Late Effects of Central Nervous System Treatment of Acute Lymphoblastic Leukemia in Childhood Are Sex‐dependent

Waber, Deborah P.; Urion, David K.; Tarbell, Nancy J.; Niemeyer, Charlotte M.; Gelber, Richard D.; Sallan, Stephen E.

doi:10.1111/j.1469-8749.1990.tb16930.x

Cited by 103 publications

(19 citation statements)

References 17 publications

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“…In a study of 60 children (aged 6-16 years) with TBI identified through a private rehabilitation center in the midwestern U.S., female children performed significantly better than male children on the California Verbal Learning Test-Children's Version, even after controlling for the impact of the severity of head injury (25). In contrast with these findings, there have been studies reporting a sex-specific decrease in intelligence test results in children treated for acute lymphoblastic leukemia, with girls showing lower IQ scores than boys (27,28), in contrast with the specific deficits in verbal learning seen in our study and the verbal intelligence deficits seen in pediatric intracranial hemorrhage and TBI studies.…”

Section: Discussioncontrasting

confidence: 99%

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

Lima¹,

Kvalsund²,

Souza³

et al. 2013

Clinics

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OBJECTIVE:To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores.METHODS:A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406.RESULTS:Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children.CONCLUSIONS:The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

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Section: Discussioncontrasting

confidence: 99%

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

Lima¹,

Kvalsund²,

Souza³

et al. 2013

Clinics

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“…25 In addition, cognitive impairment, short stature, and excessive weight were all more prevalent among females than males. 26 Females responded more to the chemotherapy and remained in higher EFS than that of males. All these facts may suggest that girls are more sensitive to anti-leukemic drugs, resulting in better outcome of ALL and developed more therapy-related secondary AML/MDS.…”

Section: Discussionmentioning

confidence: 96%

“…We had not performed neurocognitive assessment as a group, but many studies showed the negative influence of the cranial irradiation on the neurocognitive function particularly for the young patients, 26 and other study described that normal neurological function was preserved when irradiation was omitted. 29 In the next study of TCCSG ALL L99-15, irradiated patients were limited to o10%.…”

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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“…These cognitive impairments are associated with significantly reduced intelligence quotient and academic difficulties [130]. Deficits can first emerge several years after diagnosis [121] and are most severe in those treated at an age younger than 6 years [129] and among females [134]. …”

Section: Neurocognitive Impairmentmentioning

confidence: 99%

Adverse effects of treatment in childhood acute lymphoblastic leukemia: general overview and implications for long-term cardiac health

Ness¹,

Armenian²,

Kadan‐Lottick³

et al. 2011

Expert Review of Hematology

104

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Survival of childhood acute lymphoblastic leukemia (ALL) is one of the greatest medical success stories of the last four decades. Unfortunately, childhood ALL survivors experience medical late effects that increase their risk of morbidity and premature death, often due to heart and vascular disease. Research has helped elucidate the mechanisms and trajectory of direct damage to the heart from treatment exposure, particularly to anthracyclines, and has also contributed knowledge on the influences of related chronic conditions, such as obesity and insulin resistance on heart health in these survivors. This article summarizes the key issues associated with early morbidity and mortality from cardiac-related disease in childhood ALL survivors and suggests directions for interventions to improve long-term outcomes.

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Late Effects of Central Nervous System Treatment of Acute Lymphoblastic Leukemia in Childhood Are Sex‐dependent

Cited by 103 publications

References 17 publications

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

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

Adverse effects of treatment in childhood acute lymphoblastic leukemia: general overview and implications for long-term cardiac health

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