Journal Logo



Palmisani, E.1; Miano, M.1; Lanza, T.2; Terranova, P.2; Lanciotti, M.2; Zanardi, S.3; Facchini, E.4; Ladogana, S.5; Mastrodicasa, E.6; Corti, P.7; Russo, G.8; Pillon, M.9; Farruggia, P.10; Cesaro, S.11; Barone, A.12; Maggiore, R.1; Montanari, E.1; Dufour, C.1; Fioredda, F.1

doi: 10.1097/01.HS9.0000559616.91240.a0
Poster Session I: Bone marrow failure syndromes incl PNH - Clinical

1Haematology Unit

2Laboratorio di Ematologia

3Servizio di Epidemiologia e Biostatistica, IRCCS Istituto Giannina Gaslini, Genova

4Clinic of Pediatric Hematology Oncology, Policlinico S. Orsola-Malpighi, Bologna

5Dipartimento di Ematologia,, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo

6Unità di Oncoematologia pediatrica, Ospedale Santa Maria della Misericordia, Perugia

7Clinica Pediatrica dell'Università Milano, Bicocca, A.O. San Gerardo - Fondazione MBBM, Milano

8Divisione Ematologia - Oncologia Pediatrica, Clinica Pediatrica, Catania

9Dipartimento di Pediatria Università di Padova, Cattedra Di Oncoematologia Pediatrica, Padova

10U.O. Oncoematologia Pediatrica A.R.N.A.S, Civico di Cristina e Benfratelli, Palermo

11Dipartimento di EmatoOncologia, Aziena Ospedaliera Universitaria Integrata, Verona

12U.O. di Pediatria e Oncoematologia Pediatrica, Az. Osp. Di Parma Ospedali Riuniti, Parma, Italy

Back to Top | Article Outline


Autoimmune lymphoproliferative syndrome (ALPS) defined according to the clinical/biochemical criteria (NIH 2009) is known to be mainly caused by FAS, FASL, FADD and CASP10 gene mutations. Nevertheless, several patients carrying a clear ALPS phenotype are not associated with these mutations

Back to Top | Article Outline


Describe the clinical, biochemical and therapeutic characteristic in ALPS patients with and without the classical mutations and correlate them with genetics.

Back to Top | Article Outline


The demographic, clinical, biochemical, genetic informations and details about treatment are derived from the ALPS Italian Network. Search of mutations was performed with Sanger PCR and/or Next Generation sequencing techniques (extended to immunodeficiency genes panel).

Back to Top | Article Outline


Among 68 ALPS patients registered in the data base (Males, 60%), 42 subjects (62%) received a genetic definition: 14 pts (33%) carried classical mutations in FAS/CASP genes, 16 pts (37%) showed mutation in genes other than FAS/CASP (LRBA, STAT, CTLA4, CECR, BAFF, TACI, RAG, NEMO, IKBKG, Gaucher) and 12 pts (28%) were negative for FAS/CASP.

Clinical phenotype in the two groups appeared rather different being “more complex“ in the ALPS FAS negative group if compared with the FAS/CASP one. (p = 0.003) (Table 1).The multi-organ involvment was often associate with positivity of autoimmune markers (p = 0.002) (Table 1).

Cytopenia affecting one or more haematopoietic lineages was present in both groups (69% and 82%) without difference; while leucopenia/lymphocytopenia was shown more frequently in FAS/CASP mutated group rather than in the ALPS FAS negative one (p = 0.03) (Table 1). As for lymphocyte subclasses and immunoglobulin dosage no differences were shown within the two groups. Vitamin B12 and IL-10 were more frequently raised in ALPS FAS/CASP mutated group than in the non mutated FAS/CASP genes (p = 0.01, p = 0.001).

Four of 42 (9%) patients did not require any treatment, while the remaining 38 received one or more lines or drug combinations. First line treatment (steroid or intravenous immunoglobulins) controlled the disease in 4/38 (10%). In the ALPS FAS/CASP POS group response rate to second line treatment (mostly MMF and rapamycin) was 100%, while in the ALPS FAS/CASP negative group MMF and rapamycin were not able to control symptoms in the majority of subjects (response rate 40%). Drug combinations or target therapies were more commonly applied in patients belonging to FAS/CASP negative group rather than in the ALPS FAS/CASP POS group (p = 0.002, p = 0.02) (Table 1).



Back to Top | Article Outline


Patients carryng ALPS phenotype without FAS or CASP mutations probably represent a distinct entity as compared to those with classical ALPS phenotype and genotype regarding clinical appearance, biochemical characteristic and genetic pattern. Moreover genes frequently associated with immunodeficiency/disimmunity patterns are more represented in FAS/CASP negative group. These findings are relevant for therapeutic management, especially in the cases when target therapies are available. In ALPS FAS/CASP POS group, MMF or rapamycin are highly effective to manage disease. Their use would allows steroid-sparing strategy and in some cases should be proposed even as a first line choice.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.