Graft Versus Leukemia (GVL) Effect in the Central Nervous System Sanctuary: Successful Treatment with Donor Lymphocyte Infusion (DLI) in a Patient with Resistant Ph1+ Acute Lymphoblastic Leukemia.

Ph1+ ALL requires allo- BMT in first CR, however disease relapse continues to be a concern. We report a patient with refractory ALL Ph+1 treated with conventional allo-BMT who had an isolated CNS relapse 2 years later successfully rescued with chemotherapy followed by DLI. In September 2002 a 35-year-old male patient presented with deep venous thrombosis of the right popliteal vein. The WBC was 84X10⁹ / l (52% blasts). Bone marrow: ALL Ph1+, bcr/abl, pre-B CALLA+. CSF: normal. Induction chemotherapy according to LAL-adult French protocol included idarubicin, vincristine, cytoxan, corticosteroids and MADIT weekly. CR obtained D+28. CHOP + MADIT were then administered. In the next 2 weeks he had a marrow relapse (39% blasts) just before start allo-BMT conditioning and we decided together to go on: FTBI (12 Gy-6 fractions) + CTX 120mg/kg, GVHD prophylaxis with CSA alone and infusion of 3,5 X 10⁶ CD34/kg of peripheral stem cell from his HLA identical brother. Chronic extensive GVHD was observed 6 months later treated with a short course of corticosteroids. 2 years after BMT pt presented severe radicular pain and weakness in his right leg. Bone marrow showed persistent cytologic, cytogenetic and molecular CR. VNTR 100% donor. CSF was infiltrated with blasts (bcr / abl +) and MRI showed a paravertebral tumor at L4 level. 4 cycles of salvage chemotherapy with high dose methotrexate (3g/m²) and ara-C (2g/m² x 2 x 3 days) + MADIT obtained clinical and CSF CR. DLI from the same donor was performed twice at 1 month interval without GVHD. One year has elapsed since then and he is in continuous CR. We conclude that DLI might induce a GVL effect on CNS acute leukemia and therefore DLI should be helpful in achieving higher donor immunoreactivity and a better GVL effect.