Apheresis in grade 4 bone marrow transplant associated thrombotic microangiopathy: a case series

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limited to a fatal disorder. There has been no specific therapy for this condition. We have previously described a clinical grading system for BMT-TM, based upon lactate dehydrogenase level (LDH) and percentage fragmented cells (FC) as follows: grade 0, normal or increases LDH and % FC < or = to 1.2%; grade 1, normal LDH and FC > or = to 1.3%; grade 2, increases LDH and FC = 1.3-4.8%; grade 3, increases LDH and FC = 4.9-9.6%; and grade 4, increases LDH and FC > or = to 9.7%. Patients with grade 4 BMT-TM usually have fulminant disease and generally succumb. This study summarizes results using a variety of apheresis procedures in a series of 16 patients with grade 4 BMT-TM. The apheresis procedures consisted of plasma exchange (with replacement with fresh frozen plasma or cryo-poor plasma), and protein A immunoadsorption (PAI). The PAI exchanges were not done concurrently with plasma exchange procedures. Fifteen patients had undergone an allogeneic BMT and the 16th patient had undergone an autologous peripheral blood stem cell transplant. Half showed hematologic improvement with a downstaging of their TM to grades 1-3. All non-responders died a median of 11 days following the onset of grade 4 BMT-TM. The median survival in the responders was significantly (P = 0.001) increased to 218 days with three responders surviving more than 400 days following the onset of this severe complication. These results suggest a role for apheresis in the treatment of this lethal complication. Nevertheless grade 4 BMT-TM represents a major complication of BMT; the median survival in this group of 16 patients with grade 4 BMT-TM was only 31 days.