Bone Marrow Failure Disorders

Presentation

A 36-year-old male with no significant past medical history presented to the emergency department with a dry cough and fatigue that had persisted for a couple of weeks. He reported easy bruising and subjective fevers, stating that he thought he had had “the flu.” The diagnostic work-up included CBC with differential, which showed a WBC of 2.4, absolute neutrophil count of 850/µL, Hgb 4.5, and platelet count of 22,000/µL. Iron studies, B12 and folate, LDH and haptoglobin were all within normal limits. The HIV/hepatitis work-up findings were negative. An abdominal ultrasound revealed normal spleen and normal liver. Flow cytometry for T-cell large granular lymphocyte (LGL) leukemia and paroxysmal nocturnal hemoglobinuria (PNH) was negative.

Differential Diagnosis

The differential diagnoses in this case included megaloblastic anemia, hypoplastic myelodysplastic syndrome (MDS), LGL leukemia, paroxysmal nocturnal hemoglobinuria (PNH), reversible infectious/toxin etiology, hypersplenism, and infiltrative malignancies (myeloproliferative neoplasms, acute myeloid leukemia, lymphomas, myeloma).

Final Diagnosis and Recommendations for Treatment

Bone marrow biopsy revealed hypocellular marrow (25%) with trilineage hypoplasia, no dysplasia or increase in blasts, no atypical lymphoid infiltrate identified, and no reticulin fibrosis. Cytogenetics revealed a normal male 46, XY karyotype, and FISH studies for MDS were normal. A next-generation sequencing 54-gene myeloid mutation panel revealed no mutations. Given the bone marrow biopsy findings and results of the other diagnostic studies mentioned above, the diagnosis was confirmed to be aplastic anemia.

The patient underwent immunosuppressive therapy—antithymocyte globulin plus cyclosporine with eltrombopag—as first-line treatment. He tolerated treatment well with no side effects. If the patient had not responded to this treatment, then the management plan would have been to proceed with an allogeneic HSCT.

A possible risk of this immunosuppressive regimen includes a hypersensitivity type of reaction such as fevers, hypotension, shortness of breath or wheezing, and rash. Therefore, an initial subcutaneous test dose should be given. Another possible risk is increased risk of infection, so patients should be monitored carefully. Patients are discharged on a 30-day steroid taper with GERD prophylaxis and are given oral antifungal prophylaxis during this time. In addition, patients should receive antiviral therapy and PCP prophylaxis while they being treated with cyclosporine. Transfusion requirements increase initially. Hypokalemia and hypomagnesemia occur frequently; therefore, potassium and magnesium levels should be monitored weekly, as should cyclosporine levels, until they are stable. It can take up to 6 months to see a response to treatment, and the goal would be to taper off of cyclosporine and eltrombopag at that time. It is important to monitor for evolving MDS or PNH following treatment. The advanced practitioner collaborates with the bone marrow transplant team should the patient need to undergo HSCT.