Jingshi Wang

Early diagnostic value of low percentage of glycosylated ferritin in secondary hemophagocytic lymphohistiocytosis

Elevated levels of serum ferritin and a low percentage of glycosylated ferritin have been reported in adult-onset Still’s disease (AOSD) as well as in hemophagocytic lymphohistiocytosis (HLH). The objective of the current study was to investigate total ferritin levels and the percentage of glycosylated ferritin in patients with secondary HLH. From October 2007 to October 2008, 29 patients with suspected HLH older than 14 years of age treated at Beijing Friendship Hospital were enrolled. Twenty-five healthy volunteers were recruited as controls. The suspected HLH patients were further divided into secondary HLH-confirmed (confirmed) (22 out of 29) and HLH-unconfirmed (unconfirmed) (7 out of 29) groups based on HLH-2004 diagnostic criteria. Total serum ferritin levels and the percentage of glycosylated ferritin were determined in subjects at the time of admission. Significantly higher levels of total serum ferritin were observed in confirmed (2,897.6 ± 1,837.2 μg/L) compared with unconfirmed (653.1 ± 249.1 μg/L) patients (P < 0.01) or controls (414.6 ± 212.6 μg/L) (P < 0.01). A significantly lower percentage of glycosylated ferritin was observed in the confirmed (20.5 ± 10.1%) compared with the unconfirmed (48.7 ± 12.1%) group (P < 0.01) or the control group (53.6 ± 13.3%) (P < 0.01). In addition, a low percentage of glycosylated ferritin was observed in HLH patients. Finally, regarding the diagnosis of HLH based on a low percentage of glycosylated ferritin, the sensitivity and specificity, as well as positive and negative predictive values were 0.86, 0.71, 0.91, and 0.63, respectively. For the diagnosis of HLH based on hyperferritinemia, the sensitivity, specificity, positive, and negative predictive values were 0.82, 0.43, 0.82, and 0.43, respectively. The results of this study suggest that a low percentage of glycosylated ferritin is associated with HLH. On comparison with hyperferritinemia, a low percentage of glycosylated ferritin appeared to be more specific, sensitive, and predictive of HLH. In conclusion, a low percentage of glycosylated ferritin may be a useful marker for the early diagnosis of secondary HLH.

Haploidentical hematopoietic stem cell transplantation for adult patients with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

Abstract To assess the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) in adult patients with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), we retrospectively analyzed 30 cases that presented at our institution. At the time of HSCT, 20 patients (66.7%) had achieved a response after receiving HLH-94 or salvage therapies. All patients underwent myeloablative conditioning followed by peripheral blood HSCT from their related, haploidentical donors. Twenty-six patients (86.7%) achieved donor cell engraftment. Of these, 23 (88.5%) achieved complete chimerism and three (11.5%) demonstrated mixed chimerism. Reactivated EBV infection was found in 25 (96.2%). Acute graft-versus-host disease occurred in 18 (69.2%), with grade I–II in 11 patients and grade III–IV in seven. Chronic graft-versus-host disease occurred in six (23.1%). Nineteen patients survived until the end of follow-up. The three-year overall survival rate was 63.3%. Our results indicate that haploidentical HSCT is an effective treatment for adult patients with EBV-HLH.

Multivariate analysis of prognosis for patients with natural killer/T cell lymphoma-associated hemophagocytic lymphohistiocytosis

ABSTRACT Objective: A major cause of hemophagocytic lymphohistiocytosis (HLH) is malignant neoplasms of the blood system, among which NK/T cell lymphoma is one of the most common risk factors. Patients with NK/T cell lymphoma hemophagocytic lymphohistiocytosis (NK/T-LAHS) have a worse prognosis and higher mortality. We aimed to explore the factors that affect the prognosis of NK/T-LAHS. Methods: Clinical data of 42 patients with NK/T-LAHS diagnosed by Beijing Friendship Hospital from June 2008 to June 2016 were analyzed retrospectively. The survival time was counted until 1 August 2016. Results: For the 42 NK/T-LAHS patients, 1-month survival rate was 48.9%, 2-month survival rate was 36.7%, 3-month survival rate was 28.8%, 6-month survival rate was 23.0%, and 12-month survival rate was 15.4%. NK/T-LAHS patients who underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT) (p = 0.000), exhibited peripheral blood Epstein–Barr virus (EBV)-positivity (p = 0.004), and achieved overall response (OR) remission after initial induction therapy (p = 0.007) had statistical significance. Conclusion: NK/T-LAHS is a disease of poor prognosis and high mortality. NK/T-LAHS patients who achieved OR remission after the initial induction therapy had a better prognosis than non-remission patients and Allo-HSCT was an effective way to prolong the survival of NK/T-LAHS patients. However, EBV positivity in peripheral blood was a poor prognostic factor in NK/T-LAHS patients.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults and adolescents—a life-threatening disease: analysis of 133 cases from a single center

ABSTRACT Objectives: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis is the most common type of infection-associated HLH. Previous studies were focused on pediatric EBV-HLH patients, therefore there lack of adult data. Method: We performed a retrospective analysis of 133 EBV-HLH patients (≥14 years old) in Beijing Friendship Hospital from March 2009 to April 2016 to evaluate the clinical manifestation and the effects and prognosis of existing regimens of EBV-HLH in adult and adolescents. Results: Of these patients, 91 male and 42 female cases had a median age of 26 (14–77) years. EBV-DNA load on admission was at a median of 6.6E + 05 IU/ml. The one-year mortality of these patients was 78%. 112 patients received the HLH-94/04 regimen as the initial treatment, 52 patients (46.43%) had response. Of the 6 patients who received the L-DEP regimen as the initial treatment, 5 patients (83.33%) had response. The rest 15 patients received initial treatment without etoposide, 5 cases achieved PR. 69 refractory or relapsed patients received DEP or L-DEP regimen, 55 (79.71%) cases had response. In addition, who received the L-DEP regimen, with the overall response rate significantly higher than the DEP regimen (88.37% VS 65.38%, P = 0.031). 36 out of 133 EBV-HLH patients eventually received allo-HSCT, with the overall survival rate of 52.78%. In summary, EBV-HLH is a highly lethal disease. Conclusion: DEP/L-DEP was a good salvage treatment. L-DEP might be a more effective first-line initial regimen than HLH-94/04 regimen for EBV-HLH. Finally, allo-HSCT is an effective radical treatment for EBV-HLH.

Elevation of CD16+CD56+ NK-cells and down-regulation of serum interleukin-21 (IL-21) and IL-1α after splenectomy in relapsed hemophagocytic lymphohistiocytosis of unknown cause

ABSTRACT Objectives: Encouraging progress has been made in application of splenectomy in the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause. The aim was to determine the roles of lymphocyte subpopulations and inflammatory cytokines in splenectomy. Methods: We retrospectively analyzed changes in lymphocyte subpopulations and levels of inflammatory cytokines at different time-points before and after splenectomy in the patients with relapsed HLH of unknown cause, as well as the correlations between these changes and the disease prognosis. Results: During the period from June 2006 to June 2016, we enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were available for analysis. Results showed a significant increase in both percentage of CD16+CD56+ NK cells (P = 0.003) and NK cell activity (P = 0.028) at 24 wk after splenectomy compared to their baseline pre-surgery levels. We also examined seven patients for the changes in cytokine levels before and after splenectomy and found that IL-21 and IL-1α decreased at 4 wk after splenectomy (P < 0.05). Seven non-lymphoma patients determined as no response to treatment (NR) prior to splenectomy had significantly longer survival (P = 0.001) compared to the 24 patients with relapsed HLH of unknown cause who were also determined as NR but not treated by splenectomy. Discussion: Splenectomy can improve clinical symptoms and survival of patients with relapsed HLH of unknown cause. The mechanism is likely related to the changes in percent NK cells and cytokines (IL-21 and IL-1α) after surgery.