Bulky Splenomegaly Associated With Worse Outcomes in Patients With MF Undergoing Allo-HCT

New study findings indicate massive splenomegaly could have a profound impact on outcomes in patients with myelofibrosis (MF) who receive an allogenic hematopoietic cell transplantation (allo-HCT).

Appearing in the American Journal of Hematology, the retrospective analysis offers new insight into the use of splenectomy for these patients. It’s long been debated what role spleen size and splenectomy have on allo-HCT outcomes, as conflicting research on the impact on survival and relapse rates has been published.

“The presence of huge splenomegaly in MF candidates prior to allo-HCT is a frequent cause of concern for transplant physicians,” researchers explained. “Fear of delayed hematological recovery with potential increase in non-relapse mortality (NRM) leads a number of transplant physicians to consider splenectomy as a fundamental step prior to allo-HCT.”

The findings from the new analysis support the use of splenectomy for patients with progressive disease and large splenomegaly, with results indicating bulky splenomegaly is associated with a delay in hematologic recovery, higher rates of NRM, and lower survival.

The analysis included nearly 1200 patients with MF who received an allo-HCT between 2000 and 2017. Over the course of the study period a total of 202 splenectomies were performed.

Having an increasing spleen size at the time of allo-HCT was significantly associated with worse overall survival (P = .034). Splenectomy was associated with a 36% drop in NRM, which, according to the researchers, occurred even with a greater proportion of these patients having a higher HCT-comorbidity index and lower Karnofsky Performance Status (KPS) scores—2 indicators of poor prognosis for allo-HCT outcomes.

Patients who underwent transplant with less bulky splenomegaly experienced faster engraftment, with a 28-day cumulative incidence of neutrophil recovery of 87% in patients with spleen <5 cm, compared with 81% and 82% for patients with larger splenomegaly. The 100-day cumulative incidence of platelet recovery also decreased with increasing spleen size, dropping from 85% to 79% to 66%.

However, the researchers found that splenectomy did increase the risk of relapse by 43% and appeared to have no benefit on overall survival (hazard ratio = 0.86).

Of note, the researchers observed a decrease in the use of splenectomy over time, with the rate of splenectomy dropping by half in 2017 (28.3% from 2000 to 2009 vs 14.1% from 2010 to 2017). According to the researchers, this could potentially be due to the emergence of novel therapies. For example, the rate dropped further after 2012 when ruxolitinib (RUX) was widely available.

Throughout the study, the researchers also determined the impact of RUX treatment prior to transplant.

“As documented in the non-transplant setting for RUX responding patients, patients achieving spleen length < 5 cm had an improved transplant outcome, with a borderline, although not-statistically significant, survival benefit in RUX-treated patients,” the researchers wrote.

“The potential positive impact of JAK-inhibition on splenomegaly and disease-related symptoms may well have led to improvement of performance status and linked with this observation.”

Reference: Polverelli N, Mauff K, Kröger N, et al. Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT). Am J Hematol. Published online October 16, 2020. doi:10.1002/ajh.26020