4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Published online 7 July 2009
Haematologica, Vol 94, Issue 12, 1743-1747 doi:10.3324/haematol.2009.007815
Copyright © 2009 by Ferrata Storti Foundation
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Bone Marrow Failure

Changes in cytokine profile pre- and post-immunosuppression in acquired aplastic anemia

Carlo Dufour1, Elisa Ferretti2, Francesca Bagnasco3, Oriana Burlando1, Marina Lanciotti1, Ugo Ramenghi4, Paola Saracco4, Maria Teresa Van Lint5, Daniela Longoni6, Giovanni Fernando Torelli7, Marta Pillon8, Anna Locasciulli9, Aldo Misuraca10, Milena La Spina11, Andrea Bacigalupo5, Vito Pistoia2, Anna Corcione2,*, Johanna Svahn1,* on behalf of Marrow Failure Study Group of the AIEOP

1 Haematology Unit, G.Gaslini Children’s Hospital. Genoa
2 Oncology Laboratory, G.Gaslini Children’s Hospital, Genoa
3 Epidemiology and Biostatistics Unit, G.Gaslini Children’s Hospital, Genoa
4 Haematology Unit, Regina Margherita Hospital, Torino
5 Haematology Unit, San Martino Hospital, Genoa
6 Pediatric Clinic, University of Milan "La Bicocca", Monza
7 Haematology Unit, University "La Sapienza", Rome
8 Pediatric Onco-Haematology Clinic, University of Padua, Padua
9 Haematology Unit, San Camillo-Forlanini Hospital, Rome
10 Pediatric Hematology Unit, Pausillipon Hospital, Naples
11 Pediatric Onco-Haematology Clinic, University of Catania, Catania, Italy

Correspondence: Carlo Dufour, MD Haematology Unit, G. Gaslini Children’s Hospital, Largo G.Gaslini 5, 16147 Genoa, Italy., E-mail: carlodufour{at}ospedale-gaslini.ge.it

Cytokine expression assessed by flow cytometry in 53 acquired aplastic anemia patients before and after combined immunosuppression (EBMT WPSAA protocols) showed that CD3+ marrow cells containing TNF-{alpha}, IFN-{gamma} and IL4 were similar in subjects with disease at onset (DO) and responsive to treatment who had more CD3+/TNF-{alpha}+ and CD 3+/IFN-{gamma}+ cells than normal controls. In vitro block of TNF-{alpha} and/or IFN-{gamma} significantly increased BFU-e over baseline in 28 patients. In responsive to treatment patients only TNF-{alpha} block significantly incremented colonies over normal controls. Absolute marrow CD3+/TNF-{alpha}+ and CD3+/IFN-{gamma}+ cells prospectively tested in a group of 21 subjects declined significantly more in Responders than in Non Responders to immunosuppression at Response Evaluation Time respect to Diagnosis. Both in Responders and in Non Responders these cells remained higher than in normal controls. This study suggests that immunosuppression does not fully clear excess TNF-{alpha} and IFN-{gamma} from marrow of patients with good outcome and raises the hypothesis that additional cytokine blockade might be useful in immunosuppression for acquired aplastic anemia.

Key words: TNF-{alpha}, IFN-{gamma}, IL4, aplastic anemia, immunosuppression.