Research ExplorerPublicationsTargeted busulfan-based reduced-intensity conditioning and H...

Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis

Standard

Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis. / Felber, Matthias; Steward, Colin G; Kentouche, Karim; Fasth, Anders; Wynn, Robert F; Zeilhofer, Ulrike; Haunerdinger, Veronika; Volkmer, Benjamin; Prader, Seraina; Gruhn, Bernd; Ehl, Stephan; Lehmberg, Kai; Müller, Daniel; Gennery, Andrew R; Albert, Michael H; Hauck, Fabian; Rao, Kanchan; Veys, Paul; Hassan, Moustapha; Lankester, Arjan C; Schmid, Jana Pachlopnik; Hauri-Hohl, Mathias M; Güngör, Tayfun.

In: BLOOD ADV, Vol. 4, No. 9, 12.05.2020, p. 1998-2010.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Felber, M, Steward, CG, Kentouche, K, Fasth, A, Wynn, RF, Zeilhofer, U, Haunerdinger, V, Volkmer, B, Prader, S, Gruhn, B, Ehl, S, Lehmberg, K, Müller, D, Gennery, AR, Albert, MH, Hauck, F, Rao, K, Veys, P, Hassan, M, Lankester, AC, Schmid, JP, Hauri-Hohl, MM & Güngör, T 2020, 'Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis', BLOOD ADV, vol. 4, no. 9, pp. 1998-2010. https://doi.org/10.1182/bloodadvances.2020001748

APA

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., Müller, D., Gennery, A. R., Albert, M. H., Hauck, F., Rao, K., Veys, P., Hassan, M., ... Güngör, T. (2020). Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis. BLOOD ADV, 4(9), 1998-2010. https://doi.org/10.1182/bloodadvances.2020001748

Vancouver

Felber M, Steward CG, Kentouche K, Fasth A, Wynn RF, Zeilhofer U et al. Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis. BLOOD ADV. 2020 May 12;4(9):1998-2010. https://doi.org/10.1182/bloodadvances.2020001748

Bibtex

@article{954ffcf19ff3453e988d31253f25a5dc,
title = "Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis",
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.",
keywords = "Animals, Busulfan, Hematopoietic Stem Cell Transplantation, Humans, Lymphohistiocytosis, Hemophagocytic/therapy, Neoplasm Recurrence, Local, Rabbits, Transplantation Conditioning",
author = "Matthias Felber and Steward, {Colin G} and Karim Kentouche and Anders Fasth and Wynn, {Robert F} and Ulrike Zeilhofer and Veronika Haunerdinger and Benjamin Volkmer and Seraina Prader and Bernd Gruhn and Stephan Ehl and Kai Lehmberg and Daniel M{\"u}ller and Gennery, {Andrew R} and Albert, {Michael H} and Fabian Hauck and Kanchan Rao and Paul Veys and Moustapha Hassan and Lankester, {Arjan C} and Schmid, {Jana Pachlopnik} and Hauri-Hohl, {Mathias M} and Tayfun G{\"u}ng{\"o}r",
note = "{\textcopyright} 2020 by The American Society of Hematology.",
year = "2020",
month = may,
day = "12",
doi = "10.1182/bloodadvances.2020001748",
language = "English",
volume = "4",
pages = "1998--2010",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",
number = "9",

}

RIS

TY - JOUR

T1 - Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis

AU - Felber, Matthias

AU - Steward, Colin G

AU - Kentouche, Karim

AU - Fasth, Anders

AU - Wynn, Robert F

AU - Zeilhofer, Ulrike

AU - Haunerdinger, Veronika

AU - Volkmer, Benjamin

AU - Prader, Seraina

AU - Gruhn, Bernd

AU - Ehl, Stephan

AU - Lehmberg, Kai

AU - Müller, Daniel

AU - Gennery, Andrew R

AU - Albert, Michael H

AU - Hauck, Fabian

AU - Rao, Kanchan

AU - Veys, Paul

AU - Hassan, Moustapha

AU - Lankester, Arjan C

AU - Schmid, Jana Pachlopnik

AU - Hauri-Hohl, Mathias M

AU - Güngör, Tayfun

N1 - © 2020 by The American Society of Hematology.

PY - 2020/5/12

Y1 - 2020/5/12

N2 - 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.

AB - 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.

KW - Animals

KW - Busulfan

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Lymphohistiocytosis, Hemophagocytic/therapy

KW - Neoplasm Recurrence, Local

KW - Rabbits

KW - Transplantation Conditioning

U2 - 10.1182/bloodadvances.2020001748

DO - 10.1182/bloodadvances.2020001748

M3 - SCORING: Journal article

C2 - 32384542

VL - 4

SP - 1998

EP - 2010

JO - BLOOD ADV

JF - BLOOD ADV

SN - 2473-9529

IS - 9

ER -