Your Family as a Lifeline:  

How often do we find ourselves telling patients that the only way to potentially cure their leukaemia or other diseases is through an allogeneic stem cell transplant? Unfortunately, not every patient has a perfectly matched 10/10 or 9/10 donor available, nor a matched sibling. This news often brings disappointment, but there is hope—half-matched (haploidentical) donors within the family are a viable option. Parents, children, and even half-matched siblings can now serve as donors, thanks to advancements in haploidentical stem cell transplantation.  

Haploidentical transplants offer a promising solution, especially for patients from ethnic groups where finding a fully matched unrelated donor is difficult. Family members, who share half of the genetic information, are increasingly being used as safe and effective donors. Over the past decade, clinical trials have shown that outcomes from haploidentical transplants are comparable to those of mismatched unrelated donors, with no significant difference in overall survival (https://doi.org/10.1182/blood.V128.22.1234.1234). 

This progress has been led by Italian study groups in collaboration with many European centres. The key innovation was the use of post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis. PTCy selectively depletes alloreactive T-cells that could attack the recipient’s tissues, reducing the risk of GVHD while preserving the Graft-versus-Leukaemia (GVL) effect. Moreover, this approach allows for a more natural and gradual recovery of the immune system, promoting immune tolerance and facilitating successful outcomes (https://doi.org/10.1182/blood.2019000487).  

One critical area of ongoing research is understanding immune reconstitution post-transplant, which remains complex and requires more study. Immunosuppression strategies are evolving, particularly for elderly or less fit patients. Reduced-intensity conditioning protocols are now available for those who might not tolerate the full toxicity of more intensive treatments, allowing them the opportunity for a potentially curative transplant. 

Further trials are essential, especially for elderly or semi-fit patients, to advance personalized medicine and improve outcomes for those without specific genetic mutations that can be targeted.