Hypoplastic MDS with PNH Clone Treated Successfully with Eculizumab
Authors: John Sonia , Parekh Hiral , Qubaiah Osama , Selby George B. , Holter Chakrabarty Jennifer L. 
Published: October 2019

Abstract
Abstract 4380
Myelodysplasia (MDS) is a myeloid clonal disorder with a relatively heterogeneous spectrum of presentation characterized by dysplastic and ineffective hematopoiesis. Hypocellular or hypoplastic MDS is a rare variant of MDS and is found in <15 % of patients at the time of diagnosis. Severe aplastic anemia (SAA) is defined as less than 10% marrow cellularity associated with anemia, thrombocytopenia and neutropenia and global marrow failure. Paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal hematopoietic disorder which presents as chronic intravascular hemolysis, venous thrombosis, deficient hematopoiesis and can be found in both severe aplastic anemia and MDS. The diagnosis of PNH can be made by measuring the direct expression of the phosphatidylinositolglycan (PIG) anchored surface molecules. Surface markers for CD59 (all lineages), CD55 (neutrophils, monocytes, lymphoid cells) and CD14 (monocytes) are analyzed for deficiency. In clinical practice, these three diagnoses often have significant overlap, with no clear thresholds for the level of clone for which therapy should be directed. Although treatment of PNH and aplastic anemia has been well defined, treatment of small clones that are PIG deficient in MDS and aplastic anemia patients is not clear.
Here we present a case of a 69-year-old patient who was found to have macrocytic anemia leading to a diagnosis of hypoplastic MDS/aplastic anemia by bone marrow biopsy and flow cytometry. Bone marrow biopsy showed hypocellular marrow with granulocytic and megakaryocytic hypoplasia and had 1% myeloblasts, mild myelodysplastic features and no chromosomal abnormalities. Standard treatment with Anti-thymocyte globulin (ATG) and cyclosporine (CSA) was initiated at diagnosis 2 years ago. Patient achieved transfusion independence, and went into a complete remission that lasted 6 months. As shown in attached graph, patient developed recurrent thrombocytopenia, and was retreated with ATG & CSA with minimal improvement. Our patient has remained transfusion dependent of both platelets and red cells. Bone marrow biopsy was repeated which showed persistent aplastic anemia/hypoplastic MDS. PNH evaluation was performed showing a small clone of PIG deficient cells quantified as 0 % red cell, 2% granulocytes and 0.9% monocytes cells. Of note, PNH evaluation at the initiation of therapy showed no PNH clone. Eculizumab was instituted after failure of second dosing of ATG, dosed weekly for the last 18 months. Transfusion independence was obtained within 2 months, and as seen in the attached graph, the platelet counts improved significantly after therapy with Eculizumab. Similar response was reflected in other cell lineages. Bone marrow biopsy performed 4 months after therapy showed hypercellular marrow with mild dysplastic changes, cytogenetic analysis remains normal. Patient continues to be treated with eculizumab and has maintained a complete remission for over 18 months. As noted in a study done by Kaiafa et al, up to 15.5% of of MDS patients may exhibit a PNH clone, defined in the study by deficiency of CD55 and CD59 on granulocytes. The diagnosis Hypoplastic MDS/aplastic anemia is usually highly sensitive to therapy with ATG and CSA. Although our patient initially responded to ATG, retreatment at relapse was not successful. Eculizumab has documented a significant and sustained response in this patient’s treatment. We report a patient with a less than 1% clone that achieved complete transfusion independence with eculizumab and full resolution of hypoplastic MDS/severe aplastic anemia by marrow histology.

Disclosures:
No relevant conflicts of interest to declare.