Post-Transplant Thrombotic Thrombocytopenic Purpura (TTP), a Complication of High Risk Myeloablative and Non-Myeloablative Transplantation, Is Not Associated with von Willebrand Factor-Cleaving Protease (vWF-CP) Deficiency.

Ref ID: 2838

Author: Michelle A. Elliott, William L. Nichols, Elizabeth A. Plumhoff, Stephen M. Ansell, Angela Dispenzieri, Dennis A. Gastineau, Morie A. Gertz, David J. Inwards, Martha Q. Lacy, Ivana N. Micallef, Ayelew Tefferi, Mark R. Litzow.

Author address:

Hematology, Mayo Clinic, Rochester, MN

Full conference title:

43rd American Society of Hematology (ASH) Annual Meeting

Abstract:

TTP has been increasingly recognized as a complication of bone marrow transplantation (Tx). Deficiency of vWF-CP has been causally linked to classic TTP. The etiology post-Tx remains poorly defined, but may be due to diffuse endothelial damage. Methods: We reviewed our recent Tx experience during the period of 3/1/99 to 6/30/01 in which vWF-CP assay was available. Results: Ten cases of post-Tx TTP were diagnosed (dx) and all but one (conditioned with Homium/melphalan (H/M) elsewhere), underwent Tx at our institution, where the incidence of TTP following allogeneic and autologous Tx was 6.8 % (8/118) and 0.25% (1/400), respectively. Among allogeneic Tx, the incidence of TTP post non-myeloablative (NMA), matched unrelated and sibling Tx was 15.4% (2/13), 11.8% (2/17) and 4.5% (4/88), respectively. In the latter group, TTP occurred in 4/25 (16%) bone marrow versus 0/76 peripheral blood stem cell sibling Tx. Median (med) age of the 10 at dx of TTP was 39.5 yrs (range: 14-61). Indications for Tx were refractory NHL (n=4), high risk MDS or secondary AML (n=4), refractory CLL (n=1) and MM (n=1). 90% had received extensive prior therapy (Rx), including a prior autologous Tx in both NMA Tx recipients. Conditioning Rx included CY/TBI (n=5), H/M (1), CTX/VP16/thiotepa (1), BEAC (1), Ara-F/M and 2-CDA/thiotepa for NMA Tx (2, respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate in most. TTP was dx at a med. of 44 days (range 6-240) post-Tx. All met the dx criteria of thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on blood film, decreased haptoglobins) without DIC and LDH above normal. Mental status changes (MS) occurred in 80%. At dx (med. and range): Hb 9.4 g/dl (7-12.12.1), platelets: 18 x10 9/L (8-76), creatinine: 1.6 mg/dl (0.7-5.9) and LDH: 648 u/L (276-2817). Med. vWF antigen was 290 % (108-565). vWF multimeric analysis revealed unusually large forms in three and was normal in the others. vWF- CP activity was normal in all. During active TTP, 7 had grade II-IV acute GVHD and 4 developed CMV viremia. 90% received corticosteroids, for TTP, GVHD, or prior diffuse alveolar hemorrhage. Plasma exchange (PE) was performed in all (med. 7 PE, range: 3-30). Improvement in MS, LDH and haptoglobins, was complete (n=1), partial (n=8) and absent (n=1), and PE was often held when a plateau was achieved. Platelet count was not a reliable indicator of response, as bone marrow hypocellularity (5-10%) was seen in 5/5 studied during active TTP. 5 patients died at a med. of 29 days post TTP dx, 3 with active TTP at the time of death due to intracranial hemorrhage (1), aspergillosis (1) and CMV pneumonitis (1). Two died of septic omplications of GVHD, without evidence of TTP. 5 patients remain alive at a med. of 219 days (61-689) post TTP dx. All are in remission from underlying disease and TTP. Two are on hemodialysis and two have extensive GVHD. Conclusion: Post-Tx TTP is not due to vWF-CP deficiency. The finding of increased vWF in these patients is consistent with diffuse endothelial injury, likely due to multiple interacting factors including extensive prior Rx, CSA, GVHD and CMV reactivation, any or all of which could account for the thrombotic microangiopathy. NMA-Tx did not appear to confer a lesser risk, possibly on the basis of GVHD and/or extensive prior Rx.

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Conference Year: 2001

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