Abstract
Simple SummaryB-cell malignancies, like leukemias and lymphomas, are neoplasms that emerge from the malignant proliferation of B cells. Hematopoietic stem cell transplant (HSCT) is an effective medical treatment for these malignancies, but unfortunately, relapse of the disease after HSCT remains a challenge and is associated with poor long-term survival. A cell-based immunotherapy, the chimeric antigen receptor (CAR) T-cells, has proven to improve the clinical outcome of relapsed/refractory HSCT B-cell lymphoproliferative disorders patients in clinical trials. Even though results are promising, in this review, we discuss about the importance to determine T cell chimerism in HSCT patients, the origin of the manufactured CAR T-cells (autologous vs. allogenic) and the future perspective of the CAR-T cells in transplanted patients.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.
Highlights
hematopoietic stem cell transplant (HSCT) can be classified into two types of procedures: (a) autologous HSCT and (b) allogeneic HSCT
Many clinical trials have used T-cells sourced from the patient, whether previously allo-HSCT or not
The origin of the “autologous” cells used for chimeric antigen receptor (CAR)-T treatment is a main aspect to have in mind when this treatment is used, specially when the patient arrives to this advance therapy after an allo-HSCT
Summary
B-cell malignancies are a diverse group of neoplasms that emerge from the malignant proliferation of B cells during their different stages of development [1], and they include lymphomas and leukemias [2]. Given that the aim of allo-HSCT is to remove the patient’s malignant hematopoietic cells, a conditioning regimen based on chemotherapy or radiation is administered This depletion of the patient’s bone marrow stem cells (and usually partially tumor cells) induces severe pancytopenia, requiring donor-derived healthy stem cells to re-establish a new blood cell production system. Clinicians can perform bridge chemotherapy to lower the tumor burden temporarily Another disadvantage is the CAR-T cell-associated toxicities such as cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS), both clinically manageable. Another big hurdle is the tumor escape by target antigen loss, relapse patients with CD19 negative disease have been described in several clinical trials [39]. Clinical trials testing CAR-T targeting CD22 or BCMA are presenting encouraging results for B-ALL [42] and multiple myeloma [43], and additional information will arrive soon from the recently FDA-approved CAR-BCMA [44,45], in this review, we focus on the already approved anti-CD19+ CAR T-cell therapies
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