THE POTENTIAL OF TARGETED RADIOTHERAPY IN THE TREATMENT OF CENTRAL-NERVOUS-SYSTEM LEUKEMIA

We describe the results of clinical studies investigating the role of monoclonal antibody (MoAb) targeted radiotherapy in the treatment of c entral nervous system (CNS) leukaemia. Seven children, aged 3-16 years , in second or subsequent meningeal relapse of acute lymphoblastic leu kaemia (ALL), have been treated. Each patient received a single inject ion into the cerebrospinal fluid (CSF) of between 629 and 1,702 MBq of 131-Iodine (I-131) conjugated to MoAb HD37 (CD19, n = 2), WCMH 15.14 (CD10, n = 4) or both antibodies (n = 1). One patient underwent a cour se of repeated targeted therapy following his initial treatment. Acute toxicity was manifest in five patients by a transient aseptic meningi tis. Myelosuppression was observed in four children. Pharmacokinetic s tudies investigated whole body, blood and CSF clearance of radioisotop e. Progressively more rapid systemic clearance of I-131 was noted in t he patient receiving repeated therapy, indicating the development of t he 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 d ose to the subarachnoid CSF was between 12.2 and 25.3 Gy, over six tim es 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 disapp earance of lymphoblasts from the CSF, was observed. These studies demo nstrate the feasibility of targeted radiotherapy in CNS ALL. The discu ssion focuses on both future developments, by which the response to th erapy may be improved, and the potential of this technique in becoming part of accepted therapy for meningeal leukaemia.