Bone marrow transplant and leukaemia: understanding relapse mechanisms helps prevent them

Bone marrow transplant, technically haematopoietic stem cell transplant, is a cornerstone treatment for blood cancers, including leukaemia. Yet in a significant share of transplanted patients the disease still returns, because leukaemic cells can learn to evade the donor’s immune system. A new international study coordinated by Vita-Salute San Raffaele University and IRCCS Ospedale San Raffaele has analysed this mechanism in one of the largest patient cohorts ever assembled and has developed a model that predicts the risk of this specific relapse pathway. The results, published in the Journal of Clinical Oncology, open the way to more targeted donor selection and more personalised treatment strategies to reduce the risk of relapse. 

The study, led by Professor Luca Vago, associate professor of Haematology at Vita-Salute San Raffaele University, builds on a research line the same group started more than fifteen years ago. In 2009, a study published in the New England Journal of Medicine showed that some leukaemias can escape immune control by losing HLA molecules, the proteins that allow the immune system to distinguish the body’s own cells from “foreign” ones to be eliminated. The new study confirms that mechanism on one of the largest international cohorts available and goes further: it defines how often it occurs, identifies the factors that favour it, and turns that knowledge into a tool that can guide clinical decisions. 

The researchers analysed 533 relapses of blood cancers after allogeneic transplant, collected across 27 centres in 7 countries. They found that in 15.6% of cases, leukaemic cells lose the HLA molecules that allow the donor’s immune system to recognise them as foreign, allowing the cells to evade the immune response. Based on these findings, the team developed an algorithm that estimates the risk of HLA loss according to the genetic characteristics of patient and donor, offering a new tool to personalise both donor selection and treatment strategy in the event of relapse. 

Already more than fifteen years ago, we showed that HLA loss is a key mechanism of immune evasion in leukaemia after transplant. This new work extends those findings, defining more precisely how often this happens, in which contexts, and what it means for clinical practice,

says Luca Vago. 

The research involved the Unit of Immunogenetics, Leukaemia Genomics and Immunobiology, the Haematology and Bone Marrow Transplantation Unit at IRCCS Ospedale San Raffaele, and CUSSB, the University Centre for Statistics in the Biomedical Sciences at Vita-Salute San Raffaele University. The study was also supported by Fondazione AIRC. 

For people facing leukaemia, understanding the mechanisms behind relapse means we can offer new treatment options and greater confidence in the care pathway. Research has to keep turning complex knowledge into concrete tools that improve patients’ lives,

says Fabio Ciceri, full professor of Haematology at Vita-Salute San Raffaele University and director of the Haematology and Bone Marrow Transplantation Unit and the Comprehensive Cancer Center at IRCCS Ospedale San Raffaele.