Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transformed chronic myeloid leukemia (CML) has a dismal prognosis, and treatment with a variety of chemotherapeutic agents is extremely disappointing. A novel therapeutic approach was initiated to improve the outcome of this condition. Nine patients, four females and five males, with either acceleration of CML or blast crisis (myeloid), or, in two instances, both, entered this pilot study. Median age was 60 years; seven patients were Philadelphia chromosome positive; two were negative but showed a bcr/abl rearrangement. All patients had a well-defined preceding period of stable chronic phase, for which they received sequentially hydroxyurea (N = 9), interferon (IFN) (N = 3), busulfan (N = 2), melphalan (N = 1), 6-MP (N = 1), or allogeneic BMT (N = 1). Median length of preceding chronic phase to acceleration or blast crisis was 56 months. All patients responded to treatment with a starting dose of IFN (9 Mio U/day), subcutaneously, and hydroxyurea (3 g/day), orally, by reversal to chronic phase. Three of the patients responded repeatedly during their course of disease. Median time for reversal to chronic phase was 4 weeks. Adverse side effects like nausea, vomiting, hair loss, fever, and prolonged cytopenia as seen after chemotherapy were not observed. The duration of chronic phase varied, and lasted, in six instances, more than 5 months, while the Philadelphia chromosome persisted. One additional patient received an unrelated bone marrow transplantation after reaching chronic phase (+24 months). Disease progression occurred 2 months after cessation of treatment. This treatment has proven very promising so far.
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PMID:Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon-alpha combined with hydroxyurea. 961 49

We performed an early phase II study of KRN8602, a new anthracycline derivative for refractory or relapsed acute leukemias. KRN8602 was given at a dose of 15 mg/m2 for 3 to 5 consecutive days, repeating every 3-4 weeks. Among 53 patients entered in the study, 51 were evaluable for safety, and 46 were evaluable for efficacy. The response rate at schedules of 3 and 4 consecutive days was 9.1% (1 PR/11), while that at a schedule of 5 consecutive days was 22.9% (3 CR + 5 PR/35). With the 5 consecutive day schedule, the response rates were 21.4% (1 CR + 2 PR/14) for acute myelogenous leukemia and 29.4% (2 CR + 3 PR/17) for acute lymphocytic leukemia, but no response was observed in 4 patients with blastic crisis of chronic myelogenous leukemia. Major toxicities were nausea/vomiting and anorexia, however, all these toxicities were clinically manageable. From these results it is concluded that KRN8602 is effective against acute leukemias, and the optimal dose is 15 mg/m2 for 5 consecutive days.
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PMID:[Early phase II study of KRN8602 (MX2), a novel anthracycline derivative for acute leukemia]. 988 Oct 81

METHODS: Evaluated are surgical difficulties, management problems and weight loss in patients with distal gastric bypass as a revisionary procedure. Eighty patients were followed up to 3 years; four were lost to follow-up. Mean age was 43; mean prebariatric surgery weight 134 kg; height 1.65 meters; body mass index 40.1; ideal body weight 62.7 kg; excess weight 70.5 kg; per cent excess weight 214%. A 250 cm stomach-to-ileocecal valve segment of small bowel was used, and the biliopancreatic secretions were brought into the terminal ileum 100 6 in from the ileocecal valve. Mean pouch size was 63 cc; length of hospital stay 5 days; operative blood loss 616 cc; operative time 130 min. RESULTS: Intraoperative complications included three splenic injuries (without splenectomy). Early complications included one deep vein thrombosis, two marginal ulcers, one GI hemorrhage, one wound dehiscence, one pouch outlet obstruction and one pancreatitis. Late complications included: one death from protein malnutrition/ ARDS; 21 hypoproteinemia; six protein malnutrition, and of these, three had hyperalimentation; three cholecystitis; 27 anemia; 22 incisional hernia; two staple-line disruption (reoperated); 26 low serum iron; 11 prolonged (>6 months) diarrhea; three prolonged frequent vomiting; and two unrelated deaths (chronic myelogenous leukemia and amyotrophic lateral sclerosis). Mean excess weight loss was 83% at 12 months; 89% at 24 months; and 94% at 36 months. CONCLUSION: The distal gastric bypass is fraught with the operative and immediate post-operative complications experienced in any revisionary bariatric surgery. Distal gastric bypass is very effective in producing long-term weight loss. Nutritional problems are common but usually easily corrected. The most serious nutritional complication is protein malnutrition, which must be identified and corrected early. Success of this procedure is dependent upon patient compliance with proper nutrition and supplements, and regular office follow-up with monitoring of laboratory data. Patients who are noncompliant are at significant risk for complications.
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PMID:The Gastric Bypass for Failed Bariatric Surgical Procedures. 1072 55

Chronic myeloid leukaemia (CML) is characterised by the occurrence of the Philadelphia (Ph) chromosome (9/22 translocation) and the formation of a fusion protein--the BCR-ABL transcript with constitutive activation of the BCR-ABL tyrosine kinase and consequent changes in the intracellular signal transduction, which is responsible for the deregulated myeloid cell proliferation. STI571 (signal transduction inhibition number 571) is a potent and selective inhibitor of the BCR-ABL tyrosine kinase. In the chronic phase of the disease, normal peripheral blood values are achieved within the first month of treatment in the large majority of patients and in many patients also a cytogenic response within the following months. The results in the advanced phase are far less favourable, which is explained by the development of resistance owing to reactivation of the BCR-ABL signal transduction. Side effects are primarily nausea, vomiting, various rashes, oedema, most often in the periorbital region, and musculoskeletal symptoms, including muscle cramps. Perspectives for treatment with STI571 are described, as are combinations with alpha-interferon and other cytostatics with a synergistic profile.
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PMID:[STI571 (Glivec)--a new drug for the treatment of chronic myeloid leukemia]. 1208 21

Despite nine studies reporting the results achieved when treating patients with chronic myeloid leukemia (CML) with interferon (rIFNalpha) and cytarabine (araC), the optimal doses and schedule for this combination remain to be determined. Results of imatinib mesylate (STI-571) in chronic phase CML are preliminary, thus, trials of rIFNalpha-2b/araC in CML are of continued interest. We report the results of CALGB study 9013, providing a 10-year follow-up on 88 evaluable previously untreated patients. Cycles of therapy with rIFNalpha-2b and araC sufficient to cause a decline in either the white blood cell (WBC) count to < 2000/microl or platelets to < 50,000/microl were given. The starting dose of rIFNalpha-2b was 5 million units (mu)/m2/day subcutaneously (s.c.) and of araC 10 mg/m2 twice daily s.c. Treatment was discontinued when cytopenia occurred and was restarted when both the WBC and platelet counts had recovered. Bone marrow was obtained regularly for morphologic, cytogenetic and molecular studies. Medians at entry included age 48 years, WBC = 89,900/microl and platelets = 345,000/microl. The performance status was 0 or 1 in 88%; splenomegaly was present in 46%. Fifty five (63%) patients had a complete hematologic response and 10 (11%) had a partial hematologic response for an overall response rate of 74%. Median time to best response was 5.3 months. Median survival for all patients from study entry was 81 months, the 5-year survival probability was 65%. When 28 patients were censored at the time of bone marrow transplantation the median survival was 82 months. Grade 3 anorexia, nausea, vomiting and diarrhea developed in 15, 27, 13 and 7%, respectively. Mild to moderate elevations of transaminases occurred in 42%, and were severe in 5%. Sixty-three patients had adequate follow-up cytogenetic studies: 10 had a complete cytogenetic response (CCyR), 23 partial (PCyR, 50-99% normal cells), 20 minor and 10 no response (CALGB criteria). Thus, the CCyR plus PCyR rate among these 63 patients was 52%. Assuming the 25 patients with no cytogenetic follow-up as non-responders, 38% of the 88 patients had at least a PCyR. The median time to CCyR or PCyR was 5.6 months. The median time to best response in these 33 patients was 10.0 months, and median duration of cytogenetic response was 28 months. Cytogenetic responders had significantly longer survival than non-responders (p = 0.01) using a landmark analysis at 18 months. This intermittent schedule of rIFNalpha-2b/ara-C has a high response rate in patients with CML with acceptable toxicity.
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PMID:Treatment of the chronic phase of chronic myeloid leukemia with an intermittent schedule of recombinant interferon alfa-2b and cytarabine: results from CALGB study 9013. 1269 Nov 41

The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph(+)) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m(2). Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m(2) dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m(2). Doses of 260 and 340 mg/m(2) provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively.
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PMID:Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: results from a Children's Oncology Group phase 1 study. 1523 74

Clofarabine (2-chloro-2'-fluoro-deoxy-9-beta-D-arabinofuranosyladenine) is a second-generation nucleoside analog with activity in acute leukemias. As clofarabine is a potent inhibitor of ribonucleotide reductase (RnR), we hypothesized that clofarabine will modulate ara-c triphosphate accumulation and increase the antileukemic activity of cytarabine (ara-C). We conducted a phase 1-2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25 acute myeloid leukemia [AML], 2 acute lymphoblastic leukemia [ALL]), 4 high-risk myelodysplastic syndrome (MDS), and 1 blast-phase chronic myeloid leukemia (CML).(1) Clofarabine was given as a 1-hour intravenous infusion for 5 days (days 2 through 6) followed 4 hours later by ara-C at 1 g/m(2) per day as a 2-hour intravenous infusion for 5 days (days 1 through 5). The phase 2 dose of clofarabine was 40 mg/m(2) per day for 5 days. Among all patients, 7 (22%) achieved complete remission (CR), and 5 (16%) achieved CR with incomplete platelet recovery (CRp), for an overall response rate of 38%. No responses occurred in 3 patients with ALL and CML. One patient (3%) died during induction. Adverse events were mainly less than or equal to grade 2, including transient liver test abnormalities, nausea/vomiting, diarrhea, skin rashes, mucositis, and palmoplantar erythrodysesthesias. Plasma clofarabine levels generated clofarabine triphosphate accumulation, which resulted in an increase in ara-CTP in the leukemic blasts. The combination of clofarabine with ara-C is safe and active. Cellular pharmacology data support the biochemical modulation strategy.
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PMID:Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. 1548 72

Imatinib related non-haematological side-effects are reported in <10% of chronic myeloid leukaemia patients and include oedema, weight gain, nausea, vomiting and muscle cramps. Cutaneous reactions are well-recognized events occurring mostly in patients treated at doses of 600 mg/d and higher, either in stable or progressive disease. We report on our experience relating to dermatological toxicities in imatinib treated CML patients showing a spectrum of skin reactions ranging from rashes to cutaneous carcinoma.
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PMID:Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib. 1565 2

Imatinib targets KIT and platelet-derived growth factor receptors (PDGFR) and is highly effective in the treatment of CML and GIST patients. Pancreatic cancers express KIT and PDGFRs. Therefore, 26 patients with unresectable pancreatic cancer were randomized to either gemcitabine (1000 mg/m2 weekly) or imatinib (2x400 mg po) treatment daily. Pancreatic adenocarcinoma was confirmed histologically and expression of KIT and PDGFRbeta was determined immunohistochemically in the biopsy specimens. Quality of life was assessed with two standard questionnaires. No objective responses were seen in either group. Median time to progression was 77 and 29 days (P=0.411) and median survival time was 140 and 60 days (P=0.517) for gemcitabine and imatinib, respectively. Survival and treatment responses were independent of KIT and PDGFRbeta expression in patients treated with imatinib. Grade 3/4 toxicities of imatinib treatment were anemia, elevated liver enzymes, vomiting, and dyspnea. Patients treated with imatinib reported diarrhoea and/or altered bowel function more frequently, which were treatable symptomatically. Quality of life was similar in both groups. In this small series of pancreatic cancer patients, treatment with imatinib was not associated with a significant control of cancer progression.
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PMID:The tyrosine kinase inhibitor imatinib fails to inhibit pancreatic cancer progression. 1589 16

Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is a rare event. Imatinib mesylate has become the treatment of choice, especially for patients for whom allogenic stem cell transplantation is not an option. Imatinib produces complete cytogenetic responses in excess of 80%. However, the penetration of the drug and its metabolites into the CNS (Central Nervous System) is poor. Hence for patients who are on prolonged imatinib therapy and continue to have complete cytogenetic responses, the central nervous system may become a sanctuary site. We report a patient who had a complete hematologic and cytogenetic response and presented with headache and vomiting. The MRI showed meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive for blasts. He was started on cranial radiotherapy and triple intrathecal chemotherapy. He showed good symptomatic improvement and cleared the blasts in the CSF. At the end of radiation, he was in complete hematological remission but had 50% marrow metaphases positive for Philadelphia chromosome. As he did not have a matched sibling donor, the dose of imatinib was increased to 600 mg daily. He continues to be in complete hematologic remission at the time of this report.
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PMID:Isolated central nervous system blast crisis in chronic myeloid leukemia. 1599 75


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