Hemophagocytic lymphohistiocytosis secondary to composite lymphoma:Two case reports

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a rare and life-threatening disease caused by inherited pathogenic mutations and acquired dysregulations of the immune system.Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphomas that occur in a single patient.Here,we report two cases of HLH secondary to composite lymphoma with mixed lineage features of T-and B-cell marker expression both in the bone marrow and lymph nodes in adult patients.CASE SUMMARY Two patients were diagnosed with HLH based on the occurrence of fever,pancytopenia,lymphadenopathy,splenomegaly,hemophagocytosis and hyperferritinemia.Immunohistochemical staining of the axillary lymph node and bone marrow in case 1 showed typical features of combined B-cell and T-cell lymphoma.In addition,a lymph node gene study revealed rearrangement of the T-cell receptor chain and the immunoglobulin gene.Morphology and immunohistochemistry studies of a lymph node biopsy in case 2 showed typical features of T cell lymphoma,but immunophenotyping by flow cytometry analysis of bone marrow aspirate showed B cell lymphoma involvement.The patients were treated with high-dose methylprednisolone combined with etoposide to control aggressive HLH progression.The patients also received immunochemotherapy with the R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)regimen immediately after diagnosis.Both patients presented with highly aggressive lymphoma,and died of severe infection or uncontrolled HLH.CONCLUSION We present two rare cases with overwhelming hemophagocytosis along with composite T-and B-cell lymphoma,which posed a diagnostic dilemma.HLH caused by composite lymphoma was characterized by poor clinical outcomes.

Chronic active Epstein-Barr virus infection treated with PEGaspargase: A case report

BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV(CAEBV),and hematopoietic stem cell transplantation is the only effective treatment.We here report a CAEBV patient treated with PEG-aspargase,who achieved negative EBV-DNA.CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017.EBV-DNA was positive with a high copy number.She was diagnosed with chronic active EB virus infection.PEGaspargase was administered at a dose of 1500 U/m2 at a 14-d interval,resulting in eradication of EBV for more than 6 mo.The effect of PEG-aspargase in this patient was excellent.CONCLUSION A chemotherapy regimen containing PEG-aspargase for CAEBV may be further considered.

Ruxolitinib treatment for bronchiolitis obliterans syndrome following hematopoietic stem cell transplant in a patient with primary hemophagocytic lymphohistiocytosis

To the Editor:A 20-year-old man who developed hemophagocytic lymphohistiocytosis(HLH)was treated with methylprednisolone combined with etoposide(VP-16)for 24 weeks.One month after treatment completion,HLH recurred.The patient visited the Hematology Department of the Beijing Friendship Hospital and was diagnosed with primary HLH with PRF1 fusion gene mutation.

Innovative analysis of predictors for overall survival from systemic non-Hodgkin T cell lymphoma using quantile regression analysis

Background:Non-Hodgkin T/NK cell lymphoma is a rare and widely variable type of lymphoma with the most dismal prognosis. This study aimed to investigate varied impact of the clinical indicators to the overall survival (OS).Methods:We conducted a retrospective study to identify the non-invasive clinical features of T cell lymphoma that can predict prognosis with an innovative analysis method using quantile regression. A total of 183 patients who visited a top-tier hospital in Beijing, China, were enrolled from January 2006 to December 2015. Demographic information and main clinical indicators were collected including age, erythrocyte sedimentation rate (ESR), survival status, and international prognostic index (IPI) score.Results:The median age of the patients at diagnosis was 45 years. Approximately 80% of patients were at an advanced stage, and the median survival time after diagnosis was 5.1 months. Multivariable analysis of the prognostic factors for inferior OS associated with advanced clinical staging [HR=3.16, 95%CI (1.39-7.2)], lower platelet count [HR=2.57, 95%CI (1.57-4.19), P<0.001] and higher IPI score [HR=1.29, 95%CI (1.01-1.66), P=0.043]. Meanwhile, T cell lymphoblastic lymphoma [HR=0.40, 95%CI (0.20-0.80), P=0.010], higher white blood cell counts [HR=0.57, 95%CI (0.34-0.96), P=0.033], higher serum albumin level [HR=0.6, 95%CI (0.37-0.97), P=0.039], and higher ESR [HR=0.53, 95%CI (0.33-0.87), P=0.011] were protective factors for OS when stratified by hemophagocytic lymphohistiocytosis (HLH). Multivariable quantile regression between the OS rate and each predictor at quartiles 0.25, 0.5, 0.75, and 0.95 showed that the coefficients of serum β2-microglobulin level and serum ESR were statistically significant in the middle of the coefficient curve (quartile 0.25-0.75). The coefficient of IPI was negatively associated with OS. The coefficients of hematopoietic stem cell transplantation (HSCT) and no clinical symptoms were higher at the middle of the quartile level curve but were not statistically significant.Conclusions:The IPI score is a comparatively robust indicator of prognosis at 3 quartiles, and serum ESR is stable at the middle 2 quartiles section when adjusted for HLH. Quantile regression can be used to observe detailed impacts of the predictors on OS.