as first-line therapy in elderly patients with acute myeloid leukaemia (AML). One hundred and four patients with a median age of 68 (range 60-81) were studied, in whom 86 had de-novo AML, and 18 had preceding myelodysplasia or secondary AML. Complete remission was achieved in 64% of de-novo cases, in 28% of MDS/secondary cases, and in 58% overall. The incidence of early death within 28 d of chemotherapy was 11%. The median disease-free survival (DFS) was 11 months with an actuarial DFS of 15% at 43 months. The median overall survival was 9 months with an actuarial survival of 10% at 44 months. The incidence of non-haematological toxicity was acceptably low, and usually of mild to moderate severity. Quality of life was improved, or unchanged, in 90% of responders. We conclude that mitozantrone and ara-C is an effective and well-tolerated regimen which produces high remission rates in elderly patients with AML.
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PMID:Mitozantrone and cytosine arabinoside as first-line therapy in elderly patients with acute myeloid leukaemia. 158 Dec 25

63 evaluable patients with myelodysplastic syndromes (MDS) and 15 with acute myelogenous leukemia (AML) were randomized between low-dose ara-C (arm A) and low dose ara-C in combination with 13-cis-retinoic acid (13-CRA) and 1 alpha-hydroxy-vitamin D3 (1 alpha D3) (arm B). 69 patients were evaluable and 18 (26.1%) responded to therapy. The addition of 13-CRA and 1 alpha D3 had no positive influence on survival of the patients, remission rates or duration of remissions. 12/27 patients in arm A and 6/29 patients in arm B progressed from MDS to AML during the course of the study (p = 0.0527). Arm B gave significantly more side-effects than arm A (p = 0.005). Therapeutic effects of 13-CRA and 1 alpha D3 on MDS is not supported by this study. However, an inhibiting effect on AML development in some MDS subgroups cannot be excluded.
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PMID:Treatment of myelodysplastic syndromes with retinoic acid and 1 alpha-hydroxy-vitamin D3 in combination with low-dose ara-C is not superior to ara-C alone. Results from a randomized study. The Scandinavian Myelodysplasia Group (SMG). 226 51

In this retrospective study, 61 induction treatment periods in 57 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) were evaluated. According to the WHO performance status, 6 patients received no chemotherapy, 20 had low dose cytosine arabinoside (LD ara-C) induction courses, and 35 received standard induction consisting of daunorubicin and cytosine arabinoside. Untreated patients had a poor survival. Of the 20 patients with LD ara-C induction courses, 4 (20%) achieved complete remission (CR). Three patients (15%) died during induction. Of 35 patients with standard induction, 21 patients (60%) achieved CR. Toxicity was considerable - 11 patients (31%) dying during treatment. We conclude that patients over 60 yr of age with RAEB, RAEB-t or AML had a CR rate and survival comparable to those of younger patients if treated with standard induction chemotherapy at the cost of serious therapy-related complications. In patients who were judged not to be able to tolerate standard induction and who were subsequently treated with LD ara-C, complications occurred less frequently, but the CR rate was low and survival short.
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PMID:Standard induction and low dose ara-C treatment in patients over 60 with AML or MDS. 260 90

Bone marrow cells from 15 patients with myelodysplastic syndromes and 2 with acute myeloid leukemia were incubated in vitro with all-trans-retinoic acid (RA), 1,25-dihydroxy vitamin D3 (D3), cytosine arabinoside (ara-C) and alpha-interferon (IFN). 3H-thymidine incorporation (3H-TdR), differentiation and clonal growth were studied. D3 was found to be the most effective inducer of differentiation and differentiation was correlated with a decreased 3H-TdR. Differentiation with one of the inducers was significantly correlated to differentiation with any of the other inducers. Patterns of differentiation and spontaneous and D3-induced 3H-TdR were used to divide the patients into 3 different groups. In the first group, 5 patients with extremely low spontaneous 3H-TdR and differentiation in combination with a slightly increased 3H-TdR after induction differed from all other patients by a higher percentage of bone marrow blast and a more pronounced pancytopenia. The two other groups had a high spontaneous 3H-TdR but differed with respect to the D3-induced differentiation which was absent in one group (n = 6) and present in the other (n = 5). The two groups showed no difference in the clinical features.
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PMID:Effects of retinoic acid, 1,25-dihydroxyvitamin D3, cytosine arabinoside and alpha-interferon on bone marrow cells from patients with myelodysplastic syndromes. 261 68

In a pilot study, five patients with myelodysplastic syndromes with an excess of blast cells were treated with a combination of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine-arabinoside (ara-C) in an attempt to selectively kill the leukemic blast cells and thereby to restore normal hemopoiesis. The treatment schedule consisted of three 14-day-cycles of 250 micrograms/m2 rhGM-CSF and 20 mg/m2 ara-C given daily s.c. with four-week treatment-free intervals. In all four evaluable patients the percentage of bone marrow blast cells decreased significantly with an increase in the mature myeloid cells but without bone marrow aplasia. Toxic side effects attributable to the drugs were minor with fever, mild bone pain, erythema and itching at the site of subcutaneous injection of rhGM-CSF. In conclusion, the combined therapy of rhGM-CSF and low-dose ara-C appears to be effective in the short-term control of the leukemic cell population.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine arabinoside in patients with myelodysplastic syndrome. A pilot study. 265 86

A case of AML (M 4) with t(6; 11) showed recovery to myelodysplastic syndrome (MDS)-like bone marrow after one course of DCMP regimen. Dysplastic changes of three cell-lineages were observed and micromegakaryocytes were markedly increased in number. Recovering hematopoiesis was incomplete. During MDS-like phase, t(6; 11) disappeared, reverting to normal karyotypes. Low dose ara-C regimen did not show any effect. AML soon relapsed with reappearance of t(6; 11). MDS-like abnormal hematopoiesis has recently been reported to occur after remission induction therapy or at the time of relapse. G-6PD isozyme study revealed in a remission case of AML that hematopoiesis still consisted of abnormal clone in spite of karyotypic normalization. The abnormal hematopoiesis observed in our case can be referred to such a clonal disorder predominating after disappearance of blastic component of AML. It seems important to reveal what proportion of de novo AMLs shows such an abnormal hematopoiesis and to establish suitable therapeutic approach.
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PMID:[Marked dysmyelopoiesis after induction chemotherapy in a case of acute myelomonocytic leukemia (M 4) with t(6; 11)]. 274 77


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