Stem cell transplants eliminate the disease-causing mutation in patients with systemic mastocytosis (SM) and associated hematological neoplasm (AHN) long before their tryptase levels normalize, according to results from a study published recently in the British Journal of Haematology.
SM-AHN is a rare subtype of SM where SM and a blood cancer occur together. The study of 13 patients with SM-AHN who underwent hematopoietic cell transplantation at a single center found that both full donor cell chimerism (meaning a patient’s blood-forming cells were completely replaced by donor cells) and disappearance of the KITD816V mutation occurred rapidly and together, while tryptase levels, a sign of mast cell activity, lagged behind.
“Molecular remissions and establishment of full donor chimerism were closely associated,” explained this study’s authors. “Although these observations need to be validated in larger trials, tryptase persistence and increase after HCT [hematopoietic cell transplantation] were not associated with relapse.”
Patients reached full donor chimerism a median of 31 days after transplant. At 36 days after hematopoietic cell transplantation, the KITD816V mutation, a hallmark of SM, became undetectable. This strong link was shown by a nearly perfect negative correlation between donor cell levels and mutation presence. In contrast, tryptase levels normalized only after a median of 228 days, despite their decline beginning earlier.
Read more about SM treatment and care
These differences suggest that while the mutation may vanish quickly with effective treatment, other indicators of disease, such as tryptase, may persist longer and not signal relapse on their own. In fact, tryptase levels rose temporarily around day 100 in some patients as their graft-versus-host disease medication was reduced, but this did not indicate the cancer’s return. Similarly, a jump in tryptase was observed even without relapse in most cases.
Notably, a rapid drop in tryptase was seen in a patient who underwent spleen removal, highlighting how removing heavily diseased organs may help speed recovery. Another patient experienced a fast decrease in tryptase after receiving radiation-based conditioning before transplant.
The three-year outcomes for these patients were promising: overall survival was 82% and disease-free survival was 77%. No non-relapse deaths occurred, underscoring the potential benefit of hematopoietic cell transplantation for this complex disease. For patients and caregivers, these results mean that although symptoms and lab values may improve at different speeds, early clearance of the SM mutation and full donor engraftment are strong signs of a successful transplant.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
