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 des cribed a simple clinical grading system (grade 0-4) for BMT-TM; patien ts with grade 3-4 BMT-TM do poorly. A previous study in our institutio n suggested that a combination of exchange with cryosupernatant replac ement and protein-ii immunoadsorption (PAI) might be of benefit. There fore we performed a pilot study to evaluate the effectiveness of cryos upernatant 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 a llogeneic-BMT a median of 25 days (range of 5-458 days) prior to the o nset of grade 3-4 BMT-TM. The thirteenth patient had undergone autolog ous peripheral stem cell transplant 11 days prior to grade 4 BMT-TM. P re-therapy, 10 patients had grade 4 BMT-TM and three had grade 3. Eigh t (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 respon ders have died at 21, 44, and 226 days following the development of BM T-TM of interstitial pneumonia in one, aspergillus in one, and multior gan failure syndrome (MOFS) in one. The remaining responders are alive 65-465 days post-TM. All non-responders died of MOFS at 6-31 days pos t-TM. These results suggest that combined exchange with cryosupernatan t alternating with PAI is effective therapy for some patients with mod erate to severe BMT-TM and may improve survival.