Pilot study of combined cryosupernatant and protein A immunoadsorption exchange in the treatment of grade 3-4 bone marrow transplant-associated thrombotic microangiopathy.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limiting to a fatal disorder. There is no specific therapy for this condition to date. We have previously described a simple clinical grading system (grade 0-4) for BMT-TM; patients with grade 3-4 BMT-TM do poorly. A previous study in our institution suggested that a combination of exchange with cryosupernatant replacement and protein-A immunoadsorption (PAI) might be of benefit. Therefore we performed a pilot study to evaluate the effectiveness of cryosupernatant alternating with PAI exchange for 2 weeks in a series of 13 patients with grade 3-4 BMT-TM. Twelve of 13 patients had undergone allogeneic-BMT a median of 25 days (range of 5-458 days) prior to the onset of grade 3-4 BMT-TM. The thirteenth patient had undergone autologous peripheral stem cell transplant 11 days prior to grade 4 BMT-TM. Pre-therapy, 10 patients had grade 4 BMT-TM and three had grade 3. Eight (62%) showed a response to treatment. Post-therapy, four responders had grade 3, three had grade 2 and one had grade 0 BMT-TM. The median follow-up of the responders is 90 days (range 21 to 464). Three responders have died at 21, 44, and 226 days following the development of BMT-TM of interstitial pneumonia in one, aspergillus in one, and multiorgan failure syndrome (MOFS) in one. The remaining responders are alive 66-465 days post-TM. All non-responders died of MOFS at 6-31 days post-TM. These results suggest that combined exchange with cryosupernatant alternating with PAI is effective therapy for some patients with moderate to severe BMT-TM and may improve survival.