Aplastic Anemia: Effectiveness and Safety of Treatment Profiles Depending On Age

The treatment of acquired aplastic anemia (AA) is based on allogeneic hematopoietic cell transplantation (HCT) and immunosuppressive therapy (IST). The choice between immunosuppression or HCT is based on the availability of a sibling donor and on the patient's age. According to the PETHEMA group's guidelines for the diagnosis and management of aplastic anaemia, patients over 40 years old are not considered for HCT as first-line therapy, while there is no age limit for immunosuppressive treatment. The decision of whether to treat older patients is based on their performance status.

To compare the safety and effectiveness of treatment profiles, mortality rates and causes of death in adults with AA depending on age (over or under 60 years old).

We reviewed clinical histories of patients who have been treated for AA at our hospital over the last ten years (2002–2012). Patients were divided in to 2 groups: over 60 year olds and under 60 year olds. We collected data on age, sex, disease severity, treatment protocols and toxicities, type and duration of response to therapy, mortality and cause of death. Data source: clinical histories. Statistical desciption, non inferential because of the low level of patients.

We identified 15 patients in total, 7 over 60 and 8 under 60 years old. One of the over 60 year olds was excluded from the study due to incomplete follow-up. Of the 6 remaining over 60 year old patients all were female and they had a median age of 73 years (r, 63–87 years), while in the under 60 group, 50% of the patients were male with a median age of 30.5 years (r, 19–49 years).

50% of the over 60 year olds had a Charlson Index score of 2 or more. The Charlson index in the under 60 year olds was 0, with the exception of 1 subject (11.1%) with a score of 2 (due to chronic lung and liver disease).

We observed a higher rate of moderate AA in the under 60 year olds (62.5% vs 50%) and 1 case of severe AA and 2 cases of very severe AA in each group respectively.

100% of over 60 year olds received treatment with ciclosporin (CsA) in combination with other immunosuppresant drugs (in 3 cases associated with antithymocyte-globulin (ATG) and corticosteroids). After a median follow-up of 300 days (r, 90–1044 days), only 1 patient of the 6 responded to therapy, obtaining a partial response (PR) which lasted 953 days.

In the under 60 group 2 of the patients (25%) recieved an allogeneic HCT obtaining a complete response (CR) in both cases, which they maintain after a median follow-up of 1870 days (r, 1781–1960 days). The remaining 75% received treatment with IST. In this group we observed 2 CR, 3 PR and one non-responder. All responses are maintained after a median follow-up of 1038 days.

Toxicities observed in the over 60s consisted of 3 cases of diabetes mellitus, 1 case of renal failure and 3 severe infections in three different patients, while 62.5% of the under 60s suffered from infectious complications.

In the over 60 year old group we observed 3 cases of exitus (50%). At 15 months global survival was of 40% for non-responders, clearly inferior to the survival of the only responder. However in the under 60 year old group there was only 1 case of exitus corresponding to the non-responder and a global survival of 87.5% after a median follow-up of 1602 days (r, 643–3094).

Treatment of AA in patients under 60 years old is effective and safe. The incidence of serious adverse events and mortality rates are low. Survival is superior in patients treated with HCT than in those treated with IST. Outcomes of IST are related to patient age. Response rates in over 60 year olds are low, although the higher survival rates in responders clearly support the indication of IST.

No relevant conflicts of interest to declare.