Myelosuppression toxicity of palliative splenic irradiation in myelofibrosis and malignant lymphoma.

Objectives: Distinctive splenomegaly resulting from extramedullary hematopoiesis and infiltration of neoplastic cells is observed in some patients with myelofibrosis (MF) or malignant lymphoma. Palliative splenic irradiation is known to be effective for such patients and is widely performed. However, little is known about the biological mechanism of palliative splenic irradiation. Various reports have focused on irradiation doses, in terms of efficacy and safety. We examined the toxicity of myelosuppression and the timing of the platelet, white blood cell, and red blood cell count nadirs within 3 months after the start of irradiation in a total of eight patients with MF or malignant lymphoma, all of whom underwent palliative splenic irradiation at our hospital between 2004 and 2013.
Methods: Five patients with idiopathic MF and three patients with non-Hodgkin's lymphoma (NHL) treated with splenic irradiation between 2004 and 2013. Of the three patients with NHL, two had diffuse large B-cell lymphoma and one had mantle cell lymphoma. There were four male and four female patients, with median age of 61 years (range, 51-73). Patients with MF received irradiation at 20-100 cGy per fraction dose; four patients received irradiation five times a week and one patient received irradiation three times a week. In three of these patients, the irradiation dose was gradually increased while observing for hematotoxicity. Patients with NHL received irradiation at a fraction dose of 150-200 cGy, and all received irradiation five times a week. Irradiation was terminated when we judged symptoms to be alleviated, splenomegaly reduced, or efficacy to be poor. With regard to the total irradiation dose, 175, 320, 400, 600, and 640 cGy were given to one MF patient each, and 1050 and 3000 cGy were given to one and two NHL patients, respectively.
Results: Symptoms diminished or disappeared in five of the six symptomatic patients (83%). A reduction in the size of the spleen was confirmed in five of six patients (83%) with splenomegaly. For MF, the platelet count nadir was observed at week 3 in two patients, week 5 in two, and week 6 in one patient. For NHL, it was observed at week 1 in one patient, week 4 in one, and week 9 in one patient. For MF, the white blood cell count nadir was observed in at week 2 in one patient, week 3 in two, and week 5 in two patients. For NHL, it was observed at week 1 in one patient and week 4 in two patients. For MF, the red blood cell count nadir was observed at week 1 in two patients, week 3 in one, week 7 in one, and week 8 in one patient. For NHL patients, it was observed at week 1 in one patient, week 4 in one, and week 9 in one patient. Discussion There was a trend for the nadir to be steeper in patients with MF than in those with NHL. With regard to the total dose, symptoms diminished at the minimum dose of 175 cGy in MF patients, whereas the maximum dose of 3000 cGy was not effective in NHL patients. These observations suggest that a splenic lesion in NHL patients may be the primary site of neoplastic cell infiltration and that extramedullary hematopoiesis may not necessarily occur in the spleen.
Conclusion: Although palliative irradiation of splenic lesions in patients with MF or NHL is safe and effective, optimal irradiation doses may differ for MF and NHL. More cases need to be accumulated to elucidate these differences.