Tuğrul ELVERDİ, Seniz ÖNGÖREN, zafer BAŞLAR, Yıldız AYDIN, Muhlis Cem AR, Ayşe SALİHOĞLU, Sevil SADRİ, Tuğçe APAYDIN, Teoman SOYSAL, Ahmet Emre EŞKAZAN

Vincristine as an Adjunct to Therapeutic Plasma Exchange for Thrombotic Thrombocytopenic Purpura: A Single-Institution Experience

Background: Thrombotic thrombocytopenic purpura is a potentiallylife-threatening condition. Although the introduction of therapeuticplasma exchange has reduced mortality rates from over 90% to 10%-20%, approximately 40% of patients relapse, and outcomes maybe fatal in refractory patients. There is clearly a need for additionaltherapeutic approaches.Aims: To describe the outcomes of relapsed/refractory thromboticthrombocytopenic purpura patients treated with vincristine as anadjunct to therapeutic plasma exchange.Study Design: Cross-sectional study.Methods: The medical records of all relapsed/refractory patients withthrombotic thrombocytopenic purpura treated with vincristine adjunctto therapeutic plasma exchange between October 2000 and December2016 were retrospectively reviewed. Diagnosis of thromboticthrombocytopenic purpura was based on clinical history, physicalexamination, and laboratory examinations. Patient demographics,laboratory findings, initial date and duration of therapeutic plasmaexchange, dosage and time of administration of vincristine, andoutcomes were recorded.Results: The study included 15 patients [median age: 37 years (range:26-65); 7 women and 8 men] with either relapsed or refractorythrombotic thrombocytopenic purpura who were treated withvincristine as an adjunct to therapeutic plasma exchange for a total of22 episodes. Eighty-seven percent of patients achieved remissions in20 of 22 episodes, with a median duration of remission of 29.5 months(range: 3-105). After a median follow-up of 55 months, 11 patientswere alive. Vincristine was well tolerated with no safety concerns.Conclusion: Vincristine offers a reasonable option for the treatmentof patients with relapsed/refractory thrombotic thrombocytopenicpurpura. Further studies evaluating vincristine in the front-line settingand in the relapsed/refractory setting are needed to validate the role ofvincristine in thrombotic thrombocytopenic purpura patients.

PDF

___

1. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood 2015;125:3860-7.
2. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol 2014;164:759-66.
3. Coppo P, Veyradier A. Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura. Presse Med 2012;41:163-76.
4. Rock G, Porta C, Bobbio-Pallavicini E. Thrombotic thrombocytopenic purpura treatment in year 2000. Haematologica 2000;85:410-9.
5. Frankel AE, Rubenstein MD, Wall RT. Thrombotic thrombocytopenic purpura: prolonged coma with recovery of neurologic function with intensive plasma exchange. Am J Hematol 1981;10:387-90.
6. Gutterman LA, Stevenson TD. Treatment of thrombotic thrombocytopenic purpura with vincristine. JAMA 1982;247:1433-6.
7. Schreeder MT, Prchal JT. Successful treatment of thrombotic thrombocytopenia purpura by vincristine. Am J Hematol 1983;14:75-8.
8. Sennett ML, Conrad ME. Treatment of thrombotic thrombocytopenic purpura. Plasmapheresis, plasma transfusion, and vincristine. Arch Intern Med 1986;146:266- 7.
9. Blitzer JB, Granfortuna JM, Gottlieb AJ, Smith JR, Theodorakis ME, Zamkoff KW, et al. Thrombotic thrombocytopenic purpura: treatment with plasmapheresis. Am J Hematol 1987;24:329-39.
10. Welborn JL, Emrick P, Acevedo M. Rapid improvement of thrombotic thrombocytopenic purpura with vincristine and plasmapheresis. Am J Hematol 1990;35:18-21.
11. Levin M, Grunwald HW. Use of vincristine in refractory thrombotic thrombocytopenic purpura. Acta Haematol 1991;85:37-40.
12. Dervenoulas J, Karakassis D, Belia M, Pappa V, Economopoulos T, Papageorgiou E, et al. Thrombotic thrombocytopenic purpura: a multimodality model of treatment including plasma exchange, i.v. immunoglobulin, prednisone, antiplatelet agents, vincristine and splenectomy. Infusionsther Transfusionsmed 1992;19:294-6.
13. O'Connor NT, Bruce-Jones P, Hill LF. Vincristine therapy for thrombotic thrombocytopenic purpura. Am J Hematol 1992;39:234-6.
14. Okamoto M, Abe T, Shouno M, Kitabata Y, Narukawa N, Kobata H, et al. A case of thrombotic thrombocytopenic purpura refractory to plasma exchange. Ther Apher 2001;5:49-53.
15. Ferrara F, Annunziata M, Pollio F, Palmieri S, Copia C, Mele G, et al. Vincristine as treatment for recurrent episodes of thrombotic thrombocytopenic purpura. Ann Hematol 2002;81:7-10.
16. Van Gool S, Brock P, Van Laer P, Van Damme-Lombaerts R, Proesmans W, Casteels- Van Daele M. Successful treatment of recurrent thrombotic thrombocytopenic purpura with plasmapheresis and vincristine. Eur J Pediatr 1994;153:517-9.
17. Schulz A, Sitzler G, Scheid C, Deutsch HJ, Chemnitz J, Abelius R, et al. A case of thrombotic thrombocytopenic purpura in an adult treated with vincristine. Ann Hematol 1999;78:39-42.
18. Bobbio-Pallavicini E, Porta C, Centurioni R, Gugliotta L, Vianelli N, Tacconi F, et al. Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma-exchange. The Italian Cooperative Group for TTP. Eur J Haematol 1994;52:222-6.
19. Vesely SK, George JN, Lammle B, Studt JD, Alberio L, El-Harake MA, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003;102:60-8.
20. Wolf G, Thaiss F, Dhrsen U, Weh HJ, Hossfeld DK, Stahl RA. [Treatment of thrombotic thrombocytopenic purpura (Moschcowitz's disease) with vincristine]. Dtsch Med Wochenschr 1995;120:442-6.
21. Walia SS, Walia MS, Walia HS. Thrombotic thrombocytopenic purpura treated with vincristine in a Jehovah's witness. Asian J Transfus Sci 2011;5:180-1.
22. Dabak V, Kuriakose P, Raman S. Successful management of a Jehovah's Witness with thrombotic thrombocytopenic purpura unwilling to be treated with therapeutic plasma exchange. J Clin Apher 2007;22:330-2.
23. Chai W, Chaudhry A, Rabinowitz AP. Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange. J Clin Apher 2015;30:46-9.
24. Mazzei C, Pepkowitz S, Klapper E, Goldfinger D. Treatment of thrombotic thrombocytopenic purpura: a role for early vincristine administration. J Clin Apher 1998;13:20-2.
25. Ziman A, Mitri M, Klapper E, Pepkowitz SH, Goldfinger D. Combination vincristine and plasma exchange as initial therapy in patients with thrombotic thrombocytopenic purpura: one institution's experience and review of the literature. Transfusion 2005;45:41-9.
26. Yang CW, Chen YC, Dunn P, Chang MY, Fang JT, Huang CC. Thrombotic thrombocytopenic purpura (TTP): initial treatment with plasma exchange plus steroids and immunosuppressive agents for relapsing cases. Ren Fail 2003;25:21-30.
27. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010;116:4060-9.