The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.

George, Stephen L.; Ochs, Judith; Mauer, AM; Simone, Joseph V.

doi:10.1200/jco.1985.3.6.776

Cited by 54 publications

(19 citation statements)

References 13 publications

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“…Informed consent was obtained from all patients' parents in accordance with national ethic rules. Median age was 5.2 years (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). ALL was of the B lineage in 1195 cases (86%) and T cell in 200 cases (14%).…”

Section: Methodsmentioning

confidence: 99%

“…The symptoms resolved within 48 h in 12/20 children (1/2-48 h). Sixteen cases occurred during consolidation, three during intensification and one during maintenance therapy with median TIT number of 6 (3-14) and median of 9 days after the last IT injection (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Imaging studies were abnormal in 12/17 documented cases, showing mainly signs of leukoencephalopathy (10 cases) associated with ischemia features in three cases, hemorrhage in two cases and thrombosis in one case.…”

Section: Encephalopathy (N ¼ 20)mentioning

confidence: 99%

“…The patients had received a median of three TIT (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), and the seizures occurred a median of 8 days after the last injection.…”

Section: Seizures (N ¼ 15)mentioning

confidence: 99%

“…[1][2][3][4] However, majority of ALL patients have occult CNS involvement 5 and the prognosis of CNS relapses is still unsatisfactory, although recent improvement has been reported with event free survival up to 70%. [6][7][8] CNS prophylaxis is currently based on intrathecal chemotherapy (IT) with MTX7steroid and cytarabine (Cyt) and prophylactic cerebral irradiation indicated for children with ALL with a HR of CNS relapse. The incidence of CNS relapse is currently between 1.5 and 5% depending on the study.…”

Section: Introductionmentioning

confidence: 99%

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Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

et al. 2006

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The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)7high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n ¼ 182) were randomized to weekly low-dose MTX at 25 mg/m 2 /week (LD MTX, n ¼ 81) or HD MTX at 1.5 g/m 2 /2 weeks Â 6 (n ¼ 77). Intermediate-risk group (IR, n ¼ 672) were randomized to LD MTX (n ¼ 290) or HD MTX at 8 g/m 2 /2 weeks Â 4 (n ¼ 316). Higherrisk group (HR, n ¼ 541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n ¼ 15 (1.1%), peripheral and spinal neuropathy: n ¼ 17 (1.2%) and encephalopathy: n ¼ 20 (1.4%). Age 410 years was significantly associated with neurotoxicity (P ¼ 0.01) and use of HD MTX is associated with encephalopathy (P ¼ 0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.

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Section: Methodsmentioning

confidence: 99%

Section: Encephalopathy (N ¼ 20)mentioning

confidence: 99%

“…The patients had received a median of three TIT (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), and the seizures occurred a median of 8 days after the last injection.…”

Section: Seizures (N ¼ 15)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

et al. 2006

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“…In the St Jude's series of studies, there was a 2-3.5-fold increased risk of haematological relapse for those children who experienced an isolated CNS relapse. In the Total VI Study, 58% of patients who had received presymptomatic craniospinal irradiation remained in remission 8-11 years post-diagnosis, compared with only 35% of those given CNS treatment at the time of overt relapse (George et al, 1985). In contrast, the CCGF101 study contained one arm in which patients were treated only with intrathecal methotrexate.…”

mentioning

confidence: 99%

CNS minimal disease therapy in childhood leukaemia: the place for irradiation

1990

Br J Cancer

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In the 1960s, when the initial trials of combination chemotherapy began to prolong remission duration in childhood acute lymphoblastic leukaemia, an increasing incidence of central nervous system relapse was noted with rates between 50 and 70% (Hardisty & Norman, 1967;Evans et al., 1970;Hustu et al., 1973). Overt CNS leukaemia appeared difficult to control, but its major significance was that it was almost invariably followed by bone marrow relapse, whilst deaths from neurological dysfunction were quite rare, even in the presence of multiple CNS recurrences (Ortega et al., 1987). Symptom-free remission post overt CNS relapse was short and, in the MRC trials between 1977 and 1987, only 23 of 116 children survived without subsequent event. The length of first remission and whether relapse occurred on or off therapy significantly determined the chance of survival. There were serious long-term sequelae with 50% of survivors severely disabled neurologically, educationally or on both counts. A more favourable salvage rate of over 50% has been reported by the Paediatric Oncology Group but it is in a series with a shorter follow-up time (Land et al., 1985). The full impact of disability caused by therapy requires long-term follow-up.Prevention of CNS relapse has clearly been deemed a better option than salvage post relapse. Although for some time controversial it is now accepted that CNS involvement results from leukaemic cells lying in the walls of superficial arachnoid veins which then migrate into the surrounding adventitia. As cell numbers increase the arachnoid trabeculae are destroyed with subsequent penetration of cerebrospinal fluid channels over the surface of the brain. al., 1971;Hustu et al., 1973). Whether such treatment prevents subsequent haematological relapse is more controversial. The Cancer and Leukaemia Group B in a randomised study showed a median remission duration of 26 months for those receiving intrathecal methotrexate compared with only 15 months for the group which did not (Holland & Glidwello, 1972). In the St Jude's series of studies, there was a 2-3.5-fold increased risk of haematological relapse for those children who experienced an isolated CNS relapse. In the Total VI Study, 58% of patients who had received presymptomatic craniospinal irradiation remained in remission 8-11 years post-diagnosis, compared with only 35% of those given CNS treatment at the time of overt relapse (George et al., 1985). In contrast, the CCGF101 study contained one arm in which patients were treated only with intrathecal methotrexate. This group had an increased CNS relapse rate, but neither marrow relapse nor overall survival rates were significantly affected after medium-term follow-up (Ortega et al., 1987). However, these patients were

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Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis

Lowichik¹,

Bernini²,

Tonk³

et al. 1996

Med. Pediatr. Oncol.

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The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.

Cited by 54 publications

References 13 publications

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

CNS minimal disease therapy in childhood leukaemia: the place for irradiation

Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis

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