Chronic myelomonocytic leukemia (CMML) is a myelodysplastic and myeloproliferative neoplasm (MDS/MPN) characterized by cytopenias, persistent monocytosis, morphologic dysplasia and a tendency to transform to acute myeloid leukemia (AML). Similar to MDS, multiple genetic, molecular, microenvironmental and immunologic mechanisms of pathogenesis have been linked to CMML. Autoimmunity results from inflammation and tissue damage caused by inappropriate T and B cell self-recognition. The prevalence of autoimmunity in the U.S. population (not age adjusted) was estimated to be 3.2% prior to 1996 and is now 5 –8% according to 2004 data with a female prevalence (M: F= 1:3) (http://www.niaid.nih.gov/topics/autoimmune/documents/adccfinal.pdf). The prevalence of autoimmunity is estimated to be higher (10–17%) in MDS and MDS derived AML compared to the general population (Giannouli S et al.2012, Emadi A abstract 2012 ASCO).
Recent investigations have shown a close link between autoimmune disorders and cancer. A recent study indicated that a history of autoimmununity might predict a better clinical response to DNA methyltransferase inhibitors (DNMTI) in MDS [Emadi A abstract 2012 ASCO]. The current study was conducted to identify the prevalence of autoimmune diseases in patients with CMML and compare it with the general population and to patients with a non-MDS-related MPN chronic myelogenous leukemia (CML).
A retrospective analysis was performed of a series of 123 patients with CMML at Moffitt Cancer Center diagnosed between January 1999 and June 2011. A consecutive collection of 116 patients who were diagnosed with CML between January 2007 and June 2011 was included for comparison. Patients with a past medical history of autoimmunue disorders e.g. idiopathic thrombocytopenic purpura (ITP), Sjogren's syndrome, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), chronic autoimmune hemolytic anemia, inflammatory bowel diseases (IBD, ulcerative colitis or Crohn disease), psoriasis etc. were retrieved and clinical findings were correlated to published prevalence of these conditions in the general population.
Among 123 CMML patients (average age of 68.6, ranging from 30 to 90 y/o, M: F = 2.61), 20 (16.26%, 8 Female, 12 Male) had a history of autoimmune related disorders: RA(3, 2.4%), MS (2, 1.6% ), Sjogren's syndrome (1, 0.8%), IBD(1, 0.8%), autoimmune anemia (1, 0.8%), psoriasis (4, 3.25%), polymyalgia rheumatica (1, 0.8%), ITP(6, 4.9%), hyperthyroidism (2, 1.6%); and 3 patients have more than 1 autoimmune disorder. In addition, 9 of 123 cases (7.3%) had a history of the other malignancies (7 with solid tumors and 2 with hematopoietic neoplasms other than MDS/CMML/AML, but no CML). In the CML group (average age of 55.5, ranging from 21 to 84 y/o, M: F = 1.2), history of autoimmunity was found in 6 of 116 patients (5.2%), which is similar to reports of these conditions in the general population. The autoimmune phenomenon included 2 RA, 2 polymyalgia rheumatica, 1 IBD, and 1 psoriasis. There was a statistically significant difference in the rate of autoimmune diseases between CMML and CML (p=0.0066, X2test). Of note, 5 CMML patients were considered secondary CMML; however, none of the 5 patients in the study had documented autoimmununity in his/her past medical history.
The presence of autoimmune disorders is significantly higher in CMML compared to historical data on the general population and Moffitt Cancer Center patients with CML. Identifying autoimmune process in CMML may relevance to development of novel therapeutic strategies. A larger study to explore the detailed relationship between a history of autoimmune diseases and CMML is needed to define the molecular pathogenesis.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.