Use of L‐asparaginase and cytosine arabinoside for refractory acute lymphocytic leukemia with particular reference to T‐cell leukemia

Cp, Steuber; Gj, Levy; Wl, Nix; Da, Shepherd; Starling, Kenneth A.; Dj, Fernbach

doi:10.1002/mpo.2950050105

Cited by 11 publications

(2 citation statements)

References 14 publications

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“…Each combination chosen had been well documented to have activity against newly diagnosed or relapsed T cell ALL or lymphoblastic lymphoma. 7,[40][41][42] After an intensive induction and consolidation, continuation consisted of 10 repetitions of a 9 week cycle with three different drug combinations. Total duration of therapy was planned to be 2 years from the time of initiation of treatment.…”

Section: Treatmentmentioning

confidence: 99%

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study

Shuster²,

et al. 1999

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This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.

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Section: Treatmentmentioning

confidence: 99%

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study

Shuster²,

et al. 1999

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Section: Treatmentmentioning

confidence: 99%

True

1999

Leukemia

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This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25 000 IU/m 2 ) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of Ͼ50 000/l or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value Ͻ0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.

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Anaphylactoid reactions to escherichia coli and erwinia asparaginase in children with leukemia and lymphoma

Evans

Tsiatis

Rivera

et al. 1982

Cancer

101

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The incidence and clinical characteristics of anaphylactoid reactions to intravenous asparaginase were assessed in 196 patients given E. coli asparaginase and 49 patients given Erwinia asparaginase. All patients were given a 50 IU intravenous test dose followed in 30 min by the full dosage (10,000 IU/m2), if no reaction occurred to the test dose. Twenty-nine of 196 patients (14.8%) given E. coli asparaginase had an anaphylactoid reaction, occurring after their first through 12th doses. The probability of an anaphylactoid reaction was significantly greater in those patients not receiving concomitant prednisonevincristine and patients with a hiatus between courses of asparaginase therapy. By logistic regression analysis, other variables such as age, sex, race, diagnosis, total number of doses and concurrent methotrexate or arabinosylcytosine did not contribute significantly to the probability of a reaction. Twentythree of the patients who had reacted to E. coli asparaginase and 26 patients who had not reacted to E. coli asparaginase were subsequently given Erwinia asparuginuse. Seven of these 49 patients (14%) had an anaphylactoid reaction. The probability of a reaction to Erwinia asparaginase was significantly related to a prior reaction to E. coli asparaginase, concomitant prednisone-vincristine therapy, total number of asparaginase doses, number of prior E. coli asparaginase doses, and diagnosis, when assessed by a logistic regression model. However, after adjusting for prior reaction to E. coli asparaginase and the total number of asparaginase doses given, the other variables did not contribute significantly to the probability of a reaction. Only 5/29 patients reacting to E. culi asparaginase and 1/7 reacting to Erwinia asparaginase had a reaction to the test dose. None of the reactions were fatal.Cancer 491378-1383, 1982.HE ENZYME L-asparaginase has been used clinically T to treat leukemia and lymphoma for over ten years. Despite the extensive clinical experience with this drug, the optimal dosage and schedule of asparaginase remain undefined. Likewise, the characteristics and incidence of asparaginase toxicities have not been clearly established for the various treatment protocols and combination regimens containing this agent. One of the well

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Use of L‐asparaginase and cytosine arabinoside for refractory acute lymphocytic leukemia with particular reference to T‐cell leukemia

Abstract: Ten patients with late-stage acute lymphocytic leukemia were treated with L-asparaginase and cytosine arabinoside. Complete remission was achieved in 8 patients including 5 of 5 patients with T-cell leukemia. Major toxicity included anaphylactic reactions in 3 of the 10 patients.

Cited by 11 publications

References 14 publications

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study

True

Anaphylactoid reactions to escherichia coli and erwinia asparaginase in children with leukemia and lymphoma

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