Study Examines Treatment Link to Transplant Complication in GVHD

For the first time, a study has shown that ruxolitinib is associated with transplant-associated thrombotic microangiopathy (TA-TMA) in patients with graft-vs-host-disease (GVHD) after receiving an allogeneic hematopoietic cell transplant.

Based on the association seen in their study, the researchers highlight the need for further studies to confirm this finding, as ruxolitinib is increasingly being used in patients with GVHD.

“A significant portion of ruxolitinib-treated patients with myelofibrosis or GVHD are expected to present with thrombocytopenia due to underlying diseases, as well as poikilocytosis in peripheral blood smear,” wrote the researchers. “In such patients, TMA might not be suspected by physicians, although its suspicion basically relies on the peripheral blood smear, an easily accessible tool for hematologists. Therefore, the finding of the present study is significant and useful for treating physicians.”

Among the 160 patients included in the study, 18 experienced TA-TMA. Analyses of these patients showed that TA-TMA was associated only with ruxolitinib treatment and severe GVHD. Patients receiving the JAK2 inhibitor were significantly more likely than patients not receiving the treatment to develop TA-TMA (37% vs 8%).

Notably, there was no correlation between ruxolitinib treatment and severe GVHD.

In patients with TA-TMA, management included steroids, cyclosporine inhibitor cessation, plasma infusions, and plasma exchange. Management strategies also included complement inhibition with eculizumab, which was associated with a significantly higher Endothelial Activation and Stress Index (EASIX) and soluble C5b-9 levels.

“In terms of TA-TMA management, our study is in line with previous reports in adult TA-TMA suggesting that OS remains low (approximately 30%) despite effectiveness of eculizumab,” explained the researchers. “Several issues remain to be further investigated: timing of initiation, proper patient selection, dosing, and duration of therapy in transplanted patients. In terms of timing of initiation and patient selection, our study confirms previous findings suggesting that EASIX might be used as a prognostic marker in patients with endothelial dysfunction syndrome.”

Surviving patients were followed for a median of 38.4 months, with a 5-year overall survival of 52.9%, which was unfavorably predicted by TA-TMA, severe acute GVHD, and lower number of infused CD34+ cells.

Reference

Gavriilaki E, Sakellari I, Chatzikonstantinou T, et al. Predictors of transplant-associated thrombotic microangiopathy in patients with overlap or chronic graft-vs-host-disease. Transplant Proc. Published online August 18, 2021. doi:10.1016/j.transproceed.2021.07.043