Romiplostim for the treatment of a megakaryocytic thrombocytopenia secondary to remission-inducing immunomodulation in a patient with relapsing acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation.

Abstract

6609 Background: Amegakaryocytic thrombocytopenia (AmegTP) is a rare immune mediated cause of thrombocytopenia (TP). We report a 57 y.o. woman who developed AmegTP as a result of immune modulation with interferon-α (IFN-α) and GM-CSF for acute B lymphoblastic leukemia (B-ALL) recurrence after allogeneic hematopoietic stem cell transplantation (HSCT). Results: B-ALL relapse was documented on day +71 post HSCT both extramedullary (subcutaneous scalp nodule) and with leukemic cells comprising 10% of bone marrow (BM) cellularity. Donor unavailability did not allow for 2nd HSCT or donor lymphocyte infusion. Immunosuppression was stopped immediately. On day +80, IFN-α (1-3x10E6 units) and GM-CSF (500μg) were commenced three times a week in order to augment graft versus leukemia responses. The nodule resolved within 3 weeks and BM analysis on day +97 showed a hypocellular marrow but no evidence of disease. IFN-α was stopped on day +101 due to pancytopenia. GM-CSF (if ANC <1/nl) and transfusion support were continued. TP persisted and transfusion refractoriness evolved. BM analysis on day +125 confirmed remission with 35% overall cellularity, spotty aplasia and absent megakaryocytes, consistent with AmegTP. A positive ANA screen suggested an immune-mediated cause. The patient received 1 course of high dose methylprednisolone plus IVIG (1g/kg). Parallel, a thrombopoietin receptor agonist (TRA) Romiplostim was started on day +127 at 1μg/kg and then increased by 1μg/kg every 7 days. No platelet transfusions were required after day +181 at a Romiplostim dose level of 8μg/kg, and platelets increased to 54/nl at a max. dose of 10 μg/kg. BM analysis on day +205 confirmed remission with normal myelo- and erythropoiesis and adequate maturing megakaryocytes. Conclusions: The observed supportive effects of Romiplostim on megakaryocyte expansion and proliferation in the context of AmegTP in our patient support the need for further studies on the efficacy and safety of TRAs in the post-HSCT setting.