The patient has aplastic anemia (AA). He presents with an insidious clinical course and has severe pancytopenia. The absolute neutrophil count is only 50/µL (0.05 × 109/L). Despite severe neutropenia, AA may present with clinically unimpressive infections. This contrasts with the acute leukemias. The bone marrow biopsy demonstrating less than 10% cellularity confirms the diagnosis of aplasia. AA may occur secondary to infections or toxins. However, it usually presents without preceding insult. Such patients respond to immunosuppressive therapy, and allogeneic hematopoietic stem cell (HSC) transplantation can be curative in young otherwise healthy patients.
Acute lymphoblastic leukemia (ALL) is a reasonable consideration in this patient, because ALL is more common in adolescents and young adults. It can present with pancytopenia rather than hyperleukocytosis. However, the bone marrow biopsy excludes ALL, because leukemic blasts more typically cause marrow hypercellularity; very few blood-making cells are present on this patient's biopsy. For the same reason, acute myeloid leukemia can be excluded.
The myelodysplastic syndromes (MDS) are clonal HSC disorders characterized by ineffective hematopoiesis and a variable rate of transformation to acute myeloid leukemia. MDS can present with pancytopenia, although it occurs less commonly in younger patients. However, the bone marrow in MDS is classically hypercellular. Although hypocellular MDS exists, crossover with AA is considerable, and the decrease in marrow cellularity is not this striking.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired HSC disorder that should be considered in patients presenting with hemolytic anemia, pancytopenia, or unprovoked atypical thrombosis. The bone marrow is usually hypocellular with PNH, but other features such as hemolysis and thrombosis are present, distinguishing it from AA. Likewise, the degree of hypocellularity is not as severe as that of AA.
