Hemophagocytic Lymphohistiocytosis (HLH) is an aggressive disorder of immune regulation that carries a grave prognosis; stem cell transplant (SCT) after induction therapy is the recommended defi nitive treatment. Unrelated donors (UD) are used for patients (pts) lacking a matched family donor, and for those lacking a molecular diagnosis (as sibling donors might themselves be genetically at risk but not yet affected). Two pediatric centers collectively transplanted 22 pts with HLH between 1991 and 2011. Etiologies included mutations of Perforin (7 pts), Munc 13 (2), Munc 18 (3), Syntaxin (1), as well as T-cell lymphoma (1) and EBV infection (1). No molecular or infectious etiology was identi- fi ed in two extensively evaluated pts, and treatment predated the availability of molecular diagnosis in 5 pts. Twelve pts were in complete response at the time of transplant and 6 had less than a complete response; response data were unavailable in 4 pts. Unrelated donors were used for 10 children. Grafts were derived from marrow (12), peripheral blood (8), cord blood (1), or cord blood + marrow (1). Six pts, mostly transplanted in the 1990’s, received fully ablative conditioning; others received fl udarabine containing regimens; 91% received serotherapy during conditioning. Cyclosporine was administered after transplant usually in combination with either methotrexate or mycophenolate mofetil. Fifteen patients (68%) are alive (8/10 UD, 7/12 related donors) without evidence of disease, four of whom have stable mixed donor chimerism of less than 70%. Four of 6 pts with signs of active HLH at the time of SCT survive, as did 4/5 children with HLH involvement of the central nervous system at diagnosis (two without apparent developmental delay). Fatal cases of pneumonia were caused by CMV (1), RSV (2), and adenovirus together with aspergillus (1), suggesting that aggressive anti-viral and anti-fungal prophylaxis is imperative in this high-risk population. The child with lymphoma died of multi-organ failure 1 day after transplant, and an additional pt succumbed to pulmonary venoocclusive disease 5 months after SCT. Severe graft vs. host disease occurred in only one child. SCT from related and unrelated donors using fl udarabine-based reduced intensity conditioning with the addition of serotherapy is an effective treatment for HLH.
Full conference title:
Annual Meeting of the EBMT, 38th
- EBMT 38th (2012)