Usefulness of the modified hemophagocytic syndrome diagnostic score as a prognostic factor in lung transplantation patients

Background: Lung transplantation (LTX) is an established treatment for end-stage lung disease; however, the post-LTX mortality rate remains high. This study aimed to evaluate the prognostic value of the modified reactive hemophagocytic syndrome diagnostic score (mHScore) and its individual components on mortality after LTX.Methods: We retrospectively analyzed 294 patients who underwent LTX at Severance Hospital, Yonsei University, Korea, from January 2012 and December 2020, and classified them into high (n=114, mHScore > 104.0) and low mHScore (n=180, mHScore ≤ 104.0) groups. Triglyceride, ferritin, serum glutamic oxaloacetic transaminase, fibrinogen, and cytopenia were used to calculate the mHScore. We compared baseline characteristics and mortality rates as LTX prognostic factors.Results: The high mHScore group had significantly more cytopenia and higher ferritin, triglyceride, lactate dehydrogenase, and C-reactive protein levels than the low mHScore group. The mortality rate was significantly higher in the high than in the low mHScore group (hazard ratio, 4.429, p < 0.001). Multivariate regression analysis revealed that a high mHScore was significantly associated with postoperative mortality, even after adjusting for other confounding factors. A high mHScore was also associated with postoperative complications.Conclusions: The mHScore can be used to estimate post-LTX prognosis and predict postoperative mortality.

Infectious Mononucleosis Resulting in Acute Necrotizing Mediastinitis: A Case Report and Literature Review

The serological prevalence of Epstein-Barr virus (EBV) among young adults exceeds 90% worldwide. Even though EBV primary infection is usually benign, severe complications can occur in adolescents and young adults and so the disease must be promptly diagnosed. The development of an oropharyngeal abscess leading to a descending necrotizing mediastinitis (DNM) is exceptional and potentially lethal, so early diagnosis with a CT scan, appropriate antibiotics and surgery are essential. The authors present a case where DNM was associated with reactive hemophagocytic syndrome as a result of infectious mononucleosis, as well as a review of similar cases in the English literature.

Fulminant and rapidly fatal hemophagocytic lymphohistiocytosis in patients with HIV infection: A report of five cases and a review

Hemophagocytic lymphohistiocytosis is a rare entity and diagnosis can be elusive. Commonly recognized inciting causes include autoimmune disorders, malignancies, and a wide variety of infections. With prompt recognition and treatment, survival rates approach 50%. Five cases of reactive hemophagocytic syndrome in patients with underlying HIV infection are reported. All of the patients had CD3/CD4 cell counts of <200 cells/µL. All cases presented with fever and all had marked cytopenias, with platelet counts falling to 10–15,000/µL. Ferritin levels were >5000 ng/mL in all cases. Concomitant inciting conditions included Epstein–Barr virus infection, Pneumocystis jiroveci, multiple myeloma, and Hodgkin’s lymphoma; in one case, no inciting condition was identified. Despite broad-spectrum antimicrobial and immunosuppressive therapy, all five patients died within one month of presentation. The finding of fever and cytopenia in a patient with underlying HIV infection should prompt the clinician to determine a ferritin level. If markedly elevated, an aggressive work-up for hemophagocytic syndrome should be conducted. However, even with prompt recognition, mortality rates may be high in patients with underlying HIV infection.

Reactive hemophagocytic syndrome in the setting of acute human immunodeficiency virus 1 infection: case report and review of the literature

We report a case of reactive hemophagocytic syndrome (RHS) in the setting of acute human immunodeficiency virus type 1 infection (AHI). In addition, we review 11 previously reported cases of RHS precipitated by AHI and discuss strategies in the diagnosis and management of these overlapping clinical entities.

Reactive Hemophagocytic Syndrome after Hematopoietic Stem Cell Transplantation: A Multicenter Retrospective Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

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.