Hematologic toxicity during craniospinal irradiation: the impact of prior chemotherapy

The purpose of this work was to determine the frequency of hematologic toxicity during craniospinal radiation (CSI) and the impact of preirradiation chemotherapy on this frequency. The charts of 37 patients who received CSI were reviewed. Twenty did not have prior chemotherapy (CT-), while 17 did receive 1 to 18 (mean 5) cycles of multi-agent systemic chemotherapy (CT+). Leukopenia/thrombocytopenia necessitating treatment interruptions occurred in 1/20 (5%) in the CT- group, compared to 8/17 (47%) among the CT+ group. This difference was statistically significant, P < 0.0001 (Fisher's exact two-tailed test). The duration of treatment interruption in the CT+ patients was 4-24 days (mean 14). Compared to the CT- group, the CT+ group had a statistically significant greater decline in their white blood cell count (WBC), platelet count, and hematocrit (HCT) during CSI (percent reduction per Gy; (P = 0.018, 0.006, and 0.047, respectively). Although not statistically significant, the CT+ group also experienced lower nadir ratios (nadir count/baseline count) in terms of WBC and platelets (P = 0.07 and 0.22, respectively). While the mean pretreatment baseline blood counts were lower in the CT+ group compared to the CT- group, these differences reached statistical significance for the HCT (P = 0.02), but not the WBC (P = 0.59) or platelets (P = 0.43). Leukopenia and thrombocytopenia are very common in patients who receive craniospinal irradiation following multi-agent systemic chemotherapy. This appears to be due to more rapid and marked reductions in counts during CSI. Since this toxicity may cause treatment interruptions that are potentially therapeutically disadvantageous, aggressive hematologic support with transfusions and growth factors may be necessary. This problem may become more common as combined modality therapy is used more frequently.