ALMOST NORMAL COGNITIVE FUNCTION IN PATIENTS DURING THERAPY FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CRANIAL IRRADIATION ACCORDING TO ALL-BFM 95 AND COALL 06-97 PROTOCOLS: Results of an Austrian–German Multicenter Longitudinal Study and Implications for Follow-Up

Krappmann, P.; Paulides, Marios; Stöhr, Wolfgang; Ittner, Edith; Plattig, Bernhard; Nickel, Petra; Lackner, Herwig; Schrappe, Martin; Janka, Gritta; Beck, J. D.; Langer, Thorsten

doi:10.1080/08880010601123281

Cited by 31 publications

(26 citation statements)

References 38 publications

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Section: Org Fromsupporting

confidence: 82%

“…16,18,38 It is possible that our null results were due to the challenges of measuring a complex construct such as attention, which was variably defined and assessed in the included studies. Consistent with our study, however, other researchers have also found subtle 39 or no deficitis 40,41 in studies that were not included in our meta-analysis.The mechanism of neurocognitive impairments from chemotherapy-only treatment is likely related to the specific chemotherapy agents included in treatment protocols that are associated with neurotoxicity. 42 Methotrexate is associated with white matter changes in the brain, 43 acute seizures and paralysis, 44,45 and neurocognitive changes.…”

supporting

confidence: 82%

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Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

Iyer

Balsamo

Bracken

et al. 2015

Blood

161

132

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• Children treated for ALL without cranial radiation display significant IQ deficits of 6 to 8 points compared with healthy controls.• Moderate deficits occur in other neurocognitive domains including working memory, information processing speed, and fine motor functioning.Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic review to identify studies that evaluated long-term neurocognitive functioning following treatment of ALL by searching MEDLINE/PubMed, Database of Abstracts of Reviews of Effects, and secondary sources. Studies were included if ALL survivors were in continuous first remission, did not receive any radiation, were at least ‡2 years off therapy or ‡5 years since diagnosis, and were compared with a healthy control group. Weighted mean differences with 95% confidence intervals (CIs) were calculated. Ten nonexperimental studies met all eligibility criteria and included 509 patients and 555 controls. Meta-analysis demonstrated statistically significant moderate impairment across multiple neurocognitive domains evaluated, with intelligence most affected. Significant differences in standard deviation (SD) scores were found for Full Scale intelligence quotient (IQ) (20.52 SD; 95% CI, 20.68 to 20.37), Verbal IQ (20.54 SD; 95% CI, 20.69 to 20.40), and Performance IQ (20.41 SD; 95% CI, 20.56 to 20.27); these SD scores correspond to changes in IQ of 6 to 8 points. Working memory, information processing speed, and fine motor domains were moderately, but statistically significantly, impaired. Meta-analysis of ALL survivors treated without cranial radiation demonstrated significant impairment in IQ and other neurocognitive domains. Patients and their families should be informed about these potential negative effects to encourage surveillance and educational planning. Both preventive and intervention strategies are needed. (Blood. 2015;126(3):346-353) IntroductionAcute lymphoblastic leukemia (ALL) is the most common malignancy in children, accounting for 18% of all cancers and 74% of all leukemias.1 As a result of improvements in treatment and supportive care over recent decades, the current 5-year relative survival rate is 89% for children diagnosed with ALL before age 20 years 1 and exceeds 93% for children with standard risk features diagnosed before age 10 years.2 Because the vast majority of children with ALL are expected to survive their disease, it is important to understand the long-term burden of therapy.Neurocognitive and psychological difficulties as a result of chemotherapy have been documented in survivors of adult cancer across a variety of cancer types.3 However, most pediatric studies have focused on children with brain tumors or central nervous system (CNS)-directed radiation treatment. 4 Although the deleterious neurocognitive ...

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Section: Org Fromsupporting

confidence: 82%

supporting

confidence: 82%

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

Iyer

Balsamo

Bracken

et al. 2015

Blood

161

132

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“…51,52 When analyzing the different treatment components, the following conclusions can be drawn from a BFM point of view:…”

Section: Discussionmentioning

confidence: 99%

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Möricke¹,

Zimmermann

Reiter³

et al. 2009

Leukemia

465

303

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“…29 In the next study of TCCSG ALL L99-15, irradiated patients were limited to o10%. In the currently active study, T-ALL and prednisolone poor responders were irradiated.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984–1999

et al. 2009

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We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)±s.e. was 67.2±2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0±1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because 460% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate-or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m 2 had no advantage over prednisolone 60 mg/m 2 in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to o2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies. Leukemia (2010) 24, 383-396; doi:10.1038/leu.2009 published online 24 December 2009 Keywords: acute lymphoblastic leukemia; children; long-term results; cranial irradiation; secondary malignancy IntroductionWe present here the long-term results of four studies for childhood acute lymphoblastic leukemia (ALL) of Tokyo Children's Cancer Study Group (TCCSG) conducted between 1984 and Treatment protocol for SR and IR of the L84-11 study 1,2 was based on the early St Jude's total therapy.3 ALL-BFM 81 4 protocol was modified and introduced to extremely high-risk group regimen for the first time. The protocols of the following three studies L89-12, 1,5 L92-13, 1,6 and L95-14, 7 were designed on the basis of the ALL-BFM framework. All the four protocols contained trials to reduce the number of patients who received irradiation, as had been reported in other studies. 8,9 The second point of analysis was on a gender difference [10][11][12] with respect to long-term event-free survival (EFS) and overall survival (OS). Randomized studies were mostly designed to test whether or not intermediate-dose methotrexate (ID-MTX) and high-dose methotrexate (HD-MTX) could replace the cranial irradiation. It is needed to describe the further long-term outcome of the patie...

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ALMOST NORMAL COGNITIVE FUNCTION IN PATIENTS DURING THERAPY FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CRANIAL IRRADIATION ACCORDING TO ALL-BFM 95 AND COALL 06-97 PROTOCOLS: Results of an Austrian–German Multicenter Longitudinal Study and Implications for Follow-Up

Cited by 31 publications

References 38 publications

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984–1999

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