Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation
Platelet recovery is significantly hampered following umbilical cord blood (UCB)
transplantation. Median time to platelet engraftment (defined as the first of 7 consecutive
days of an unsupported platelet count of at least 20,000/microliter) in a large
retrospective study was more than 70 days and cumulative incidence of platelet recovery at
6 months was 50.5%. In the pediatric population with acute leukemia median time to platelet
engraftment with UCB transplantation was 59 days and cumulative incidence of platelet
recovery at 6 months was 43%-73%, depending on human leukocyte antigen (HLA) disparity and
cell dose. Recently, in a cohort of adult patients given myeloablative conditioning followed
by double UCB transplantation, the cumulative incidence of platelet recovery (≥
50,000/microliter)at 100 days was 53%. In another cohort of patients given reduced intensity
conditioning regimen followed by single or double UCB transplantation, the median time to
platelet recovery (≥ 50,000/microliter) and cumulative incidence of platelet recovery at 6
months were 49 days and 65%, respectively. Thus, after UCB transplantations, patients are
platelet transfusion-dependent for prolong periods of time, resulting in many drawbacks,
such as exposure to blood transfusions hazards, higher incidence of platelet allo-reactivity
and extended periods of bleeding diathesis and undesirable costly and long hospitalizations.
Eltrombopag is a thrombopoietin-receptor agonist that initiates thrombopoietin-receptor
signaling and thereby inducing proliferation and maturation of megakaryocytes.Administration
of eltrombopag increased platelet production in volunteers with normal platelet counts,
patients with thrombocytopenia secondary to hepatitis C virus infection and in patients with
chronic immune thrombocytopenic purpura.
We will evaluate the safety and efficacy of eltrombopag treatment given early after UCB
transplantation. The study is an open non-comparative study. The primary outcome will be
cumulative incidence of partial platelet engraftment (first of 7 consecutive days of an
unsupported platelet count of at least 20,000/microliter)at day 50 post transplantation.
Secondary objectives are safety, tolerability and other transplantation related outcomes.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Platelet engraftment rate up to 50 days post transplantation, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter.
Moshe Yeshurun, MD
Rabin Medical Center
Israel: Ethics Commission