PANCYTOPENIA OF UNKNOWN PATHOGENESIS

It is important that a diagnosis be established between aplastic anemia due to the hypocellular nature of the specimen and a hypoplastic myelodysplastic syndrome. Although both of these entities can be treated with immunosuppressive agents such as ATG and Cyclosporin, it is my opinion that a repeat bone marrow aspirate and biopsy should be performed, including cytogenetic analysis, FISH analysis can be performed on the bone marrow specimen looking for chromosome 5, 7 and 8 abnormalities. In addition, the patient should be evaluated for the possibility of paroxysmal nocturnal hemoglobinuria with flow cytometries looking for the absence of CD55 and the absence of CD59 on granulocytes since this patient is heavily transfused. In addition, the bone marrow should be evaluated for iron stores if there are ring sideroblasts present in the bone marrow that would suggest myelodysplasia. Absence of iron would suggest paroxysmal nocturnal hemoglobinuria. These frequent transfusions may reflect enhanced hemolysis seen in patients with paroxysmal nocturnal hemoglobinuria so I feel that this diagnosis should be evaluated and, again, flow cytometry looking for CD55 and 59 expressions on peripheral blood granulocytes would be in the standard diagnostic approach.

Since the erythropoietin level is elevated it suggests that she is less likely to respond to erythropoietin, nonetheless, I would recommend that erythropoietin be started with weekly treatments. If the patient has a myelodysplastic syndrome then treatment options include the use of Revlimid which can be given especially if there is evidence for (5q) chromosome abnormality. If that is negative, then Vidaza (5 azacytidine) would be an appropriate choice in reducing transfusion requirements. On the other hand, the use of Cyclosporin and ATG is reasonable if this appears to be a hypoplastic myelodysplasia or aplastic anemia, but this would depend on a very good morphological evaluation of a repeat bone marrow, a cytogenetic analysis as well, to identify that diagnosis and, also, to rule-out the possibility of paroxysmal nocturnal hemoglobinuria causing this primary abnormality or resulting in the secondary defect causing the transfusion requirements that you are experiencing.

For now then, I think that additional diagnostic studies are required. The prognosis for this patient, if this is myelodysplastic syndrome, is poor, however, the newer treatments using Revlimid or Vidaza or Dacogen have been very helpful in improving quality of life and reducing transfusion requirements and reducing the time to blast transformation. Aplastic anemia can be treated successfully with Cyclosporin, ATG and prednisone with very good results. So the prognosis is really dependent on the diagnosis that is established. Paroxysmal nocturnal hemoglobinuria can be treated successfully now with a new antibody directed against compliment. This antibody, given weekly, can reduce the transfusion requirements and also reduce the risk of possible thromboembolic complications.