Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers

Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare “hairy” B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the BM tumour microenvironment would identify prognostic biomarkers of response to CDA. HCL BM immunology pre and post CDA treatment and healthy controls were analysed using Digital Spatial Profiling to assess the expression of 57 proteins using an immunology panel. A bioinformatics pipeline was developed to accommodate the more complex experimental design of a spatially resolved study. Treatment with CDA was associated with the reduction in expression of HCL tumour markers (CD20, CD11c) and increased expression of myeloid markers (CD14, CD68, CD66b, ARG1). Expression of HLA-DR, STING, CTLA4, VISTA, OX40L were dysregulated pre- and post-CDA. Duration of response to treatment was associated with greater reduction in tumour burden and infiltration by CD8 T cells into the BM post-CDA. This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation and identify biomarkers of response to CDA. With validation in future studies, prospective application of these biomarkers could allow early identification and increased monitoring in patients at increased relapse risk post CDA.

Ascites in A Patient with Hairy Cell Leukaemia and Carcinoma of Breast: A Diagnostic Challenge

Hairy cell leukaemia (HCL) is a rare indolent B-cell lymphoproliferative disorder. We report a diagnostic challenge in detecting the cause of ascites, which is a rare, unique manifestation of HCL. A 72-year-old lady presented with 1-month-history of pain in left upper abdomen and loss of weight. There was hepatomegaly, splenomegaly, bilateral inguinal lymphadenopathy, anaemia, and lymphocytosis. She was diagnosed as HCL, based on morphology, immunophenotyping of peripheral blood and bone marrow biopsy examination. In 2009, she was diagnosed as carcinoma of breast when she presented with a mass in left breast; and she received treatment. For HCL, she received intermittent chemotherapy (Chlorambucil+Prednisolone). Her HCL was stable until 2018 when she presented with recurrent ascites which needed frequent, regular peritoneal paracentesis. Since she had HCL and carcinoma of breast, determining the aetiology of ascites was challenging. Possible causes of her ascites included metastatic carcinoma of breast, HCL, cirrhosis of liver with portal hypertension and peritoneal tuberculosis. Cytology of peritoneal fluid showed mature-looking lymphocytes but no malignant cells. Interestingly, flow cytometry analysis of peritoneal fluid showed the presence of clonal B cell population with lambda light chain restriction. Therefore, it was concluded that her ascites was a manifestation of HCL. A few months later, she succumbed to septicaemia. Impact of ascites on disease course of HCL included rapid disease progression, poor prognosis and shortened survival. We highlight the important role of immunophenotyping in addition to cytomorphology to guide us in confirming the aetiology of ascites in a patient with haematological and solid organ malignancies.

Sacubitril/Valsartan to Treat Heart Failure in a Patient with Relapsing Hairy Cell Leukaemia: Case Report

Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment.

Two Atypical Cases of Classical Hairy Cell Leukaemia and Hairy Cell Leukaemia Variant: A Case Study

Introduction: Classical Hairy Cell Leukaemia (cHCL) and Hairy Cell Leukaemia variant (HCL-v) are both rare and slow-growing mature B cell neoplasms. According to flowcytometry data, they fall into the group classified as CD5- CD10- B cell lymphoproliferative disorders. Methods: Two cases with features atypical to two neoplasms at the time of diagnosis were studied. Results: Case 1 was a 15 year old male with right cervical lymph nodes (1x1 cm) in the posterior triangle, a few ecchymotic patches on the arm and a massive splenomegaly. C-reactive protein (CRP) level was 53 mg/dL. Erythrocyte Sedimentation Rate (ESR) was 98 mm/1 st hour. Full Blood Count (FBC) revealed typical features of pancytopenia with monocytopenia. The liver and renal profiles were normal. Morphology of bone marrow was suggestive of cHCL. Flowcytometry and BRAF V600E mutation was positive confirming the diagnosis of cHCL. Case 2 was a 55 year old male presenting with moderate splenomegaly and absolute lymphocytosis. The FBC revealed leukocytosis which is commonly seen with monocytopenia. Blood pictures revealed many hairy cells with moderately basophilic cytoplasm and visible nucleoli suggesting HCL-v. Flowcytometry findings and negative BRAF V600E mutation confirmed HCL-v. Conclusions: Clinical findings, blood images, morphology of bone marrow, flowcytometric findings and positive BRAF V600E mutation confirmed the diagnosis of cHCL in case 1 (15 year old boy) making it as a very rare case. The morphological findings on blood, the presence of characteristic CD markers on flowcytometry and negativity of BRAF V600E confirmed the case 2 as HCL-v, despite having CD10 positivity and monocytopenia.Keywords: Flowcytometric immunophenotyping, Hairy cell leukaemia, Hairy cell leukaemia variant