Investigation of the relationship between autoimmune diseases in patients with CLL, HL and NHL diagnosis

Hodgkin lymphoma (HL), Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are malignancies originating from different cells of the lymphatic system and showing different clinical features, and there are different treatment approaches for each. While HL is distinguished by the presence of Reed-Sternberg cells, NHL and CLL are more heterogeneous and complex diseases originating from B or T cells. Autoimmune diseases are increasingly recognized due to their association with various lymphoid hematological malignancies, including HL, NHL and CLL. The relationship between these autoimmune conditions, lymphomas and CLL is a complex situation that may include genetic and environmental factors as well as immunological factors and is multifaceted. In our study, it was planned to evaluate the relationship between autoimmune diseases in cases of CLL, HL and NHL from hematological malignancies. We conducted a retrospective analysis of the relationship between autoimmune diseases in 290 chronic lymphocytic leukemia, 138 Hodgkin lymphoma and 326 Non-Hodgkin lymphoma patients followed up in our hospital' s Adult Hematology Clinic between January 2013 and December 2023. We examined the demographic characteristics of patients over the age of 18 with autoimmune diseases diagnosed with CLL, HL, and NHL, laboratory findings at the time of diagnosis [erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), C-reactive protein (CRP), leukocytes (WBC), hemoglobin (HGB), hematocrit (HCT), platelets (PLT)], subtype and stage of current diagnosis, additional systemic diseases, last visit dates, if chemotherapy was received, how many lines of chemotherapy they received and their responses, and 5- and 10-year survival times. The study data were analyzed with IBM SPSS v23. Of the 78 patients included in the study, 44 were male (56.4%) and 34 were female (44.6%). In the HL group, 7 (53.8%) of the patients were male and 6 (46.2%) were female; in the CLL group, 20 (71.4%) of the patients were male and 8 (28.6%) were female; and in the NHL group, 17 (45.9%) of the patients were male and 20 (54.1%) were female. The median age of all patients included in the study was 60.23 (18.17 - 93.36). The median age of the HL group was 44.36 (18.17 - 73.81), the median age of the CLL group was 68.6 (44.04 - 93.36), and the median age of the NHL group was 59.49 (18.19 - 85.39) years. The median age at diagnosis was higher in patients with CLL compared to HL and NHL groups. Autoimmune disease was diagnosed in 13 (9.42%) of 138 HL patients, 28 (9.65%) of 290 CLL patients, and 38 (11.65%) of 326 NHL patients screened for the study. In the HL group, there was no autoimmune disease diagnosis in Stage 1 and Stage 2, the rate of Stage 3 was 38.5% and the rate of Stage 4 was 61.5%. In the NHL group with autoimmune disease diagnosis, the rate of Stage 1 disease was 10.8%, Stage 2 was 16.2%, Stage 3 was 13.5%, and Stage 4 was 59.5%. In the CLL group with autoimmune disease diagnosis, RAI 0 stage rate was found as 32.1%, RAI 1 rate as 17.9%, RAI 2 rate as 28.6%, RAI 3 rate as 10.7% and RAI 4 rate as 10.7%. In the HL group with autoimmune disease diagnosis, patients with cHL diagnosis constituted 84.62% of the group, while the rate of patients with NLPHL diagnosis was found as 15.38%. In the NHL group, DLBHL constituted 70.27% of the group. When the cases were evaluated in terms of additional systemic diseases other than autoimmune disease, it was seen that 53.9% of the HL group, 92.8% of the CLL group and 81.1% of the NHL group had additional systemic diseases. In HL cases with autoimmune disease diagnosis, according to the International Prognostic Score-3, 7.69% of the patients were found to be at low risk, 76.91% to be at moderate risk and 15.38% to be at high risk. In NHL cases diagnosed with autoimmune diseases, according to the International Prognostic Index, 13.51% of the patients were found to have low risk, 21.62% low-moderate risk, 43.24% moderate-high risk, and 21.62% high risk. In CLL cases, the rate of those who were under drug-free follow-up was 42.9%, the rate of those who received 1-step treatment was 21.4%, the rate of those who received 2-step treatment was 28.6%, and the rate of those who received 3-step treatment was 7.1%. In HL cases, the rate of those receiving 1-step treatment was 53.8%, the rate of those receiving 2-step treatment was 15.4%, the rate of those receiving 3-step treatment was 15.4% and the rate of those receiving 4-step treatment was 15.4%. The rate of disease progression in HL patients was 15.4%, in CLL patients 31.3% and in NHL patients 32.4%. The rate of refractory disease in HL patients was 23.1%, in CLL patients 6.3% and in NHL patients 5.4%. The rate of treatment response in HL patients was 61.5%, in CLL patients 62.5% and in NHL patients 62.2%. The mean survival time from the date of diagnosis was 11,743 years in the HL group, 6,717 years in the CLL group and 5,013 years in the NHL group. As a result, in our study, we found similar rates of autoimmune disease association in HL and CLL compared to previous studies, and reported higher rates in cases with NHL. It was observed that some of the cases had an autoimmune disease diagnosis at the time of diagnosis, while others were diagnosed later. The most commonly diagnosed hematological autoimmune disease was Immune Thrombocytopenic Purpura (ITP), followed by Autoimmune Hemolytic Anemia (AIHA). It was observed that the frequency of ITP and AIHA diagnoses increased after the diagnosis of hematological malignancy. In our study, it was observed that the most common non-hematological autoimmune diseases were Rheumatoid arthritis, Hashimoto' s thyroiditis and Ulcerative colitis. We found that the frequency of cases with HL and NHL diagnosis increased in women according to the literature we reviewed. We found that patients with autoimmune diagnoses received hematological malignancy diagnoses at a more advanced stage, and that their 5-year and 10-year survival rates were lower. In addition, it was observed that the frequency of additional systemic diseases in the cases whose data we scanned in our study increased. The incidence of autoimmune diseases in cases diagnosed with HL, NHL and CLL has increased compared to the normal population. Therefore, cases diagnosed with these diseases should be investigated for autoimmune diseases. Autoimmune cytopenias are screened especially in patients diagnosed with CLL in hematology clinics. In our study, we came to the conclusion that both hematological and non-hematological autoimmune diseases should be screened in detail at the time of diagnosis and during the follow-up of both CLL and lymphomas.