Background: Aplastic anemia (AA) is a rare disease, with an incidence of 1-2 new cases per million per year in Europe and North America. Primary therapies for AA for patients who do not have a sibling or matched unrelated donor or are unfit for allogeneic hematopoietic stem cell transplantation (HSCT) include immunosuppressive therapy (IST) with the combination of antithymocyte globulin (ATG) and calcineurin inhibitors. Therapeutic options beyond IST are limited and include eltrombopag, which was approved by the US FDA for use in patients with severe AA who fail to respond adequately to IST. The health economic burden of this rare and debilitating condition is poorly understood, especially for refractory cases.

Objective: To examine health resource utilization associated with severe AA among patients with insufficient response to IST in real-world practice settings in a recent time period.

Methods: We conducted a retrospective, longitudinal chart review of patients with severe AA treated at clinical centers in the US (Dana-Farber Cancer Institute [DFCI]) and France (Service d'Hématologie Greffe, Hôpital Saint-Louis [AGRAH]). Severe AA in this study was identified as having bone marrow cellularity <25%, or 25-50% with <30% residual hematopoietic cells; and at least two of the following laboratory findings: neutrophil count <500 cell/µL, platelets <20,000/µL, reticulocyte count <20,000/µL. Eligible patients were ≥18 years old, first diagnosed with severe AA between January 1, 2006 and January 31, 2016, had insufficient response to at least one course of IST following severe AA diagnosis, and had ≥12 months of medical data after first diagnosis with severe AA. Patients with congenital disorders of hematopoiesis were excluded. Kaplan-Meier method was used to analyze time from first IST to time of HSCT. Cumulative incidence and incidence rates were used to summarize frequency of blood transfusions and AA-related health care resource utilization. The study was approved by local IRB.

Results: The study included 34 refractory severe AA patients (NDFCI=20; NAGRAH =14). Mean age at severe AA diagnosis was 43.3 (standard deviation [SD]: 16.8) years and 52.9% (18/34) of patients were women. Median follow-up time after severe AA diagnosis was 56.1 (range: 12.0-118.7) months. Thirty-three (97.1%) patients received ATG in combination with calcineurin inhibitor (cyclosporine or tacrolimus) with or without corticosteroid as primary therapy. Among patients treated with ATG, 51.5% (17/33) patients received only one course of ATG and 48.5% (16/33) patients received ≥2 courses of ATG. The most common secondary AA therapy included eltrombopag (17.6%, N=6) and androgens (8.8%, N=3). The median treatment duration for eltrombopag was 6.4 (range: 5.6-53.4) months. The average frequency of transfusions per patient per month was 2.8 (SD: 2.8) red blood cell (RBC) and 3.3 (SD: 3.5) platelet transfusions. The mean AA-related health care utilization rates per patient per year were 0.8 (95% confidence interval [CI]: 0.6, 1.0) for inpatient visits, 0.5 (95% CI: 0.4, 0.8) for emergency room visits, and 19.1 (95% CI: 17.9, 20.5) for office visits prior to undergoing HSCT. Among the subgroup of patients treated with eltrombopag, the mean number of RBC transfusions per patient per month was reduced from 2.4 (SD: 2.0) before to 0.9 (SD: 0.8) after eltrombopag treatment, and from 3.0 (SD: 2.3) to 1.3 (SD: 1.6) for platelet transfusions. Similarly, AA-related health care utilization rates were lower after eltrombopag initiation (∆inpatient visits: -0.3 (95% CI: -1.1, 0.5); ∆emergency room visits: -0.6 (95% CI: -1.5, 0.4); ∆office visits: -11.7 (95% CI: -16.2, -7.1) per patient per year). Thirty (88.2%) patients received HSCT with a median time of 12.9 (95% CI: 7.9, 17.3) months after first IST initiation. During the follow-up period, 29.4% (10/34) patients died; nine patients died after HSCT. Two (5.9%) patients transformed to myelodysplastic syndrome and/or acute myeloid leukemia.

Conclusion: This is one of the first studies to quantify the transfusion and health resource burden of refractory severe AA. In a small subgroup of patients receiving eltrombopag, there was a trend toward reduction in blood transfusion frequency, AA-related hospitalization rate, and outpatient office and emergency room visits after eltrombopag initiation.


Peffault De Latour: Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Amgen: Research Funding. Huynh: Novartis Pharmaceuticals Corporation: Research Funding. Ivanova: Novartis, GSK, Teva, Lilly: Research Funding. Totev: Novartis Pharmaceuticals Corporation, Shire Pharmaceuticals Inc.: Research Funding. Bilginsoy: Novartis Pharmaceuticals Corporation: Research Funding. Roy: Novartis: Employment, Equity Ownership. Duh: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.