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Childhood Leukemia: October 1995

Last modified on: Tuesday, April 20, 1999 12:03:10
Copyright © 1994-2008, Information Ventures, Inc.
Childhood Leukemia - Effective treatment of childhood acute lymphoblastic leukemia (ALL) requires eradication of leukemic cells sequestered in the central nervous system (CNS), where they are protected from drugs in the blood, and can give rise to relapses. Twenty years ago, a combination of cranial radiotherapy and intrathecal (IT) chemotherapy was found most effective in eradicating these fugitive cells, with greatest advantage to those patients with poor prognoses. However, as the number of long-term survivors increased, it became evident that there was permanent damage to the brain causing such problems as learning and growth deficits, principally ascribed to radiation. Girls are more sensitive to developing deficits than boys, but fortunately they usually require less intensive treatment than boys to prevent relapses. The level of radiation has been reduced to a more acceptable 18 Gy, but most groups in the US have chosen to avoid radiation and intensify the IT chemotherapy. But IT chemotherapy is not innocuous and may itself lead to similar deficits. Three groups of investigators report on this topic in the October, 1995 issue of the Journal of Clinical Oncology.

The Dana-Farber ALL Consortium (DFAC; Dr. Waber and colleagues) report on 66 patients treated under DFAC's protocol 87-01 who have now been followed for 4 or more years. Standard risk patients received no cranial radiation, high risk received 18 Gy; all patients received intravenous high-dose or conventional-dose methotrexate during induction, and intrathecal and systemic continuation chemotherapy. There was no difference between irradiated and non-irradiated in cognitive outcomes (p >> 0.4), but high-dose methotrexate with cranial irradiation was associated with a decreased IQ (by 9.3 points) for girls only (p << 0.08). A specific deficit in verbal coding and memory was seen in all patients, independent of radiation and possibly due to a chemotherapy component, perhaps prednisone. Can methotrexate before radiotherapy be protective as has been found to be the case in animal studies?

The Italian Pediatric Hematology Oncology Association (AIEOP) reported on 396 children with non-B-cell ALL of low, intermediate, and high risk (risk index > 1.2 or CNS involvement at diagnosis) who received intensive chemotherapy (BFM) that included high-dose intravenous methotrexate plus nine doses of intrathecal methotrexate, extended for intermediate risk, and with cranial irradiation for high risk (18 Gy for those above 2 years, 12 Gy for those 1-2 years). Event-free survivals were 66.6% overall, 80.7% for standard risk, 77.5% for intermediate risk, and 54.5% for high risk. Estimated six-year CNS-leukemia- free survivals were 94.6% overall, 99.1% for intermediate, 93.5% for standard, and 92.3% for high risk. The authors concluded that cranial irradiation may safely be omitted for intermediate risk patients (risk index between 0.8 and 1.2).

In the third paper from Christie Hospital, Manchester, UK, pubertal growth and final height was measured in children who had received 18 Gy and 24 Gy cranial irradiation. Asparaginase, VCR, prednisone plus one or two additional drugs were used for induction, followed by intensification, and then four-drug maintenance therapy. Reduced height standard deviation score was recorded for both sexes and dose groups. Earlier puberty occurred in girls but not in boys, while peak height velocity decreased in both sexes, with no reduction in duration of puberty.

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