eltrombopag for enhancing platelet engraftment in adult patients undergoing cord blood transplantation

Conditions: Hematological Malignancy; Bone Marrow Failure Syndrome

Summary: the purpose of this study is to determine whether eltrombopag may shorten time to platelet engraftment after allogeneic 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.

Eligibility criteria:
inclusion criteria: 1. patient ≥ 18 year old. 2. patients receiving unmanipulated single or double umbilical cord blood allogeneic grafts. 3. malignant and non malignant indications for transplantation. 4. myeloablative and reduced intensity conditioning regimens. 5. patients must meet all other pre-transplantation criteria of the transplantation center including acceptable tests of heart, liver, kidney, and lung function (standard screening for transplantation per pi, and co-investigators). 6. able to give written informed consent for a clinical trial. 7. able to comply with study protocol. exclusion criteria: 1. indications for transplantation 1. patients with primary myelofibrosis. 2. m7 (french-american-british classification) acute myeloid leukemia. acute leukemia secondary to a myeloproliferative neoplasm. 3. patients with persistent acute leukemia (\>5% bone marrow blasts) at the time of transplantation. 2. patients with prior thromboembolic event. patients with previous catheter related thrombosis will be eligible if more than 3 months elapsed. 3. hypersensitivity to eltrombopag. 4. liver enzymes abnormalities: alanine transaminase (alt) levels \> 3 times the upper limit of normal (uln) or serum bilirubin \> 1.5 uln (unless due to gilbert's syndrome or hemolytic bilirubin). 5. pregnancy: women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. a woman of child-bearing potential is defined as a woman who has not been naturally post-menopausal for at least 12 consecutive months or with no previous surgical sterilization.

Keywords: cord blood transplantation eltrombopag platelet engraftment