Ponatinib-Induced Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant
lar response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease
... ed a rapid decrease in minimal residual Abstract We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecu-• Ponatinib is a highly effective treatment for Philadelphia-positive acute lymphoblastic leukemia with and without T315I mutation, and it is well tolerated. Novel Insights • Ponatinib as a single-agent treatment can induce molecular complete responses in Philadelphia-positive acute lymphoblastic leukemia patients without T315I mutation after early relapse following allogeneic stem cell transplantation, and it can induce a graft-versus-host disease/graft-versus-leukemia (GVHD/GVL) effect through immunomodulatory activity. Petrungaro et al. 354 disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib treatment was well tolerated and considered safe with easily manageable side effects.