The transformation of chronic lymphocytic leukemia to an aggressive lymphoma, called Richter transformation, is often accompanied by resistance to chemotherapy and high mortality. Thus, novel therapeutic strategies are required for the successful treatment of these patients. One possibility is cellular immunotherapy with chimeric antigen receptor T cells. However, the time delay until cells are available and the limited number of effector cells due to the impaired immune system of these patients potentially compromises the efficacy of this approach. Another promising attempt might be the therapy with γδ T cells. Once activated, they exhibit various antitumor effects against several types of malignancies. Furthermore, they can be safely used in an allogeneic setting and can be multiplied in vivo as already demonstrated in clinical studies. In vitro data, in addition, show that the cytotoxicity of γδ T cells can be significantly enhanced by monoclonal antibodies. Here we present a patient, who suffered from Richter transformation and did not respond to several lines of immunochemotherapy. Due to the lack of further therapy options, we conducted an individual therapy with adoptive transfer of haploidentical γδ T cells combined with the application of the monoclonal antibody obinutuzumab. A histologically confirmed complete remission was achieved through this therapy approach, whereby relevant side effects were not seen. This case highlights the potential of γδ T cells and the feasibility of this therapeutic approach for further clinical trials.

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Introduction Graft‐versus‐host disease (GvHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and is highly influenced by the degree of HLA matching between recipient and donor. The HLA‐class Ib molecule HLA‐G has been shown to promote tolerogenicity through its interaction with inhibitory receptors found on several immunocompetent cells. We hypothesized that in an allo‐HSCT setting, HLA‐G mismatches may negatively impact the HLA‐G‐mediated tolerogenicity either due to inefficient interaction with the inhibitory receptors of the transplanted immune cells or due to direct allorecognition of mismatched HLA‐G on host cells by the immune cells of the donor. Methods In order to explore this hypothesis, we investigated the impact of HLA‐G mismatching in 2.083 10/10 matched high resolution HLA‐typed allo‐HSCT transplants. Results We found that the risk of chronic GvHD was significantly higher in HLA‐G‐mismatched transplant cases as compared with the HLA‐G‐matched control group (HR: 1.46, 95%CI = 1.11–1.91, p = 0.006). Sub‐analysis of the mismatch vector revealed that this effect was only detectable in the GvH (HR: 1.89, 95%CI 1.39–2.57, p < 0.001) but not the HvG direction (HR: 1.01, 95%CI = 0.63–1.63, p = 0.967). In addition, the negative impact of HLA‐G mismatching on chronic GvHD was only significant in younger patients (<30y HR: 3.02, 95%CI = 1.25–7.28, p = 0.014; >29y HR: 1.28, 95%CI = 0.94–1.72, p = 0.113). Discussion Our results indicate that HLA‐G mismatches may contribute to the onset of chronic GvHD, especially in younger patients and should therefore be avoided when possible.

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