The Potential of Targeted Radiotherapy in the Treatment of Central Nervous System Leukaemia

We describe the results of clinical studies investigating the role of monoclonal antibody (MoAb) targeted radiotherapy in the treatment of central nervous system (CNS) leukaemia. Seven children, aged 3-16 years, in second or subsequent meningeal relapse of acute lymphoblastic leukaemia (ALL), have been treated. Each patient received a single injection into the cerebrospinal fluid (CSF) of between 629 and 1,702 MBq of 131-Iodine (¹³¹I) conjugated to MoAb HD37 (CD 19, n = 2), WCMH 15.14 (CD 10, n = 4) or both antibodies (n = 1). One patient underwent a course of repeated targeted therapy following his initial treatment. Acute toxicity was manifest in five patients by a transient aseptic meningitis. Myelosuppression was observed in four children. Pharmacokinetic studies investigated whole body, blood and CSF clearance of radioisotope. Progressively more rapid systemic clearance of ¹³¹I was noted in the patient receiving repeated therapy, indicating the development of the human anti-mouse Ig (HAMA) response. Dosimetric studies revealed a radiation dose to the red bone marrow of between 0.6 and 2.2 Gy. The dose to the subarachnoid CSF was between 12.2 and 25.3 Gy, over six times higher than that to the surface tissue of the brain and spinal cord and between 40 and 140 times higher than that to the whole brain. In all but one patient, a transient complete response, in terms of disappearance of lymphoblasts from the CSF, was observed. These studies demonstrate the feasibility of targeted radiotherapy in CNS ALL. The discussion focuses on both future developments, by which the response to therapy may be improved, and the potential of this technique in becoming part of accepted therapy for meningeal leukaemia.