Highlights from the American Society of Hematology (ASH) annual meeting, San Diego CA, December 3-6, 2016 – With the advent of tyrosine kinase inhibitor (TKI) therapies, stem-cell transplantation (SCT) is less commonly used to treat CML. While it does offer the potential of curing CML, it is a difficult and painful procedure that is associated with significant, possibly fatal side effects.
Three new studies have looked at how well people do over the long term after receiving a transplant. Between 2002 and 2014, 191 SCTs were performed in France in people with CML (Nicolini and colleagues. ASH 2016; abstract 3476). Most were done when Gleevec was the only TKI available (2002-2006), suggesting that the need for transplant has declined over the past decade with the introduction of second-generation TKIs (Tasigna, Sprycel, Bosulif). People in this later period were also older when they were transplanted, indicating that they were tried on various medications before SCT was attempted. The mortality rate at 10 years post-transplant was 28%.
The mortality rate was slightly better in a U.S. study: 28% at 20 years and 30% at 30 years post-transplant (Wu and colleagues. ASH 2016; abstract 823). This analysis only included people who had survived the first two years post-transplant, so the overall mortality rate would have been a bit higher. Death due to a CML relapse was low (about 4% at 20 years); most deaths were due to transplant-related complications, such as infections, and graft-versus-host disease (GvHD). (Eliminating the bone marrow removes a person’s immune response. However, the transplanted tissue does have an immune response, and these cells can attack the host, which it considers to be “foreign”.) If a person was able to survive 15 years without complications, their mortality risk was similar to that seen in the general population. However, the overall mortality risk was 4-fold higher in transplant recipients compared to non-transplanted individuals.
Long-term results may be improved somewhat if a person starts a TKI after transplantation. A group of researchers looked at 435 people who received either Gleevec or another TKI (Sprycel, Tasigna, Bosulif, Iclusig) following transplantation (Chalandon and colleagues. ASH 2016; abstract 4685). Many were transplanted because of advanced disease (accelerated-phase or blast-crisis CML); they received a TKI because transplantation didn’t eradicate their leukemia. Overall, 18% achieved a complete molecular response (i.e. undetectable disease). However, most people had no response or suffered a relapse/progression. Overall survival in these very ill individuals was 60% after five years.