José-Tomás Navarro

Influence of highly active anti‐retroviral therapy on response to treatment and survival in patients with acquired immunodeficiency syndrome‐related non‐Hodgkin's lymphoma treated with cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone

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‐Hodgkins 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.

Hepatosplenic T-Gammadelta Lymphoma in a Patient with Crohn's Disease Treated with Azathioprine

Hepatosplenic γ δ T-cell lymphoma (HS γ δ TCL) 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 HS γ δ TCL with a leukaemic course in a patient with Crohns disease who had received azathioprine during the previous 55 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 HS γ δ TCL in patients with hepatosplenomegaly, B-symptoms and any immunosuppressive condition.

Immunohistochemical detection of MYC protein correlates with MYC gene status in aggressive B cell lymphomas

Tapia G, Lopez R, Muñoz‐Mármol A M, Mate J L, Sanz C, Marginet R, Navarro J‐T, Ribera J‐M & Ariza A 
(2011) Histopathology59, 672–678

Prognostic impact of highly active antiretroviral therapy in HIV-related Hodgkin's disease.

To evaluate the influence of highly active antiretroviral therapy (HAART) on the outcome of HIV-related Hodgkins disease (HD), two groups were studied: patients without previous HAART, and patients treated with HAART previously or concomitantly with HD therapy. In the second group, the complete response was higher and the disease-free survival and overall survival probabilities were significantly longer. HAART is thus associated with an improvement in response to therapy and survival in patients with HIV-related HD.

Translocation (3;8)(q27;q24) in two cases of triple hit lymphoma.

Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.

Decrease in the frequency of meningeal involvement in AIDS-related systemic lymphoma in patients receiving HAART

We evaluated the frequency of primary central nervous system lymphoma and leptomeningeal involvement in systemic non-Hodgkin’s lymphoma (NHL) in HIV-infected patients. Those receiving highly active antiretroviral therapy (HAART) showed a decrease in leptomeningeal involvement in systemic NHL (0/30 vs. 12/87; p=0.023). Therefore HAART could prevent CNS involvement in systemic NHL.

Favorable Impact of Virological Response to Highly Active Antiretroviral Therapy on Survival in Patients with AIDS-related Lymphoma

We have retrospectively studied the influence of highly active antiretroviral therapy (HAART) on the outcome of AIDS-related lymphomas (ARL) as well as the possible influence of the virological response to HAART on complete response (CR) rate and survival in our series of ARL treated with CHOP. Two groups of patients were studied: (1) 44 patients who did not take HAART when the lymphoma was diagnosed, and (2) 26 patients treated with HAART concomitantly and after chemotherapy. There were 4 (9%) women in group 1 versus 11 (42%) in group 2 (P =0.01), and serum lactate dehydrogenase (LDH) level was lower in group 2. The response rate to CHOP was higher in group 2 patients (15 out of 23, 65%) than in those of group 1 (16 out of 44, 36%) (P =0.025). The factors associated with improvement of CR in the multivariate analysis were the administration of HAART (P =0.004) and International Prognostic Index (IPI) score ≤ 2 (P =0.006). Among group 2 patients, those with a virological response to HAART and with IPI score ≤ 2 had better response rate to chemotherapy (odds ratios 9.3 and 11.8, respectively). The median (95% CI) overall survival (OS) for group 1 patients was 7 (3-11) months, whereas it has not been reached for group 2 (P =0.002). The only parameters influencing OS in the multivariate analysis were HAART (0.003), as a protective factor and IPI score>2 (P =0.015) with negative influence. Among patients treated with HAART, those with virological response had higher OS probability (P =0.004), whereas those with IPI score>2 had an unfavorable prognosis (P =0.014). The only variable with statistical significance for disease free survival (DFS) in the univariate and multivariate analyses was HAART (P =0.0168 and P =0.028, respectively). We conclude that HAART is an independent prognostic factor for CR attainment, OS and DFS in patients with ARL treated with CHOP. Those patients with virological response to HAART had a better survival.

MYC protein expression is associated with poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

MYC and BCL2 gene translocations and protein expression have recently demonstrated to be of prognostic significance in systemic diffuse large B‐cell lymphoma (DLBCL). However, their role in primary central nervous system DLBCL (CNS‐DLBCL) prognosis has been scarcely analyzed. We studied the immunophenotype, the status of the MYC, BCL2, and BCL6 genes and the clinical features of a series of 42 CNS‐DLBCL and evaluated their prognostic significance. We found high MYC protein expression in 43% of cases, and this was associated with lower overall survival (OS). Cases with concurrent expression of MYC and BCL2 showed a lower OS, although the difference did not reach statistical significance. Translocations involving the MYC or BCL2 genes were not detected. The BCL6 gene was frequently translocated, but was unrelated to survival. We conclude that MYC protein expression detected by immunohistochemistry identifies a CNS‐DLBCL subset with worse prognosis and may contribute to a more accurate risk stratification of CNS‐DLBCL patients.

Primary myeloid sarcoma of the gynecologic tract: a report of two cases progressing to acute myeloid leukemia.

Primary gynecologic myeloid sarcomas are rare, and their diagnosis is often difficult. Differential diagnosis includes lymphomas and carcinomas of the gynecologic tract. We report the clinical, morphological, immunohistochemical and cytogenetic features of two cases of chloromas of the female genital tract, which progressed to acute myeloid leukemia in spite of aggressive therapy.

Human immunodeficiency virus-related non-Hodgkin’s lymphoma

Highly active antiretroviral therapy (HAART) has improved the survival of human immunodeficiency virus (HIV)-infected patients dramatically. Nonetheless, HIV-related lymphomas still constitute a major cause of death in HIV-infected patients. In this perspective article, Drs. Ribera and Navarro, examine this serious complication of AIDS. See related article on page 1178.