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

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.
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PMID:Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. 220 4

DWA2114R (DWA) is a new derivative of platin compounds that is currently being used in Phase II studies of solid tumors in Japan. The dose-limiting factor is myelotoxicity with mild extramedullary toxicity. This Phase I study consisted of adult patients with relapsed hematologic malignancies. Eight patients received a total of 15 treatment courses of DWA. The starting dose was 800 mg/m2 over 24 hours by continuous infusion. The dose was first increased to 1200 mg/m2 and then to 1600 mg/m2. Clinical toxicity and urinary excretion studies of DWA suggested that 1200 mg/m2/d for successive days would be the best type of administration. When 1200 mg/m2/d was given for 5 days, Grade 2 to 3 diarrhea and nausea and vomiting were encountered requiring parenteral fluids and nutritional support. This suggested that the dose-limiting factor with this schedule was gastrointestinal toxicity. Myelotoxicity was severe, as expected, but tolerable. One of the five patients with acute nonlymphocytic leukemia (ANLL) entered into complete remission and one patient with chronic myelogenous leukemia (CML) in crisis returned to the chronic phase. A Phase II trial of DWA is warranted for hematologic malignancies, especially in myeloid diseases.
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PMID:A phase I study of a new cisplatin derivative for hematologic malignancies. 222 59

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Of 501 patients with chronic myeloproliferative diseases (c-MPD) 18 developed thrombosis of major abdominal vessels including 6 with hepatic vein thrombosis (Budd-Chiari syndrome). The complication was seen in 14 of 140 (10%) patients with polycythemia vera (PV), 3 of 23 (13%) patients with essential thrombocythemia (ET), 1 of 106 (1%) patients with idiopathic myelofibrosis (IMF), and none of 232 patients with chronic myelogenous leukemia (CML). Leading symptoms and signs were abdominal pain, progressive splenomegaly, widening abdominal girth, ascites, venous collaterals, and nausea and vomiting. The diagnostic modalities with highest specificity were angiography and explorative laparotomy. A causal relationship between the thrombotic event and hematocrit, thrombocyte count, or hemostatic abnormalities at the time of diagnosis could not be established. Detailed laboratory tests of platelet function and coagulation and fibrinolytic parameters of 5 surviving patients did not show any specific defect. Despite medical and surgical intervention, 39% of the patients died within 2 months after diagnosis of the thrombosis. The majority of the survivors developed further complications like liver cirrhosis with portal hypertension and esophageal varices or the short bowel syndrome after extensive bowel resection for mesenterial infarction.
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PMID:Budd-Chiari syndrome and thrombosis of other abdominal vessels in the chronic myeloproliferative diseases. 279 52

A 38-year-old woman with megakaryoblastic chronic myelocytic leukemia (CML) crisis developed recurrent episodes of severe hypercalcemia, manifested by nausea and vomiting and later by dyspnea and hypoxia. The levels of serum parathyroid hormone and serum and urine cyclic AMP were normal. Autopsy revealed widespread metastatic calcifications in various organs, including the lungs. The case suggests that hypercalcemia complicating blast crisis of CML is not related to blast cell phenotype, can cause severe pulmonary malfunction, and is a terminal event. The hypercalcemia most probably resulted from bone resorption, either directly by the megakaryoblasts or by secretion of osteolytic substances.
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PMID:Hypercalcemia complicating a megakaryoblastic crisis of chronic myelocytic leukemia. 316 88

Sixteen patients [13 acute nonlymphocytic leukemia (ANLL), 2 acute lymphocytic leukemia, 1 chronic myelogenous leukemia in a blast crisis; median age, 40 yr; range, 25-78 yr; 9 male, 7 female] received 23 courses of carboplatin given as a bolus on a daily X 5 schedule. Six patients were given 7 courses of carboplatin at 200 mg/m2/day; 3 patients received 5 courses at 250 mg/m2; 9 patients received 11 courses at 300 mg/m2; 2 patients initially treated at 200 mg/m2 were given their 2nd course at 300 mg/m2. Significant hearing loss documented by audiometry occurred in five patients, including three of nine treated at 300 mg/m2. All five had prior or recent exposure to aminoglycoside antibiotics. Three patients developed cancer and acute leukemia group B grade 3 or 4 mucositis, and 18 of 23 courses were complicated by nausea and vomiting. Marrows were hypocellular or aplastic in all patients treated at the highest dose. No complete responses occurred, although two patients with ANLL treated at 300 mg/m2 achieved partial responses lasting 71 and 138 days. The t1/2 alpha [half-life (t1/2)], t1/2 beta, and total body clearance of ultrafilterable platinum were comparable to those previously described by us in patients receiving bolus doses of carboplatin of 22-77 mg/m2/day X 5. Carboplatin has activity in ANLL.
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PMID:Phase I and pharmacokinetic trial of carboplatin in refractory adult leukemia. 327 22

Twelve patients affected by different types of acute leukemia received idarubicin (4-demethoxy-daunorubicin) by oral route at the total dosage of 45, 60 or 90 mg/m2 distributed over three consecutive days. Drug response was assessed by the decrease in blast cells in peripheral blood and showed some variations between the different types of leukemia. Acute myelogenous leukemia patients and those with blastic crisis of chronic myeloid leukemia appeared to be the more responsive groups; however, the lower dose schedule could explain the less satisfactory results obtained in lymphatic leukemia patients. Data suggest that idarubicin is absorbed rapidly after oral ingestion, in spite of nausea and vomiting, which appeared 3-4 h later and were easily controlled by antiemetic therapy. The purpose of fractionating the drug dosage over three consecutive days is to prolong in the blood an elevated concentration of the main idarubicin metabolite (13-dihydro-derivative), which presents in experimental models an antileukemic potency similar to the parent compound. This study confirms that idarubicin is effective in acute leukemia also by oral route. This formulation could offer some advantages for subjects who cannot tolerate parenteral chemotherapy and it could be proposed in maintenance leukemia protocols.
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PMID:Oral idarubicin in adult acute leukemia: a preliminary experience. 345 37

A phase II study of MCNU tablet has been performed on 70 patients with hematological disorders including mostly myeloproliferative disorders. MCNU tablet was given p.o. at a dose of 50 mg daily for 2-6 days (total 100-300mg) as one course with average intervals of 3 to 5 months or more for patients responding to this drug. The effective rates were 72% in 18 patients with chronic myelogenous leukemia, 88% in 25 patients with polycythemia vera and 68.5% in 19 patients with essential thrombocythemia. Side effects of MCNU tablet were nausea and vomiting (31%) which had a dose-dependent relationship, mild liver dysfunction (5%) and elevation of BUN and creatinine (2%) which were not serious. The results were almost comparable to those of the phase II study of MCNU given intravenously.
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PMID:[Phase II study on oral administration of MCNU (ranomustine) tablet. Hanshin Cooperative Study Group on Hematological Disorders]. 345 32

Considering the good penetration of systemic high-dose ara-C (HDara-C) into the CNS, we used this approach for treating overt meningeal leukemia, either isolated or with concurrent extraneurologic disease, in 15 adults with high-risk acute lymphoblastic leukemia (ALL), one adult with lymphoid blast crisis of chronic granulocytic leukemia (LBC-CGL), and four adults with poor-prognosis non-Hodgkin's lymphoma (NHL). Treatment consisted of ara-C, 3 g/m2 every 12 hours by three-hour infusion for eight doses followed by a second course of four doses on day 21. Remitters received consolidation with monthly courses of HDara-C for four doses. Additional systemic multi-drug reinduction therapy and direct CNS treatment with intrathecal methotrexate (IT MTX) and cranial irradiation (CRT) was administered to the three remitters last treated. Thirteen of 20 patients (65%) achieved complete remission (CR): seven of seven patients with isolated meningeal leukemia and six of 13 patients with concurrent CNS and bone marrow disease. Of the remaining seven patients, five had a complete CSF clearing with persistent marrow disease. In all cases there was prompt resolution of neurologic signs and symptoms. The median duration of CR was 5 months (range 2 to 8 months). The most significant toxicity seen was myelosuppression, which was predictable and manageable. Nonhematologic toxicity was generally acceptable and included moderate nausea and vomiting, diarrhea, drug fever, transient liver dysfunction, and dermatitis. No cases of CNS toxicity occurred. There were no treatment-related deaths. Disease-free survival was limited by marrow relapse, either isolated or with concurrent CNS disease. No instances of isolated meningeal relapse occurred. These results obtained in a poor-risk subset of patients indicate that HDara-C is an effective treatment for the induction of remission in ALL and NHL with meningeal leukemia. Therefore, HDara-C should be considered for inclusion in multiagent consolidation programs for patients at high risk for CNS disease.
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PMID:Systemic high-dose ara-C for the treatment of meningeal leukemia in adult acute lymphoblastic leukemia and non-Hodgkin's lymphoma. 346 Nov 34

The toxicity of high dose cytosine arabinoside (Ara-C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated. The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitt's lymphoma. Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes. All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia. Adverse reactions were mild and reversible in all patients. No serious neurologic toxicity was seen. The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients. The only life-threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy. While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara-C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis. Side effects of high dose Ara-C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors.
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PMID:Toxicity of high dose Ara-C in children and adolescents. 359 53


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