Myelodysplasia Following Therapy with Tumour Necrosis Factor-alpha (TNF α) Inhibitors - An Uncommon Occurence.

Introduction-Tumour necrosis factor- alpha (TNF α) inhibitors such as infliximab & etanercept have various applications such as severe rheumatoid arthritis, seronegative spondyloarthritis, vasculitis, crohn’s disease & psoriasis. There have been few reports of haematological complications arising in patients treated with anti-TNF a therapies. There has been only one reported case of development of acute myeloid leukaemia after initiation of etanercept therapy.

Case report-A 57year old gentleman with HLA B27 negative ankylosing spondylitis presented with chest infection. His full blood count showed Hb 5.9 g/l WBC 3.8 × 10^9/L Neutrophil count 2.7 × 10^9/L Lymphocyte count 0.7 × 10^9/L Platelet count 89 × 10^9/L & Reticulocyte count 21 × 10^9/L. Occasional myeloblasts were seen on the blood film. He had been on biological therapy for ankylosing spondylitis with infliximab 5mg/kg infusion on 8 weekly basis for 18 months which was stopped due to lack of efficacy. Subsequently he had been treated with etanercept 50 mg subcutaneous once weekly for the past 16 weeks prior to this presentation. His full blood count prior to initiation of infliximab & etanercept was Hb 11.6 g/l WBC 16 × 10^9/L Neutrophil count 12.8 × 10^9/L Lymphocyte count 2.1 × 10^9/L Platelet count 655 × 10^9/L and Hb 11.0 g/l WBC 8.2 × 10^9/L Neutrophil count 4.9 × 10^9/L Lymphocyte count 2.4 × 10^9/L Platelet count 591 × 10^9/L, respectively. He underwent bone marrow investigations. Bone marrow aspirate was aparticulate with dyshaemopoeisis. Dyserythropoeisis in form of irregular nuclei, occasional binucleated cells & delayed nucleo-cytoplasmic maturation was seen along with dysmyelopoeisis in form of binucleated cells & pelger forms. Blasts amounted to 14% of nucleated cells. Overall, impression was in keeping with refractory anemia with excess of blasts (RAEB-2). Trephine biopsy showed mildly hypocellular bone marrow with markedly disordered haemopoeisis. There was trilineage dysplasia with abundant micromegakaryocytes with immunocytochemistry for CD117 showing increased number of progenitors (10–20%). The appearances were in keeping with myelodysplasia with excess of CD117 positive progenitors. Cytogenetic study failed. The sepsis responded to broad spectrum antibiotics but he continues on red cell & platelet support on a weekly basis.

Conclusion The chronology points to a TNF α inhibitor mediated effect in this patient. Despite the close temporal association between exposure to TNF α inhibitor therapy and the presentation of myelodysplasia in this patient, a causal relationship cannot be established with confidence. Tumour necrosis factor inhibitors find wide applications in inflammatory conditions with high TNF. Such treatment may be associated with uncommon complications. It is of interest to note there are ongoing trials using TNF α inhibitors in myelodysplastic syndrome. Checking a full blood count periodically, and immediately if the patient is unwell is recommended.