Hematological malignancies, including multiple myeloma, lymphoma, and leukemia, are a heterogeneous group of neoplasms that affect the blood, bone marrow, and lymph nodes. They originate from uncontrolled growth of hematopoietic and lymphoid cells from different stages in their maturation/differentiation and account for 6.5% of all cancers around the world. During the last decade, it has been proven that the gut microbiota, more specifically the gastrointestinal commensal bacteria, is implicated in the genesis and progression of many diseases. The immune-modulating effects of the human microbiota extend well beyond the gut, mostly through the small molecules they produce. This review aims to summarize the current knowledge of the role of the microbiota in modulating the immune system, its role in hematological malignancies, and its influence on different therapies for these diseases, including autologous and allogeneic stem cell transplantation, chemotherapy, and chimeric antigen receptor T cells.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the standard treatments for B-cell lymphoproliferative disorders; however, deep relapses are common after an allo-HSCT, and it is associated with poor prognosis. A successful approach to overcome these relapses is to exploit the body’s own immune system with chimeric antigen receptor (CAR) T-cells. These two approaches are potentially combinatorial for treating R/R B-cell lymphoproliferative disorders. Several clinical trials have described different scenarios in which allo-HSCT and CAR-T are successively combined. Further, for all transplanted patients, assessment of chimerism is important to evaluate the engraftment success. Nonetheless, for those patients who previously received an allo-HSCT there is no monitorization of chimerism before manufacturing CAR T-cells. In this review, we focus on allo-HSCT and CAR-T treatments and the different sources of T-cells for manufacturing CAR T-cells.