title: Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience.
abstract: BACKGROUND
  The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP).
  
  
  METHODS
  During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (<10% of normal value) acquired ADAMTS13 deficiency are reported here.
  
  
  RESULTS
  Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%.
  
  
  CONCLUSIONS
  Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies.
authors.affiliation: Service de Néphrologie, Dialyse et Transplantation, Service des Maladies du Sang, Hôpital d'Angers, and Inserm U892 UMR S892, Université d'Angers, Angers, France.
authors.forename: François
authors.initials: F
authors.lastname: Beloncle
authors.forename: Marc
authors.initials: M
authors.lastname: Buffet
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Coindre
authors.forename: Nicolas
authors.initials: N
authors.lastname: Munoz-Bongrand
authors.forename: Sandrine
authors.initials: S
authors.lastname: Malot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pène
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Baudel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Subra
authors.forename: Aline
authors.initials: A
authors.lastname: Tanguy-Schmidt
authors.forename: Jacques
authors.initials: J
authors.lastname: Pourrat
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D020551:Pulse Therapy, Drug; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000401:mortality*; D012042:Registries / Q000706:statistics & numerical data; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D012720:Severity of Illness Index; D013156:Splenectomy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide