The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis.

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.

α4 integrin levels on mobilized peripheral blood stem cells predict rapidity of engraftment in patients receiving autologous stem cell transplantation.

Rapidness of leukocyte engraftment in patients receiving peripheral blood stem cell transplantation is clinically important because the risk of fatal opportunistic infections increases with time to engraftment. Adhesion receptor molecules on hematopoietic stem cells (HSCs) have been shown to modulate homing and engraftment of HSCs. Therefore, we correlated expression levels of α4 (CD49d) and α6 (CD49f) integrins in the CD34(+) HSC compartment with time to engraftment. Leukapheresis products from 103 patients were retrospectively analyzed for CD34, CD38, CD3, CD49f, and CD49d surface molecules by multiparameter flow cytometry. High expression levels of α4 integrin, but not α6 integrin on CD34(+) cells, were associated with regular engraftment of leukocytes (days 8-19), whereas low surface expression correlated with delayed recovery (> 19 days; P < .0005). We show that α4 integrin expression levels on HSCs in leukapheresis products predict the engraftment capacity of mobilized peripheral blood stem cells in peripheral blood stem cell transplantation patients.