Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.

Waber, Deborah P.; Tarbell, Nancy J.; Fairclough, Diane; Atmore, K; Castro, Ricardo Dias de; Isquith, Peter Κ.; Lussier, Francine; Romero, Ivonne; Carpenter, Paul J.; Schiller, Meinhard

doi:10.1200/jco.1995.13.10.2490

Cited by 142 publications

(62 citation statements)

References 14 publications

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“…27,[34][35][36] We show for the first time that the estimated odds of development of academic difficulties increase by 18% for each month younger in age at the time of CRT. Although intensive CNS-directed chemotherapy may also adversely affect the immature CNS, 28,35,37 its impact is likely to be less than that of CRT. Indeed, Kaleita et al 38 recently showed a substantial improvement in neurodevelopmental outcomes of infant leukemia survivors evaluated at a mean age of 5 years who were treated on the CCG107 protocol that does not include CRT.…”

Section: Discussionmentioning

confidence: 99%

Late effects in survivors of infant leukemia

et al. 2000

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Little is known about the incidence of and risk factor for late effects of infant leukemia. We evaluated 19 children with acute lymphoblastic leukemia and 15 with acute myeloid leukemia who were diagnosed at age 12 months or younger and have survived for more than 5 years after the diagnosis (median length of follow-up, 13 years; range, 5.7-29 years). Ten patients received chemotherapy alone (group A), 17 received chemotherapy and CNS-directed radiation therapy (CRT) (group B), and seven received chemotherapy, CRT and bone marrow transplantation (group C). The most frequently observed late sequelae included problems in growth (66% of survivors), learning (50%), hypothyroidism (15%), and pubertal development (12%). Cataract, cardiac and hearing abnormalities occurred in 6% of patients. Only eight patients (24%) survive without late effects. In comparison to patients in group A, patients in groups B and C had a higher incidence of having at least one late complication (P = 0.009), a greater decrease in height Z score at 5 years after diagnosis (P = 0.023), and a higher incidence of academic difficulties (P = 0.004). The estimated odds of academic difficulties increased by 18% (P = 0.032) for each month younger in age at the time of CRT. These results indicate that late sequelae are common in longterm survivors of infant leukemia and are often related to CRT and the patient's age at the time of CRT. Leukemia (2000) 14, 1185-1190.

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Section: Discussionmentioning

confidence: 99%

Late effects in survivors of infant leukemia

et al. 2000

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“…We have begun exploring the effect of various systemic therapies on neurocognitive status in long-term survivors, and have found that patients who received both high-dose methotrexate and cranial radiation had more marked impairments than those who received either therapy alone. 8 Also, patients who received dexamethasone during post-remission therapy were at increased risk for developing neurocognitive late effects compared with those who received prednisone. 36 To improve EFS for all patients, we conducted two randomized trials studying high-dose methotrexate during remission induction (protocol 87-01) and high-dose i.v.…”

Section: Figurementioning

confidence: 99%

“…[3][4][5] Late toxicities include asymptomatic echocardiographic abnormalities related to anthracycline exposure, 6 osteonecrosis from corticosteroids, 7 as well as short stature and learning disabilities of varying severity, presumably secondary to central nervous system (CNS)-directed therapy. 8 The focus of randomized studies has been to improve efficacy while minimizing acute and late toxicities. In this report, we review the results of four consecutive clinical trials conducted between 1981 and 1995 by the DFCI ALL consortium.…”

Section: Introductionmentioning

confidence: 99%

Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981–1995)

et al. 2000

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“…Chronic MTX-induced leukoencephalopathy, a commonly described but poorly understood phenomenon, may severely impair neuropsychologic function, is associated with the use of HD-MTX or inadequate leucovorin rescue, and may be exacerbated by prior cranial irradiation. [7][8][9][10][11] By contrast, MTX can also cause acute or subacute neurotoxicity that is characterized by confusion, disorientation, seizures, and focal neurologic deficits. [12][13][14][15][16] Whereas chronic MTX-induced leukoencephalopathy is progressive and dose-limiting, acute While acute encephalopathy has been well-described in osteosarcoma patients, occurring in up to 15% of cases, 13 relatively little is known about this complication in children with ALL.…”

Section: Introductionmentioning

confidence: 99%

Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia

et al. 1998

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The purpose of this study was to determine the incidence of and pharmacokinetic parameters associated with the development of transient encephalopathy following the administration of high-dose methotrexate and intrathecal chemotherapy in children with acute lymphoblastic leukemia (ALL). Two hundred and fifty-nine children with newly diagnosed ALL treated on one of two consecutive trials were analyzed. Presenting features in patients who developed transient encephalopathy were compared with those of patients who did not experience this event. For each patient who developed transient encephalopathy, methotrexate pharmacokinetic parameters were compared with those of matched controls. The cumulative incidence of acute encephalopathy was 3% (SE 1%) at 1 year and was associated with age greater than or equal to 10 years at diagnosis. Pharmacokinetic data did not differ between patients who developed transient encephalopathy and those who did not. The majority of patients had no long-term sequelae and were able to receive further courses of methotrexate without modification. Transient focal neurologic deficits occur in about 3% of children with ALL following the administration of intravenous and intrathecal methotrexate. These events cannot be predicted by pharmacokinetic parameters of methotrexate disposition. However, these events are generally benign, suggesting that patients who experience acute encephalopathy should continue to receive this important chemotherapeutic agent.

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Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.

Cited by 142 publications

References 14 publications

Late effects in survivors of infant leukemia

Late effects in survivors of infant leukemia

Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981–1995)

Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia

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