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A 32-year-old woman is referred for evaluation because of a three-month history of fatigue, easy bruising, and menorrhagia. Physical examination shows multiple ecchymoses on the extremities. Laboratory studies show the following:

Examination of a bone marrow biopsy specimen shows five percent cellularity, no dysplasia, and normal cytogenetics. A diagnosis of severe aplastic anemia is made. HLA typing reveals no match with the patient’s sole sibling, and upon initial analysis, no unrelated donors were identified in the registry. Which of the following is the most appropriate interim management?

1. Eltrombopag
2. Equine Anti-thymocyte globulin (ATG) + cyclosporine
3. Rabbit ATG + cyclosporine
4. Granulocyte-stimulating factor plus erythropoiesis-stimulating agent
5. Intravenous eculizumab
6. Tacrolimus and Oral prednisone

Answer: B

Educational Objective: Know the treatment of aplastic anemia in the younger patient.

Rationale: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice in aplastic anemia, especially in patient younger patients without co-morbidities. The risks associated with HSCT increase with age; thus, HSCT is usually second-line therapy for older patients who are refractory to immunosuppressive therapy. In this scenario, the patient is symptomatic without a donor identified.

Both forms of anti-thymocyte globulin (ATG), horse and rabbit, have been used in the setting of severe ATG. In a recent paper by Scheinberg and colleagues, horse ATG-treated patients had better hematologic response and survival outcomes, compared to rabbit ATG-treated patients in the first line setting.¹

Immunosuppressive therapy is the most appropriate choice while awaiting the availability of unrelated donor search. Patients treated with immunosuppressive therapy alone have a risk for development of clonal stem cell disorders (myelodysplasia, PNH). Whether this is due to an effect of the therapy or whether these disorders were present all along and became manifest after immunosuppressive therapy is uncertain.

Eltrombopag shows promising activity in immunosuppressive therapy refractory AA in restoring trilineage hematopoiesis, but it is still an investigation agent for this indication. There is a lack of efficacy in almost all cases of WBC and RBC colony-stimulating factors as well as in prednisone with calcineurin inhibitors alone. Eculizumab is not used for AA (even if there are “PNH-like cells”). Indications include PNH and atypical HUS.

Further Reading

Scheinberg P and Young NS. . Blood. 2012;120:1185-1196.

This question was developed for the In-Service Exam by the Test Materials Development Committee, Committee on Training, and the Trainee Council.

References

1. Scheinberg P, Nunez O, Weinstein B, et al. . N Engl J Med. 2011;365:430-438.