A plastic anaemia at Chris Hani Baragwanath academic hospital

Abstract

Aplastic (hypoplastic) anaemia (AA) is a rare condition that is characterised by pancytopenia in the peripheral blood, a hypocellular/acellular bone marrow and the absence of an abnormal infiltrate. Aplastic anaemia is classified as congenital/inherited and acquired. Acquired AA can be subdivided into idiopathic (primary) which is the most common form and secondary, depending on whether there is an identifiable cause. Inherited bone marrow failure syndromes are rare. Clinical and laboratory data implicate immune-mediated mechanisms in the pathogenesis of AA. Clinically AA manifests with features of bone marrow failure. Allogeneic haematopoietic stem cell transplantion is a potentially curable treatment in patients with severe AA who are candidates for transplantation. Immunosuppressive therapy with ATG as the backbone is effective in 60-80% of patients. The aim of this study was to document the demographic profile, clinical features, treatment modalities and outcome of patients diagnosed with AA who presented to the Clinical Haematology Unit at Chris Hani Baragwanath Academic Hospital and to compare it with studies done nationally and internationally. There is a paucity of studies on aplastic anaemia in South Africa. The data of patients diagnosed with aplastic/hypoplastic anaemia at the Clinical Haematology Unit of Chris Hani Baragwanath Academic Hospital were retrospectively reviewed and analysed. The majority of patients had idiopathic acquired aplastic anaemia (82%). The median age at presentation was 24.5 years and although a second peak occurring after 60 years is reported in the literature, there was no clear second peak in our patients. The male-to-female ratio was 1.7:1. The clinical presentation is similar to that reported in the literature with the most common presenting features being anaemia and bleeding. Infection was less common. The majority (69.9%) of patients had severe aplastic anaemia. The most common secondary cause was HIV accounting for 12% of patients. The clinical presentation was similar in both the HIV seropositive and HIV seronegative patients. Inherited bone marrow failure syndromes are rare. Two patients (2%) were confirmed genotypically to have Fanconi Anaemia. Allogeneic HLA-identical sibling stem cell transplantation is associated with a 75-90% probability of long-term cure. Most patients are candidates for a stem cell transplant but are excluded based on a lack of HLA compatibility. In this cohort, 2 patients underwent HLAidentical haemopoietic stem cell transplantation with both achieving a complete response. Immunosuppressive therapy was given to the majority of patients. The overall response rate was 60.6% which largely reflects the response to immunosuppressive therapy as only 2 patients underwent a stem cell transplant, and is similar to that reported in the literature. Less severe aplasia was associated with a better response. There were 3 (3%) patients who transformed to acute myeloid leukemia, 5 (5%) who developed haemolytic paroxysmal nocturnal haemoglobinuria and none who transformed to a solid malignancy. A significant number of patients (45%) were lost to long-term follow up. The 5 year survival probability was 69.2%. In studies from outside of South Africa, survival is reported to be 75-80% following immunosuppressive therapy. In the HIV positive patients, the 5-year survival probability was statistically significantly worse (37.5%) as compared to the HIV negative population (78.5%). There was a trend towards an inferior response (less than partial or no response versus partial or complete response) in the HIV positive patients but this was not statistically significant. Survival was significantly associated with response to treatment. Patients who responded to treatment had a 5-year survival probability of 88.9% compared to 17.3% non-responders (p=0.0001). The leading cause of mortality was sepsis.