Short Response Duration to Initial Treatment of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Introduction: The incidence of chronic lymphocytic leukemia (CLL) is believed to be low in India. Furthermore, there is no information on the incidence and outcome of autoimmune cytopenias. The incidence of autoimmune cytopenias is 5-10% at any point of the course of CLL. This diagnosis can have an important impact on therapeutic decisions. The prognostic significance of these autoimmune cytopenias in CLL continues to be a topic of debate.

Methods: This was a retrospective study done at a tertiary level referral center in North India. Patient records of all CLL patients visiting the hematology clinic for the period 1994-2014 (20 years) were analyzed. Diagnosis of autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenia (ITP) and pure red cell aplasia (PRCA) was made according to standard criteria. The initial treatment options were categorized as prednisone, chlorambucil and observation. Responses were categorized as overall response rate (ORR) including CR+PR+SD and progressive disease (PD). Time to progression (TTP) was also calculated for each of the treatments and autoimmune cytopenias.

Result: Out of a total of 412 CLL patients registered and following up at our clinic, a total of 62 patients (15.0%) developed autoimmune cytopenias. AIHA was seen in 21 patients (5.09%), ITP in 19 patients (4.6%) and PRCA in 22 (5.3%) patients. Autoimmune cytopenia at diagnosis was present in 44 and at follow-up in 18 patients. The median age of the patients was 63 years (SD±10.4). The median hemoglobin of patients with AIHA and PRCA was 70g/l (SD±28) and 60g/L (SD±16) respectively and median platelet count of patients with ITP was 81x10⁹/L (SD±78.3). The best response to steroids was seen in patients with AIHA (ORR=71.4%) and ITP (ORR=80%), while only 40% PRCA patients show response to steroids. The response to chlorambucil was best for ITP (71.4%) followed by PRCA (33.3%) and AIHA (28.5%). The median time to progression of ITP, AIHA and PRCA patients on the above treatment options was 12, 6 and 0 months respectively (p<0.05).

Conclusions: Recent studies have shown contrasting results of autoimmune cytopenias in CLL with most studies showing no impact on overall survival and a few studies showing negative impact. While most studies have concentrated on the survival impact, there is paucity of data on the initial treatment options for these cytopenias and their follow-up. Our study shows that steroids which are the first line in autoimmune conditions are effective only in 70-80% of AIHA and ITP patients, while oral chemotherapy with chlorambucil is effective only in 70% ITP patients and a third of AIHA and PRCA patients. Most other patients have progressive disease. Even those who show initial responses to treatment ultimately progress with time to progression shortest for PRCA patients followed by AIHA and ITP. In conclusion initial treatment of autoimmune cytopenias may atmost delay starting standard therapy for CLL by a few months.