Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans-retinoic acid (ATRA) alone (45 mg m-2) or with a simultaneous combination of ATRA (45 mg m-2), daunorubicin (DNR, 50 mg/m-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 10(9)/l at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 10(9)/l received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 10(9)/l) than in the group of patients receiving ATRA and chemotherapy (14.0 x 10(9)/l). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard '3 + 7' chemotherapy (DNR 45 mg m-2, 1-3 days, ARA-C 200 mg m-2, 1-7 days) followed by two courses of standard '2 + 5' chemotherapy (DNR 50 mg m-2 1-2 days, ARA-C 200 mg m-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).
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PMID:Effect of all-trans-retinoic acid alone or in combination with chemotherapy in newly diagnosed acute promyelocytic leukaemia. 933 Feb 65

Mast cells (MC) are multipotent hemopoietic effector cells producing diverse mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase+ MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plasmin-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD117/c-kit+, CD123/IL-3R alpha-, CD11b/C3biR-), biochemical analysis (cellular ratio [ng:ng] of tryptase to histamine >1), and electron microscopy. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 30% diffusely scattered MC, and a complex karyotype. No dense, compact MC infiltrates (mastocytosis) were detectable in bm sections. Despite hyperfibrinolysis and mediator syndrome (flushing, headache), the patient received remission induction polychemotherapy (DAV) followed by two cycles of consolidation with intermediate dose ARA-C (2 x 1 g/m2/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without evidence of recurring MDS. Moreover, in response to chemotherapy, the hyperfibrinolysis and mediator syndrome resolved, and the circulating c-kit+ MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement.
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PMID:Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells. 1033 14

In these last four decades there has been extraordinary progress in our understanding of the biology of, and therapeutic approach to, chronic myelogenous leukaemia (CML). During these decades new observations arising from studies of the biological behaviour of diploid and leukaemic stem cells and, recently, from clinical investigations have received the most attention. From a clinical point of view, allografting is still the only procedure which is able to cure CML. For patients without HLA-compatible donors, current therapeutic options include conventional chemotherapy (hydroxyurea), interferon-alpha (IFN-alpha) and autografting. While IFN-alpha (+/- low-dose ARA-C) must be considered the first-line therapy, autografting, according to our approach, or other procedures, raises the question of an ideal sequential strategy in the management of CML patients (diploid stem cell mobilization, autografting, IFN-alpha). Because it seems that the diploid haematopoietic reservoir declines with time, it may be desirable to mobilize and collect diploid stem cells in order to store them as soon as diagnosis is possible when the WBC count has been controlled by hydroxyurea.
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PMID:Autologous peripheral blood haematopoietic stem cell transplantation for chronic myelogenous leukaemia. 1100 Sep 94

We review improvements achieved in the treatment of acute promyelocytic leukaemia (APL) over the last ten years. The combination of all- trans retinoic acid (ATRA) and conventional anthracycline-ARA-C chemotherapy (CT) has clearly demonstrated its superiority over CT alone (in terms of relapse and survival) in newly diagnosed APL. Combination treatment probably also reduces the incidence of initial failures, and complete remission (CR) rates greater than 90% are now regularly reported in large multicentre trials. Some randomized studies strongly suggest than prolonged maintenance treatment (for 1 or 2 years) with ATRA and low dose CT, and possibly very early introduction of anthracycline CT during induction treatment (i.e. not after ATRA) may reduce the incidence of relapse. With those treatments, the risk of relapse appears to be only 10-15%, although it remains greater in patients who initially have white blood cell counts (often associated with variant M(3)morphology, short bcr(3)isoform etc.) and patients with residual disease detectable by RT-PCR at the end of consolidation courses.ATRA syndrome remains the major side effect of ATRA treatment. It occurs in 10-15% of patients and is currently fatal in at least 10% of them. Rapid onset of CT and/or high dose steroids should improve its outcome.A sizeable proportion of APL patients who relapse after ATRA and CT can be durably salvaged by the same treatment followed by allogeneic or autologous stem cell transplantation, provided the transplant (in the autologous setting) is RT-PCR negative. Arsenic trioxide can induce CR in most APL patients refractory to ATRA and CT. It acts mainly by inducing apoptosis of APL cells. A place for arsenic trioxide earlier in the treatment of APL must currently be more precisely defined. Another issue in the treatment of APL is reducing the toxicity of first line treatment without increasing the relapse risk. Preliminary findings suggest that this could be achieved by consolidation CT using an anthracycline alone, without cytarabine.
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PMID:Treatment of acute promyelocytic leukaemia. 1135 29

The paper presents the experience of the Polish Paediatric Leukaemia/Lymphoma Study Group in the treatment of high-risk acute lymphoblastic leukaemia in children using a new version of the New York (1997-1999). Protocol with treatment intensity adjusted according to the age of the patients. From April 1997 to December 1999 a group of 49 children with leukocytosis ranging from 50 900/mm3 to 580 000/mm3 (median 122 000/mm3) and 6 children with leukocytosis below 50 000/mm3 and poor response to steroids were treated with this protocol. Children below 10 years (43 patients) were treated according to the previous protocol, children above 10 years (12 patients) were treated with intensified protocol (high doses of ARA-C in consolidation and intermediate doses of Mtx in maintenance). Induction was identical for all patients. Complete remission was achieved in 92.6% patients. There were 2 relapses. Six children died - 3 without remission, 2 due to a relapse, 1 due to treatment complications. The current opinions concerning classification of HRG-ALL and treatment possibilities in this group of children are discussed.
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PMID:[High risk acute lymphoblastic leukaemia in children. Preliminary report after introducing a new version of New York (1997) protocol adjusted to the age of the patients. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group]. 1202 59

We report a new case of therapy-related acute myeloid leukemia in a child with Langerhans cell histiocytosis. This patient was previously treated with a protocol of multidrug chemotherapy, containing a relatively low dose of etoposide (total dose of 900/m(2)). Twenty-six months after the end of the therapy, the patient returned to the hospital with fever and anemia. The white blood cell count was 53 x 10(9)/L. The bone marrow examination showed massive infiltration with French-American-British acute myeloid leukemia classification M4 blast cells. The patient did not respond to an intensive treatment with high dose ARA-C and idarubicin. He died 6 months later. The cytogenetic abnormality of the blast cells was a t(11;11)(p13 -15;q23), that has not been described before in a secondary leukemia case.
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PMID:Translocation (11;11)(p13- p15;q23) in a child with therapy-related acute myeloid leukemia following chemotherapy with DNA-topoisomerase II inhibitors for Langerhans cell histiocytosis. 1207 8

Viridans streptococci (VS) are an increasing cause of bacteraemia in neutropenic patients with cancer. Case-control studies of predisposing factors for acquisition of this infection in children are not published. Between January 1989 and December 1999, 168 episodes of bacteraemia in 161 children with fever and neutropenia of haemato-oncology origin were analysed. 15 cases (9%) in 15 patients were caused by VS. Each case patient was compared with 6 matched control patients; 2 with other Gram-positive cocci (group 2), 2 with gram-negative bacilli bacteraemia (group 3) and two children with fever and neutropenia without bacteraemia (group 4). The median age of patients was 4.1 years (range: 2-15 years). 87% of children had acute leukaemia or lymphomas. Pneumonia was the predominant clinical focus (70%). Shock was observed in 13% of patients. ARDS was observed in one child who died of this complication. Multivariate analysis of risk factors for the development of VS bacteraemia showed that two factors were independent predictors: high doses of cytosine-arabinoside (ARA-C) as part of the chemotherapy treatment (Odds Ratio (OR): 9.3; Confidence Interval (CI) 1.56-55.5) (P<0.014) and the presence of pneumonia (OR: 1.36: CI 2.27-81.9) (P<0.0043). We propose that further studies are warranted to confirm these results.
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PMID:Viridans streptococci bacteraemia in children with fever and neutropenia: a case-control study of predisposing factors. 1276 18

Treatment of acute leukaemia in adult Jehovah's Witnesses (JW) is challenging because of 'a priori' refusal of most physicians to apply diagnostic and therapeutic procedures to haematological abnormalities resembling acute leukaemia. Rejection of blood transfusions by individuals of this faith is usually blamed to justify this attitude, thus leading to severe personal, medical and psychological distress related to the lack of care. We therefore intended to verify whether a standard (tailored) chemotherapy, without the use of prophylactic blood product transfusions, could be applied during treatment of acute leukaemia under such circumstances. Eleven consecutive JW adult patients with acute leukaemia, all of whom had been denied care in other institutions, were treated at the European Institute of Oncology (EIO) in Milan, Italy. Five had acute lymphoblastic leukaemia (ALL) (one bcr/abl positive), six had acute myeloid leukaemia (AML) with immunophenotype and/or cytogenetic intermediate-high risk features, except one patient with acute promyelocytic leukaemia (APML). Standard induction chemotherapy [cytosine arabinoside (ARA-C) and daunorubicin (DNR) for AML, vincristine (VCR), DNR and prednisone (PDN) for ALL, all-trans retinoic acid (ATRA) and DNR for APML] with the antracycline dose of at least 30 mg/sqm were used. All patients experienced severe anaemia after induction chemotherapy despite erythropoietin. Median haemoglobin nadir for patients with ALL and AML was 4.5 g/dL (range 1.3-6.9) and 5.1 g/dL (range 2.6-6.8), respectively. Median platelet nadir counts for all patients was 14.5 x 10(9))/L (range 1-24). One patient died during induction probably due to haemorrhage. Four of five patients with ALL achieved a complete remission (CR) (including the bcr/abl case) while among patients with AML only the one with APML achieved CR. Three patients (APML = 1 and ALL = 2) are still alive and disease-free. This small series of adult patients with leukaemia illustrates difficulties in treating patients who are practising JW, yet nevertheless provides a significant argument against the prejudicial decision leading to evasion of treatment in these patients.
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PMID:Tailored therapy of adult acute leukaemia in Jehovah's Witnesses: unjustified reluctance to treat. 1508 64

Cholesterol levels are abnormally increased in many acute myeloid leukemia (AML) samples exposed in vitro to chemotherapy. Blocking these acute cholesterol responses selectively sensitizes AML cells to therapeutics. Thus, defining the molecular mechanisms by which AML cells accomplish these protective cholesterol increments might elucidate novel therapeutic targets. We now report that the levels of mRNAs encoding the cholesterol synthesis-regulating enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and the cholesterol-importing low-density lipoprotein (LDL) receptor were both increased by daunorubicin (DNR) or cytarabine (ARA-C) treatments in almost three fourths of cultured AML samples. However, less than one third of AML samples significantly increased LDL accumulation during drug treatments, suggesting that de novo synthesis is the primary mechanism by which most AML cells increase cholesterol levels during drug exposures. LDL increments were not correlated with cholesterol increments in ARA-C-treated AML samples. However, LDL and cholesterol increments did correlate in DNR-treated AML samples where they were measured, suggesting that a subset of AMLs may rely on increased LDL accumulation during treatment with particular drugs. Our data suggest that cholesterol synthesis inhibitors may improve the efficacy of standard antileukemia regimens, but that for maximum benefit, therapy may need to be tailored for individual patients with leukemia.
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PMID:Cholesterol synthesis and import contribute to protective cholesterol increments in acute myeloid leukemia cells. 1516 71

The uptake of nucleosides and nucleoside analogs into human leukemia K562 cells is facilitated by the equilibrative transporters ENT1 and ENT2. Incubation of K562 cells with a variety of protein kinase inhibitors inhibited the transport of both uridine (ARA-C) and cytidine (CPEC) analogs. These inhibitory effects were observed for a large number of kinase inhibitors including those against p38 MAPK, the EGF receptor kinase, protein kinase C, TOR and others. Thus these results suggest that the nucleoside transporters are unexpected targets for kinase inhibitors and may influence the design and application of combinatorial approaches of nucleoside analogs and kinase inhibitors in clinical applications.
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PMID:Regulation of equilibrative nucleoside uptake by protein kinase inhibitors. 1557 Dec 74


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