Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacokinetic studies of intermediate and high dose 1-beta-D-arabinofuranosylcytosine (araC) therapy were performed in 14 children with acute leukemia and four with non-Hodgkin's lymphoma (NHL). AraC administration differed by method, dosage, and time of infusion to obtain the optimal tumorcidal concentration. The toxicity of these regimens was limited to transient severe nausea and vomiting, which were tolerable. Infusion time and dose are important factors to obtain optimal and clinically effective cerebrospinal fluid (CSF) araC concentrations. A concentration of araC above 1 micrograms/mL in CSF, which was lethal to cells in culture, was obtained by intravenous infusion of more than 2,000 mg/m2 of araC for four hours. We propose that araC 2,000 mg/m2 by constant intravenous infusion is preferable in the treatment of leukemia and is associated with the fewest side effects.
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PMID:Pharmacokinetic studies of intermediate-to high-dose 1-beta-D-arabinofuranosylcytosine in children with acute leukemia and lymphoma. 368 May 93

Ten cases of newly diagnosed pediatric B cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia (B-NHL, stage I & II 6 cases, stage III & IV 2 cases/ALL 2 cases) experienced during the last 7 years (1987-1994) were treated by BLK88 protocol, which consisted of HD-CPM (1,200 mg/m2), and HD-MTX (1,000 mg/m2) with VCR, ADR, and/or AraC combination, and CNS prophylaxis by triple intrathecal injection. The therapy duration was 24 weeks for B-NHL (36 weeks for B-ALL). The results showed that while one of the six cases in stage I & II relapsed, and other 4 cases of stage III & IV B-NHL/ALL remained in complete remission. On the other hand, all of the four cases in stage III & IV in historical controls had relapsed. Neutropenia and liver dysfunction were observed during therapy, but they were tolerable. We conclude that BLK88 is a very useful protocol for B-NHL/ALL in childhood.
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PMID:[Chemotherapy for B lymphoid malignancy in childhood--results in BLK88 protocol]. 884 99

High-dose cytosine arabinoside (HD-AraC) has been used in relapsed and refractory cases of acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Sixty-two poor-prognosis ALL patients were treated with HD-AraC between 1983 and 1995 at the Cancer Institute, Chennai, India. Of them, 37 had experienced a relapse, 16 were partial responders (refractory) to the induction regimen, and 9 were high risk due to central nervous system or testicular involvement or total counts above 200,000/mm3 at presentation. Of the 37 patients with relapses, 22 (59.5%) achieved complete remission (CR) and 10 had no evidence of disease (NED); of the 16 refractory group patients, 10 achieved CR and 2 had NED; and of the 9 high-risk patients, 5 had NED at the end of the study. The 5-year event-free survival (EFS) values of relapsed, refractory and high-risk group categories were 21.7%, 12.5%, and 55.6%, with a mean duration of 41 months, 18 months, and 85 months, respectively. Total alopecia and grade IV myelosuppression were the predominant toxicities. HD-AraC is an effective drug in the treatment of relapsed and refractory acute leukemias and can overcome relative drug resistance in high concentrations.
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PMID:Impact of high-dose cytosine arabinoside in poor-prognosis acute lymphoblastic leukemia: Cancer Institute experience, Chennai, India. 965 32

Cytosine arabinoside (AraC) is rapidly inactivated via systemic deamination with half-lives ranging from 1 h (i.v.) to 4 h (s.c.) -- and cannot be applied orally due to its hydrophilic properties. These limitations might be overcome by YNK01 -- a lipophilic prodrug of AraC -- that is resistant to deoxycytidine deaminase and can be applied orally. In the present study the therapeutic activity, side-effects and pharmacokinetics of YNK01 were evaluated in a phase I/II study including patients with relapsed or refractory acute myeloid leukemia (AML) (n=23) or low-grade non-Hodgkin's lymphoma (NHL) (n=20). YNK01 was given by 14 day cycles with escalating doses starting with a daily dose of 50 mg/m2 (equivalent to 20 mg/m2 AraC on a molar basis). The maximum tolerated dose was reached at the 600 mg/m2 dose level with WHO grade 3-4 diarrhoea as the main toxicity. In the 23 patients with AML two complete remissions, four partial remissions and three patients with stable disease were observed. In the 23 patients with AML two complete remissions, four partial remissions and three patients with NHL two cases reached partial remission and six other patients mainained stable disease. Pharmacokinetic evaluations were performed during 34 treatment cycles in 28 patients. The data suggest that YNK01 was absorbed in the distal part of the small intestine and taken up into hepatocytes. After hepatic psi and subsequent beta-oxydation of YNK01 the released AraC (and its deamination product AraU) appeared in the systemic circulation. Time of maximum concentration (h), half-life (h) and area under the curve (ng x h/ml, at the 1200 mg dose level) were as follows (VC variation coefficient) YNK01: 1.0 (0.58), 10.1 (0.43), 12622 (0.65); AraC: 23.2 (0.57), 22.6 (0.36), 3496 (0.76); AraU: 19.2 (0.58) 22.3 (0.33) 15441 (0.66). Of the total dose of YNK01 15.8% was absorbed and metabolized to AraC and AraU, defining the metabolic bioavailability of this prodrug. A linear relationship was observed between YNK01 dose and YNK01 AUC and AraC AUC over the whole dose range tested. AraC was released from hepatocytes over a prolonged period of time resulting in long lasting plasma levels similar to a continuous i.v. infusion. After administration of YNK01 at a dosage of 100-150 mg/m2 plasma levels of AraC were comparable to those achieved after low-dose AraC treatment (20 mg/m2) while at doses of YNK01 of 450-600 mg/m2 concentrations of standard-dose AraC (100 mg/m2) were obtained. We conclude that YNK01 shows considerable activity against relapsed and refractory AML and NHL and that its pharmacokinetic properties offers advantages in comparison to (standard) i.v. or s.c. AraC in clinical practice.
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PMID:Oral cytarabine ocfosfate in acute myeloid leukemia and non-Hodgkin's lymphoma--phase I/II studies and pharmacokinetics. 976 8

The purine analogues fludarabine and cladribine (CdA) have recently become established to be effective treatment for low-grade non-Hodgkin's lymphoma (NHL). The pyrimidine nucleoside analogue cytarabine (AraC) has an important place in the treatment of acute leukemia, and gemcitabine is a new pyrimidin antimetabolite which has shown clinical activity against solid tumors. We have used the semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA), to study these drugs. Eighty samples from 60 patients with low-grade NHL were studied. Fifty samples from patients with acute lymphoid leukemia (ALL) and 118 samples from patients with acute myeloid leukemia (AML) were included for comparison. The results indicate that the purine- and pyrimidine nucleoside analogues tested may be as active against low-grade NHL as against acute leukemia. In low-grade NHL, AraC seems to be even more active in comparison to CdA (p=<0.0001) and fludarabine (p=0.001). Untreated patients were more drug sensitive than previously treated patients. Gemcitabine showed the highest correlation with AraC (0.90) whereas CdA showed the highest correlation with fludarabine (0.84). Based on these results we propose that AraC and gemcitabine may have a role in the treatment of low-grade NHL.
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PMID:Evaluation of purine and pyrimidine analogues in human tumor cells from patients with low-grade lymphoproliferative disorders using the FMCA. 1035 56

We report a patient with T-cell non-Hodgkin's lymphoma (NHL) who relapsed after treatment with relatively intensive third-generation chemotherapy, VACOP-B, and who was safely and effectively treated with allogeneic peripheral blood stem cell transplantation (allo PBSCT) with double conditioning. The first conditioning consisted of carboplatin and etoposide. Twenty-one days later, the second conditioning was performed with cytosine arabinoside, cyclophosphamide, and total body irradiation (AraC/Cy/TBI). Between the periods of the first and second conditioning, autologous (auto) PBSCT (4.4 x 10(5) colony-forming units granulocyte/macrophage (CFU-GM)/kg, 3.8 x 10(6) CD34+ cells/kg) was performed to rescue marrow aplasia after the first conditioning. After the second conditioning, allo PBSCT (2.1 x 10(5) CFU-GM/kg, 8.2 x 10(6) CD34+ cells/kg) was performed from a human leukocyte antigen-identical sibling. Marrow reconstitution after allo PBSCT was rapid. Grade I acute graft-vs.-host disease (GVHD) involving skin and chronic GVHD on the eye was observed. No severe transplantation-related complications occurred. With a follow-up of 22 months after allogeneic PBSCT, the patient is alive without evidence of the disease. This case shows that allo PBSCT with intensive double conditioning may become a new treatment strategy to achieve long-term disease-free survival for young NHL patients of resistant relapse with a great deal of tumor burden and invasion of lymphoma cells in bone marrow.
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PMID:Successful treatment of relapsed T-cell non-Hodgkin's lymphoma with allogeneic peripheral blood stem cell transplantation with double conditioning. 1040 85