Induction of REMISSION with Clofarabine IN CHILDREN with Relapsed Acute LYMPHOCYTIC Leukemia.

Abstract 4112

New treatment protocols have improved significantly the survival of patients with acute lymphocytic leukemia (ALL). However, there is a risk of relapse, which depends on disease classification and the protocol of chemotherapy administered. In case of relapse, new remission has to be achieved to proceed to bone marrow transplantation (BMT). For this reason, new therapies for remission induction, except standard chemotherapy, are under investigation. Clofarabine, a new class agent, is a nucleoside analogue of purine which inhibits DNA synthesis and repair by blocking ribonucleoside reductase and DNA polymerase. It also disrupts mitochondrial membrane, driving to cell apoptosis. We describe two children with B-cell ALL, in whom clofarabine was administered because of disease resistance. Case 1: Girl, 12 years old, with ALL, presented a second bone marrow (BM) relapse. The first relapse was also in BM and was presented 30 months after the end of primary chemotherapy. Remission was achieved with chemotherapy based on protocol ALL-REZ-BFM 96. In the second relapse, that occurred one year after the end of ALL-REZ-BFM 96, conventional cytogenetics analysis showed an apparently normal female karyotype 46,XX, while molecular cytogenetics analysis (FISH) showed 3 and 4 copies of AML1 gene in 10.7% and 82.4%, of analyzed nuclei respectively. Clofarabine was administered in 52mg/m²/24h for 5 days, every 4-6 weeks. It was well tolerated. Moderate myelotoxicity presented, early after the end of regimen that was uncomplicated. Mild and transient elevation of transaminases was detected in the peripheral blood. Reevaluation after 3 cycles of clofarabine, revealed morphologic and cytogenetic remission. The patient underwent successful heterologous BMT. Case 2: Boy 18 years old with ALL presented a first BM relapse 22 months after the end of initial chemotherapy. Conventional cytogenetics analysis showed an apparently normal male karyotype 46,XY, while molecular cytogenetics analysis (FISH) was negative for clonal rearrangement involving the MLL gene and TEL/AML1, or BCR/ABL hybrid genes. Chemotherapy was administered based on protocol ALL-REZ BFM 96, but remission was not achieved. Clofarabine in 52mg/m²/24h for 5 days was administered. The patient presented mild uncomplicated myelotoxicity. Remission was achieved after the first cycle of clofarabine and the patient underwent successful heterologous BMT.