Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three children with ALL having poor prognostic features developed clinical and laboratory evidence of disseminated intravascular coagulation (DIC). Two developed a bleeding diathesis associated temporally with a rapid drop in blast cell counts during induction therapy with L-asparaginase, prednisone, and vincristine. One of these children died of massive cerebral hemorrhage. The third patient developed episodes of superficial thrombophlebitis associated with relapses and rising blast cell counts which responded to chemotherapy and treatment with heparin. The unusual association of ALL with DIC and the fact that all 3 patients had multiple poor prognostic signs have led us to monitor carefully the coagulation system and withhold L-asparaginase in patients with massive disease until the white cell count and organomegaly have responded to prednisone and vincristine. The more common association of DIC with non-lymphocytic leukemia and recent reports of the presence of the Ph' chromosome in children with leukemia morphologically resembling ALL suggest that chromosomal evaluation be done in selected leukemic patients.
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PMID:Disseminated intravascular coagulation in childhood acute lymphocytic leukemia with poor prognostic features. 27 70

A 71-year-old female was diagnosed as hypoplastic leukemia (ALL, L 2). Vitamin D3 (D3) therapy with alfacalcidol was successful and remission continued for approximately 4 months. However, the leukemia became refractory to D3, and low dose Ara-C combined with D3 was ineffective. Combined chemotherapy with vincristine, cyclophosphamide, L-asparaginase and prednisolone, low dose aclarubicin, OK-432 and etretinate ended in a failure. Treatment with mepitiostane was started and 1 month later obvious elevation of hemoglobin concentration, white cell and platelet count was observed. A bone marrow aspirate showed distinct recovery of normal hemopoiesis without residual leukemic cells. The patient has been staying in the complete remission for over 15 months with mepitiostane therapy (30 mg, daily). Androgen therapy, such as mepitiostane, appears to be effective in some patients with hypoplastic leukemia which does not indicate intensive chemotherapy.
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PMID:[Complete remission by mepitiostane in hypoplastic leukemia]. 268 84

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.
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PMID:Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia. 349 11

One hundred and ninety-one cases of acute lymphoblastic leukaemia were entered in a trial in which, for five months, all received cytotoxic therapy with prednisolone, vincristine, mercaptopurine, L-asparaginase, and methotrexate (the latter in high dosage followed by folinic acid). Patients were then randomized to receive immunotherapy (B.C.G.), twice-weekly methotrexate, or no further treatment.One hundred and seventy-seven patients (93%) achieved full remission and at the time of analysis, 26 months from the beginning of the trial, 143 were still alive, including 70 in their first remission. Median "post-intensive" remission lengths were 17 weeks (no treatment), 27 weeks (B.C.G.), and 52 weeks (methotrexate). The prolongation of remission by methotrexate was most evident in those patients with low initial white cell counts. B.C.G. seemed to cause lymphocytosis but was without other conspicuous effect. The incidence of toxic reactions is reported, including an unusually low rate of anaphylaxis with L-asparaginase.These preliminary results are discussed and compared with those of similar trials.
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PMID:Treatment of acute lymphoblastic leukaemia. Comparison of immunotherapy (B.C.G.), intermittent methotrexate, and no therapy after a five-month intensive cytotoxic regimen ((Concord trial). Preliminary report to the Medical Research Council by the Leukaemia Committee and the Working Party on Leukaemia in Childhood. 494 Jan 57

A 15-year-old boy with T-cell acute lymphoblastic leukemia (ALL) (FAB L1), diagnosed in 1995, received combination chemotherapy consisting of 6 weeks of induction (vincristine, epirubicin, L-asparaginase, prednisolone) and 2 weeks of consolidation (cytosine arabinosides, etoposide). After achieving remission, for further maintenance of remission, he was treated with 14 cycles of intensive chemotherapy consisting of 6-MP, 10 mg/kg orally on the first 4 days, and cyclophosphamide, 1200 mg/m2, vincristine, 1.5 mg/m2, epirubicin, 15 mg/m2, and cytosine arabinoside, 40 mg/m2, intravenously on days 4, 11, 39, and 40, respectively. On day 18 of each cycle, he received intravenous methotrexate (MTX) infusion in a total dose of 150 mg/m2 plus oral leucovorin (30 mg/m2 ) rescue 36 h after starting MTX therapy. In addition, oral trimethoprim-sulfamethoxazole was given regularly to prevent Pneumocystis carinii infection. The patient achieved remission during the first course of treatment, but 8 months later the disease relapsed. He then received four doses of MTX (800 mg intravenously) plus leucovorin rescue in the following 4 months. During the last MTX therapy, small hemorrhagic bullae were found on the lateral side of the right ankle, but subsided after a few days. Due to partial remission of the disease, he was admitted again in January 1999 for high-dose MTX therapy. An initial hemogram on admission revealed hemoglobin 7.2 g/dL, white cell count 15,200/mm3, platelet count 153/mm3, blood creatinine 0.5 mg/dL, and alanine leucine aminotransferase (ALT) 20 U/L. He received 8500 mg of MTX (5000 mg/m2 ) as a continuous intravenous infusion for 24 h. Thirty-six hours after the start of MTX infusion, leucovorin (30 mg, intravenous) rescue was initiated every 6 h for 3 days. Another preventive measure to cover MTX toxicity included aggressive intravenous fluid replacement (4 L/m2 /day) and the addition of 25 meq/L sodium bicarbonate to the intravenous fluid to alkalinize the urine. Concurrent medication included 6-MP (50 mg) once daily and trimethoprim-sulfamethoxazole (120 mg, 600 mg) twice daily every other day. Plasma MTX levels were 52.36 micromol/L 24 h after MTX infusion, 1.87 micromol/L after 48 h, 0.57 micromol/L after 72 h, and 0.41 micromol/L after 96 h. These indicated delayed MTX plasma clearance. The blood creatinine level was mildly elevated from 0.5 mg/dL to 0.7 mg/dL. Thirty-six hours after the administration of MTX, the patient developed an erythematous painful swelling on the right middle finger. The erythema, with subsequent large bulla formation, progressed to all the fingers, toes, palms, and the soles of the feet. Some erythematous to hemorrhagic papules also appeared on the bilateral elbows. Subsequently, diffuse tender erythema with extensive erosions and focal tiny pustules developed on the back, abdomen, proximal extremities, and face (Fig. 1a,b). A positive Nikolsky's sign was also present. A biopsy specimen of the right dorsal hand lesion revealed parakeratosis, detached acanthotic epidermis with scattered necrotic keratinocytes, dyskeratotic cells and nuclear atypia, neutrophilic exocytosis, and many neutrophils in the papillary dermis (Fig. 2). The skin condition deteriorated rapidly. Toxic epidermal necrolysis-like lesions involved 90% of the total body surface on the fifth day after MTX infusion. Mucositis, diarrhea, involuntary tremor, fever, and chills were noted. The patient was then sent to the burn unit for intensive skin care. Ten days after MTX therapy, profound agranulocytosis and thrombocytopenia (white cell count 100/mm3, platelets 14,000/mm3, and hemoglobin 5.6 g/dL) were found. The patient was then started on granulocyte colony stimulation factor (G-CSF, 5 microg/kg/day), but his general condition deteriorated rapidly and he died 6 days later due to septic shock and multiple organ failure.
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PMID:Toxic epidermal necrolysis following combination of methotrexate and trimethoprim-sulfamethoxazole. 1097 34