Abstract
We report the successful treatment and sustained molecular remission using single agent nilotinib in a relapsed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. Compared to previously published studies, this is the first report where a patient did not receive additional chemotherapy after relapse, nor did she receive donor lymphocyte infusions. With nilotinib, the patient reverted back to normal blood counts and 100% donor reconstitution by single tandem repeat (STR) chimerism analysis in the bone marrow and in peripheral blood, granulocytes, T and B-lymphocytes. This report also highlights the use of nilotinib in combination with extracorporeal photopheresis (ECP) for concomitant graft-versus-host disease. Our data suggests that ECP, together with nilotinib, did not adversely affect the overall Graft-versus-leukemia (GVL) effect.
Highlights
Philadelphia chromosome (Ph+) is the most common cytogenetic abnormality in adult ALL and is the translocation between chromosome 9 and 22 demonstrating BCR-ABL gene rearrangement and accounts for approximately 20-30% of all adult ALL cases [1]
A phase II study of nilotinib (400 mg twice a day) in relapsed or refractory Ph + ALL reported that 24% of patients attained a complete hematologic response (CHR) [6]
We report the successful use of nilotinib as a single agent treatment in obtaining molecular remission for over one year in Ph + ALL that relapsed after allogeneic SCT
Summary
Philadelphia chromosome (Ph+) is the most common cytogenetic abnormality in adult ALL and is the translocation between chromosome 9 and 22 demonstrating BCR-ABL gene rearrangement and accounts for approximately 20-30% of all adult ALL cases [1]. She responded to this treatment and her immunosuppression was weaned down to 10 mg of Prednisone daily along with cyclosporine She was in complete molecular remission based RT-PCR and was 100% donor chimerism by single tandem repeat testing for Granulocytes, T-Lymphocytes and BLymphocytes and had male XY chromosome cytogenetics in the bone marrow. In light of this new evidence, the patient expressed her wishes not to undergo aggressive reinduction chemotherapy regimen followed by additional donor lymphocyte infusions Due to this relapse, in January 2011, fourteen months after her transplant, imatinib was discontinued and nilotinib was started at a dose of 800 mg daily (400 mg p.o.b.i.d.). Nilotinib dose is maintained at 800 mg/day and no toxicities were noted requiring dose adjustment or modification She is currently stable from the leukemia standpoint, with her last biopsy being negative for residual disease, and chimerism studies showed 100% donor cells.
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