title: Mycophenolate mofetil and Sirolimus as second or further line treatment in children with chronic refractory Primitive or Secondary Autoimmune Cytopenias: a single centre experience.
abstract: The management of refractory autoimmune cytopenias in childhood is challenging due to the lack of established evidence on escalating treatments. The long-term efficacy of immunosuppressive drugs was evaluated in children with refractory autoimmune cytopenias referred to the Haematology Unit of the Gaslini Children's Hospital between 2001 and 2014. Patients were grouped into three categories: autoimmune lymphoproliferative syndrome (ALPS), ALPS-related syndrome (at least one absolute/primary additional criterion for ALPS) and primary autoimmune cytopenia (PAC, cytopenia with no other immunological symptoms/signs). Fifty-eight children (aged 1-16 years) entered the study: 12 were categorized with ALPS, 24 were ALPS-related and 22 had PAC. Five didn't receive treatment. Fifty-three were initially treated with steroids/intravenous immunoglobulin. Fourteen responded, whereas 39 did not. Of these 39 patients, 34 (87%) received mycophenolate mofetil (MMF) as second/further-line treatment and 22 (65%) responded. Within these 34 subjects, ALPS patients responded better (11/11, 100%) than the two other groups pooled together (11/23, 48%; P = 0·002). Sirolimus was given as second/further-line treatment to 16 children, and 12 (75%) responded, including 8 who previously failed MMF therapy. Median follow-up was 3·46 years. MMF and Sirolimus were well-tolerated and enabled partial/complete and sustained remission in most children. These drugs may be successfully and safely used in children with refractory autoimmune cytopenias with or without ALPS/ALPS-related disorders and may represent a valid second/further line option.
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Miano
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Scalzone
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Perri
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Palmisani
authors.affiliation: Infectious Disease Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Caviglia
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Micalizzi
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Johanna
authors.initials: J
authors.lastname: Svahn
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Michaela
authors.initials: M
authors.lastname: Calvillo
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Banov
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Terranova
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lanza
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Clinical and Experimental Haematology Unit, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fioredda
keywords: autoimmune cytopenia; children; immunosuppressive therapy; mycophenolate mofetil; sirolimus