Inl I Rad,mon Oncology Bml Phvr Vol. IO. DP. 1851-1853 t int ed in the U.S.A. All n&s resewed. 03603016/84 103.00 + .oO Copyright $ I984 Pcrgamon Press Ltd. ?? Original Contribution THE SOMNOLENCE SYNDROME IN LEUKEMIC CHILDREN FOLLOWING REDUCED DAILY DOSE FRACTIONS OF CRANIAL RADIATION PHILIP LITTMAN, M.D.,’ JEFFREY ROSENSTOCK, M.D.,’ GORDON GALE, M.D., ROBERT E. KRISCH, M.D., PH.D., * ANNA MEADOWS, M.D.,3 HARLAN SATHER, M.D.,4 PETER CGCCIA, M.D.5 AND BEATRIZ DECAMARGO, M.D.6 A group of children with acute lymphocytic leukemia was studied to investigate if a reduction in daily dose fraction of cranial radiation would reduce the incidence of somnolence syndrome. Thirty-one evshrable patients received 100 rod X 18 cranial radiation therapy. Sixty-six similar evnhrable patients were given 180 rad X 10. Both groups received the same chemotherapy including intrathecal methotrexate. Clinically detectable somnolence appeared in 58% of ech group without significant differences in the overall frequency or severity of somnolence (p > 0.5). This study failed to substantfate a radiation dose fraction size dependence for somnolence syndrome in children with acute lymphocytic leukemia. Acute lymphocytic leukemia, Somnolence syndrome, Central nervous system leukemia. INTRODUCI’ION Cranial radiation plus intrathecal methotrexate is effective in preventing the development of central nervous system (CNS) leukemia in children with acute lymphocytic leukemia (ALL). In 1973, investigators at St. Jude Children’s Research Hospital reported that a dose of 2400 rad appearedto be more effective than 1200 rad.’ Subsequently, a dose of 2400 rad for central nervous system prophylaxis was reported to be associated with a decrease in the IQ score and with cognitive disturbances.8 Children’s Cancer Study Group meanwhile demonstrated that a dose of 1800 rad is as effective as 2400 rad in preventing CNS relapse9 with a minimum follow-up of 5 years. It has not yet been determined whether the cerebral dysfunctions observed after 2400 rad have been decreased in either incidence or severity by the reduction to 1800 rad. Animal studies show that frequency and severity of late radiation damage to at least the micro- vasculature of the CNS is related to the dose and rate of administration of the radiation.’ Evaluation of late neuropsychologic adverse effects requires several years of study, because of the lag time between CNS irradiation and the time when the apparently permanent CNS dysfunction becomes definable. in one study lag time was three or more years. Another consideration is that large numbers of long-term survivors need to be accrued because the incidence and severity of the dysfunction may depend on both the child’s age at irradiation and IQ.8 One of the more immediate complications following cranial irradiation is the somnolence syndrome (SS), first described in 1929 by Druckmann4, which consists of mild drowsiness to moderate lethargy associated sometimes with low grade fever. It is uniquely associated with cranial irradiation, and usually appears 4 to 6 weeks after completion of therapy. This syndrome has not been related to underlying aspects of the leukemia such as age of patient and initial white blood count, which are factors known to affect the response of the leukemia itself to therapy.3 The pathophysiology is un- known, but electroencephalogram (EEG) and cerebral spinal fluid abnormalities are found in affected chil- dren.3~‘~“.‘2The EEG’s showed slowing in all children who received cranial radiation, unrelated to clinical evidence of SS but the degree of abnormality correlated with the clinical occurrence of SS.’ In one study the EEG abnormalities remained abnormal for at least 1 ’ Department of Radiation Therapy, University of Pennsyl- vania School of Medicine. * Cardinal Glennon Hospital for Children. 3 Department of Pediatrics, Children’s Hospital of Philadel- phia. 4 Children’s Cancer Study Group. 5 Division of Pediatric Hematology Oncology, Rainbow Babies & Childrens Hospital. 6 Service de Pediatria, Hospital A.C. Camargo. This investigation was supported by grant number CA 11796 and CA 13539 awarded by the National Cancer Institute, DHHS, and the Canuso Foundation. Acknowledgements-We would liketo thank Dr.Giulio D’An- gio for his advice and support, and Barbara Bayton for her technical assistance. Accepted for publication 17 May 1984. 1851