Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis
Blood Advances, vol. 4, pp. 1998–2010
Abstract
Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation-approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti-T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH.
Authors 23
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University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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Bristol Royal Hospital for Children
Affiliation as printed
Department of Hematology, Oncology and BMT, Bristol Royal Hospital for Children, Bristol, United Kingdom;
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Affiliation as printed
Department of Pediatrics, Jena University Hospital, Jena, Germany;
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Affiliation as printed
Department of Pediatrics, Institut of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;
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Royal Manchester Children's Hospital
Affiliation as printed
Department of Blood and Marrow Transplant, Royal Manchester Children’s Hospital, Manchester, United Kingdom;
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University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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Affiliation as printed
Department of Pediatrics, Jena University Hospital, Jena, Germany;
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University of Freiburg · University Medical Center Freiburg
Affiliation as printed
Institute of Immunodeficiency, Center for Chronic Immunodeficiency, University Medical Center, Faculty of Medicine, University Hospital, Freiburg, Germany;
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
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Affiliation as printed
Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland;
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Great North Children's Hospital
Affiliation as printed
Institute of Cellular Medicine, Pediatric Immunology Department, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom;
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LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany;
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LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany;
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Affiliation as printed
Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom;
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Affiliation as printed
Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom;
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Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Experimental Cancer Medicine, KFC, Novum Karolinska University Hospital and Karolinska Institutet Huddinge, Huddinge, Sweden; and
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Leiden University Medical Center · Willem-Alexander Kinderziekenhuis
Affiliation as printed
Department of Pediatrics/Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands
Department of Pediatrics/Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands
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University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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Mathias M. Hauri-Hohl corresponding
University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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Tayfun Güngör corresponding
University Children's Hospital Zurich
Affiliation as printed
Department of Immunology. Hematology, Oncology and SCT, University Children’s Hospital, Zurich, Switzerland;
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