Aplastic Anaemia in Patients Aged Over 40, or Without an HLA-Matched Sibling Donor: First-Line Treatment
Acquired severe or very severe aplastic anaemia (SAA/VSAA) follows a different first-line pathway when allogeneic transplantation from an HLA-matched sibling is not the chosen option — whether because no matched donor exists, or because the patient is older than 40 years.
Clinical Scenario
This protocol applies to patients with acquired SAA or VSAA in two overlapping settings: the absence of an available HLA-matched sibling donor (MSD), or the presence of an MSD in a patient aged over 40 years. For patients aged 40–50 with a matched sibling, transplantation may remain appropriate depending on performance status, comorbidities, and centre expertise; for those outside that window, non-transplant first-line treatment is the indicated path.
First-Line Treatment Approach
The established approach for this population is combination immunosuppressive therapy, with horse anti-thymocyte globulin (ATG) as a central component. The full regimen — including all agents involved, their sequencing, and monitoring requirements — is contained in the complete protocol.
Treatment Goals
The target is haematological response by 6 months, including transfusion independence. A complete response requires haemoglobin normalisation for age and sex, together with defined neutrophil and platelet count thresholds.
References
DOI: 10.1111/bjh.19236
- SAA/VSAA in the absence of a MSD.
- SAA/VSAA with a MSD and >40 years of age (patients aged between 40 and 50 years with MSD could be considered for HSCT depending on performance status and comorbidities, in addition to centre expertise).
- The dose of horse ATG (ATGAM®) is 40 mg/kg/day for 4 days.
- CSA is commenced on Day 1 of ATG at a dose of 5 mg/kg/day to achieve trough blood levels of 150–200 μg/L.
- Eltrombopag is administered orally at a dose of 150 mg per day from Day 14 through 6 months or through 3 months in patients who have achieved a CR at 3 months.
- Prednisolone is used with ATG for the sole purpose to abrogate infusion-related side effects and prevent serum sickness.
- Response to ATG (as defined in Table 7) is delayed, starting after an average of 3–4 months.
- For SAA, the 6-month response rate is 50%–70%, and it is lower in VSAA (23%).
- Complete | Haemoglobin concentration normal for age and gender | Neutrophils >1.5 × 10⁹/L | Platelets >150 × 10⁹/L