Abstract
An 80-year old gentleman with very severe aplastic anemia was treated
with standard combination therapy of equine antithymocyte globulin and
cyclosporine A. His death shortly after treatment could be attributed to
his advanced age, severe pancytopenia at diagnosis, absence of minor
paroxysmal nocturnal hemoglobinuria clone and immunosuppressive
therapy-related complications.
Introduction
Aplastic anemia (AA) is an acquired bone marrow failure syndrome
characterised by fatty replacement and diminished production of
haematopoietic precursor stem cells of the bone marrow. Immune-mediated
destruction of hematopoietic stem cell precursors in AA is triggered by
the activated cytotoxic T-cells which express a variety of inhibitory
cytokines such as interferon-gamma through the Fas-dependent apoptosis
pathway1. AA demonstrates a bimodal age distribution
in which, it occurs most frequently in those aged between 20-30 and over
602. AA has an annual incidence of 2 per 1,000,000
population in the West but it is higher in Asia2. The
common causes for aplastic anemia are exposure to toxic chemicals such
as benzene, certain drugs such as chloramphenicol, ionizing radiation,
history of cytotoxic chemotherapy, viral infections and autoimmune
diseases3. Most AA diagnosed in the elderly are
idiopathic and they do not exhibit any underlying secondary
etiology4. Age over 60 years is an important
independent risk factor for mortality in AA4. One
should consider other possibilities such as hypoplastic myelodysplastic
syndrome(h-MDS), paroxysmal nocturnal hemoglobinuria (PNH), nutritional
deficiency, late onset telomeropathy and delayed onset inherited bone
marrow failure syndromes when diagnosing AA in the elderly. Here, we
describe a case of idiopathic very severe aplastic anemia in an 80-year
old male who was treated with standard first line therapy but
subsequently succumbed to severe infection.
Case presentation
An 80-year-old Chinese gentleman with no known prior medical illness
presented to the department of hematology with lethargy, reduced effort
tolerance, easy bruising, anorexia, and loss of weight for the past 6
weeks. He has no significant family history. He is a non-smoker, a
teetotaler and does not consume any recreational or therapy-related
drugs. He worked as a bank clerk previously. He is married with 5
children, whom are all healthy.
On examination, he was alert with a body weight of 75 kilogrammes. He
demonstrated a Charlson comorbidity index (CCI) score of 4 (low risk)
with an Eastern Cooperative Oncology group (ECOG) performance status of
0 (fully active). His blood pressure was 140/70 with a pulse rate of 96
beats per minute. He was afebrile. Visible cutaneous bruising was
evident. His cardiovascular and respiratory system examinations were
unremarkable. There was no palpable organomegaly or lymphadenopathy.
A complete blood count revealed severe pancytopenia. The blood
parameters are tabulated in Table 1.
The peripheral blood film revealed erythrocyte anisopoikilocytosis and
severe pancytopenia. The bone marrow aspiration (Figure 1A) was
aparticulate and markedly hypocellular. No abnormal cells were seen. The
bone marrow trephine biopsy (Figure 1B) revealed a hypocellular marrow
which was replaced mainly with non-hematopoietic tissue such as fat.
Flow cytometry analysis did not show any evidence of leukemia.
Cytogenetic studies using Giemsa banding technique revealed -Y and
trisomy 8 abnormalities. Multiparameter flow cytometry and Fluorescent
aerolysin (FLAER) of erythrocytes, polymorphonuclear neutrophils and
monocytes did not detect any paroxysmal nocturnal hemoglobinuria (PNH)
clone. Whole-body CT imaging did not reveal any organomegaly or
lymphadenopathy.
He was diagnosed with very severe idiopathic aplastic anemia (based on
Camitta criteria, 1976).
In view of his advanced age, he was not suitable for an allogenic stem
cell transplant. He was treated with triple therapy consisting of
Intravenous equine Antithymocyte globulin (ATGAM) 40 mg/kg for 4 days,
oral ciclosporin A (CsA) 75 mg twice daily (total daily dose of 2mg/kg
per body weight) and concomitant upfront subcutaneous granulocyte-colony
stimulating factor (G-CSF) 300mcg once daily. Serum sickness prophylaxis
in the form of intravenous methylprednisolone 1mg/kg 30 minutes before
and after the ATGAM was also administered. The oral CsA was titrated
slowly to a maximum of 125mg twice daily (total daily dose of 3mg/kg per
body weight) in view of the patient’s age and risk of nephrotoxicity in
the elderly. He was also given a thrombopoietin receptor agonist, oral
eltrombopag 50mg once daily and triple antimicrobial prophylaxis
(acyclovir, trimethoprim/sulfamethoxazole, and fluconazole). However, he
developed severe pneumonia and sepsis on Day 8 of ATGAM therapy which
necessitated oxygen support. The chest radiograph (Figure 2) showed
diffuse bilateral interstitial and nodular consolidation. The family
opted for palliation. He succumbed to his illness on Day 10 of
treatment.