Introduction
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem
cell disorder characterized by overlapping features of myelodysplastic
syndromes and myeloproliferative neoplasms. Autoimmune and inflammatory
diseases (AID) are classical complications of CMML, occurring in up to
20% of patients in monocentric retrospective studies (1,2). These
complications can precede the onset of CMML, be concomitant to the
diagnosis or occur later during the course of the disease.
CMML-associated AID are as various as systemic vasculitis, connective
tissue diseases, skin diseases such as neutrophilic dermatosis,
polychondritis or seronegative inflammatory arthritis (1–3). Autoimmune
cytopenias (AIC) have also been reported, encompassing mainly
immunologic thrombocytopenias and AIHA (2–4). Based on the optimal
binding temperature of autoantibodies, AIHA can be classified into three
categories, warm AIHA (wAIHA), cold AIHA and mixed forms AIHA. The few
reported cases of CMML-associated AIHA were wAIHA and their rarity
precludes definite therapeutic recommendations to be drawn. As with AIHA
observed in other settings, frontline treatment is mainly based on
corticosteroids but steroid dependence is frequent. Efficacy of
subsequent treatments has not been reported, conversely to
CMML-associated ITP where the second line treatments used in primary ITP
have proved efficacy. Eculizumab (Soliris®, Alexion Pharmaceuticals) is
a humanized monoclonal antibody that binds with high affinity to the C5
complement protein and blocks its cleavage in two components: C5a and
C5b (5). It is approved for the treatment of paroxysmal nocturnal
hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. Because of
the pivotal role of complement in cold agglutinin disease (CAD),
eculizumab has also been evaluated in this disease and provided
responses in rituximab refractory cases. Eculizumab has also been used
in anecdotal cases of wAHAI but none of them were associated with CMML.
We report herein the efficacy of eculizumab in a case of
life-threatening refractory wAIHA associated with CMML.