Adverse drug reactions following lymphocyte immunotherapy for the treatment of infertility: A retrospective study.

AIM: Unexplained infertility is a major burden for couples who want to have children. Lymphocyte immunotherapy (LIT) could be a therapeutic help for these couples. Although LIT has been carried out for decades, the data on the success of therapy are still controversial and there is hardly information on possible adverse drug reactions. METHODS: In this study, we used a questionnaire to determine the frequency of local and systemic adverse drug reactions in our patients who were treated with LIT between 2017 and 2020 (n = 302). In addition, we asked about pregnancies and/or live births after LIT in a 2-year follow-up (n = 140). RESULTS: Most of the patients reported the occurrence of mild local adverse drug reactions in a period of less than 4 weeks: Over 75% reported moderate erythema, itching or swelling, over 10% erythema, itching or swelling as more pronounced adverse drug reaction. Blistering was specified in 10% of the cases. Serious adverse drug reactions or adverse events were not described. In the follow-up, 69% of our patients stated a pregnancy after LIT, and 50% a life birth. CONCLUSIONS: Overall, LIT represents a well-tolerated therapy for couples with unexplained infertility, however, more evidence is needed on the benefits.

An alternative for extracorporeal photopheresis: 8-methoxypsoralen and UVA-treated leucocytes from allogeneic donors improve graft-versus-host disease in mice.

BACKGROUND AND OBJECTIVE: Extracorporeal photopheresis (ECP) is an important immune tolerance inducing therapy for graft-versus-host disease (GvHD). However, a sufficient number of ECP cycles cannot be performed in patients with severe GvHD and contraindications for apheresis. Allogeneic sources of leucocytes for use as ECP treatment would be of great benefit. Therefore, this study aimed to test the therapeutic potential of novel sources of leucocytes for ECP. MATERIALS AND METHODS: Graft-versus-host disease mice were treated with ECP using therapeutic cells from different allogeneic sources. Splenocytes were incubated with 8-methoxypsoralen (8-MOP), irradiated with UVA light and injected into GvHD mice as a model for ECP. RESULTS: The therapy with 8-MOP/UVA-treated cells from healthy mice of the bone marrow transplantation (BMT) donor strain reduced the GvHD symptoms, at least in a model of chronic GvHD. In the acute GvHD model, 8-MOP/UVA-treated cells from the BMT donor or recipient strain did not show significant improvements in GvHD symptoms or survival time. Pre-activation of cells by mixed lymphocyte reactions before 8-MOP/UVA treatment also failed to result in significant differences in survival time or GvHD score. In contrast, ECP with third-party 8-MOP/UVA-treated cells from a HLA-mismatched donor resulted in a mean survival time of 37 days compared to 21 days in the control group. CONCLUSION: In our analysis of novel allogeneic leucocyte sources for ECP, we could demonstrate that the source of the 8-MOP/UVA-treated cells is crucial. The underlying immunologic effect of allogeneic 8-MOP/UVA-treated cells needs to be investigated in future studies.

Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines.

Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment. In this study, patients were monitored for 12 months after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently associated with the occurrence of GvHD in the observation period. However, the largest area under the receiver operating characteristic curve with 0.90 was observed when a 5-parameter biomarker score based on CD4+ T cells, CD8+ T cells, CD19- CD21+ precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor was used to predict GvHD. In addition, CD8+ T cell levels above 2.3% of all mononuclear cells after engraftment may predict relapse-free survival at least for 12 months. In summary, we found a new biomarker panel for prediction of GvHD which is featured by established laboratory assays and high statistical significance. In order to introduce the biomarker panel into routine clinical protocols, we suggest performing a larger multi-center study.