Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

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]. It carries an adverse prognosis with standard chemotherapy alone, requiring allogeneic bone marrow transplant for a curative approach. First and second generation TKI's were developed to target the BCR-ABL fusion protein [2]. The availability of these new agents is changing the treatment paradigm and the prognosis for these patients. Using imatinib as a single agent showed short-lived responses to treatment, and thus new studies were done using imatinib with concomitant chemotherapy. One such study showed 96% of patients achieving complete remission after a median of 21 days [3]. Second generation TKI's have significantly more potent antileukemia activity against BCR-ABL positive leukemia’s and are under active investigation for ALL [4]. They have also shown great activity in patients with imatinib resistant Ph？+？ALL. Nilotinib is approximately 30 fold more potent than imatinib and is active in vitro against 32 of 33 BCR/ABL mutations [5]. 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].The utility of second generation TKIs as monotherapy in relapsed disease has not yet been fully evaluated [6,7]. 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. This patient reverted back to full donor reconstitution, leading to development of chronic graft-versus-host disease (GVHD). Despite additional immunosuppression and extracorporeal photopheresis (ECP), graft-versus-leukemia (GVL) effect was sustained and the patient remains in molecular remission.A 54- year-old woman presented with Philadelphia chro