Use of Romiplostim to Facilitate Platelet Engraftment in Allogeneic Hematopoietic Transplantation

Abstract

Abstract 1947 Background:Thrombocytopenia requiring platelet transfusions is a constant in the hematopoietic transplantation (HT). In some situations, like the adult non-related donor and cord blood HT, the platelet engraftment is delayed for a long time. Hemorrhagic cystitis, venooclusive disease, graft-vs-host disease could to worse these procedures with a very high risk of bleeding and to increase the transplantation morbi-mortality. The agonists of thrombopoietin receptor (TRAs) have demonstrated to increase the platelet production in different pathological situations, like in the ITP and MDS patients. Thus, these new drugs could have a potential benefit in other clinical situations with low platelet production. Methods:We describe our experience in seven patients with Allogeneic HT using Romiplostim (NPlate®, Amgen Inc.), a parenteral TRA peptide, to accelerate the platelet engraftment or to increase the platelet level in the thrombocytopenia induced by HT conditioning or HT related complications. We have administrated Romiplostim in a compassionate basis (off-label). In all cases the drug was administered subcutaneously at a dose of 250 mcg. Most of the patients received only one dose, with the exception of patients #1 and 7, whom received two doses separated by seven days. The first case, a woman diagnosed as Acute Lymphoblastic Leukemia (ALL) with severe HLA platelet refractoriness acquired in the induction and consolidation chemotherapy treatments previous to HT, received two doses of 250 mcg of Romiplostim on days +4 and +12 after peripheral blood progenitor cells infusion from an HLA matched brother. Results:In the first case, a rapid and sustained platelet level increase was obtained, without platelet transfusional support. Encouraged by this successful result, we have used Romiplostim in six more patients with platelet refractoriness to platelet transfusions with or without bleeding. In all the patients the spleen was present. The patient #6, obtained a previous platelet engraftment that was loosed with the beginning of severe cGVHD. (see table) Conclusion:The use of Romiplostim could be very useful in HT complicated by severe platelet transfusions refractoriness. Our data encourages the realization of a randomized prospective study with this drug in HT.#Sex AgeDiagnosis DateBaseline plateletsHT type Rationale for NPlate@Platelets on day +14 after administrDate day 0 HTDays after day 0 (Date administration)DosesResponse1♀ALL6PBC HLA matched brother11416/Dec/2009+5 & +122Yes56August 2009PSR(21 & 28/Dec/2009)2♂CMML3Cord Blood (3°)323/Feb/2010+12 (12/Jul/2010)2 (†)NO*58March 2006SSR3♂ALL19PBC MRD13129/Jun/2010+82 (04/Jan/2011)1Yes35April 2010aGVHD Delayed platelet engraft4♂AML14Cord Blood SSR3419/Jan/2011+29 (18/Feb/2011)1Yes21March 20065♂ALL22ANR14509/Feb/2011+11 (20/Feb/2011)1Yes18April 2010SSR6♀NHL23Alog MDR PBSC18023/Feb/2010+363 (21/Feb/2011)1Yes34August 2007VOD + Pneumonia ICU Bleeding34August 2007VOD + Pneumonia ICU Bleeding18023/Feb/2010+363 (21/Feb/2011)1Yes7♂AML4Cord Blood12505/Apr/2011+8 & +142Yes*49July 2010VOD+Hemorrhagic cystitis+Sepsis Gram-SSR(14 & 19/Apr/2011)Abbreviations: ALL: Acute Lymphoblastic Leukemia; AML: Acute Myeloblastic Leukemia; aGVHD: Acute Graft-vs-host disease, cGVHD: Chronic Graft-vs-host disease; ANR: Adult non-related; CMML: Chronic Myelomonocytic Leukemia; ICU: Intensive Care Unit; MRD: “Mismatched Related Donor “: 1 locus; NHL: Non-Hodgkin Lymphoma; PBSC: Peripheral blood stem cell; PSR: Primary severe HLA platelet refractoriness; SRR: Secondary severe platelet refractoriness; † death. VOD: venooclusive disease; * Patient # 2 received platelet transfusional support every 12 hours from the Romiplostim administration, patient #7 a daily platelet transfusion until the day +14 post-day 0 and the rest without platelet transfusional support from Romiplostim administration day. Number of platelets x109/LGraphic evolution of platelet count over time is depicted in the next figure: [Display omitted] Days after Romiplostim administration. Number of platelets x109/L. Disclosures:Ojeda:Amgen Inc.: Consultancy, Honoraria. Off Label Use: Romiplostim (Nplate)is an agonist of thrombopoietin receptor (TRAs) that have demonstrated to increase the platelet production in different pathological situations, like in the ITP and MDS patients.