Outcome of children with high‐risk acute lymphoblastic leukemia (HR‐ALL): Nordic results on an intensive regimen with restricted central nervous system irradiation

Saarinen‐Pihkala, Ulla M.; Gustafsson, Göran; Carlsen, Niels; Flægstad, Trond; Forestier, Erik; Glomstein, Anders; Kristinsson, Jakob; Lanning, Marjatta; Schrøeder, Henrik; Mellander, Lotta

doi:10.1002/pbc.10461

Cited by 42 publications

(46 citation statements)

References 52 publications

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“…6,22 Finnish results compare favorably with those in Europe. 25 That the results for young adults treated with adult ALL protocols in Finland are comparable to those treated with pediatric protocols is remarkable.…”

Section: Discussionmentioning

confidence: 64%

“…Three different treatment protocols were used for the pediatric intermediate risk group during the study period: BFM-83 IR (n=9), 13 NOPHO ALL-92 IR (n=40) 22 and NOPHO ALL-2000 IR (n=7), whereas two protocols were used for the high risk group: Nalle-90 HR (n=49) 6,22 and NOPHO ALL-2000 HR (n=23). The NOPHO IR protocols consisted of induction, consolidation, delayed intensification and maintenance, the total duration of treatment being 2 to 2.5 years.…”

Section: Treatment Protocolsmentioning

confidence: 99%

“…The NOPHO HR protocol included an LSA2-L2 type of maintenance. 6,22 No risk stratification was employed for adult ALL. Three protocols of the Finnish Leukemia Group were used during the study period: ALL90 (n=31), ALL94 (n=43), and ALL2000 (n=23).…”

Section: Treatment Protocolsmentioning

confidence: 99%

“…6 For adult ALL the improvement has been modest, with 5-year EFS figures in the range of 30-50%. [7][8][9][10] Within the pediatric population children over 10 years old and infants have worse outcome 6,[11][12][13] while among adult ALL patients younger adults have better outcomes. 10,14,15 There may be multiple explanations for why adult ALL patients do more poorly.…”

Section: Introductionmentioning

confidence: 99%

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Acute lymphoblastic leukemia in adolescents and young adults in Finland

Usvasalo¹,

Räty²,

Knuutila³

et al. 2008

Haematologica

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BackgroundInterest has recently been paid to adolescents and young adults with acute lymphoblastic leukemia, particularly because all reports so far published indicate that these patients have a better outcome when treated with pediatric rather than adult therapeutic protocols. There are different biological subtypes of acute lymphoblastic leukemia with distinct features and prognoses; the distribution of these subtypes is not well known among adolescents. We, therefore, studied acute lymphoblastic leukemia in adolescents and young adults aged 10 to 25 years in Finland.

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Section: Discussionmentioning

confidence: 64%

Section: Treatment Protocolsmentioning

confidence: 99%

Section: Treatment Protocolsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acute lymphoblastic leukemia in adolescents and young adults in Finland

Usvasalo¹,

Räty²,

Knuutila³

et al. 2008

Haematologica

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“…4,6,22 The risk group assignment was based on age and white blood cell count (WBC) at diagnosis (standard risk (SR): age 2.0-9.9 years and WBC o10.0 Â 10 9 /l; intermediate risk (IR): age 1.0-1.9 or X10.0 years and/or WBC 10-49.9 Â 10 9 /l; higher risk (that is, HR or very high risk (VHR)): WBCX50.0 Â 10 9 /l) and the presence of higher risk features: Tlineage ALL, the presence of CNS or testicular involvement, translocations t(9;22)(q34;q11) or t(4;11)(q21;q23), lymphomatous leukemia or mediastinal lymphoma, and/or a poor treatment response (M3 BM at day 15 or M2/M3 at day 29). 4 Patients who had higher risk features were assigned to the VHR treatment arm, if they were at least 5 years of age at diagnosis (because of the use of cranial irradiation in that protocol arm) and in addition had (i) T-cell disease with one or more additional HR-features, (ii) CNS leukemia, (iii) lymphomatous leukemia and/or (iv) higher risk ALL at diagnosis and a day 15 M3 or a day 29 M2/M3 bone marrow.…”

Section: Nopho All-92 Risk Groupingmentioning

confidence: 99%

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

et al. 2009

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Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors. Improvements in systemic and intrathecal chemotherapy have reduced the use of central nervous system (CNS) irradiation to o10% of the patients and provided a 5-year risk of isolated CNS relapse of 2.6%. Improved risk stratification and chemotherapy have eliminated the previous independent prognostic significance of gender, CNS leukemia and translocation t(1;19)(q23;p13), whereas the post-induction level of minimal residual disease (MRD) has emerged as a new risk grouping feature. Infant leukemia, high leukocyte count, T-lineage immunophenotype, translocation t(4;11)(q21;q23) and hypodiploidy persist to be associated with lower cure rates. To reduce the overall toxicity of the treatment, including the risk of therapy-related second malignant neoplasms, the current NOPHO ALL-2008 protocol does not include CNS irradiation in first remission, the dose of 6-mercaptopurine is reduced for patients with low thiopurine methyltransferase activity, and the protocol restricts the use of hematopoietic stem cell transplantation in first remission to patients without morphological remission after induction therapy or with high levels of MRD after 3 months of therapy.

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Early post‐induction augmented therapy improves outcome in children and adolescents with T‐cell acute lymphoblastic leukemia

et al. 2022

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Introduction T‐cell acute lymphoblastic leukemia (T‐ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre‐B ALL. We aimed to decrease T‐ALL relapses by intensifying our regimen. Methods Patients with T‐ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Reintensification. Cranial radiation was limited to patients with WBC ≥ 100 k/μl at diagnosis and/or patients with CNS2/CNS3 status. Results Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed up for a median of 70 months (range 14–181). Median age at diagnosis was 9 years (range 0.5–17.8). Forty‐eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range 14–74). The 5‐year‐EFS estimates for patients who received the augmented regimen versus standard regimen were 87% ± 4.9% versus 67% ± 6.8% (p = .03); and the 5‐year‐OS estimates were 87% ± 5.1% versus 71% ± 6.3% (p = .06), respectively. Treatment related mortality (TRM) was reported in two patients treated per standard regimen but none for patients who received the augmented regimen. Conclusions We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total‐XV regimen for patients with T‐ALL that resulted in improved outcome with no treatment related mortality.

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Outcome of children with high‐risk acute lymphoblastic leukemia (HR‐ALL): Nordic results on an intensive regimen with restricted central nervous system irradiation

Abstract: HR-ALL was successfully treated on the NOPHO-92 regimen, with a relatively low CNS relapse rate for non-irradiated children. WBC > or =200 x 10(9)/L and very slow response emerged as strong poor prognostic factors.

Cited by 42 publications

References 52 publications

Acute lymphoblastic leukemia in adolescents and young adults in Finland

Acute lymphoblastic leukemia in adolescents and young adults in Finland

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

Early post‐induction augmented therapy improves outcome in children and adolescents with T‐cell acute lymphoblastic leukemia

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