Matched Unrelated vs. Haploidentical Donors for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia

Acute leukemia is a malignant disease of the blood-forming cells characterized by the uncontrolled production of abnormal white blood cells (blasts) in the bone marrow and blood. This pathological overproduction of blasts disrupts blood formation and the immune system. Depending on the origin of the affected cells, this disease is classified as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Myelodysplastic syndrome (MDS) is also a blood disorder characterized by the abnormal formation of blood cells; here, too, white blood cells are frequently affected. Initially, MDS is often not as acutely severe as leukemia; however, MDS is also frequently associated with a poor prognosis. MDS can also progress to leukemia over time. Symptoms of acute leukemias and MDS may include fatigue, anemia, blood clotting disorders, fever, increased susceptibility to infections, swollen lymph nodes, and an enlarged spleen. In many cases, these symptoms are due to a shortage of healthy blood cells. The exact cause of these diseases is not fully understood, but genetic mutations and environmental factors play a role. To ensure long-term survival, these diseases must be completely eliminated. The goal of treatment is therefore a cure. This requires intensive chemotherapy and, in many cases—depending on certain risk factors associated with the disease and the patient—a stem cell transplant. In this procedure, the patient’s own blood system is completely destroyed and replaced with another person’s blood system. To do this, patients receive stem cells from another person (donor). It is crucial that the new blood system “accepts” the new patient and does not recognize it as “foreign,” as this would otherwise lead to severe and potentially fatal immune reactions. Therefore, the donor’s new blood system must be a good match for the patient. This can be achieved in various ways: Either the patient and donor are related, in which case there is usually a high degree of similarity between the patient and the new blood system (= haploidentical). Another option is that certain characteristics of the patient and the new blood system match. Human leukocyte antigens (HLA) play a crucial role here. The better these match (ideally 10 out of 10 of the most important HLA patterns), the greater the chance that blood from a complete stranger will be well tolerated. This is verified using large blood bank registries. A very important side effect of administering new blood cells is that they may be able to kill any remaining malignant leukemia cells in the patient (which chemotherapy can no longer do), thereby further increasing the chance of a cure. There is evidence that this effect may be greater with related donors (= haploidentical variant).

The goal of this Phase 2 study is to compare the efficacy and effect against any remaining leukemia cells in patients who have undergone stem cell transplants from matched unrelated donors (10/10 HLA match) with that of related donors, recognizing that the HLA match may be less precise in this case (at least a 5/10 HLA match). Participants will be randomly assigned to one of two groups as part of the study. The haploidentical group (=relatives) receives cyclophosphamide after the transplantation of the corresponding stem cells to prevent the immune reactions described above (graft-versus-host disease (GvHD)). Cyclophosphamide is a classic and commonly used chemotherapy drug. The study is open-label, meaning that both the medical staff and the patient know which treatment is being administered. The study will last up to 2 years, during which the effectiveness of the therapy and the occurrence of side effects will be evaluated. The key factor is whether or when the disease recurs during therapy. The primary endpoint of the study is the proportion of participants in both groups who experience a relapse (recurrence of the disease) within 2 years after treatment.

Patients between the ages of 18 and 70 with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome are eligible to participate in this study. Patients with ALL and AML must be in complete remission before the start of treatment, meaning the disease has been completely suppressed by standard intensive chemotherapy.