Reactive hemophagocytic syndrome (HS) is a rare but serious complication that may occur after both autologous and allogeneic hematopoietic stem cells transplantation (HSCT). Our knowledge of this post-HSCT complication mainly derives from single reports or small series and only about sixty cases have been reported in the literature so far. We present here the results of a multicenter retrospective study, performed on behalfof the SFGM-TC, including adult (>16 years) HSCT recipients transplanted in France, Switzerland or Stockholm (Sweden) and diagnosed with HS after transplantation. Patient data were extracted from medical files and the recently reported HScore [Fardetet al., Arthritis Rheumatol. 2014 66(9):2613-20] was applied for confirmation of HS diagnosis. Among the thirty-two patients reported, one patient was excluded because of insufficient data for HScore calculation and four patients for an HScore less than 169. We included in the final analysis 27 patients in which the HS diagnosis was confirmed (median HScore 218, median HS probability of 97%). The median age was 45 years (range 21-68) and 10 patients were female (37%). Three patients underwent autologous HSCT for non-Hodgkin lymphoma (NHL). Twenty-four patients received allogeneic HSCT for hematological malignancies (n=23) or severe aplastic anemia (n=1) from HLA-identical siblings (n=4), HLA-matched (n=10) or HLA-mismatched (n=6) unrelated donors, haploidentical donors (n=2) or cord blood (n=2). The median time from transplantation to HS diagnosis was 66 days (range 6-326). Fever was present in almost all patients (n=25, 93%) while we observed splenomegaly in 13 (48%), hepatomegaly in 11 (41%), and lymphadenopathy in 8 (30%) patients. All patients had cytopenia in at least one hematopoietic lineage and we found pancytopenia in 14 patients (52%). All patients displayed elevated ferritin levels with 22 patients (81%) having levels higher than 7500 µg/L. Eleven patients (41%) had triglyceride levels at >4 mmol/l, while only 7 patients (26%) had fibrinogen <2.5 g/L. Aminotransferases were elevated in half of the patients (n=14). Bone marrow hemophagocytosis was observed in 15 patients (56%). Twenty patients (74%) had pharmacological immune suppression at time of HS diagnosis. Twenty-two patients (81%) had an infection at HS diagnosis, mainly viral infections [17 patients with evidence of one or more viral infection or reactivation: Epstein-Barr virus (n=14), cytomegalovirus (n=10), adenovirus (n=2), human herpesvirus 6 (n=1), metapneumovirus (n=1) and human parainfluenza virus type 3 (n=1)], but also pyogenic bacterial infections (n=6), parasitic infections (n=3, toxoplasmosis) and fungal infections (n=3: two aspergillosis and one disseminated Rhizomucor infection). Eleven patients (41%) had evidence of active cancer at time of HS diagnosis, either as primary disease progression/relapse (n=5) or as post-transplant lymphoproliferative disease (PTLD; n=6). Graft-versus-Host-Disease (GvHD) was present in 11 patients (41%) at time of HS diagnosis (grade II-IV acute GvHD in 8 patients; chronic GvHD in 3 patients) and was considered a contributing triggering factor for HS in 4 of them. The median survival after HS diagnosis was 58 days (95%CI 21-86) and the 1-year overall survival (OS) was 22% (95%CI 8%-41%) [Figure 1]. Treatments most frequently employed, either alone or in combination, were glucocorticoids (GCs, n=16), intravenous immunoglobulins (IVIG, n=7) and Etoposide (VP-16, n=7). Etiological anti-infectious or anti-cancer agents were employed alone in 7 patients. We found no significant difference in OS of patients with malignancy-associated HS or infection-triggered HS compared with HS from other causes. Similarly, we detected no impact of the use of GCs, IVIG or VP-16 on patients survival. However these results should be interpreted with caution given the limited number of patients. Three patients underwent a second allogeneic HSCT that provided long-term rescue in one patient, while offered only a short-term benefit to the others. Our study, which is to the best of our knowledge the largest series of HS following HSCT reported so far, provides a description of HS as a rare but devastating complication of HSCT associated with an extremely high mortality.

Disclosures

Peffault De Latour:Alexion: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.

This icon denotes a clinically relevant abstract