Low Dose Lenalidomide Induces Remission in Therapy Related 5q- Acute Myeloid Leukemia (AML).
Authors: Mageed Aly A. , Pietryga Daniel W. , Kidd Pamela G. , Warzynski Michael J. , Cornelius Albert S. , Nielsen Amy D. 
Published: October 2019

Abstract
Treatment of 5q- myelodysplastic syndrome (MDS) with single agent lenalidomide therapy eliminates hematologic and cytogenetic abnormalities resulting in decreased transfusion requirements (NEJM2005; 352(6):549–557). We report the induction and maintenance of disease remission by lenalidomide in a 20 year old white female with 5q- AML that developed following extensive treatment of stage 2A nodular sclerosing Hodgkin’s Lymphoma (HL). Remission after initial HL therapy with COPP/ABV lasted 21 months. Following first relapse, she received gemcitabine and vinorelbine with local radiotherapy. HL recurred and progressed. Therefore, 36 months after initial diagnosis, she was given Dexa miniBEAM (BCNU, etoposide, cytarabine, and melphalan) followed by BEAC and autologous PBSC transplant. With localized HL relapse 12 months after autologous PBSC transplant, her bone marrow showed mild dyspoiesis and multiple cytogenetic abnormalities including 5q−, 7q−, der17 and t(5:17). She was given three courses of RICE (rituximab, ifosfamide, carboplatin, and etoposide) followed by reduced intensity busulfan, fludarabine, ATG conditioning and MUD PBSC transplant. Within 2 months of this second transplant, peripheral blood blasts were noted and bone marrow again showed the previously noted cytogenetic abnormalities with 13% blasts consistent with MDS. A second MUD PBSC transplant followed FLAG (fludarabine, cytarabine, G-CSF) conditioning. Early after transplant, there was 95% donor chimerism but low levels of the cytogenetically abnormal clone remained. Within 4 months of the third transplant, bone marrow was dyspoietic with 43% erythroid blasts morphologically consistent with erythroleukemia (AML-M6). Cytogenetic abnormalities persisted and VNTR analysis showed only 35% donor cells. Treatment was started with lenalidomide 5mg po daily for 3 weeks followed by a one week rest. During therapy, there was resolution of fatigue and generalized bone pain. Hgb increased and only mild thrombocytopenia and neutropenia were noted at the end of week 3, course 1. There was clearance of peripheral blood blasts. Lenalidomide 10mg po daily during course 2 was not tolerated due to severe nausea. With return to 5mg po daily on day 6, there were no further adverse reactions during course 2. Platelet count increased and there was no neutropenia. Lenalidomide 5mg po daily was again well tolerated during a third course. Hgb increased with stable to slightly decreased platelet and neutrophil counts. Bone marrow aspirate during week 2 of course 3, showed normal 46 XX karyotype and absence of 5q-abnormality by FISH. Flow cytometry did not reveal the abnormal leukemic phenotype. VNTR analysis showed 100% allogeneic MUD chimerism. Of interest was the development of persistent eosinophilia up to 54% (absolute eosinophil count 2408/ML) during course 2. In a previous report of Lenalidomide therapy for MDS, 2 of 3 patients with eosinophilia responded to the treatment (NEJM2005; 352(6):549–557). This case demonstrates the efficacy of low dose Lenalidomide for AML developing from therapy related MDS in a heavily treated HL patient. To our knowledge, this is the first such case reported for a pediatric patient.