Abstract 3908

Autoimmune lymphoproliferative syndrome (ALPS) associated with heterozygous mutations in the FAS gene is an inherited disorder of apoptosis resulting in lymphocyte accumulation leading to massive lymphadenopathy, hypersplenism, as well as chronic and refractory multilineage cytopenias.* Here we summarize our experience with long-term follow up of asplenic ALPS-FAS patients seen in our clinic under the ALPS Natural History Study. In a subset of 70 ALPS-FAS patients with adequate documentation, 34 individuals (49%) from 25 families were asplenic. This group included 21 males and 13 females with an average length of post-splenectomy follow up of 13 years (range 3 months to 38 years) accounting for a total follow up of 454 person years. The median age at the time of splenectomy was 10 years (range 1–53 years). All but five patients were 21 or younger at the time of splenectomy. Twenty-four of the 34 patients (70%) had their FAS mutations in the intracellular death domain known to be associated with a more severe clinical pheontype. The documented reasons of splenectomy include splenomegaly with cytopenias (79%), splenomegaly without cytopenias (15%) and cytopenias without splenomegaly (6%). Two patients failed treatment with mycophenolate mofetil (Cellcept, MMF) for refractory cytopenias prior to their splenectomy.

Post Splenectomy Clinical Course:

Cytopenias:

Post-splenectomy, 19 patients (56%) developed or relapsed with multilineage cytopenias of grade 2 or higher including anemia (29%), neutropenia (26%), and thrombocytopenia (44%). Most of these patients experienced recurrence of multiple episodes of cytopenias involving more than one lineage post-splenectomy requiring further treatment interventions. To control refractory post-splenectomy cytopenias, 26% (5/19) of them needed long-term steroid sparing measure using MMF.

Sepsis:

Ten patients developed sepsis post-splenectomy. Of the 32 patients with information on prophylactic antibiotic use post-splenectomy to prevent pneumococcal sepsis, 22 (69%) received antibiotics (Penicillin 14, others 8). However, 8 (36%) of the 22 patients that received prophylactic antibiotics developed sepsis. Sepsis occurred 8 months to 36 years post-splenectomy. Two patients with sepsis were critically ill requiring hospitalization in intensive care and one died at home before receiving medical care. Among these 10 patients, 9 developed pneumococcal sepsis ranging from 1–6 episodes per patient (median 2). Two (6% of the total cohort of 34) patients died due to sepsis post-splenectomy. Relationship between prophylactic antibiotics use and risk of sepsis is difficult to interpret because in this observational study those most at risk for sepsis could have been the ones more likely to receive antibiotics. Information related to vaccine administration and pneumococcal titer responses were not available at the time of infection. Of interest, three patients belonging to one family, included here, developed pneumococcal sepsis post-splenectomy.

Lymphoma:

There were 8 patients (24%) with B cell lymphoma in this cohort of 34 patients, one of whom developed lymphoma pre-splenectomy. Two asplenic adult patients with lymphoma developed pulmonary hypertension as adults. Two patients with lymphoma died due to non-infectious causes.

Conclusion:

Overall ALPS-FAS patients have a high prevalence of recurrent cytopenias (56%) as well as sepsis (29%) following splenectomy. The morbidity and mortality associated with splenectomy, as well as the persistence of cytopenias, raise important questions as to the timing and efficacy of splenectomy in this rare disorder of immune dysfunction leading to multilineage cytopenias due to autoimmune destruction and splenic sequestration.

*Reference:

Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome: report from the 2009 NIH International Workshop. Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, Rieux-Laucat F, Siegel RM, Su HC, Teachey DT, Rao VK. Blood. 2010 Jun 10. PMID: 20538792.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
autoimmune lymphoproliferative syndrome, splenectomy, cytopenia, sepsis, lymphoma, antibiotic prophylaxis, congenital absence of spleen, follow-up, splenomegaly, antibiotics

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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