Although cancer immunotherapy has long been studied, its efficacy was largely unproven until recently. CAR-T cells are T cells transduced with a chimeric protein consisting of immunoglobulin variable regions and cytoplasmic domains of the T cell receptor. CAR-T cells can be activated without antigen-presenting cells, exhibit cytotoxicity, and produce cytokines. Although early clinical trials of these cells failed to show efficacy, second-generation CAR-T cells targeting CD19 are highly effective for treatment of refractory/relapsed acute lymphoblastic leukemia. However, safety issues such as severe cytokine release syndrome and neurological toxicities are major concerns. Here, the history of the development of CAR-T cells and clinical experiences with CD19-directed CAR-T cell therapy are reviewed, and the near future of this new therapy is discussed.

 Haploidentical stem cell transplantation, a transplantation from a family donor who shares one of two HLA haplotypes with a patient, has widened the donor pool, and prevailed all over the world. We started haploidentical transplantation on 1998, and have experienced more than 700 cases. The concept of our regimen is not to eliminate the activated T cells but to control them using low-dose antithymocyte globulin (ATG) and steroid. We have two haploidentical regimens, myeloablative one and reduced-intensity (RIC) one consisting of FLU/CA/CY/ATG 3 mg/kg/TBI 8 Gy, and FLU/CA/MEL/ATG 2.5 mg/kg/TBI 3 Gy as a preconditioning regimen, respectively. GVHD prophylaxis consists of methylprednisolone and tacrolimus. In this review, I would like to show the outcome of our haploidentical transplantation using low-dose ATG and steroid. I also demonstrate our attempts for topics concerning haploidentical transplantation such as HLA antibodies, HHV6 reactivation, homo-to-hetero transplantation, HLA loss of heterozygosity (HLA-LOH), and 2-HLA-haplotype-mismatched transplantation.

 Bone marrow aspiration of a 64-year-old woman with incomplete remission of pure erythroid leukemia revealed leukemic cells 19 days after undergoing a cord blood transplant (CBT). She also developed concurrent idiopathic pneumonia syndrome (IPS) on day 35, and was treated with steroid pulse therapy and etanercept. However, this strategy was ineffective. She developed lower back pain on day 45, and blood findings revealed progressive pancytopenia, and elevated serum T-Bil, ALP and LDH. Serum ferritin was significantly elevated to 186,160 ng/mL. Bone marrow aspiration showed only degenerated necrotic cells, indicating a diagnosis of bone marrow necrosis (BMN). Her general status rapidly deteriorated, mixed acidosis progressed, and she died on day 55 after CBT. An examination of blood cytokines showed elevated levels of tumor necrosis factor receptor 1 before the onset of BMN, and elevated interleukin-6 that was consistent with the onset of BMN. The prognosis of rare BMN that can follow hematological malignancies and infections is poor. In this patient, we supposed that progressive leukemia, in association with some inflammatory cytokines, could result in BMN.