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

The myelodysplastic syndromes (MDS) are characterized by hemopoietic insufficiency associated with severe cytopenias, leading to serious morbidity, and acute leukemia development. MDS typically occur in elderly people, with a median age at diagnosis ranging between 60 and 75 years. The patients' prognosis, estimated according to the International Prognostic Scoring System, age and performance status should be considered before choosing among the various treatment options. A therapeutic dilemma exists in MDS, due to the multifactorial pathogenetic features of the disease, the heterogeneous stage and the elderly age of patients at diagnosis. This is underlined by the absence of a Food and Drug Administration-approved agent with an indication for this disease. The therapeutic end-points vary from symptom management (using low-intensity treatment with biological targeted agents, or only supportive therapy), to attempts to change the natural history of the disease (generally using high intensity treatment, including intensive chemotherapy and hemopoietic stem cell transplantation). The main goal of low-intensity therapies is generally to induce hematological improvements and is mainly used for low-risk disease. On the other hand, high-intensity therapies generally aims to alter the disease's natural history (improving survival, and decrease progression to acute myeloid leukemia), and are mainly used for high-risk disease. This review will focus on the current role of low-dose Ara-C therapy in the management of MDS. In fact, there is evidence that low-dose chemotherapy with Ara-C can induce responses in patients with MDS. In particular, the use in combinations with growth factors, such as G-CSF or M-CSF, looks promising, suggesting further investigations about this old new therapeutic tool.
 ...
PMID:Low dose Ara-C for myelodysplastic syndromes: is it still a current therapy? 1537 Feb 3

Treatment of acute myelogenous leukemia (AML) incorporates the use of growth factors towards several objectives, including abbreviating the time of neutropenia, reducing susceptibility to infections, reducing length of hospitalization, and increasing susceptibility of the blasts to chemotherapy drugs, or priming. Priming is defined as the driving of leukemia cells into cell cycle in order to increase response to S-phase-specific drugs such as cytarabine (Ara-C). Growth factors that have been used in priming include both filgrastim (G-CSF) and sagramostim (GM-CSF). Priming has often been applied in the treatment of older patients, who do not respond as well to standard treatment regimens, and whose disease was transformed from a myelodysplastic syndrome (MDS), or preleukemia. Recent, large randomized trials have demonstrated that although subgroups of patients may benefit, there does not appear to be any improvement in the complete remission rate sustained by inclusion of growth factor priming as part of the initial therapy of acute myelogenous leukemia.
 ...
PMID:Growth factor priming in therapy of acute myelogenous leukemia. 1549 74

Twenty-eight of 285 patients (9.8%) with primary myelodysplastic syndrome (MDS) survived more than 5 yr (long-term survivors). There were 21 females and 7 males, median age 60 yr (range 18-84 yr). None had circulating blasts, and 14 had refractory anemia (RA), 8 RA with ringed sideroblasts (RARS) and 6 RA with excess of blasts (RAEB). Thirty-seven percent of the 27 patients who were karyotyped had an abnormal clone, but none of them had -7/7q- or complex cytogenetic abnormalities. Only one of the 13 patients tested had abnormal (i.e., "leukemic") in vitro growth of GM progenitors. During 5 yr following the diagnosis, none of the 28 patients progressed to AML. Two patients with an initial diagnosis of RA showed progression to RAEB and CMML. After 5 yr, 23 of the 28 long-term survivors had stable disease (follow-up period ranged from 64 to 216 mo). One patient progressed to AML (113 mo after diagnosis) and another to RAEBT (80 mo after diagnosis). Eight asymptomatic patients were not treated and 12 patients received only supportive therapy. Except for 6 of 8 treated patients who responded to low-dose Ara-C, danazol, androgens, or immunosuppressive treatment, prolonged survival seemed to result mainly from the natural course of the disease. Except for Valensia score (p=0.033), other scoring systems (Bournemouth, Dusseldorf, Lille, and IPSS score) proved of relatively limited value in differentiating between intermediate (2-5 yr) and long-term survivors.
 ...
PMID:Long-term survivors in myelodysplastic syndromes: clinical and biological characteristics. 1557 17

Seventy to 80% of patients with acute myeloid leukemia (AML) achieve complete remission (CR) by chemotherapy, but more than 50% of them then relapse. Phase III clinical trials in the treatment of patients with previously untreated AML and acute promyelocytic leukemia (APL) are ongoing in Japan (JALSG AML 201, APL 204). And continuous efforts are being made to improve the efficacy of chemotherapy. We discussed six topics in the treatment of AML. (1) To determine whether adding the MDR-1 modulator to chemotherapy provided clinical benefits to patients with AML and high-risk myelodysplastic syndrome (MDS), a phase III randomized study was performed using PSC 833. CR rates and overall survival (OS) were not improved by using PSC 833 compared to chemotherapy alone. (2) A large randomized study selectively focused on the G-CSF priming was performed. Among patients in this study attaining CR, the probability of relapse was reduced when they had been assigned to treatment with G-CSF along with induction chemotherapy. The benefit of chemotherapy-sensitization by G-CSF was particularly evident among the intermediate-risk. (3) Fludarabine in addition to Ara-C increases the accumulation of Ara-CTP, which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase III trial, patients with high-risk MDS or patients with AML were randomized to receive 2 induction courses consisting of Ara-C and G-CSF during and after chemotherapy with or without fludarabine (FLAG versus AG). Although Ara-CTP accumulation in leukemic cells after FLAG was enhanced, the clinical outcome in terms of CR rate, OS, event-free survival, and disease-free survival was not significantly improved by combining fludarabine with Ara-C. (4) Calicheamicin-conjugated humanized anti-CD 33 mouse monoclonal antibody, mylotarg, has recently been introduced. In combined phase II studies of 277 patients with CD 33-positive AML in their first relapse, the overall response rate was 26%. (5) Arsenic trioxide (ATO) has been established as a highly effective therapy for patients with APL, even for those with disease refractory to ATRA. ATO was recently approved in Japan. (6) There has been great interest in developing FLT 3 inhibitors because of the high frequency and poor prognosis of AML patients with mutant FLT 3. Some compounds are currently under development.
 ...
PMID:[Current and new therapeutic strategies in acute myeloid leukemia]. 1579 11

One hundred twelve patients with geriatric acute myeloid leukemia (AML), refractory or relapsed AML, or myelodysplastic syndrome and refractory anemia with excess of blasts in transformation (MDS-RAEBt) were entered into this study to receive CAG (aclarubicin and low-dose cytosine arabinoside [Ara-C]in combination with granulocyte colony-stimulating factor [G-CSF]) with the objective of evaluating the efficacy and tolerance of this regimen. Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days 1 to 14. Aclarubicin was administered intravenously at a dosage of 14 mg/m2 per day on days 1 to 4 (CAG regimen A) or 7 mg/m2 on days 1 to 8 (CAG regimen B). Recombinant G-CSF was given subcutaneously at a dosage of 200 3g/m2 per day on days 1 to 14. We demonstrated comparable overall complete remission rates for the 4 groups of patients: 30.8% (8/26) in the elderly patients, 48.4% (30/62) in the refractory AML patients, 44.4% (8/18) in the relapsed AML patients, and 38.5% (5/13) in the MDS-RAEBt patients. Of the 52 patients followed up, the 12-month progression-free survival (PFS) and overall survival (OS) rates estimated by the Kaplan-Meier method were 40.73% 3 8.15% and 42.85% 3 8.23%, respectively. The median PFS and OS times were 9.0 3 2.2 months and 11.0 3 1.6 months, respectively. Toxic effects were very rare and mainly consisted of neutropenia and thrombocytopenia due to myelosuppression; approximately 70% to 80% of patients had neutropenia or thrombocytopenia that exceeded National Cancer Institute grade II. Nonhematologic toxicities were not observed in this study. The CAG regimen seems promising, with acceptable toxicity, for the treatment of various categories of poor-prognosis AML and MDS-RAEBt.
 ...
PMID:Aclarubicin and low-dose Cytosine arabinoside in combination with granulocyte colony-stimulating factor in treating acute myeloid leukemia patients with relapsed or refractory disease and myelodysplastic syndrome: a multicenter study of 112 Chinese patients. 1610 59

Distinct morphologic and clinical features associated with specific chromosomal abnormalities have been described in subgroups of myelodysplastic syndromes (MDS), which often are losses or gains and only rarely translocations. Among 103 consecutive MDS patients diagnosed and karyotyped at the Albert-Ludwigs University of Freiburg (ALU) between 1993 and 1999, two chronic myelomonocytic leukemias (CMMoL) displayed trisomy 19 (+19) as the sole chromosomal abnormality. Three further CMMoL cases with +19 as the single abnormality, two of which previously reported, were collected from other centers. Four of the five patients presented with leukocytosis and splenomegaly, and an increased number of ringed sideroblasts was observed in two cases. Treatment was low-dose Decitabine (cases 1 and 2), oral steroids (case 3), hydroxyurea (case 4), and daunorubicin/Ara-C (case 5). Transformation to acute myeloid leukemias (AML) occurred in three/five patients (cases 1, 2, and 4) 26, 12, and 22 months after diagnosis of CMMoL, respectively. We conclude that +19 as the sole anomaly is a rare but recurrent change in CMMoL, in particular of the proliferative type. It is at present unclear which gene(s) located on chromosome 19 might have a functional role for the development of this phenotype.
 ...
PMID:Trisomy 19 as the sole chromosomal abnormality in proliferative chronic myelomonocytic leukemia. 1646 94

We describe an unusual case of a thoracic aortic aneurysm caused by Aspergillus. A 70-year-old man underwent prednisolone and Ara-C treatments for a myelodysplastic syndrome. Blood examination revealed pancytopenia. Under these treatments, an aneurysm presented at the distal aortic arch. He underwent resection of the aneurysm with a graft repair covered by a pedicled omentum flap, followed by prolonged administration of micafungin and itraconazole for a mycotic aneurysm. The postoperative course was favorable without complications. Serum C-reactive protein became negative and he was discharged 2 months after the surgery. However, 4 months after the surgery, he died from worsening of the myelodysplastic syndrome. The prognosis for patients with mycotic aneurysms is poor due to their immunocompetent condition arising from underlying diseases. Therefore, in addition to prompt treatment with antifungal agents combined with surgical debridement, control of the underlying disease is essential for improving the outcome.
 ...
PMID:Mycotic aneurysm of the distal aortic arch caused by Aspergillus. 1664 22

Although allogeneic stem cell transplantation from a human leukocyte antigen (HLA)-identical related donor offers a potential cure for patients with myelodysplastic syndrome (MDS), a suitably matched related donor is unavailable for approximately two thirds of patients. Recently, umbilical cord blood from unrelated donors have been used as an alternative stem cell source for adult patients with MDS. Here, we updated the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning for 22 adult patients with MDS. Diagnosis at transplantation included refractory anemia (RA) (n = 3), refractory anemia with excess blasts (RAEB) (n = 2), RAEB-t (n = 2), and MDS-related secondary acute myeloid leukemia (AML) (n = 15). All patients were treated with total body irradiation (12 Gy), cytosine arabinoside (Ara-C) and cyclophosphamide followed by unrelated HLA-mismatched CBT. The median age was 40 years (range, 19 - 51 years), the median weight was 54.5 kg (range, 43 - 75 kg), and the median number of cryopreserved nucleated cells was 2.43 x 10(7)/kg (range, 1.82 - 4.10 x 10(7)/kg). Twenty one patients had myeloid reconstitution and the median time to more than 0.5 x 10(9)/l absolute neutrophil count was 22.5 days. A self-sustained platelet count more than 50 x 10(9)/l was achieved in 19 patients at a median time of 49 days. Acute GVHD above grade II occurred in seven of 21 evaluable patients and chronic GVHD in 16 of 19 evaluable patients. Among 16 chronic GVHD patients, in eight patients the disease was extensive. Seventeen patients are alive and free of disease at between 371 and 2562 days after transplantation. With a median follow-up of 1505 days, the probability of disease-free survival at 4 years was 76.0%. These results suggest that adult MDS patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.
 ...
PMID:The efficacy of unrelated cord blood transplantation for adult myelodysplastic syndrome. 1669 May 15

Designing stem cell transplantation (SCT) conditioning regimens for Fanconi anemia (FA) has proved difficult because of hypersensitivity to the DNA cross-linking agents. We performed chromosome fragility tests with 56 FA patients and with 50 non-FA patients with severe aplastic anemia or myelodysplastic syndrome. We evaluated peripheral blood lymphocyte specimens cultured for 72 hours and treated with mitomycin C, diepoxybutane (DEB), cyclophosphamide (CY) metabolites, cytosine arabinoside (Ara-C), and fludarabine (Flu) metabolite (9-beta-D-arabinofuranosyl-2-fluoroadenine [2-F-Ara-A]). The DEB and CY metabolite tests were highly sensitive and specific for FA (P<10(-4)) for both tests), and the number of aberrations per cell for DEB correlated with that for the CY metabolite test (P < 10(-4)) but did not correlate with the number of aberrations per cell for the Ara-C and 2-F-Ara-A tests. The difference in breakage frequencies between FA and non-FA patients for cultures treated with 2-F-Ara-A was not statistically significant. Most of the breakages observed in cells treated with 2-F-Ara-A-and Ara-C were chromatid breaks. It may be possible to determine the appropriate CY dose in the preconditioning regimen for SCT in FA patients on the basis of the in vitro effects on fragility, and Flu or Ara-C may be a safer drug than high-dose CY for conditioning in FA patients.
 ...
PMID:In vitro effect of fludarabine, cyclophosphamide, and cytosine arabinoside on chromosome breakage in Fanconi anemia patients: relevance to stem cell transplantation. 1748 82

Allogeneic haematopoietic cell transplantation (HCT) is the most effective curative therapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Incidence of AML and MDS increases with age, peaking in the seventh decade. Despite improved Ara-C and anthracyclin-based chemotherapy regimens, the prognosis of AML in patients beyond 60 years of age is dismal. The introduction of peripheral blood-derived stem cell grafts into allogeneic HCT and the known anti-leukaemic effect of donor lymphocyte infusions paved the way for reduced-intensity conditioning (RIC) allogeneic stem-cell transplantation, which makes transplant in advanced age possible and significantly reduces transplant-related organ toxicity and mortality. The success of RIC HCT relies on the alloreactivity of the donor immune system and the graft-versus-leukaemia effect. We try to answer the following questions in this paper: who should receive RIC HCT? when and how should the transplant be performed? is there an upper age limit and what is the future of RIC HCT?
 ...
PMID:Viewpoint: What is the role of allogeneic haematopoietic cell transplantation in the era of reduced-intensity conditioning--is there still an upper age limit? A focus on myeloid neoplasia. 1750 2


<< Previous 1 2 3 4 5 6 7 8 9 10