Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.

The incidence of childhood cancer in twins was evaluated by linking a roster of 30,925 twins born in Connecticut (United States) between 1930 and 1969 with the Connecticut Tumor Registry. Cancer, exclusive of nonmelanoma skin cancer, was identified in 19 females and 12 males under 15 years of age. The incidence rate among twins was 7.9 cancers per 100,000 person-years (PY) overall, and 9.7 and 6.1 per 100,000 PYs for females and males, respectively. Four of 13 leukemias occurred in two female twin pairs, representing concordance rates of 18 percent overall and 29 percent for like-sex pairs, which are somewhat higher than values reported previously. The number of cancers expected was computed on the assumption that twins experienced the same sex-, age-, and calendar time-specific cancer rates as recorded for all Connecticut-born children. Because active follow-up of individuals was not conducted, an adjustment to person-years of observation was made to account for childhood mortality, including the high perinatal mortality characteristic of twins. Childhood cancer was 30 percent less frequent than expected (standardized incidence ratio [SIR] = 0.7; 95 percent confidence interval [CI] = 0.5-0.9), a deficit that is marginally greater than those found in previous studies. Both leukemia (SIR = 0.8; CI = 0.4-1.4), and all other cancers combined (SIR = 0.6; CI = 0.3-0.9) occurred less often than expected. The deficit was greater among males (SIR = 0.5; CI = 0.2-0.8) than among females (SIR = 0.9; CI = 0.5-1.4) and was especially pronounced among males younger than five years (SIR = 0.2; CI = 0.0-0.7). The data support the view that twins, particularly male twins, have a lower risk of childhood cancer than single-born children. Any added risk for twins associated with their greater frequency of exposure to prenatal X-rays appears to have been insufficient to offset an 'effect' of twinning per se. Possible explanations for this finding include (i) the low birthweight distribution of twins, or (ii) selective early mortality of twin fetuses or neonates who would otherwise have developed a clinical cancer.

We conducted a case-control study to investigate the relation between prenatal exposure to x-rays and childhood cancer, including leukemia, in over 32,000 twins born in Connecticut from 1930 to 1969. Twins as opposed to single births were chosen for study to reduce the likelihood of medical selection bias, since twins were often exposed to x-rays to diagnose the twin pregnancy or to determine fetal positioning before delivery and not because of medical conditions that may conceivably pre-dispose to cancer. Each of 31 incident cases of cancer, identified by linking the Connecticut twin and tumor registries, was matched with four twin controls according to sex, year of birth, and race. Records of hospitals, radiologists, and private physicians were searched for histories of x-ray exposure and other potentially important risk factors. Documented prenatal x-ray exposures were found for 39 per cent of the cases (12 of 31) and for 26 per cent of the controls (28 of 109). No other pregnancy, delivery, or maternal conditions were associated with cancer risk except low birth weight: 38 per cent of the cases as compared with 25 per cent of the controls weighed under 2.27 kg at birth. When birth weight was adjusted for, twins in whom leukemia or other childhood cancer developed were twice as likely to have been exposed to x-rays in utero as twins who were free of disease (relative risk, 2.4; 95 per cent confidence interval, 1.0 to 5.9). The results, though based on small numbers, provide further evidence that low-dose prenatal irradiation may increase the risk of childhood cancer.