We were recently asked if we could describe the progress in treatment of FA over the last 25 years, so we’ve put together a short summary based on the Fanconi Cancer Foundation’s Clinical Care Guidelines and reviewed by an expert FA haematologist/oncologist.
In the past 25 years, Fanconi Anaemia treatment has shifted from high-risk interventions to more personalised, targeted approaches. Advances in gene therapy, improved transplantation protocols, better GVHD management, and proactive cancer screening have significantly extended survival and improved quality of life for FA patients.
Over this period average life expectancy has increased from teenage years to the late 30’s, and within the past few years, in both the US and the UK, the number of people with FA 18 years of age and over exceeds those under 18. A consequence of this is that adult patients with FA are not yet well served, since most of the expertise in FA is still in the hands of paediatricians. Patient Support Groups worldwide are increasingly focused on supporting the transition to adulthood, empowering patients with the information they need to self-advocate and supporting increasing awareness and education of adult healthcare professionals.
Here are some specifics on the progress in treatment over the last 25 years:
Improvements in Bone Marrow Transplants (Technically Hematopoietic Cell Transplantation (HCT)
- Then: HCT was a high-risk procedure for FA patients due to sensitivity to chemotherapy and radiation.
- Now: Reduced-intensity conditioning (RIC) regimens using agents like fludarabine, anti-thymocyte globulin (ATG) and more recently (and more effectively) Campath, have improved survival rates and reduced transplant-related complications.
- Matched unrelated donor (MUD) transplants and alternative donor sources, such as haploidentical transplants and umbilical cord blood, have become more viable.
Management of Graft-Versus-Host Disease (GVHD) (side effect of BMT)
- Then: GVHD was a major post-transplant complication with limited treatment options. GvHD was also a significant risk factor for cancer in later years.
- Now: The use of post-transplant cyclophosphamide, JAK inhibitors (e.g., ruxolitinib), and mesenchymal stromal cell therapy has improved GVHD management, particularly for steroid-refractory cases.
Gene Therapy and Editing
- Then: No gene therapy options existed.
- Now: Advances in gene therapy trials using lentiviral vectors have shown promising results in correcting FA gene mutations, potentially reducing the need for bone marrow transplants in the future. CRISPR-based gene editing is also being explored.
Cancer Surveillance and Prevention
- Then: FA patients had a high cancer risk, but screening protocols were less structured.
- Now: Early surveillance strategies (e.g., oral brush biopsies, regular HPV screenings) help detect cancers early, leading to better outcomes. New targeted therapies for FA-related head and neck squamous cell carcinoma (HNSCC) are under investigation.
Supportive Care Advances
- Then: Blood transfusions and androgens (e.g., oxymetholone) were standard for bone marrow failure, but with limited long-term efficacy.
- Now: Supportive care has improved with better transfusion management, hormone replacement therapy for endocrine dysfunction, and improved patient monitoring protocols.