Lessons from Epstein-Barr virus DNA detection in cerebrospinal fluid as a diagnostic tool for EBV-induced central nervous system dysfunction among HIV-positive patients.

BACKGROUND Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART). METHODS A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS. RESULTS A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8-29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups. CONCLUSIONS Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China.

Acute promyelocytic leukemia (APL) is typically characterized by PML-RARα expression. However, variant RARA rearrangement as well as RARB or RARG rearrangement can generate variant APL (vAPL), whic...

MLL-rearrangement can resemble acute promyelocytic leukemia.

Increased expression of progranulin (PGRN) has been reported in some hematological cancers, but limited information regarding its significance in acute lymphoblastic leukemia (ALL) is available. This study involved 60 subjects (40 de novo adult ALL patients and 20 controls). Serum PGRN level was measured by enzyme-linked immunosorbent assay and was correlated with patient outcome. Serum PGRN level was significantly higher in patients than controls. Serum PGRN level did not correlate with age, total leukocytic count, hemoglobin, platelets, absolute blast count in peripheral blood, lactate dehydrogenase, percent of blasts in bone marrow, gender, comorbidities, the presence of central nervous system infiltration, ALL phenotype, cytogenetics and risk of the disease. High serum PGRN level was not associated with inferior overall survival (OS) on univariate analysis. Regarding cumulative incidence of relapse (CIR) and disease-free survival (DFS), high PGRN level was associated with poor results on univariate analysis. Moreover, it tended to be independent risk factor on multivariate analysis for CIR but was not an independent predictor of inferior DFS. Serum PGRN level is significantly elevated in de novo adult ALL patients and may be used as a predictor of increased relapse risk.

Prognostic significance of serum progranulin level in de novo adult acute lymphoblastic leukemia patients

Lessons from Epstein-Barr virus DNA detection in cerebrospinal fluid as a diagnostic tool for EBV-induced central nervous system dysfunction among HIV-positive patients

The introduction of combined antiretroviral therapy (cART) in 1996 has significantly influenced the care of people living with human immunodeficiency virus (HIV) by reducing the risk of opportunist...

The option of treatment and outcomes for patients with AIDS-related diffuse large B-cell lymphoma from a resource-limited setting in China

Objective: To analyze the clinical characteristics, pathological features and survival of patients with AIDS related non-Hodgkin's lymphoma (ARL) . Methods: The clinical data of 53 ARL cases diagnosed and received care at Zhongnan hospital of Wuhan University were retrospectively studied, and 106 controls were enrolled as control group according to 1∶2 for paired cases and control. SPSS 13.0 package was used for statistical analysis. Kaplan-Meier was applied to assess the survival probability. Results: The mean age of patients with ARL was 43 (11-67) years. Male versus female was approximately 4∶1. The median CD4(+) T cell count was (146±20) /ml. The Ann Arbor clinical classification showed that 52.8% of the cases were of stage Ⅲ and Ⅳ. Approximately 54.7% of the patients had elevated serum lactate dehydrogenase (LDH) . According to international prognosis index score, 64.2% of the patients were in high risk group. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype. Among 53 cases, 33 cases (62.3%) received combination of anti-HIV therapy and anti-NHL (CHOP) chemotherapy regimen, 8 cases (15.1%) only received anti-HIV therapy, and 12 cases (22.6%) asked for alleviative treatment. Median survival time was (6.0±1.3) months for ARL cases versus (48.0±10.0) months for controls (P<0.05) . After eliminating cases who did not receive anti-lymphoma treatment, ARL cases showed a lower 1-year OS rates than control group (60.6% versus 83.0%) , but no difference about 2-, 3- and 5-year OS rates (53.5% versus 60.5%, 48.1% versus 45.9%, and 39.1% versus 27.5%, respectively) . Conclusions: ARL is more common in young adults; one-year mortality rate is high. Anti-HIV therapy combined with anti-NHL therapy could significantly improve the prognosis of ARL patients. CHOP regimen may be more suitable for ARL patients.

[Clinicpathological features and survival of patients with AIDS related non-Hodgkin's lymphoma].

Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B-lymphocyte (SIBC) lines from HIV-infected patients with and without Non-Hodgkin's Lymphoma (AIDS-NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV-infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV-SIBC were generated from HIV-infected patients without AIDS-NHL (10%, 8/77), while 14 SIBCs named AIDS-NHL-SIBC were from 13 of the AIDS-NHL patients (32.5%, 13/40). Among the 14 AIDS-NHL-SIBCs, 12 were derived from AIDS-NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3- CD20+ CD27+ ) with EBV infection. Moreover, AIDS-NHL-SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV-SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV-SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS-NHL patients and can be isolated from HIV-infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV-infected patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.2508

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.

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The option of treatment and outcomes for patients with AIDS-related diffuse large B-cell lymphoma from a resource-limited setting in China

[Clinicpathological features and survival of patients with AIDS related non-Hodgkin's lymphoma].

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.