BOF: General (Aplastic Anaemia)

Options:

A. Recombinant Human Erythropoietin (rhEpo)

B. Granulocyte Colony Stimulating Factor (GCSF)

C. Irradiated platelet transfusion

D. Red blood cell transfusion

E. ATG (Rabbit)

F. Cyclosporin

G. Allogeneic Haematopoietic Stem Cell Transplant

H. Antifungal treatment

I. Broad spectrum Antibiotics

J. Iron chelation

For each of the clinical scenarios described below (1-5) choose the SINGLE treatment from the list above (a-j) that is MOST appropriate. Each answer may be used once, more than once or not at all.

Question 1

A 37 year old woman previously fit and well. Diagnosed with idiopathic aplastic anaemia with no PNH clone detected. She is asymptomatic from her anaemia currently (Hb 9.2g/dL, N 0.8 x10⁹/L, platelets 45 x10⁹/L.)

Question 2

A 27 year old woman previously well has been recently diagnosed with aplastic anaemia (Hb 7/dL, N 0.3 x10⁹/L, platelets 15 x10⁹/L.) She has an HLA matched brother. She is currently receiving regular red cell and platelet transfusions.

Question 3

A 32 year old woman with aplastic anaemia has previously had a good response to ATG and is now maintained on an irregular red cell transfusion programme. She is now currently 21/40 pregnant and her last FBC shows Hb 9.1/dL, N 0.1 x10⁹/L, platelets 16 x10⁹/L.) She has had two recent urine infections requiring hospitalisation

Question 4

A 34 year old woman who was previously very well has been diagnosed with severe aplastic anaemia with a small PNH clone. She is having regular blood product transfusions. She has an HLA matched sibling. She is admitted with fevers, hypotension and she has had a positive urine microbiological culture.

Question 5

A 44 year old woman who has no siblings is diagnosed with very severe aplastic anaemia. She has relapsed after ATG and cyclosporin. She is currently well receiving regular red cell and platelet support.

The Answer:

1: ATG

2: Allogeneic Haematopoietic Stem Cell Transplant

3: Cyclosporin

4: Broad spectrum Antibiotics

5: Allogeneic Haematopoietic Stem Cell Transplant

The Explanation:

Corticosteroids are not effective in aplastic anaemia and increase risk of infection and gastrointestinal bleeding. In young patients (<40 yoa if fit) with a matched sibling donor who have severe or very severe aplastic anaemia, allogeneic bone marrow transplantation is advised as first line, with ablative cyclophosphamide-based conditioning if <30 and reduced intensity flu/cy conditioning in 30-40 year olds.

Treatment is not indicated in patients who have non-severe disease and have not had a serious infectious complication nor are transfusion dependent. Immunosuppression with ATG/ALG and ciclosporin (rabbit, since horse is no longer available) is a first line treatment in younger patients without sibling donors or transfusion-dependent non-severe disease, and in older patients regardless of donor status. This may be repeated for refractory or relapsed disease, except in the case of children, in whom rechallenging is rarely successful and transplantation strategies should be more actively pursued. For older patients (>60-70) particularly with cardiac comorbidities, ATG/ALG should be carefully considered due to complications, and best supportive care may be preferable. Pregnant women with aplastic anaemia should be managed primarily with supportive care, however if complications of aplasia ensure ciclosporin is safe to use.

Fludarabine-based reduced intensity conditioning allogeneic transplant should be considered in older patients if fit. Bone marrow transplantation is preferable to peripheral blood stem cells (despite equivalent engraftment rates) if ATG is incorporated in conditioning due to improved survival and reduced rates of chronic GVHD.

The Link:

Killick SB, Bown N, Cavenagh J et al. British Committee for Standards in Haematology approved document: Guidelines for the Diagnosis and Management of Adult Aplastic Anaemia (2015) Br J Haematol. 2016 Jan;172(2):187-207.