Long-Term Results of a Randomized Trial on Extended Use of High Dose <scp>l</scp>-Asparaginase for Standard Risk Childhood Acute Lymphoblastic Leukemia

Pession, Andrea; Valsecchi, Maria Grazia; Masera, Giuseppe; Kamps, Willem A.; Magyarosy, Edina; Rizzari, Carmelo; Wering, E. R. Van; Nigro, Luca Lo; Does, A van der; Locatelli, Franco; Basso, Giuseppe; Aricò, Maurizio

doi:10.1200/jco.2005.11.411

Cited by 180 publications

(127 citation statements)

References 20 publications

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“…8 In the BFM-backbone study ALL-8, early reduction of chemotherapy in SRG patients (using only protocol Ia) was applied and appeared to have no negative impact on prognosis. Patients may benefit from longer exposure to l-asparaginase; 11 the results may have been even better if l-asparaginase with a longer half-life than Erwinia l-asparaginase had been used. In both the ALL-7 and ALL-8 study patients, the adverse effect of a traumatic lumbar puncture with the presence of blasts at diagnosis is suggested and those patients may benefit from additional CNS-directed chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…In collaboration with other members of the International BFM Study Group (I-BFM-SG), Italian (AIEOP), Dutch and Hungarian SRG patients were randomized to receive or not to receive 20 weekly high doses (25 000 U/m 2 ) of intramuscular Erwinia lasparaginase (HD-L-ASP) during early maintenance treatment (IDH protocol). 11 Also Dutch MRG patients were randomized to receive either conventional doses (25 mg/m 2 /day for 56 days) of 6-MP orally or 4 high doses (1300 mg/m 2 ) of 24 h intravenous 6-MP during protocol M. Bone marrow transplantation after one series of three HR blocks was optional for HRG patients with a matched sibling donor. The total duration of chemotherapy for all patients was 24 months.…”

Section: Patients and Treatmentmentioning

confidence: 99%

“…9 The results of the Italian-Dutch-Hungarian (IDH) randomized study of high-dose Erwinia l-asparaginase during early maintenance was reported previously. 11 In the Netherlands, 165 SRG patients were eligible for randomization, but only 85 (52%) were randomized. For the IDH study as a whole it was concluded that the application of extended high-dose lasparaginase may improve outcome.…”

Section: Overall Treatment Outcomementioning

confidence: 99%

“…For the IDH study as a whole it was concluded that the application of extended high-dose lasparaginase may improve outcome. 11 Two hundred and thirty-five MRG patients were eligible for randomization to oral or high-dose intravenous 6-MP, but only 187 (76%) patients were randomized. No benefit was observed from HD-6MP.…”

Section: Overall Treatment Outcomementioning

confidence: 99%

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Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

et al. 2009

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The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Mü nster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (Po0.001) and from 78.7 to 86.4% (P ¼ 0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC 4100 Â 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.

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Section: Discussionmentioning

confidence: 99%

Section: Patients and Treatmentmentioning

confidence: 99%

Section: Overall Treatment Outcomementioning

confidence: 99%

Section: Overall Treatment Outcomementioning

confidence: 99%

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Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

et al. 2009

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13] In the earlier studies conducted in the 70s, all patients received a relatively low-intensity chemotherapy and cranial radiotherapy (CRT). In Study 82, patients were stratified into three risk groups.…”

Section: Introductionmentioning

confidence: 99%

Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia

et al. 2009

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We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.

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PEG-asparaginase treatment for acute lymphoblastic leukaemia in children: a network meta-analysis

Lynggaard

Rank

Als‐Nielsen³

et al. 2021

Cochrane Database of Systematic Reviews

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To assess the e ect of the number of PEG-asparaginase doses on survival and relapse in children and adolescents with acute lymphoblastic leukaemia (ALL). Secondary objectivesTo assess the association between the number of doses of PEG-asparaginase and asparaginase-associated toxicities (e.g. hypersensitivity, thromboembolism, pancreatitis and osteonecrosis).To undertake a network meta-analysis (NMA) at dose-level in order to generate rankings of the number of doses of PEG-asparaginase used in the treatment for ALL, according to their benefits (survival and relapse) and harms (toxicity).PEG-asparaginase treatment for acute lymphoblastic leukaemia in children: a network meta-analysis (Protocol)

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Long-Term Results of a Randomized Trial on Extended Use of High Dose l-Asparaginase for Standard Risk Childhood Acute Lymphoblastic Leukemia

Cited by 180 publications

References 20 publications

Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia

PEG-asparaginase treatment for acute lymphoblastic leukaemia in children: a network meta-analysis

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