Received: 7 July 2019 Revised: 20 August 2019 Accepted: 8 September 2019 DOI: 10.1002/pbc.28010 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology BRIEF REPORT Successful treatment with daratumumab for post-HSCT refractory hemolytic anemia Ehud Even-Or 1 Adeeb Naser Eddin 1 Bella Shadur 1,2,3 Yael Dinur Schejter 1 Mohammad Najajreh 4 Orly Zelig 5 Irina Zaidman 1 Polina Stepensky 1 1 Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 2 Immunology Division, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia 3 Graduate Research School, University of New South Wales, Sydney, New South Wales, Australia 4 The Huda Al Masri Pediatric Cancer Department, Beit Jala Hospital, Beit Jala, Palestine 5 Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Correspondence Ehud Even-Or, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, POB 12000, Jerusalem 91120, Israel. Email: udi.evenor@gmail.com Funding information Australian Government; Hadassah Australia; Deutsche Forschungsgemeinschaft, Grant/Award Number: DFG WA 1597/4-2; ERA-Net ERARE Abstract Autoimmune cytopenias (AIC) following allogeneic hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality and are often challenging to treat. We present a case of a pediatric patient with primary myelofibrosis of infancy caused by VPS45 pro- tein deficiency, who developed severe refractory hemolytic anemia and immune-mediated throm- bocytopenia 3.5 months following HSCT. After the failure of several treatments, he received dara- tumumab, an anti-CD38 specific antibody, and demonstrated fast and sustained response. The only side effect was delayed recovery of humoral immunity. Daratumumab, by targeting antibody- producing plasma cells, may be a valid treatment option for refractory post-HSCT AIC. KEYWORDS autoimmune hemolytic anemia, daratumumab, HSCT, immune cytopenia 1 INTRODUCTION Autoimmune cytopenias (AIC) following allogeneic hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality and are often challenging to treat. 1 The incidence of AIC in children following HSCT is around 3%, and may present as autoim- mune hemolytic anemia (AIHA), thrombocytopenia, red cell aplasia, neutropenia, or any combination of these phenomena. 2,3 Up to 60% of patients respond incompletely to corticosteroids or to second-line treatments such as rituximab, and in some cases remain refractory. 3,4 Daratumumab is a monoclonal antibody targeting CD38 on the sur- face of malignant plasma cells and was approved for treatment of mul- tiple myeloma in 2015. 5 As daratumumab may target autoantibody- producing plasma cells, there is a rationale for its effect on patients Abbreviations: AEs, adverse events; AIC, autoimmune cytopenia; AIHA, autoimmune hemolytic anemia; DAT, direct antiglobulin test; GvHD, graft-versus-host disease; Hgb, hemoglobin; HSCT, hematopoietic stem cell transplantation; IVIG, intravenous immunoglobulins; LDH, lactate dehydrogenase; PBSC, peripheral blood stem cell. with refractory AIC. Recently, there have been reports of successful treatment of resistant post-HSCT AIHA and of post-HSCT pure red cell aplasia with daratumumab. 6–8 We present here a case of a pediatric patient with primary myelofi- brosis of infancy caused by VPS45 protein deficiency, who developed severe refractory post-HSCT hemolytic anemia and thrombocytopenia and was successfully treated by daratumumab with complete resolu- tion of symptoms and normalization of blood counts. 2 CASE DESCRIPTION Our patient is now a 2-year-old male who initially presented at the age of 5 months with a history of multiple life-threatening infections, severe anemia, and profound neutropenia. Whole exome sequencing was performed and c.671 C > A; p.224N mutation in the VPS45 gene was found. VPS45 deficiency is a genetic disorder causing congeni- tal neutropenia and primary myelofibrosis of infancy. 9 The child was transplanted with a peripheral blood stem cell (PBSC) collected graft Pediatr Blood Cancer. 2019;e28010. c  2019 Wiley Periodicals, Inc. 1 of 4 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.28010