Avatrombopag Safe and Effective in Treatment of Severe Refractory Thrombocytopenia in a Pediatric Patient with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation

Background Severe thrombocytopenia following HSCT can be caused by poor graft function, graft-versus-host disease (GVHD), infections, drug toxicities, underlying autoimmune diseases and relapse of underlying disease which can lead to an increase in morbidity and mortality. Avatrombopag is a second generation TPO-RA approved for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients with poor response to standard treatments or in patients with chronic liver disease (CLD) associated thrombocytopenia requiring surgical interventions. Phase III clinical trials have shown greater platelet responses in chronic ITP and reduced transfusion needs in patients with CLD. We describe the use of avatrombopag in a pediatric patient with chronic severe thrombocytopenia (<10 × 103/uL) post HSCT. Objective Describe the use of avatrombopag for severe refractory thrombocytopenia in a pediatric alloHSCT recipient. Case Presentation We present a 14-year-old Hispanic male with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia who received a maternal haploidentical HSCT. His post HSCT course was complicated by adenoviremia, hepatic variant GVHD, Enterobacter cloacae bacteremia and poor graft function. Seven months following HSCT, patient was found to be severely pancytopenic. Bone marrow morphology revealed 20-30% cellularity without evidence of relapse or GVHD. He received a stem cell boost for presumed poor graft function. Patient demonstrated partial response by resolution of neutropenia and anemia; however, severe thrombocytopenia persisted. Multiple bone marrow evaluations remained negative for disease with full donor chimerism. Platelet antibodies remained negative and all findings consistent with persistent severe ITP. He failed multiple treatments including romiplostim; eltrombopag; high dose immune globulin (IVIG); rituximab; methylprednisolone; and decitabine (Fig 1). Due to the severity of disease, he was granted a compassionate use investigational new drug (IND 165837) for avatrombopag and began on day +332. Dosing was initiated at 20 mg daily with a dosage adjustment to achieve platelet recovery to >50 × 103/uL free from transfusion. The dose was titrated per manufacturer to maximum dose of 40 mg daily with response to platelet count >100 × 103/uL in approximately 6 weeks time. By 3 months of treatment, dose was titrated down 40 mg 3 times a week and 20 mg on alternating days. Patient continues to maintain platelets above 100 × 103/uL with no medication toxicities or adverse events noted. Conclusion Avatrombopag was well tolerated and provided a sustained response in a pediatric patient with refractory thrombocytopenia post haploidentical HSCT. Further data to be reported on this case, as well as the manufacturer Phase III trial will provide additional data for its use in the pediatric population (NCT04516967).