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 central nervous system reactivations, and management. Recurrence was reported in 18 patients (systemic reactivation n = 11, partial flare n = 3, isolated central nervous system 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 second HSCT was performed in 18 patients (median, DC 4%; range, 0-19%). Death from reactivation occurred in 4 patients (22% of recurrences). Six patients died of transplant complications following a second HSCT (33% of second 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 second HSCT must be based on a thorough risk assessment.

• Authors: Bernd Hartz, Rebecca Marsh, Kanchan Rao, Jan-Inge Henter, Michael Jordan, Lisa Filipovich, Peter Bader, Rita Beier, Birgit Burkhardt, Roland Meisel, Ansgar Schulz, Beate Winkler, Michael H Albert, Johann Greil, Gülsün Karasu, Wilhelm Woessmann, Selim Corbacioglu, Bernd Gruhn, Wolfgang Holter, Jörn-Sven Kühl, Peter Lang, Markus G Seidel, Paul Veys, Alexandra Löfstedt, Sandra Ammann, Stephan Ehl, Gritta Janka, Ingo Müller, Kai Lehmberg
• Journal: Blood (Blood) Vol. 127 Issue 25 Pg. 3281-90 (06 23 2016) ISSN: 1528-0020 [Electronic] United States
• PMID: 27099148 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by The American Society of Hematology.

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Chimerism
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Infant
• Infant, Newborn
• Lymphohistiocytosis, Hemophagocytic (immunology, therapy)
• Male
• Recurrence
• Retrospective Studies
• Tissue Donors
• Transplantation Conditioning (methods)
• Transplantation Immunology
• Transplantation, Homologous (adverse effects)
• Treatment Outcome
• Young Adult