Clinical Research Directory

GRanulocyte Augmented Cord Blood Transplantation for Poor Risk leukaEmia

Allogeneic stem cell transplantation is the only potentially curative therapy for patients with high-risk Acute Myeloid Leukaemia, but relapse is common and remains the leading cause of death. Patients with certain mutations and those transplanted without first clearing their disease have very poor outcomes with most relapsing soon after transplant, and then surviving only a few months. A recent trial at the Royal Manchester Children's Hospital used cord blood stem cells alongside a type of white blood cell called 'granulocytes' and produced surprisingly good outcomes for children with very resistant leukaemia. GRACE is a clinical trial for adults (\<55 years) with Acute Myeloid Leukaemia that has not responded to chemotherapy or harbours mutations that predict a very poor response to conventional transplant. Participants will receive a transplant using umbilical cord blood and be given additional infusions of white blood cells, called granulocytes. The trial will be split into two parts:-The first will study the safety of this new approach. The experience of the investigators in children is that granulocyte infusions cause a fever, rash and expansion of another type of white blood cell called lymphocytes. Children that did not have this reaction did not respond to treatment. The investigators therefore believe that the reaction is necessary for the treatment to work, but the investigators must ensure that it is safe in adult patients. The trial design allows the investigators to determine the dose of granulocytes that is best tolerated and most likely to be effective. The aim of the second part is to demonstrate that the new treatment is more effective than conventional transplantation. The study will be conducted in three NHS transplant centres. Patients will be recruited over 36 months and followed up for a minimum of 1 year. The study is funded by Blood Cancer UK.

VDJ-recombination of the B-cell Receptor Following Hematopoietic Stem Cell Transplantation

When a person undergoes a stem cell transplant-an important procedure used to treat serious blood diseases such as leukaemia, lymphoma, or myeloma-the entire immune system is affected. The transplant essentially "resets" the immune system, meaning that the patient loses much of the protection against infections that has been built up over a lifetime. After the transplant, the patient therefore needs to be revaccinated against several diseases, such as tetanus, diphtheria, polio, COVID-19, and pneumococcal disease. In this study, we aim to investigate how B cells-the immune cells that produce antibodies-reconstitute after a stem cell transplant. We are particularly interested in a genetic process called VDJ recombination, through which each B cell develops a unique receptor that enables it to recognize and fight a specific virus or bacterium. This process is what makes our immune system so effective. But what happens to this diversity after the entire immune system has been restarted with new stem cells? Does the body regain the same ability to recognize pathogens? Are there differences between patients who receive their own stem cells (autologous transplantation) and those who receive stem cells from another person (allogeneic transplantation)? To answer these questions, we will follow patients undergoing stem cell transplantation at Umeå University Hospital. We will collect blood samples before and after the transplantation and will assess whether-and how well-patients generate antibodies in response to the vaccines given after transplantation. Using flow cytometry and genetic analyses, we will examine both which B-cell populations are generated and what their genetic architecture looks like. The goal is to understand how the new immune system is rebuilt after transplantation and, ultimately, to help improve vaccination strategies and infection prevention for this vulnerable patient group

Impact of CMV-Specific Immune Reconstitution at the End of Letermovir Prophylaxis on the Development of Late Cytomegalovirus Infection in Hematopoietic Stem Cell Transplant Recipients (INMUNOEND)

Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (SCT). Fixed-duration letermovir (LTV) prophylaxis during the first 100 days post-SCT is effective and safe in preventing this infection, although it may be associated with a delay in CMV-specific immune reconstitution. Hence, it is needed a study to evaluate whether the absence of CMV-specific immune reconstitution at the end of LTV prophylaxis is associated with the development of late infection. This could facilitate the individualization of CMV prophylaxis duration in these patients. Methods and analysis: INMUNOEND is a multicenter, prospective, observational, non-interventional study including CMV seropositive patients undergoing allo-SCT who receive LTV prophylaxis during the first 100 days post-SCT. Immunological and virological monitorization will be conducted until day +200 post-SCT. The primary outcome variable is the percentage of patients who develop clinically significant CMV infection up to day +200 post-SCT after completing LTV prophylaxis. Data collected will include: baseline characteristics of the hematological diseases and comorbidities, variables related to SCT (i.e. engrafment, graft-versus-host disease, use of letermovir and CMV replication) and variables related to CMV-specific immune reconstitution.