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Daina Variakojis

Publications and source records attributed to Daina Variakojis.

8 recordsLinked to original sources

Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study.

Bcl-6 protein expression, a marker of germinal center origin, has been associated with a favorable prognosis in diffuse large B-cell lymphoma (DLBCL). To determine the prognostic significance of this marker when rituximab (R) was added to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, we prospectively studied Bcl-6 protein expression by immunohistochemical staining of 199 paraffin-embedded specimens from patients enrolled in the US Intergroup phase 3 trial comparing R-CHOP to CHOP with or without maintenance R. In Bcl-6(-) patients, failure-free survival (FFS) and overall survival (OS) were prolonged for those treated with R-CHOP alone compared to CHOP alone (2-year FFS 76% versus 9%, P < .001; 2-year OS 79% versus 17%, P < .001). In contrast, no differences in FFS and OS were detected between treatment arms for Bcl-6(+) cases. In the multivariate analysis, treatment arm (CHOP versus R-CHOP) was the major determinant of both FFS (P < .001) and OS (P < .001) for the Bcl-6(-) subset, whereas the International Prognostic Index risk group was the only significant predictor of outcome among Bcl-6(+) cases. Bcl-2 protein expression was not predictive of outcome in either group. In this study, we observed a reduction in treatment failures and death with the addition of R to CHOP in Bcl-6(-) DLBCL cases only. Our finding that Bcl-6(+) cases did not benefit from the addition of R to CHOP requires independent confirmation.

Aged↗

Respiratory damage in children exposed to urban pollution.

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.

Adolescent↗

Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status.

We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase-polymerase chain reaction, fluorescence in situ hybridization (FISH), or both. Follow-up marrow biopsies, interphase FISH for bcr-abl, and conventional cytogenetics were performed at 3-month intervals (up to 24 months) after therapy initiation. All patients exhibited a reduction in bone marrow cellularity with decreases in myeloid/erythroid ratios at 3 to 6 months after therapy. The percentage of bcr-abl-positive cells by FISH decreased in all patients (pretherapy median, 73%; 3 months median, 47%). Cytogenetic and FISH data defined 2 groups after 6 months of follow-up: 5 patients became negative for bcr-abl by FISH; 8 remained positive, 4 of whom developed signs of clonal cytogenetic evolution. Patients who became negative for bcr-abl had no morphologic evidence of CML at 15 to 24 months of follow-up, whereas patients who remained positive redeveloped morphologic features of CML as cellularity increased. Some bcr-abl-positive patients showed signs of progression, including 2 patients who developed myeloid blast phase. Although all patients demonstrated an initial decrease in bone marrow cellularity after imatinib mesylate therapy, continued follow-up showed that histopathologic findings correlated with genetic response.

Antineoplastic Agents↗

The AIDS autopsy spleen: a comparison of the pre-anti-retroviral and highly active anti-retroviral therapy eras.

Pathologic findings attributed to human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) are described in the spleen in studies that encompassed the years preceding highly active anti-retroviral therapy (HAART). Major findings included white-pulp depletion, hemosiderin deposition, spindle cell proliferations, and perivascular hyalinization. Infectious and malignant infiltrates were commonly noted and characterized. The histopathology of AIDS autopsy spleens since the introduction of protease inhibitors has not been studied. Histologic sections from 168 cases of AIDS spleens examined at autopsy over a 19-year period (1982-2000) were evaluated for significant pathologic findings. Multiple morphologic parameters were recorded, including a graded estimation of white-pulp depletion. Significantly less white-pulp depletion was observed in the 39 HAART-era spleens (1995-2000) compared with the 129 spleens from the 1982-1994 patient group (P =.001). The rates of splenic involvement by atypical mycobacteria and cytomegalovirus were similar to those in the past, although the overall clinical rates of these opportunistic infections were found to be decreased. The annual numbers of AIDS autopsies have decreased, reflecting a nationwide trend of lower autopsy rates. Increased survival with HIV infection and AIDS is now apparent. Protease inhibitors, in conjunction with other contemporary therapies, may have contributed to the preservation of white pulp observed in the HAART patient group.

Acquired Immunodeficiency Syndrome↗

Leukemic phase of B-cell lymphomas mimicking chronic lymphocytic leukemia and variants at presentation.

Six cases of non-Hodgkin B-cell lymphoma that mimicked either chronic lymphocytic leukemia (CLL) or a CLL variant at presentation are reported. The patients ranged from 54 to 89 years and included three females and three males. All six patients had prominent peripheral blood lymphocytosis at presentation; the initial morphologic impression was CLL in three cases, CLL/prolymphocytic leukemia (PLL) in two cases, and PLL in one. Five patients had bone marrow biopsies; each showed a lymphoid infiltrate in a focally random, interstitial, and/or diffuse pattern. Flow cytometric immunophenotyping showed CD20-positive B cells with surface immunoglobulin (Ig) light chain restriction in all six patients. The five cases resembling CLL or CLL/PLL had at least a subset of CD5-positive B cells, whereas CD5 was absent in the one case that resembled PLL. CD23 was positive in three of the four cases studied that resembled CLL or CLL/PLL; CD79b was positive in three, FMC7 was positive in two, and surface Ig and CD20 were brightly positive in three. A t(11;14) (q13;q32) was found in four cases that resembled CLL or CLL/PLL; they were subsequently diagnosed as mantle cell lymphoma. The remaining two cases mimicking CLL or PLL were diagnosed as lymphomas of follicle center origin with leukemic phase based on the presence of t(14;18) (q32;q21). Thus although the morphology of these six cases resembled CLL or variants, and immunophenotyping by flow cytometry showed overlapping features, genetic studies enabled distinction of these leukemic non-Hodgkin lymphoma from chronic lymphocytic leukemia or variants.

Aged↗

Comparative study of marginal zone lymphoma involving bone marrow.

Few studies have characterized or compared the pathologic features of bone marrow involvement by extranodal (EMZL), splenic (SMZL), and nodal marginal zone lymphoma (NMZL). We evaluated 45 bone marrow biopsy specimens from 39 patients with marginal zone lymphomas. As previously reported, bone marrow involvement was frequent (100%) in patients with SMZL. We also identified lymphoma involving bone marrow in 11 (44%) of 25 patients with EMZL and 1 of 2 patients with NMZL. The patterns of infiltration were mixed in all groups; however, the extent of involvement was greater in SMZL than in EMZL. In addition, germinal centers were present in bone marrow biopsy specimens involved by lymphoma in 4 patients with SMZL. Intrasinusoidal infiltration was common (10/12 [83%]) and prominent in patients with bone marrow involvement by SMZL, but was not invariably present. Intrasinusoidal infiltration of the bone marrow also was not specific for SMZL since similar infiltrates, although subtle, also were found in patients with other small B-cell lymphoproliferative disorders, including 6 (55%) of 11 patients whose bone marrow samples were infiltrated by EMZL.

Adult↗