Hematopoietic stem cell transplantation (HSCT) is an effective curative therapy for a long list of hematological malignancies. Historically HSCT was the only mode of therapy that could provide a cure for a long list of hematological malignancies including acute myeloid leukemia (AML), acute lymphatic leukemia (ALL), and myelodysplastic syndrome which are the main indications for HSCT in Europe; but also for chemosensitive non-Hodgkin lymphomas (NHL), Hodgkin lymphoma, and multiple myeloma (MM), the main indications for autologous transplantation. However, transplantation could be offered to only a rather small fraction of the patients in need due to the high risk of toxicity and mortality of the procedure especially in patients with comorbidities for age and performance status. But also due to the organ toxicity of the pre-HSCT, conditioning, and transplant-related complications, mainly graft versus host disease (GVHD). On the other hand, allogeneic transplantation mediating the graft versus tumor effect that correlates with GVHD provided the first demonstration of cellular immunotherapy and the ability to tailor the immune system against malignancies. The immune system can recognize and eliminate malignant cells and as such is a powerful tool in fighting cancer.

This was the basis for the development of donor lymphocyte infusions,nonmyeloablative conditioning, and finally the chimeric antigen receptor -T (CAR-T) adoptive immunotherapy that revolutionized anti-cancer therapeutics.

CAR-T cell therapy for hematologic malignancies turns out to be a cutting-edge therapeutic advancement that is leading the immunotherapy frontier and cancer therapy. CD19-specific CARs for lymphatic malignancies including NHL, MM, and ALL revolutionized the field and changed completely treatment paradigms in lymphatic hematological malignancies. Currently, there are 6 commercial CAR-T cell products that are FDA-approved (4 for NHL and ALL and 2 for MM). In general, the toxicities of CAR-T cell therapy are lower than those of HSCT, there are no age limits and CAR-T is effective in patients with chemoresistant, high-risk diseases that failed HSCT. In NHL they are offered already in the second line of therapy and as a result, the number of autologous transplantations is being sharply reduced in NHL and MM. However, there are major issues with the availability and affordability of CAR-T cell therapy, and many patients that are in need cannot receive it, especially in low or medium-income countries. Point-of-care academic CAR T cells may overcome these limitations. We, at Sheba Tel- Hashomer, initiated already in 2016 a point-of-care academic CAR-T cell program in which hundreds of patients with relapsed/refractory ALL, NHL patients (first as the third line, and then patients failing the first line of therapy or relapsed within 12 months), and from 2021 patients with MM are being treated with CD19 and anti-B cell maturation antigen (BCMA) based CAR-T cells, respectively. We also treated a small cohort of patients with AML harboring the 8:21 translocation that expressed CD19 with CAR-T cells. The benefits of point-of-care CAR-T cells are a shorter time, 10-11 days, from a vein (leukapheresis) to the vein (administration) and therefore, almost no need for bridging therapy but mainly lower cost significantly increasing CAR-T cells affordability and accessibility. We will try to discuss these issues in our session.