During this time period period, anti-CD19 CAR T-cells revealed rapid expansion in the peripheral blood (Fig. 3). Two patients with TKI-resistant recurrent Ph-positive ALL. == Diagnoses: == Ph-positive ALL. == Interventions: == Anti-CD19 CAR T-cell infusion. == Outcomes: == One patient’s bone marrow blasts decreased significantly, and the other reached negative minimal residual disease (MRD). However , we first recorded the development of new-onset acute graft-versus-host disease (aGVHD) after anti-CD19 CAR T-cell infusion in a patient who received allogeneic HSCT. Our 2 case reports also demonstrate the efficacy of anti-CD19 CAR T-cell therapy in the treatment of TKI-resistant Ph-positive ALL. == Lessons: == Our report suggests that anti-CD19 CAR T-cell therapy may be a promising option for the treatment of relapsed Ph-positive ALL after conventional chemotherapy or allogeneic HSCT. However , caution is due given the possibility of the adverse effects of cytokine release syndrome (CRS)-induced aGVHD for patients receiving allogeneic HSCT. == 1 . Introduction == The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality MC-Sq-Cit-PAB-Gefitinib associated with adult acute lymphoblastic leukemia (ALL), occurring in 20% to 40% of patients.[1]The presence of the t(9; 22) chromosomal translocation is the single most important adverse prognostic factor in Ph-positive ALL, with long-term survival of less than 20% with current chemotherapy regimens.[1]Tyrosine kinase inhibitors (TKIs) directed against the ABL kinase are now used routinely during first-line therapy for Ph-positive ALL and result in hematologic remission rates exceeding 90%.[2, 3]Although outcomes have improved substantially with TKI-based regimens versus with historic controls, allogeneic hematopoietic stem cell transplantation (HSCT) at the first remission provides the best chance of a cure for the majority of patients eligible for HSCT.[3]However , disease recurrence remains the main cause of failure. Treatment options are extremely limited for patients with Ph-positive ALL who experience relapse after receiving allogeneic HSCT. In nontransplanted patients, the emergence of resistance to TKI therapy also poses a challenge for patients with disease relapse after initial treatment with TKI-containing regimens. Chimeric antigen receptors (CARs) are fusion proteins that incorporate an antigen- recognition moiety and a T-cell activation domain.[4]T-cells can be modified genetically to express anti-CD19 CARs on their surface and have been shown to exert cytotoxic effects against CD19-positive B-cells. Both autologous and allogeneic anti-CD19 MC-Sq-Cit-PAB-Gefitinib CAR T-cells have produced remission in previously treated patients with B-cell malignancies.[5, 6]We describe 2 patients with Ph-positive ALL resistant to TKIs who underwent anti-CD19 CAR T-cell infusions. One patient’s bone marrow blasts decreased significantly, and the other reached negative minimal residual disease (MRD) status. == 2 . Case reports == Patient 1 was a 39-year-old woman who presented to a local hospital for systemic subcutaneous ecchymosis and nasal bleeding on January 13, 2015. Blood examination revealed a white blood cell (WBC) count of 31. 96 109/L, hemoglobin (HGB) of 85 g/L, and a platelet (PLT) count of 10 109/L. Bone marrow examination and flow cytometry suggested B-cell ALL. Cytogenetics revealed the Philadelphia chromosome and theBCR-ABLfusion gene was positive. She was thus diagnosed with Ph-positive ALL. The patient was given induction chemotherapy with the vincristine, daunorubicin, L-asparaginase, prednisone, and cyclophosphamide (VDCLP) MC-Sq-Cit-PAB-Gefitinib protocol in combination with oral administration of imatinib mesylate capsules MC-Sq-Cit-PAB-Gefitinib (0. 4 g/day) on January 21, 2015. She was then discharged after hematopoietic recovery. However , the patient stopped taking imatinib mesylate capsules on her own accord in April 2015. MC-Sq-Cit-PAB-Gefitinib On June 20, 2015, she was admitted to our hospital. At presentation, her physical examination showed multiple enlarged superficial lymph nodes in the neck, armpits, and groin (the largest was 2 ENPP3 3 cm). Blood examination revealed a WBC count of 194. 49 109/L, HGB of 78 g/L, and PLT of 18 109/L. Bone marrow examination revealed 91% lymphoblasts. Bone marrow fluorescent in situ hybridization (FISH) detected a positiveBCR-ABLfusion gene (positive rate = 97%). Bone marrow quantitative real-time polymerase chain reaction (QRT-PCR) detected a positive BCR-ABL p190 transcript (BCR-ABL/ABL, 47. 7%). Bone marrow Sanger sequencing found T315I and E355G mutations in the ABL kinase.