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Adverse prognostic significance of CD20 positive Reed-Sternberg cells in classical Hodgkin's disease

Portlock, Carol S; Donnelly, Gerard B; Qin, Jing; Straus, David; Yahalom, Joachim; Zelenetz, Andrew; Noy, Ariela; O'Connor, Owen; Horwitz, Steven; Moskowitz, Craig; Filippa, Daniel A
The prognostic significance of CD20 positive classical Hodgkin's disease (cHD) is uncertain. All cHD cases referred to the Memorial Sloan-Kettering Cancer Center (MSKCC) were retrospectively identified (5/92-11/00); the samples were immunostained, and clinical data ascertained. Cases were re-reviewed without knowledge of clinical outcome. Univariate and multivariate analyses were performed 248 patients had cHD: 28 CD20(+) (11%); 220 CD20(-). All clinical characteristics were comparable except haemoglobin level at presentation. With a median follow-up of 29.2 months, significant prognostic factors in multivariate analysis were: CD20 positivity, elevated white blood cell count (WBC) and low absolute lymphocyte count for time-to treatment failure (TTF); and for overall survival (OS), CD20 positivity, elevated WBC count, bone marrow involvement and age >/=45 years. TTF was significantly poorer for ABVD-treated patients with CD20(+) cHD as compared with CD20(-) cHD. Among 167 patients treated at MSKCC, both TTF (P < 0.0001) and OS (P = 0.017) were significantly decreased in CD20(+) patients as compared with CD20(-) cHD. CD20(+) cHD is a poor prognostic factor for TTF and OS. All cHD cases should be immunophenotyped for CD20. A large prospective trial is needed to confirm these findings.
PMID: 15180859
ISSN: 0007-1048
CID: 2580582

Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas

Houldsworth, Jane; Olshen, Adam B; Cattoretti, Giorgio; Donnelly, Gerard B; Teruya-Feldstein, Julie; Qin, Jing; Palanisamy, Nallasivam; Shen, Yingjing; Dyomina, Katerina; Petlakh, Marina; Pan, Qiulu; Zelenetz, Andrew D; Dalla-Favera, Riccardo; Chaganti, R S K
Although it has been suggested that REL is the critical target gene of 2p12-16 amplification in diffuse large B-cell lymphoma (DLBCL), little experimental evidence supports this notion. In the present study, we sought to evaluate the relationship between REL amplification and REL function in a panel of 46 newly diagnosed DLBCLs and to correlate with DLBCL subgroups as identified by gene expression profiles and clinical features. The results indicate that amplification of the REL locus is not associated with accumulation of the active form of REL, as evaluated by immunofluorescence analysis. Upon subgrouping of the DLBCL cases based on gene expression signatures, REL amplification was detected in all subgroups, while high levels of nuclear-located REL were more frequently detected in activated B-cell-like DLBCL. Correlative analyses of REL copy number and REL nuclear accumulation with clinical parameters did not reveal any significant associations. Together these results indicate that 2p12-16 amplification does not lead to abnormal REL activation, suggesting that REL may not be the functional target of the amplification event. Nonetheless, these data indicate that DLBCLs are heterogeneous with respect to REL and thus nuclear factor-kappaB (NF-kappaB) activity
PMID: 14615382
ISSN: 0006-4971
CID: 99680

MUC-1 mucin protein expression in B-cell lymphomas

Teruya-Feldstein, Julie; Donnelly, Gerard B; Goy, Andre; Hegde, Abhijith; Nanjangud, Gouri; Qin, Jing; Thaler, Howard; Gilles, Frederic; Dyomin, Vadim G; Lloyd, Kenneth O; Zelenetz, Andrew D; Houldsworth, Jane; Chaganti, R S K
We have recently shown that MUC1, mapped to the chromosomal band 1q21, is rearranged or amplified in 15% of B-cell lymphomas and that rearrangement led to over-expression of MUC-1 mucin in a case of diffuse large B-cell lymphoma (DLBCL). To determine the incidence of MUC-1 mucin expression and its clinical significance in B-cell lymphomas, we investigated a panel of 113 cases by immunohistochemistry (IHC). MUC-1 mucin expression was detected in the majority of cases (92.9%), with moderate to high levels noted in 50.4% of all histologic subsets comprising DLBCL (82 cases), follicular lymphoma (FL) (15 cases), FL with transformation to DLBCL (4 cases), and other B-cell lymphomas (12 cases). No statistically significant correlation was found between MUC-1 mucin expression and MUC1 genomic status (amplification/rearrangement) evaluated by Southern blot analysis, and 1q21 abnormality by karyotypic analysis. For all cases, MUC-1 mucin expression correlated with a previous history of lymphoma (p=0.003).
PMID: 12610353
ISSN: 1541-2016
CID: 2580592

Nuclear expression of Rel correlates with gene amplification in diffuse large B-cell lymphomas (DLBCL). [Meeting Abstract]

Donnelly, GB; Teruya-Feldstein, J; Qin, J; Zelenetz, AD; Houldsworth, J; Chaganti, RSK
ISSN: 0006-4971
CID: 2580692

Gene amplification in diffuse large B-cell lymphoma (DLBCL) detected by array-based screening predicts clinical outcome. [Meeting Abstract]

Chen, WY; Chaganti, S; Donnelly, GB; Qin, J; Lane, D; Ruffalo, T; Teruya-Feldstein, J; Zelenetz, AD; Houldsworth, J; Chaganti, RSK
ISSN: 0006-4971
CID: 2580702

Abrupt IgM rise following treatment with rituximab in patients with Waldenstrom's macroglobulinemia [Meeting Abstract]

Donnelly, GB; Bober-Sorcinelli, K; Jacobson, R; Portlock, CS
ISSN: 0006-4971
CID: 2580712

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis

Kewalramani, T; Zelenetz, A D; Hedrick, E E; Donnelly, G B; Hunte, S; Priovolos, A C; Qin, J; Lyons, N C; Yahalom, J; Nimer, S D; Moskowitz, C H
High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.
PMID: 11001890
ISSN: 0006-4971
CID: 2580602

Granulocyte-colony stimulating factor (G-CSF) may improve disease outcome in elderly patients with diffuse large cell lymphoma (DLCL) treated with CHOP chemotherapy

Donnelly, G B; Glassman, J; Long, C; Torres, P; Straus, D J; O'Brien, J P; Bertino, J; Moskowitz, C H; Zelenetz, A D; Portlock, C S
Advanced age is an adverse prognostic factor in patients with DLCL. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has frequent dose-limiting toxicities, including myelosuppression. We retrospectively reviewed 50 consecutive patients > 60 years of age (median age 72) with B-cell DLCL who received CHOP with G-CSF. Patients received CHOP (median 6 cycles) at three-week intervals. G-CSF was given following all cycles of chemotherapy ("prophylactic G-CSF") in 28 of 50 patients, and following an episode of febrile neutropenia and thereafter in 19 patients, according to ASCO guidelines. Dose intensity, treatment delays, episodes of febrile neutropenia, complete response (CR) rate, disease-free survival, time-to-treatment failure, and overall survival were all analyzed according to the age-adjusted International Prognostic Index (aaIPI). The actual dose intensity for cyclophosphamide was 225.9 mg/m2/week and 0.90, respectively and for doxorubicin was 14.9 mg/m2/week (90% of ideal CHOP dosing for both drugs). Median followup was 4 years for the patients still living. Treatment delays and episodes of febrile neutropenia were less frequent among patients receiving G-CSF with all cycles of CHOP. The CR rates were 100%, 81%, 85%, and 36% for the low, low-intermediate, high-intermediate, and high aalPI risk groups, respectively. The 5-year actuarial relapse-free and overall survival for our patients were comparable to that of the cohort < or = 60 years of age and superior to the > 60 years of age cohort used to establish the aaIPI. With optimization of CHOP dosing, advanced age may not be an adverse prognostic factor for patients with DLCL. The routine use of G-CSF in elderly patients with DLCL should be further investigated.
PMID: 10975385
ISSN: 1042-8194
CID: 2580612

Images in clinical medicine. Methemoglobinemia [Case Report]

Donnelly, G B; Randlett, D
PMID: 10928887
ISSN: 0028-4793
CID: 330342

Evidence-based medicine: Resident preferences for morning report - Reply [Letter]

Gross, CP; Reisman, AB; Donnelly, GB; Sepkowitz, KA; Callahan, MA
ISSN: 0003-9926
CID: 2580682