Questionable efficacy of plasma exchange for thrombotic thrombocytopenic purpura after bone marrow transplantation

Teruya, Jun; Styler, Michael; Verde, S. Fidalgo; Topolsky, David; Crilley, Pamela

doi:10.1002/jca.10008

Cited by 29 publications

(22 citation statements)

References 5 publications

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“…Reported response rates vary between 0–49%,138,139 compared with 78–91% in patients with idiopathic TTP 45,140. Further, rise in platelet count, the usual marker for response to plasma exchange, cannot be relied upon in TA-TMA because platelet engraftment may not yet have occurred.…”

Section: Therapeutic Modalitiesmentioning

confidence: 99%

See 1 more Smart Citation

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

Stavrou

Lazarus

2010

Mediterr J Hematol Infect Dis

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Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

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Section: Therapeutic Modalitiesmentioning

confidence: 99%

“…By analogy, there are case series of use of these agents in the setting of TA-TMA. Results were disappointing and difficult to interpret since all of the patients received concurrent therapy with plasma exchange 128,139,189…”

Section: Therapeutic Modalitiesmentioning

confidence: 99%

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

Stavrou

Lazarus

2010

Mediterr J Hematol Infect Dis

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“…The high response rate of TAM (9/13 patients) after withdrawal of calcineurin inhibitors and treatment with daclizumab demonstrates the efficacy of the approach with regard to control of TAM, which was superior compared to results reported using plasmapheresis. 1,15,20,29,42 However, only five of 13 patients achieved complete remission of GVHD, indicating that substitution of the calcineurin inhibitor by daclizumab alone is not sufficient treatment for GVHD in a significant proportion of patients who require additional treatment. This is even more important taking into account that long-term survival was observed only in patients achieving complete remission of both TAM and GVHD (4/13).…”

Section: Discussionmentioning

confidence: 99%

“…1,[22][23][24][25][26] Although plasma exchange is the treatment of choice in classical TTP, reports on the efficacy of plasma exchange in TAM suggest at best limited activity in selected patients, whereas the majority does not respond. 1,20,[27][28][29] The most likely explanation is that the vWF-cleaving protease is not involved in TAM. 2 As calcineurin inhibitors are part of the pathogenesis of TAM and are associated with RI, withdrawal may be desirable.…”

Section: Introductionmentioning

confidence: 99%

Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease

Wolff

Wilhelm

Hahn

et al. 2006

Bone Marrow Transplant

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Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week, discontinuation of the CI and continuation of the remaining GVHD treatment. All patients had acute GVHD (steroid-sensitive (n ¼ 4), steroid-refractory (n ¼ 10)) or chronic GVHD (n ¼ 4) and were treated with CI before the start of daclizumab. Nine of 13 patients with TAM treated with daclizumab and discontinuation of CI achieved complete remission of TAM, two had stable disease, and one patient did not respond. Patients receiving daclizumab for RI without TAM showed stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients with acute GVHD achieved CR, two partial remission, eight patients did not respond and 11/14 died at a median of 39 days after start of the daclizumab. Our data demonstrate that replacement of CI by daclizumab can improve TAM and RI. However, mortality remains high in patients with acute GVHD.

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“…In contrast, many patients with other serious medical problems such as complications of bone marrow transplantation, human immunodeficiency virus infection, or disseminated malignancy may present similar clinical manifestations as TTP. Most of these patients however have normal ADAMTS13 function and do not typically respond to PE therapy [38][39][40][41]. An adequate measurement of ADAMTS13 activity will help clinicians correctly recognize these complicated clinical conditions, prevent wasting of valuable blood components, and avoid unnecessary complications related to PE therapy and catheter placement [42].…”

mentioning

confidence: 99%

Application of SELDI‐TOF mass spectrometry in clinical evaluation of thrombotic thrombocytopenic purpura

Cataland²,

Bissell³

et al. 2006

Journal of Spectroscopy

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Abstract. Surface Enhanced Laser Desorption/Ionization Time Of Flight (SELDI-TOF) mass spectrometry is characterized by integration of mass spectrometry with surface chemistry, which gives rise to rapid purification and subsequent determination of protein/peptide analytes. There are several surface matrices, named proteinChips, available for analyzing a particular analyte or a subset of biomolecules in biological samples. Each proteinChip has a unique surface property suitable for fractionation of a specific group of molecules. This article demonstrates the application of SELDI-TOF for the analysis of a cleaved peptide (Mr 7739 daltons) from von Willebrand Factor by a metalloproteinase, ADAMTS13. Deficiency of ADAMTS13 is a known primary risk factor for the devastating hematological disorder, Thrombotic thrombocytopenic purpura (TTP). Rapid determination of ADAMTS13 activity helps clinicians tremendously in making the correct diagnosis and initiating timely therapy. Most patients with TTP are acquired cases who exhibit a production of autoimmune antibodies against ADAMTS13 protease. TTP's clinical course is critically controlled by the autoantibody's ability to inhibit ADAMTS13 function. Thus, a second SELDI-TOF based test has been devised to measure ADAMTS13 autoantibody activity for the evaluation of TTP disease activity. In conclusion, the unique features of SELDI-TOF which allow for the examination of the role of key proteases in disease processes have opened up new doors for the clinical application of mass spectrometer based techniques.Keywords: SELDI-TOF, mass spectrometry, thrombotic thrombocytopenic purpura, diagnosis, immobilized metal affinity capture (IMAC) Mass spectrometer as a clinical diagnostic modalityA mass spectrometer is a spectroscopic device used to identify molecules according to mass and charge. Usually, the analytes are ionized and then separated and detected by their mass-to-charge (m/z) ratios in a magnetic field. There are two broad applications of mass spectrometer based technologies. One area involves biomarker discovery, identification of new drug targets, or amino acid sequence analyses to determine protein identities or structures. This application is currently mostly research oriented, and requires substantial support in resources and personnel expertise. The second area is related to direct identification and measurement of specific compounds in a sample. This latter application is straightforward measurement of analytes, which is similar to many existing methods used in clinical laboratories. Mass spectrometry has been used considerably in the diagnostic industry in recent decades [1][2][3][4][5].Early uses of mass spectrometry in clinical laboratories were limited to the measurement of smaller molecules (M r < 1000 daltons) such as analysis of organic acids in urine for a prenatal screen of inborn errors of metabolism. Because of the complexity of sample preparation and the expertise required for interpretation of the results, these tests were primarily performed in speciali...

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Questionable efficacy of plasma exchange for thrombotic thrombocytopenic purpura after bone marrow transplantation

Cited by 29 publications

References 5 publications

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease

Application of SELDI‐TOF mass spectrometry in clinical evaluation of thrombotic thrombocytopenic purpura

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