Haematological toxicity of cranio-spinal irradiation

To assess the frequency and severity of myelosuppression due to cranio-spinal irradiation either alone or in combination with chemotherapy and to identify patients at high risk of haematological toxicity who may require supportive therapy.

Between 1965 and 1994, 210 patients received cranio-spinal axis (CSA) radiotherapy as a component of treatment for primary CNS tumours at the Royal Marsden Hospital. Full blood counts (FBC) were obtained before, during and after radiotherapy in 200 patients. Haematological toxicity was graded according to the WHO criteria and duration was measured from the onset of grades 3 and 4 toxicity until recovery to grade 2.

Sixty-six (33%) patients developed grades 3 and 4 haematological toxicity. Nadir occurred during radiotherapy and was most frequent during the second week of spinal radiotherapy. Low haemoglobin and white cell counts prior to radiotherapy increased the likelihood of myelosuppression. Nine patients had febrile episodes requiring antibiotic therapy. Treatment was interrupted in 49 patients but treatment time was extended beyond 12 weeks in only 17 (8%) patients of which nine were due to haematological toxicity. Chemotherapy (vincristine) during radiotherapy did not impact on haematological toxicity. Age and prior chemotherapy were independent predictive factors for haematological toxicity. The relative risk of leukopaenia in children compared to adults was 7.9 (95% CI 3.4-18.6%). Patients who received prior chemotherapy had a relative risk of toxicity of 6.1 (95% CI 2.9-12.8%).

One-third of patients undergoing CSA radiotherapy develop grades 3 and 4 haematological toxicity. The risk is higher in children and in patients who receive chemotherapy prior to radiation. There was no treatment-related mortality and only nine of 200 patients (9/60 of those with toxicity) required supportive treatment for neutropaenic sepsis. The low incidence severe haematological toxicity does not warrant routine use of haemopoietic growth factors during CSA irradiation and future studies should target high risk subgroups.