1. Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis
- Author
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Felber, M., Steward, C.G., Kentouche, K., Fasth, A., Wynn, R.F., Zeilhofer, U., Haunerdinger, V., Volkmer, B., Prader, S., Gruhn, B., Ehl, S., Lehmberg, K., Muller, D., Gennery, A.R., Albert, M.H., Hauck, F., Rao, K., Veys, P., Hassan, M., Lankester, A.C., Schmid, J.P., Hauri-Hohl, M.M., Gungor, T., Inborn Errors Working Party IEWP E, European Soc Immunodeficiencies ES, and University of Zurich
- Subjects
medicine.medical_specialty ,Hemophagocytic lymphohistiocytosis ,business.industry ,medicine.medical_treatment ,2720 Hematology ,610 Medicine & health ,Hematology ,Hematopoietic stem cell transplantation ,Defibrotide ,medicine.disease ,Gastroenterology ,Fludarabine ,medicine.anatomical_structure ,10036 Medical Clinic ,Cord blood ,Internal medicine ,540 Chemistry ,Medicine ,Alemtuzumab ,Bone marrow ,business ,Busulfan ,10038 Institute of Clinical Chemistry ,medicine.drug - 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.
- Published
- 2020