Patients were defined as ALPS definitive and probable according to the criteria established by the NIH in 2009.2 (link) (Table 1 ) Demographic data, clinical findings, biochemical markers (vitamin B12, interleukin 10 and interleukin 18, sFASL, immunoglobulins serum level, lymphocyte subsets analysis including CD3+CD4-CD8- TCR alfabeta+, named DNT cells), autoimmune markers (antiplatelet and antineutrophil indirect antibodies, direct and indirect Coombs test, antinuclear antibodies [ANA], extractable nuclear antigen antibodies, antismooth muscle antibody [ASMA], anti double-stranded DNA [anti-dsDNA] antibodies, antiglyadin, antitransglutaminase, antiendomysium, and antithyroglobulin antibodies) were entered into an electronic national ALPS database (ALPS Italian Network) (Tables 4 and 5 ).
All the information were retrieved from the medical records of patients after informed consent according to the Helsinki declaration of principles. Patients were referred at the ALPS Italian network through the AIEOP (Italian Pediatric Hemato-Oncology Association) centers.
Response to therapy was evaluated after at least 4–6 weeks of drug administration for each of the following clinical symptoms: cytopenia, lymphoproliferation, fever, or other autoimmune symptoms and scored as complete (CR), partial (PR), or nonresponse (NR) (See for further detail the footnotes of Table6 ). In keeping with the response criteria from our previous publication,19 (link) a patient was considered as complete responder if all the aforementioned clinical symptoms disappeared/normalized 4–6 weeks after treatment start. A patient was considered as partial responder if at least one of the aforementioned clinical symptom improved/normalized 4–6 weeks after treatment start. A patient was considered as nonresponder if none of the above symptoms improved/normalized 4–6 weeks after treatment start.
First-line treatment was steroids or intravenous immunoglobulins, whereas the second-line was MMF or rapamycin. Further lines of treatment included: Rituximab plus MMF or rapamycin, anakinra, cyclosporine A, eltrombopag or Nplate (whenever cytopenia was the dominating sign) either alone or in combination with MMF or rapamycin.
All the information were retrieved from the medical records of patients after informed consent according to the Helsinki declaration of principles. Patients were referred at the ALPS Italian network through the AIEOP (Italian Pediatric Hemato-Oncology Association) centers.
Response to therapy was evaluated after at least 4–6 weeks of drug administration for each of the following clinical symptoms: cytopenia, lymphoproliferation, fever, or other autoimmune symptoms and scored as complete (CR), partial (PR), or nonresponse (NR) (See for further detail the footnotes of Table
First-line treatment was steroids or intravenous immunoglobulins, whereas the second-line was MMF or rapamycin. Further lines of treatment included: Rituximab plus MMF or rapamycin, anakinra, cyclosporine A, eltrombopag or Nplate (whenever cytopenia was the dominating sign) either alone or in combination with MMF or rapamycin.
