Although doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is considered the standard chemotherapy regimen for Hodgkin's lymphoma (HL), information on the results of this therapy in human immunodeficiency (HIV)-related HL is scarce. We analyzed the results of the ABVD regimen and highly active antiretroviral therapy (HAART) in patients with advanced stage, HIV-related HL. Design and MethodsFrom January 1996 to December 2005, 62 HIV-infected patients with newly diagnosed HL were treated in 15 Spanish hospitals. Six to eight cycles of ABVD and HAART were planned. Response to chemotherapy, overall survival (OS) and event-free survival (EFS) were recorded. ResultsThe median age of the patients was 37 years (range, 24-61) and 29 (47%) had a previously known diagnosis of acquired immunodeficiency syndrome. The median CD4 lymphocyte count at diagnosis was 129/µL (range 5-1,209). The histologic subtype of HL was nodular sclerosis in 17 patients (27%), mixed cellularity in 25 (41%), lymphocyte depletion in 10 (16%) and non-specified in the remaining 10 (16%). Twentyone (34%) patients were in stage III and 41 (66%) in stage IV. The scheduled six to eight ABVD cycles were completed in 82% of cases. Six patients died during induction, 54 (87%) achieved a complete response (CR) and two were resistant. After a median follow-up of 39 and 47 months, 5-year EFS and OS probabilities were 71% (47-95) and 76% (65-87), respectively. An immunological response was observed in 24 out of 43 patients (56%) and a virological response in 27 out of 40 (68%). The immunological response to HAART had a positive impact on OS and EFS (p=0.002 and p=0.001, respectively). Interpretation and ConclusionsIn patients with advanced stage, HIV-related HL, treatment with ABVD together with HAART is feasible and effective. This supports the concept that patients with HIVrelated HL should be treated in the same way as immunocompetent patients if HAART, adequate supportive therapy and anti-infectious prophylaxis are given concomitantly. An immunological response to HAART has a positive impact on OS and EFS.Key words: Hodgkin's lymphoma, HIV-related, advanced stage, ABVD, HAART. Haematologica 2007; 92:191-198 ©2007 Ferrata Storti Foundation 1 Its aggressive behavior includes unfavorable histological subtypes, advanced stage and extranodal involvement at diagnosis. 2-6Although in the era of highly active antiretroviral therapy (HAART) the incidence of non-Hodgkin's lymphoma (NHL) has declined according to several studies, this does not seem to be the case for HL. In recent years improvements have been observed in the survival of both patients with HIV-related NHL and those with HL.7-9 There are several possible reasons for these improvements. First, HAART increases CD4 lymphocyte counts and, concomitantly, reduces the risk of opportunistic infections; second, an improvement in the immunodeficiency status could prevent relapse of the lymphoma; and third, improvements in supportive therapy, e.g. the use of granulocyte colony-stimulating factor (G-...

In the cART era, HIV-related DLBCL still presents more aggressive features than HIV-unrelated DLBCL, and has a worse OS despite having a similar DFS. Prevention of HIV-related complications is essential to achieve outcomes comparable with HIV-uninfected patients with DLBCL.

MYC protein expression detected by immunohistochemistry using a commercially available antibody correlates with MYC gene translocation, and could be used as a screening tool to select those cases in which confirmatory genetic testing is mandatory.

Combined highly active anti-retroviral therapy (HAART) with protease and reverse transcriptase inhibitors has modified the natural history of opportunistic infections and neoplasms in human immunodeficiency virus (HIV)-infected patients. We analysed the influence of HAART on the response to treatment and survival in a series of 58 patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) treated with CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone). Two groups of patients were included: (i) forty-one patients diagnosed with NHL between 1988 and 1996 who were not treated with HAART; (ii) seventeen patients diagnosed since 1996, who were receiving or commenced HAART when NHL was diagnosed. The response rate to CHOP was higher in group 2 (13 out of 17 cases; 75%) than in group 1 (14 out of 41 cases; 34%) (P = 0.003). The 2-year probability of event-free survival (EFS) [95% confidence interval (CI)] for group 1 was 0.5 (0.24-0.74), whereas for group 2 it was 0.85 (0.61-0.90) (P = 0.024). The lymphoma-free survival (LFS) was also significantly different for both groups (2-year LFS probability 0.53 vs. 1.0, P = 0.04). The median (95% CI) overall survival (OS) for group 1 was 7 months (range, 3-10.8 months), whereas it was not reached in group 2 (P = 0.0015). In the multivariate analysis for remission attainment, the only variables with a higher probability to achieve complete remission (CR) were HAART (P = 0.01) and International Prognostic Index score 1 (P = 0.02). The only statistically significant variable in the multivariate analysis for EFS was HAART (P = 0.049) and the variables with prognostic value for OS in the multivariate analysis were B symptoms (P = 0.01) and HAART (P = 0.003). Patients with AIDS-related NHL treated with CHOP and HAART had a higher CR rate than those treated only with CHOP. In this study, HAART was an independent prognostic factor for CR, OS and EFS in patients with AIDS-related NHL.

Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.

Hepatosplenic gammadelta T-cell lymphoma (HS-gammadeltaTCL) is an uncommon type of peripheral T-cell lymphoma, which has been associated in some cases with immunosuppression, mainly after solid organ transplants. We describe a case of HSgammadeltaTCL with a leukaemic course in a patient with Crohn's disease who had received azathioprine during the previous 5.5 years. Sinusoidal infiltration by atypical lymphocytes was observed in the liver, spleen and bone marrow and the typical cytogenetic abnormalities (isochromosome 7 and trisomy 8) were found. The patient did not respond to intensive chemotherapy. This case shows the importance of ruling out HSgammadeltaTCL in patients with hepatosplenomegaly, B-symptoms and any immunosuppressive condition.

Plasma EBV-load can be used as biomarker and as prognostic factor in HIV-related lymphomas. The presence of EBV-load in plasma can be an early predictor of HIV-related lymphoma development.

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