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Ferrata Storti Foundation
Acute Myeloid Leukemia
Gemtuzumab ozogamicin in children
with relapsed or refractory acute myeloid leukemia: a report by Berlin-Frankfurt-Münster study group
1
Haematologica 2018 Volume 104(1):120-127
Naghmeh Niktoreh,1* Beate Lerius,1* Martin Zimmermann,2 Bernd Gruhn,3 Gabriele Escherich,4 Jean-Pierre Bourquin,5 Michael Dworzak,6
Lucie Sramkova,7 Claudia Rossig,8 Ursula Creutzig,2 Dirk Reinhardt1
and Mareike Rasche1
Department of Pediatric Hematology and Oncology, University Hospital Essen, Germany; 2Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany; 3Department of Pediatrics, Jena University Hospital, Germany; 4Department of Pediatric Hematology and Oncology, Eppendorf University Hospital, Hamburg, Germany; 5Division of Pediatric Hematology/Oncology, University Children’s Hospital Zurich, Switzerland; 6St. Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Austria; 7Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic and 8University Children’s Hospital Münster, Pediatric Hematology and Oncology, Germany
*NN and BL contributed equally to this work as first authors.
ABSTRACT
Despite intensified salvage treatments, children with relapsed/refractory acute myeloid leukemia (AML) have poor survival. We evaluated gemtuzumab ozogamicin (CD33-targeted drug) used on a compassionate basis in patients diagnosed from 1995 until 2014 within Acute Myeloid Leukemia Berlin-Frankfurt-Münster studies, and identified 76 patients (<18 years) with highly-advanced and pre-treated AML [refractory de novo acute myeloid leukemia (n=10), de novo AML refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or more: n=10), and secondary AML (n=5)]. At doses of 2.5-10 mg/m2, gem- tuzumab ozogamicin was administered in 1-4 cycles as single agent (47%), combined with cytarabine (47%), or others (6%). Most common grade 3/4 adverse events were infections or febrile neutropenia (78% of severe adverse events), infusion-related immunological reactions (6%), and gastrointestinal symptoms (5%). Three patients experienced veno- occlusive disease (one fatal due to exacerbation of a pre-existing car- diomyopathy). Sixty-four percent received subsequent hematopoietic stem cell transplantation. Probability of 4-year overall survival was 18±5% in all, 27±7% in patients with and 0% in patients without hematopoietic stem cell transplantation (P<0.0001). Administration of gemtuzumab ozogamicin on a patient-specific, compassionate use basis was frequently considered in our study group and proved to be effective for bridging children with very advanced AML to hematopoietic stem cell transplantation. Uniform prospective studies for these patients are urgently needed.
Introduction
Treatment of acute myeloid leukemia (AML) in children has improved remark- ably during the past decades; however, pediatric patients with relapsed and refrac- tory AML still have poor outcomes.1-6 These outcomes rely on disease-dependent characteristics, such as initial cytogenetics, in addition to response-to-therapy-relat- ed factors like the interval between initial diagnosis and relapse.7-10 Considering poor outcome and high toxicity of current salvage therapies, new targeted molecu- lar treatments are needed.11-13
Gemtuzumab ozogamicin (GO) is an immunotoxin consisting of a potent humanized monoclonal antibody against CD33, and targets CD33 positive cells
Correspondence:
mareike.rasche@uk-essen.de
Received: February 23, 2018. Accepted: August 3, 2018. Pre-published: August 31, 2018.
doi:10.3324/haematol.2018.191841
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/1/120
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