Cyclophosphamide to Reduce Complications Following Haploidentical Stem Cell Transplantation

Non-Hodgkin lymphomas are cancers that arise from lymphocytes (a subgroup of white blood cells), which are normally responsible for defending against pathogens as part of the immune system. These diseases primarily affect the lymphatic system and usually lead to enlarged lymph nodes and B symptoms such as fatigue and fever. Treatment depends on numerous factors (type of disease, stage of the disease, the patient’s overall health, etc.) and usually consists of immunochemotherapy. If the disease cannot be controlled with therapy (refractory) or if a relapse occurs, a blood stem cell transplant (hematopoietic stem cell transplant, HSCT) may be recommended with the goal of a complete cure. In allogeneic HSCT, the patient’s diseased blood system is destroyed through intensive pretreatment (conditioning) and replaced with healthy stem cells from donors. Immunological compatibility between the donor and recipient is crucial to minimize rejection reactions (graft-versus-host disease, GvHD). Typically, the search begins with a fully matched stem cell donor. These are often siblings or unrelated individuals from international donor registries whose all major tissue markers (HLA markers) match. If no such “fully matched” donors are available, a donor whose tissue markers only partially match may also be considered—for example, a parent, child, or sibling. This type of transplant is called a “haploidentical transplant.” It is available more quickly, but the risk of rejection reactions such as GvHD is increased. The administration of the drug cyclophosphamide to suppress the immune system (immunosuppression) has shown positive results in this context and could minimize the risk of complications during transplantation. Cyclophosphamide is a chemotherapy drug and has long been approved for use in many cancer treatments. There is no specific approval for its use following an HSCT, so the drug is currently used only on an “off-label” basis (use outside the approved indications). The available data regarding this specific form of treatment are still limited, which is why clinical trials are necessary. The aim of this Phase 2 study is to investigate the efficacy and safety of immunosuppression with high-dose cyclophosphamide in the context of a haploidentical HSCT. Prior to transplantation, patients receive intensive chemotherapy to remove the diseased bone marrow and make room for the healthy donor cells. This so-called myeloablative conditioning is performed using a combination of three drugs: thiotepa, busulfan, and fludarabine (TBF regimen). The haploidentical stem cell transplant is then performed, and on days 3 and 4 after the transplant, patients receive an infusion of high-dose cyclophosphamide. All patients receive the same treatment, and the study is open-label, meaning that both the medical staff and the patient know which medications are being administered. The primary endpoint of the study is the one-year disease-free survival rate. Women and men aged 18–65 with relapsed or refractory NHL are eligible to participate in this study. The disease must have been previously treated and must have shown a recurrence or be uncontrollable (refractory). In addition, a recommendation for a haploidentical HSCT must be in place.