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.