Impact of cranial irradiation added to intrathecal conditioning in hematopoietic cell transplantation in adult acute myeloid leukemia with central nervous system involvement

Abstract

Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC).

Methods and materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT).

Results: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality.

Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.

Figure 1

Kaplan-Meier curves for estimated relapse free survival of AML patients with CNS positive disease treated with ITC alone (red), versus CNS positive disease treated with ITC and an irradiation boost (green), versus CNS negative patients (black).

Figure 2

Kaplan-Meier curves for estimated overall survival of AML patients with CNS positive disease treated with ITC alone (red), versus CNS positive disease treated with ITC and an irradiation boost (green), versus CNS negative patients (black).

Figure 3

Kaplan-Meier curves for estimated relapse of AML patients with CNS positive disease treated with ITC alone (red), versus CNS positive disease treated with ITC and an irradiation boost (green), versus CNS negative patients (black).