Case Presentation: A 56-year-old man with a history of diabetes presented to the ED with confusion and generalized lymphadenopathy. Labs were significant for severe macrocytic anemia (Hemoglobin of 3.5 g/dL, MCV of 134), low reticulocyte count, leukocytosis of 72.7k/MCL (66.1k/MCL lymphocytes), thrombocytopenia of 69000/mclThe peripheral blood film was remarkable for smudge cells and macro ovalocytes. CT abdomen and pelvis revealed extensive retroperitoneal, mesenteric, and pelvic sidewall lymphadenopathy. Flow cytometry of peripheral blood showed monoclonal B cell population (positive for CD19, CD20, CD23, CD5, and surface light chains) consistent with chronic lymphocytic leukemia (CLL). Given patient had macrocytic anemia, further investigation was performed which revealed low vitamin B 12( <50pg/ml), positive anti-parietal cell and anti-intrinsic cell antibodies, elevated gastrin at 268pg/ml. Folate level was normal and Coombs test was negative, Taken together, this was consistent with intramedullary hemolysis in the setting of severe B12 deficiency due to pernicious anemia (PA) and newly diagnosed CLL. The patient received a blood transfusion for severe anemia. He was started on intravenous methylcobalamin treatment, with the rapid improvement of encephalopathy. Intriguingly, the patient’s WBC and Platelet counts also reached normal values at 8.0k/MCL and 289/mcl respectively. Hemoglobin had not reached normal value prior to discharge, however, MCV reached normal value. As the patient did not consent, chemotherapy was never started. The patient was then discharged home with outpatient close follow up.

Discussion: CLL is the most common leukemia in adults. While CLL has been associated with autoimmune conditions, the association with PA is extremely rare. PA may be a risk factor for CLL, although the exact causal role has not been fully elucidated. In one case report, a patient with CLL was diagnosed with PA after 25 years of long-term remission, and it was assumed that it is similar to other autoimmune complications of CLL. In a large case-control study in Europe, there was almost 2-fold excess of CLL cases diagnosed within a year of hospital discharge for pernicious anemia and, PA was noted as a possible risk factor of CLL. Our case is unique in a way that not only PA and CLL were simultaneously diagnosed, but also the significant response in blood counts was noted with vitamin B12, which could possibly have implications for the management of other patients with CLL.

Conclusions: As blood counts at diagnosis have significant prognostic implications in CLL, and B12 deficiency affects hematopoiesis, routine vitamin B12 testing should be considered for patients with newly diagnosed CLL. Prompt replacement could impact cytopenias and, more importantly, staging and prognosis We also think that further investigation is needed to determine the impact that vitamin B12 deficiency and PA may have in CLL pathogenesis.