Case Descriptions
Case1. The initial course of this case was previously reported3. A currently 15-year-old male was diagnosed with ES at 9 years of age and later developed common variable immunodeficiency. He has had several lines of IST to control AIHA and ITP with initial responses followed by recurrences. He experienced long-lived remissions following rituximab therapy and later splenectomy. He presented with hemolysis and was then treated with bortezomib.
He received bortezomib at a dose of 1.3 mg/m2 on days 1, 4, 8, 11, and 26 partially based on the clinical trial for refractory autoimmune cytopenias following hematopietic stem cell transplant (Clinicaltrials.gov Identifier: NCT01930253). He experienced a dramatic clinical response with near-immediate improvement within 4 days of the first dose providing him a remission that lasted for 22 months until he developed thrombocytopenia. Following a single dose of bortezomib at 1.3mg/m2, he quickly achieved PLT count greater than 100x109/L in 2 weeks, providing an ongoing remission of 7 months so far (Table1).
Case2. A currently 2-year-old boy presented at 6 months of age with fever, severe anemia with a hemoglobin at 2.1g/dL, reticulocytes 0.1%, absent neutrophils and mild thrombocytopenia. Coombs test and anti-neutrophil antibodies (ANeA) were positive and IgM elevated at 351mg/dL (20-145). Bone marrow showed a paucity of erythroid precursors, myeloid left shift, and increased megakaryocytes consistent with pure red cell aplasia (PRCA). Investigation for known genetic causes of PRCA, hyper-IgM syndrome, a broad immune dysregulation gene panel and later whole exome sequencing (WES) did not identify a potentially causative mutation.
He had become refractory to various IST and stayed RBC transfusion-dependent due to continuing PRCA. Several episodes of infections associated with severe neutropenia requiring admissions resolved on filgrastim therapy. Later, PLT dropped to 1-2x109/L with active bleeding requiring several admissions with further elevation in IgM to 495mg/dL. Due to continuing life threatening bleeding of months duration, bortezomib therapy (total of 4 doses) was given. After the second dose of bortezomib, he showed an increase in PLT; all counts normalized with reticulocytosis two weeks from the first dose. He continues to have normal counts and normal IgM level with negative Coombs test a year following bortezomib therapy (Table1).
Case3. A 15-year-old male patient presented with persistent bleeding was found to have pancytopenia with positive Coombs test and ANeA, and elevated IgG level. He had poor response to several different therapeutic interventions (Table1). Therapy with a thrombopoietin (TPO) receptor agonist (TRA), romiplostim resulted in PLT recovery with continiuing neutropenia and mild anemia. However, he later required higher and more frequent doses of romiplostim. He developed several episodes of tonsillitis and tonsillar enlargement that has resolved after rituximab-biosimilar treatment. After a short-lived improvement in PLT, he needed romiplostim again to maintain PLT count. Therefore, he was treated on the same regimen of bortezomib. However, after a temporary improvement in his PLT and neutrophils, he dropped counts and was restarted on romiplostim. WES analysis did not identify a causative variant that could be associated with ES development. Bortezomib was tolerated well without any observed adverse effects in all three patients.