PubMed Health⌕ Search

Biomedical subjects

Jane N Winter

Publications and source records attributed to Jane N Winter.

15 recordsLinked to original sources

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

Advisory Committees↗

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↗

Current controversies in follicular lymphoma.

Follicular lymphoma (FL) is characterized by its responsiveness to initial therapy, a pattern of repeated relapses, and a tendency for histologic progression to a process resembling diffuse, large B-cell lymphoma. Treatment decisions are complicated by the many effective options now available including combinations of conventional chemotherapy and monoclonal antibody, radioimmunotherapy, new targeted agents, and autologous and allogeneic stem cell transplantation. For selected patients, "watch and wait" or involved field irradiation may still be the most appropriate strategy. When therapy is required, a combination of rituximab and conventional chemotherapy results in improved outcomes compared to chemotherapy alone. Radioimmunotherapy alone or in combination with chemotherapy is an attractive strategy for patients with relapsed disease and may prove to be appropriate first line therapy. The role of stem cell transplant in FL requires further investigation. Novel agents with varied mechanisms of action continue to be developed. Enrollment of patients into clinical trials designed to address the many unanswered questions in FL is essential to improving clinical outcomes.

Antineoplastic Agents↗

Radioimmunotherapeutic strategies in autologous hematopoietic stem-cell transplantation for malignant lymphoma.

High-dose therapy followed by autologous hematopoietic stem-cell transplantation is the preferred therapy for relapsed chemotherapy-sensitive aggressive non-Hodgkin lymphoma, and may play a role in the treatment of high-risk first-remission aggressive lymphomas, mantle-cell lymphomas and relapsed follicular lymphomas. The primary cause of failure of this approach is disease recurrence despite initial responses. Traditional high-dose regimens have relied upon myeloablative combinations of chemotherapy with or without total body irradiation. In the Western world, over 90% of lymphomas are of B-cell origin, and the vast majority of those that come to transplant remain CD20-positive. The development of radioimmunotherapeutic approaches targeting this antigen allows for either dose escalation with stem-cell support, or the addition of targeted therapy to conditioning regimens either as a replacement for total body irradiation or in addition to myeloablative chemotherapy regimens. Results to date with yttrium-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) suggest that the addition of radioimmunoconjugate therapy to conventional conditioning regimens results in a toxicity profile similar to that seen with chemotherapy conditioning alone. Demonstration of improved disease control will ultimately require phase-III studies, though preliminary results are promising.

Dose-Response Relationship, Radiation↗

Follicular lymphoma: today's treatments and tomorrow's targets.

Over the past two decades, the incidence of follicular lymphoma has increased. Contemporary treatments include combinations of chemotherapy and monoclonal antibodies, radioimmunotherapy, new targeted agents and stem-cell transplantation. Prognostic tools are becoming more important in helping clinicians and patients decide on the most appropriate therapeutic regimens. Gene expression profiling and biomarkers are promising additions to this armamentarium. When patients do require therapy, the addition of rituximab to chemotherapy seems to improve remission duration and may improve overall survival. Radioimmunotherapy capitalises on the capacity to target radiation directly to malignant cells, and is currently approved for the treatment of relapsed/refractory follicular lymphoma. Further investigation is needed to clarify the role of stem-cell transplantation in follicular lymphoma. Only well-designed clinical trials can provide answers to the many questions that remain regarding the optimal treatment and sequence of treatments for patients with follicular lymphoma.

Alkylating Agents↗

Sphingomyelin/cholesterol liposomal vincristine: a new formulation for an old drug.

Sphingomyelin/cholesterol liposomal vincristine (SV) is a novel formulation of vincristine encapsulated in the aqueous interior of liposomes composed of sphingomyelin and cholesterol. Benefits of the liposomal formulation include prolongation of the circulation half-life of total vincristine and an increase in drug delivery to sites of tumour growth resulting in enhanced efficacy. In addition, higher doses of vincristine than ordinarily administered can be prescribed without significant toxicity. Phase II studies have demonstrated that SV is active and well tolerated in relapsed diffuse large B cell lymphoma (DLBCL), including patients who have relapsed following an autologous stem cell transplant. SV has been successfully substituted for free vincristine in the CHOP regimen for those with previously untreated aggressive B cell non-Hodgkin's lymphoma, and is undergoing study in other settings. The achievement of responses in heavily pretreated patients with DLBCL and its low toxicity profile make SV a potential therapy for the palliative treatment of patients with multiply relapsed DLBCL. Ultimately, it is likely to be incorporated into combination chemotherapy regimens for use in untreated or relapsed patients. Its true value both as a single agent in heavily pretreated patients and in combination regimens will need to be established in Phase III trials.

Animals↗

Classical Hodgkin's lymphoma presenting with tongue involvement: a case report and review of the literature.

We report an unusual case of mixed cellularity classical Hodgkin's lymphoma with prominent involvement of the base of the tongue at diagnosis. In situ hybridization findings for Epstein-Barr virus were positive. Waldeyer's ring involvement by Hodgkin's lymphoma is uncommon with < 200 cases reported in the English literature and only 5 previous reports of Hodgkin's lymphoma involving the tongue.

Aged↗

Radioimmunotherapy and autologous stem cell transplantation for the treatment of B-cell lymphomas.

Relapse continues to be the primary cause of treatment failure in patients with non-Hodgkin's lymphomas (NHL) undergoing high-dose therapy and autologous stem cell transplantation. The anti-CD20 radioimmunoconjugates, Y-90 ibritumomab tiuxetan (Zevalin; Biogen Idec, Inc., Cambridge, MA, USA) and I-131 tositumomab (Bexxar; Corixa, Seattle, WA; and Glaxo Smith Kline; Philadelphia, PA, USA) have been associated with high response rates, durable remissions and limited toxicity apart from myelosuppression, making them ideal candidates for use in autotransplantation. Tested first as single agents in relapsed patients with indolent and transformed NHL, and then at much higher doses with stem cell support, these agents have now been combined with high-dose chemotherapy prior to autologous stem cell transplant. Radioimmunoconjugates have been used to replace total body irradiation (TBI) in some studies and to augment standard chemotherapy regimens in others. Thus far the results are promising, with combinations of radioimmunoconjugates and chemotherapy producing long-lasting responses in high-risk patients with no more toxicity than that caused by standard conditioning regimens. These results are notable in light of the fact that the dose of radiation delivered to the tumor is 10-fold higher than the dose achievable with TBI. Whether this increase in radiation dose to the targeted lymphoma translates into more durable remissions and an improvement in overall survival requires further investigation.

Hematopoietic Stem Cell Transplantation↗

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group.

PURPOSE: We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma. PATIENTS AND METHODS: Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles. RESULTS: We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity. CONCLUSION: In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity.

Adult↗

Multiple unrelated clonal abnormalities in host bone marrow cells after allogeneic stem cell transplantation.

A 22-year-old man with chronic myeloid leukemia (CML) received fractionated total body irradiation (TBI) (1440cGy) and etoposide (60 mg/kg) followed by infusion of 10 x 10(6) /kg CD34+ selected stem cells from his mother. Donor and recipient were 50% matched at the HLA-A and -B loci and 100% at HLA-DR. Mixed lymphocyte culture reaction was negative. Post-stem cell transplant (SCT) immunosuppression consisted of antithymocyte globulin, cyclosporine, and prednisone, and was discontinued after 7 months. The donor graft was rejected 2 years post-SCT. At 7 years post-SCT, he is clinically well with normal blood counts and no evidence of CML or myelodysplasia despite the presence over 6 years of multiple clones with balanced translocations and deletions in host bone marrow cells. The emergence of clonal hematopoiesis may provide insights into therapy-related leukemogenesis.

Adult↗

Low-grade lymphoma.

Folicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma, shows considerable heterogeneity in its clinical behavior, representative of a biology that appears increasingly complex and diverse. As our knowledge of the molecular basis of FL increases, we strive for an integration between the bench and clinic that yields treatments based on our scientific understanding and biomarkers that allow us to prescribe treatment rationally. In Section I, Dr. Randy Gascoyne describes the histologic, cytogenetic and biologic features of FL that underlie its clinical variability. Key aspects of the pathologic diagnosis of FL that have particular relevance to the clinician are highlighted. A proposed model for follicular lymphomagenesis and diffuse large B cell lymphoma transformation has emerged and continues to evolve as the molecular story unfolds. A biologic basis for clinical outcome in FL also appears to be forthcoming. In Section II, Dr. Jane Winter addresses the complex process of selecting among the many treatment options for patients with FL. Previously a simple matter of deciding between oral or intravenous alkylators, clinicians and patients must now struggle to choose among vastly different approaches ranging from "watch and wait" to stem cell transplantation. The introduction of rituximab and radioimmunoconjugates is changing the treatment paradigm, but the optimal approach to integrating these and other new agents remains to be determined. At every decision point, the best approach is always a clinical trial. In Section III, Dr. Koen Van Besien provides a well-documented update on outcomes associated with autologous and allogeneic stem cell transplantation for FL. The results of trials of autologous stem cell transplantation in first remission and recent data supporting a role for graft purging are discussed. Based on the premise that a graft-versus-lymphoma effect is operative in FL, reduced-intensity allogeneic transplantation is the preferred approach in many cases, and recently reported results are summarized. Criteria for patient selection and the optimal role of transplantation in the overall therapeutic plan for the patient with FL are presented.

Antineoplastic Agents↗

Combining yttrium 90-labeled ibritumomab tiuxetan with high-dose chemotherapy and stem cell support in patients with relapsed non-Hodgkin's lymphoma.

Targeted radioimmunotherapy, including yttrium 90-labeled ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar), has the potential to increase the cure rate for patients with CD20+ B-cell malignancies who are undergoing autologous hematopoietic stem cell transplantation. The results of phase I and II trials suggest that radioimmunoconjugates can be safely combined with high-dose chemotherapy, although the optimal approach remains to be established. This review focuses on the use of 90Y ibritumomab tiuxetan combined with high-dose chemotherapy in the setting of autologous hematopoietic stem cell transplantation.

Antibodies, Monoclonal↗

Autologous hematopoietic stem cell transplant in first remission in non-Hodgkin's lymphoma.

The PARMA trial clarified the role of hematopoietic stem cell transplant in patients with non-Hodgkin's lymphoma in chemotherapy-sensitive relapse. With the goal of improving overall response and survival rates, hematopoietic stem cell transplant has been incorporated into the front-line treatment plan in some studies. While multiple clinical trials have been designed to address this issue, they have varied in their treatment regimens, patient populations and outcomes. This review will summarize and analyze the data obtained so far and provide practitioners with recommendations for the application of high-dose chemotherapy and hematopoietic stem cell transplant as part of the initial treatment of patients with both indolent and aggressive non-Hodgkin's lymphoma. Based upon the current literature, hematopoietic stem cell transplant cannot be recommended as first-line therapy in patients with non-Hodgkin's lymphoma outside the setting of a clinical trial.

Animals↗