Angioimmunoblastic T-cell lymphomas presenting as autoimmune hemolytic anemias: clinical manifestations and circulating cytokine features.

Abstract

Dear Editor, F r om Ap r i l 2 0 0 9 t o D e c emb e r 2 0 1 2 , s e v e n angioimmunoblastic T-cell lymphoma (AITL) patients presented as overt autoimmune hemolytic anemia (AIHA) in our institution, all of which were warm AIHA. In addition to frequent appearance of erythrocyte autoantibodies, AITLrelated AIHA patients showed elevated incidence of reticulocytopenia, eosinocytosis, and bone marrow plasmacytosis (Table 1). Severe anemia was presented in three patients, and five patients had a platelet count lower than 150×10/L. One patient (#1) with pure red cell aplasia and one (#6) with severe thrombocytopenia died within 2 weeks after diagnosis, and the other three (#3, #5, #7) declined treatment options except supportive care. Only two patients (#2, #4) achieved remission after CHOP-based chemotherapeutic regimens. Within the detection panel of 40 circulating inflammationassociated cytokines (Quantibody Human Inflammatory Array 1, RayBiotech, Norcross, GA), BLC/CXCL13 [3475 (1751–5924) vs. 80.0 (56.2–100.4)pg/mL, p= 0.005], Eotaxin-2/CCL24 [942 (579–1319) vs. 303 (206–370) pg/mL, p=0.007], MIG/CXCL9 [11,510 (6700–16,852) vs. 3412 (1816–4122)pg/mL, p=0.011], MIP-1β/CCL4 [39.6 (11.9–72.1) vs. 7.4 (4.0–10.2)pg/ mL, p=0.016], IL-10 [105.0 (50.2–193.1) vs. 23.0 (14.4–26.3)pg/mL, p=0.011], and IL-8/CXCL8 [13.8 (7.7–22.6) vs. 5.6 (3.9–7.2) pg/mL, p=0.016] were found to be significantly elevated in AITL patients presenting as AIHA (Fig. 1). Plasma BLC/CXCL13 was drastically elevated in all four subjects, while Eotaxin2/CCL24 level seemed to be associated with marrow plasmacytosis and eosinocytosis. Regarded as one of the lymphoid neoplasms with significant inflammatory background and autoimmune propensity, AITL patients are particularly susceptible to autoimmune cytopenias including AIHA, immune thrombocytpopenia, and rarely pure red cell aplastic anemia [1, 2]. Those with severe anemia or thrombocytopenia are believed to have poor treatment responses and clinical outcomes, which poses a major therapeutic hurdle for AITL [2]. Based upon the data reported from Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials, up to 33 % of AITL patients had a positive Coombs test, although overt hemolytic anemia was much less frequent [1]. The chemokine receptor CXCR5 has been identified as the most important surface marker of follicular helper T cell (TFH), the recently identified T helper cell subgroup crucial for the formation and maintenance of the germinal center and the most likely candidate for the cellular origin of AITL tumor cell [3, 4]. Malignant AITL cells demonstrate aberrant production and secretion of CXCL13 which is the specific ligand for CXCR5, and we found an astounding 40-fold increase of plasma CXCL13 levels among AITL patients presenting with AIHA which might advocate aberrant TFH proliferation and severe tumor burden. As a strong chemoattractant for eosinophils, Eotaxin-2/CCL24 could contribute to proliferation and infiltration of inflammatory cells in both AITL tumor tissue and apparently unaffected bone marrow. In * Feng Li li.feng@zs-hospital.sh.cn