Flore Sicre de Fontbrune1, Claire Galambrun, Anne Sirvent, Anne Huynh, Stanislas Faguer, Stephanie Nguyen, Jacques-Olivier Bay, Bénédicte Neven, Julie Moussi, Laurence Simon, Alienor Xhaard, Matthieu Resche-Riggon, Alix O'Meara, Veronique Fremeaux-Bacchi, Agnes Veyradier, Gérard Socié, Paul Coppo, Régis Peffaut de Latour. 1. 1 Hématologie Greffe de Moelle, Hôpital Saint Louis, APHP, Université Paris Diderot, Paris, France. 2 Service d'Hématologie Pédiatrique, Hôpital de la Timone, Marseille, France. 3 Service d'Onco-hematologie Pédiatrique, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. 4 Service d'Hématologie, CHU de Purpan, Toulouse, France. 5 Département de Néphrologie et Transplantation d'organe, CHU de Rangueil, Toulouse, France. 6 Service d'Hématologie, Hôpital de la Pitié Salpetrière, APHP, Université Pierre et Marie Curie, Paris. 7 Service de Thérapie Cellulaire et d'Hématologie Clinique, Hôpital d'Estaing, CHU Clermont Ferrand, Université d'Auvergne, Clermont-Ferrand, France. 8 Service d'Immuno-hématologie et Rhumatologie pédiatrique, Hôpital Necker-Enfants Malades, Laboratoire INSERM U768, Institut Imagine, Université Sorbonne Paris-cité, Paris, France. 9 Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, APHM, Université d'Aix Marseille, Marseille, France. 10 Service d'Hématologie, Hôpital Hautepierre, Hôpitaux Universitaire de Strasbourg, Strasbourg, France. 11 Département de Biostatistiques, Hôpital Saint Louis, APHP, Université Paris Diderot, Paris, France. 12 Service d'Immunologie Biologique, Hôpital Européen George Pompidou, APHP, CHU Paris Ouest, Paris, France. 13 Service d'Hématologie Biologique, Hôpital Antoine Beclère, APHP, Université Paris Sud, Clamart, France. 14 Service d'Hématologie, Centre de Référence des Microangiopathies Thrombotiques, Hôpitaux Universitaires de l'Est Parisien, APHP, Université Pierre et Marie Curie, Paris, France.
Abstract
BACKGROUND: Thrombotic microangiopathy (TMA) occurring after allogeneic hematopoietic stem cell transplantation (HSCT) has a devastating prognosis. Response rates to current therapies (mainly plasma exchange) are unsatisfactory. Thrombotic microangiopathy after allogeneic HSCT shares similarities with atypical hemolytic uremic syndrome (aHUS) in the underlying pathomechanisms. Eculizumab has been associated with impressive results in aHUS. MATERIALS AND METHODS: We retrospectively analyzed 12 patients who received Eculizumab in France between 2010 and 2013 for severe post-HSCT TMA. RESULTS: All 12 patients had severe TMA with neurological and/or renal involvement. Fifty-eight percent were refractory to first-line plasma exchange. At the time of TMA diagnosis, infections were present in 50% of the patients and acute graft-versus-host disease in 33%. Patients were treated with Eculizumab according to the aHUS therapeutic scheme. With a median follow-up of 14 months, hematological response and overall survival were 50% and 33%, respectively. Active acute graft-versus-host disease at TMA diagnosis was the only factor associated with worse overall survival (P = 0.009). DISCUSSION: Response rate and overall survival after Eculizumab in our cohort compare favorably with previously published data in TMA after allogeneic HSCT. Prospective trials are warranted to confirm these results. Early initiation of Eculizumab may have a favorable effect on long-term renal function and further contribute to the prolongation of survival.
BACKGROUND:Thrombotic microangiopathy (TMA) occurring after allogeneic hematopoietic stem cell transplantation (HSCT) has a devastating prognosis. Response rates to current therapies (mainly plasma exchange) are unsatisfactory. Thrombotic microangiopathy after allogeneic HSCT shares similarities with atypical hemolytic uremic syndrome (aHUS) in the underlying pathomechanisms. Eculizumab has been associated with impressive results in aHUS. MATERIALS AND METHODS: We retrospectively analyzed 12 patients who received Eculizumab in France between 2010 and 2013 for severe post-HSCT TMA. RESULTS: All 12 patients had severe TMA with neurological and/or renal involvement. Fifty-eight percent were refractory to first-line plasma exchange. At the time of TMA diagnosis, infections were present in 50% of the patients and acute graft-versus-host disease in 33%. Patients were treated with Eculizumab according to the aHUS therapeutic scheme. With a median follow-up of 14 months, hematological response and overall survival were 50% and 33%, respectively. Active acute graft-versus-host disease at TMA diagnosis was the only factor associated with worse overall survival (P = 0.009). DISCUSSION: Response rate and overall survival after Eculizumab in our cohort compare favorably with previously published data in TMA after allogeneic HSCT. Prospective trials are warranted to confirm these results. Early initiation of Eculizumab may have a favorable effect on long-term renal function and further contribute to the prolongation of survival.
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