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

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 molecular 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 in minimal residual 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.

Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia

“…Acute lymphoblastic leukemia (ALL) is a common hematological malignancy in children and adults, and treatment usually involves various anticancer drugs [1, 2]. High-dose methotrexate (HDMTX) is one of the most important agents in the treatment of extramedullary infiltration of ALL [3-5].…”

Spotlight on ponatinib in the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia: patient selection and perspectives

“…Although both patients achieved deep molecular responses, they also developed cutaneous GVHD which required medication discontinuation in the patient with CML 47. Skin GVHD following initiation of ponatinib for posttransplant relapses has also been described in other case reports, suggesting a potential role of ponatinib to enhance the graft-versus-leukemia effect 48,49. Overall, 43 patients have received ponatinib for posttransplant relapses in the early phase clinical trials; however, their clinical outcomes and side-effect profile have not been reported separately 15,16…”

“…Imatinib has been used in patients who are minimal residual disease positive after transplant57 as well as for molecular relapses posttransplant and has led to high response rates 58. Although a total of 43 patients have received ponatinib in the posttransplant setting, detailed data regarding their outcomes have not been reported, and case reports of such patients suggest high incidence of GVHD, in some cases necessitating medication discontinuation 48,49. Thus, it remains unknown whether a select group of patients could benefit from posttransplant treatment with ponatinib for either prevention or treatment of molecular relapse 59…”

Long-Term Remission Achieved by Ponatinib and Donor Lymphocytes Infusion in a Ph+ Acute Lymphoblastic Leukemia Patient in Molecular Relapse After Allogenic Stem Cell Transplant and Dasatinib: A Case Report

“…B cell Acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy arising from B-cell progenitors that accounts for 20% of adult leukemias (1). Among ALL adult patients, approximately 25% presents an acquired chromosomal abnormality, the Philadelphia chromosome (Ph), resulting from a balanced translocation between chromosome 9 and 22 (2,3), which leads to the formation of the hybrid BCR-ABL transcript. The occurrence of Ph chromosome increases with age and is associated with a worse prognosis (4).…”

“…The occurrence of Ph chromosome increases with age and is associated with a worse prognosis (4). From a clinical point of view, Ph+ ALL usually presents with a higher white blood cell count (as compare to Ph-ALL) and with a 5% risk of central nervous system involvement at diagnosis (3). The 5 year survival rate range from about 40% for people aged 25-64 years to <15% for patients over 65 years (1).…”