Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood
Ayami Yoshimi,
Marry M. van den Heuvel-Eibrink,
Irith Baumann,
Stephan Schwarz,
Ingrid Simonitsch-Klupp,
Pascale de Paepe,
Vit Campr,
Gitte Birk Kerndrup,
Maureen O’Sullivan,
Rita Devito,
Roos Leguit,
Miguel Hernandez,
Michael Dworzak,
Barbara de Moerloose,
Jan Starý,
Henrik Hasle,
Owen P. Smith,
Marco Zecca,
Albert Catala,
Markus Schmugge,
Franco Locatelli,
Monika Führer,
Alexandra Fischer,
Anne Guderle,
Peter Nöllke,
Brigitte Strahm,
Charlotte M. Niemeyer
Affiliations
Ayami Yoshimi
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
Marry M. van den Heuvel-Eibrink
Sophia Children’s Hospital, Erasmus Medical Centre, Rotterdam, and Dutch Childhood Oncology Group, the Hague, the Netherlands
Irith Baumann
Department of Pathology, Boeblingen Hospital, Clinical Centre South West, Boeblingen, Germany
Stephan Schwarz
Department of Pathology, University Medical Center Erlangen, Germany
Ingrid Simonitsch-Klupp
Clinical Institute of Pathology, Medical University of Vienna, Austria
Pascale de Paepe
Department of Pathology, University Hospital Ghent, Belgium
Vit Campr
Department of Pathology, University Hospital in Motol, Prague, Czech Republic
Gitte Birk Kerndrup
Department of Pathology, Vejle Hospital, Denmark
Maureen O’Sullivan
Histology Laboratory, Our Lady’s Hospital for Sick Children, Dublin, Ireland
Rita Devito
Department of Pathology, Bambino Gesù Children’s Hospital, Rome, Italy
Roos Leguit
Department of Pathology, University Medical Centre Utrecht, and Dutch Childhood Oncology Group, the Hague, the Netherlands
Miguel Hernandez
Department of Pathology, Hospital Universitario La Fe, Valencia, Spain
Michael Dworzak
St. Anna Children’s Hospital and Children’s Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Austria
Barbara de Moerloose
Department of Pediatric Hemato-Oncology, Ghent University Hospital, Belgium
Jan Starý
Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Pediatric Hematology Working Group, Czech Republic
Henrik Hasle
Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
Owen P. Smith
Paediatric Oncology and Haematology, Our Lady’s Hospital for Sick Children Crumlin, Dublin, Ireland
Marco Zecca
Pediatric Hematology-Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Albert Catala
Department of Hematology, Hospital Sant Joan de Déu, Barcelona, Spain
Markus Schmugge
Department of Hematology and Oncology, University Children’s Hospital, Zurich, Switzerland
Franco Locatelli
Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, Rome, University of Pavia, Italy
Monika Führer
Dr von Haunersches Kinderspital, Children Hospital of the Ludwig-Maximilians-University of Munich, Germany on behalf of the European Working Group of MDS in Childhood
Alexandra Fischer
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
Anne Guderle
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
Peter Nöllke
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
Brigitte Strahm
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
Charlotte M. Niemeyer
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090)
