The diagnostic yield of bone marrow biopsy in patients with liver failure

Background: Haematological diagnoses can be associated with liver failure. Cytopenias are also common in patients presenting with liver failure and following liver transplantation. Distinguishing a primary haematological/immunological cause from secondary causes can be difficult and a bone marrow biopsy (BMB) remains a frequently performed investigation. Aims: To evaluate the diagnostic utility of a BMB and its influence on patients management in the UK's largest liver unit Methods: We retrospectively collected clinical, biochemical and pathological data on consecutives referrals to the haematology department for BMB in patients with liver failure or a liver transplant between October 2012 and December 2018. Both paper and electronic patient records were used. We defined cytopenias as Hb <100 g/l, platelets <100x10 9 /l and neutrophils <1.8x10 9 /l present in more than 2 cell lines. Results: 108 BMBs were performed in 103 patients. Five patients had two BMBs. The median age was 47.7 years (range 18–76 years) with 57 (55%) male patients. Forty‐three (42%) patients had received a liver transplant. The indications for BMB were possible haemangiolymphophagocytosis (HLH) in 28 (27%), cytopenias in 47 (46%), post‐transplant lymphoproliferative disorder (PTLD) in 14 (14%), myeloproliferative neoplasm (MPN) in 10 (10%) patients with Budd‐Chiari syndrome, myeloma in 2 (2%), lymphoma in 1 (1%) and storage disorder in 1 (1%). The final diagnosis after BMB included HLH in 8 (8%) patients, hepatosplenic T‐cell lymphoma in 2 (2%), T‐cell large granular leukaemia (T‐LGL) in 1 (1%), aplastic anaemia in 4 (4%), telemeropathy in 2 (2%), probable MDS in 4 (4%), immune thrombocytopenia in 1 (1%), and MPN in 4 (4%). All 4 with MPN had evidence of the JAK2 V617F mutation. The BMB did not inform the final diagnosis in 77 (75%) patients. In those who were confirmed to have HLH, the trigger was likely viral with CMV and/or EBV viraemia in 6, EBV and HSV viraemia in 1 and HHV8 viraemia in 1. Four patients were treated actively with various combinations of ganciclovir, rituximab, IVIG, steroids and etoposide, however, 6/8 patients died. In 4 patients diagnosed with aplastic anaemia, 1 patient was treated with ciclosporin followed by allogeneic stem cell transplant (SCT), 1 patient is awaiting a SCT and 2 patients are under active surveillance only. In the 4 patients with probable MDS, 1 was treated with supportive (GCSF and erythropoietin), 2 are under observation and 1 has died. The 2 patients with telomeropathy, 1 with immune thrombocytopenia and 1 with T‐LGL are all under active surveillance. Both patients with hepatosplenic T‐cell lymphoma have died; 1 prior to chemotherapy and 1 patient died with from relapsed disease. Although we did not diagnose PTLD from the BMB, 8 (8%) patients subsequently received this diagnosis from another biopsy site. Four of the 8 patients have died. In the 4 patients diagnosed with an MPN, all 4 patients (4%) were treated with hydroxycarbamide. The 5 patients who had repeat BMBs were referred for possible HLH of which the diagnosis was subsequently made in 4. Overall, 42 (41%) patients have died. Summary/Conclusion: Although the majority of BMBs (75%) did not reveal a diagnosis, a haematological/immunological diagnosis was made in 25% of referrals. Therefore, a BMB remains an important investigation in patients with liver failure and cytopenias with a wide range of potential diagnoses that have implications for therapy.