Bone Marrow Failure

Bone marrow failure is the decreased production of one or more major haematopoietic lineages, leading to diminished or absent precursors in the marrow and the resulting cytopenias. Suspect it in pancytopenia. Discuss with haematology — this will require an urgent bone marrow biopsy.

Bone marrow failure has triphasic peaks: at 2 to 5 years (inherited is most common), between 20 to 25 years, and after 65 years (most likely due to acquired causes).

Causes

Acquired (the majority in adults) — drugs, chemicals, radiation, viral infections, immune disorders, myelodysplastic syndrome, paroxysmal nocturnal haemoglobinuria, or large granular lymphocytic leukaemia. Aplastic anaemia is idiopathic in about half of cases; recognised triggers include benzene, antineoplastic drugs, antibiotics, NSAIDs, antiseizure medications, seronegative hepatitis, pregnancy, EBV and CMV.

Inherited — dyskeratosis congenita, Fanconi anaemia, Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, Blackfan-Diamond anaemia. These account for 10% to 15% of marrow aplasia and 30% of paediatric bone marrow failure disorders.

Approach

In patients with pancytopenia, the first step is to examine the peripheral blood smear for abnormalities, including B12 and/or folate deficiency. Then bone marrow biopsy and aspirate.

Rule out acquired causes by stopping suspected medications, treating active infections, and testing for hepatitis, pregnancy, or paroxysmal nocturnal haemoglobinuria.

Refer for inherited-syndrome testing if there is a family history of MDS, AML or squamous cell carcinoma, extra-marrow features, or age under 40 — do not discount these conditions in adults. Ten percent of patients who present with bone marrow failure have unsuspected Fanconi anaemia.

Screen all first-degree relatives of patients with an inherited syndrome on diagnosis and refer for genetic counselling — an affected HLA-matched sibling donor is dangerous, not useful.