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The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

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The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis. / Hartz, Bernd; Marsh, Rebecca; Rao, Kanchan; Henter, Jan-Inge; Jordan, Michael; Filipovich, Lisa; Bader, Peter; Beier, Rita; Burkhardt, Birgit; Meisel, Roland; Schulz, Ansgar; Winkler, Beate; Albert, Michael H; Greil, Johann; Karasu, Gülsün; Woessmann, Wilhelm; Corbaciologlu, Selim; Gruhn, Bernd; Holter, Wolfgang; Kühl, Jörn-Sven; Lang, Peter; Seidel, Markus G; Veys, Paul; Löfstedt, Alexandra; Ammann, Sandra; Ehl, Stephan; Janka, Gritta; Müller, Ingo; Lehmberg, Kai.

In: BLOOD, Vol. 127, No. 25, 20.04.2016, p. 3281-90.

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

Harvard

Hartz, B, Marsh, R, Rao, K, Henter, J-I, Jordan, M, Filipovich, L, Bader, P, Beier, R, Burkhardt, B, Meisel, R, Schulz, A, Winkler, B, Albert, MH, Greil, J, Karasu, G, Woessmann, W, Corbaciologlu, S, Gruhn, B, Holter, W, Kühl, J-S, Lang, P, Seidel, MG, Veys, P, Löfstedt, A, Ammann, S, Ehl, S, Janka, G, Müller, I & Lehmberg, K 2016, 'The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis', BLOOD, vol. 127, no. 25, pp. 3281-90. https://doi.org/10.1182/blood-2015-12-684498

APA

Hartz, B., Marsh, R., Rao, K., Henter, J-I., Jordan, M., Filipovich, L., Bader, P., Beier, R., Burkhardt, B., Meisel, R., Schulz, A., Winkler, B., Albert, M. H., Greil, J., Karasu, G., Woessmann, W., Corbaciologlu, S., Gruhn, B., Holter, W., ... Lehmberg, K. (2016). The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis. BLOOD, 127(25), 3281-90. https://doi.org/10.1182/blood-2015-12-684498

Vancouver

Hartz B, Marsh R, Rao K, Henter J-I, Jordan M, Filipovich L et al. The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis. BLOOD. 2016 Apr 20;127(25):3281-90. https://doi.org/10.1182/blood-2015-12-684498

Bibtex

@article{51a7e8834b0e4403bf2ebb603b20c91c,
title = "The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis",
abstract = "Reduced-intensity conditioning has improved survival after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) at the cost of more frequent mixed chimerism. The minimum level of donor chimerism (DC) required to prevent HLH reactivation in humans remains to be determined. In a multicenter retrospective study, 103 patients transplanted for hereditary HLH (2000-2013) and DC permanently or transiently <75% (overall, CD3(+), CD56(+)) were analyzed regarding DC, specific immunologic function, occurrence of systemic reactivations (≥5/8 HLH criteria), partial systemic flares (<5 criteria and HLH-directed treatment), isolated CNS reactivations, and management. Recurrence was reported in 18 patients (systemic reactivation n=11, partial flare n=3, isolated CNS reactivation n=4). Ten events occurred during profound immune suppression before day 180 (median DC 10%, range 1-100%; CD3(+)if available, otherwise overall DC), which renders a differentiation between secondary post-HSCT HLH and HLH related to the genetic defect difficult. Eight events occurred between 0.5 and 6.7 years post-HSCT (median DC 13%, range 0-30%). In 5 patients, overall and lineage-specific DC were ≤10% for >6 months (median 5.1, range 1.1-10 years) without reactivation. A 2nd HSCT was performed in 18 patients (median DC 4%; range 0-19%). Death due to reactivation occurred in 4 patients (22% of recurrences). Six patients died of transplant complications following a 2nd HSCT (33% of 2nd HSCT). We conclude that a DC >20-30% is protective against late reactivation. Lower levels do not, however, inescapably result in recurrences. The decision for or against 2nd HSCT must be based on a thorough risk assessment.",
author = "Bernd Hartz and Rebecca Marsh and Kanchan Rao and Jan-Inge Henter and Michael Jordan and Lisa Filipovich and Peter Bader and Rita Beier and Birgit Burkhardt and Roland Meisel and Ansgar Schulz and Beate Winkler and Albert, {Michael H} and Johann Greil and G{\"u}ls{\"u}n Karasu and Wilhelm Woessmann and Selim Corbaciologlu and Bernd Gruhn and Wolfgang Holter and J{\"o}rn-Sven K{\"u}hl and Peter Lang and Seidel, {Markus G} and Paul Veys and Alexandra L{\"o}fstedt and Sandra Ammann and Stephan Ehl and Gritta Janka and Ingo M{\"u}ller and Kai Lehmberg",
note = "Copyright {\textcopyright} 2016 American Society of Hematology.",
year = "2016",
month = apr,
day = "20",
doi = "10.1182/blood-2015-12-684498",
language = "English",
volume = "127",
pages = "3281--90",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "25",

}

RIS

TY - JOUR

T1 - The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

AU - Hartz, Bernd

AU - Marsh, Rebecca

AU - Rao, Kanchan

AU - Henter, Jan-Inge

AU - Jordan, Michael

AU - Filipovich, Lisa

AU - Bader, Peter

AU - Beier, Rita

AU - Burkhardt, Birgit

AU - Meisel, Roland

AU - Schulz, Ansgar

AU - Winkler, Beate

AU - Albert, Michael H

AU - Greil, Johann

AU - Karasu, Gülsün

AU - Woessmann, Wilhelm

AU - Corbaciologlu, Selim

AU - Gruhn, Bernd

AU - Holter, Wolfgang

AU - Kühl, Jörn-Sven

AU - Lang, Peter

AU - Seidel, Markus G

AU - Veys, Paul

AU - Löfstedt, Alexandra

AU - Ammann, Sandra

AU - Ehl, Stephan

AU - Janka, Gritta

AU - Müller, Ingo

AU - Lehmberg, Kai

N1 - Copyright © 2016 American Society of Hematology.

PY - 2016/4/20

Y1 - 2016/4/20

N2 - Reduced-intensity conditioning has improved survival after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) at the cost of more frequent mixed chimerism. The minimum level of donor chimerism (DC) required to prevent HLH reactivation in humans remains to be determined. In a multicenter retrospective study, 103 patients transplanted for hereditary HLH (2000-2013) and DC permanently or transiently <75% (overall, CD3(+), CD56(+)) were analyzed regarding DC, specific immunologic function, occurrence of systemic reactivations (≥5/8 HLH criteria), partial systemic flares (<5 criteria and HLH-directed treatment), isolated CNS reactivations, and management. Recurrence was reported in 18 patients (systemic reactivation n=11, partial flare n=3, isolated CNS reactivation n=4). Ten events occurred during profound immune suppression before day 180 (median DC 10%, range 1-100%; CD3(+)if available, otherwise overall DC), which renders a differentiation between secondary post-HSCT HLH and HLH related to the genetic defect difficult. Eight events occurred between 0.5 and 6.7 years post-HSCT (median DC 13%, range 0-30%). In 5 patients, overall and lineage-specific DC were ≤10% for >6 months (median 5.1, range 1.1-10 years) without reactivation. A 2nd HSCT was performed in 18 patients (median DC 4%; range 0-19%). Death due to reactivation occurred in 4 patients (22% of recurrences). Six patients died of transplant complications following a 2nd HSCT (33% of 2nd HSCT). We conclude that a DC >20-30% is protective against late reactivation. Lower levels do not, however, inescapably result in recurrences. The decision for or against 2nd HSCT must be based on a thorough risk assessment.

AB - Reduced-intensity conditioning has improved survival after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) at the cost of more frequent mixed chimerism. The minimum level of donor chimerism (DC) required to prevent HLH reactivation in humans remains to be determined. In a multicenter retrospective study, 103 patients transplanted for hereditary HLH (2000-2013) and DC permanently or transiently <75% (overall, CD3(+), CD56(+)) were analyzed regarding DC, specific immunologic function, occurrence of systemic reactivations (≥5/8 HLH criteria), partial systemic flares (<5 criteria and HLH-directed treatment), isolated CNS reactivations, and management. Recurrence was reported in 18 patients (systemic reactivation n=11, partial flare n=3, isolated CNS reactivation n=4). Ten events occurred during profound immune suppression before day 180 (median DC 10%, range 1-100%; CD3(+)if available, otherwise overall DC), which renders a differentiation between secondary post-HSCT HLH and HLH related to the genetic defect difficult. Eight events occurred between 0.5 and 6.7 years post-HSCT (median DC 13%, range 0-30%). In 5 patients, overall and lineage-specific DC were ≤10% for >6 months (median 5.1, range 1.1-10 years) without reactivation. A 2nd HSCT was performed in 18 patients (median DC 4%; range 0-19%). Death due to reactivation occurred in 4 patients (22% of recurrences). Six patients died of transplant complications following a 2nd HSCT (33% of 2nd HSCT). We conclude that a DC >20-30% is protective against late reactivation. Lower levels do not, however, inescapably result in recurrences. The decision for or against 2nd HSCT must be based on a thorough risk assessment.

U2 - 10.1182/blood-2015-12-684498

DO - 10.1182/blood-2015-12-684498

M3 - SCORING: Journal article

C2 - 27099148

VL - 127

SP - 3281

EP - 3290

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 25

ER -