Home About us Contact
|
Home About us Contact | ||
|
|
||
Durable Responses (durable + response)
Selected AbstractsConventional allogeneic hematopoietic stem cell transplantation for lymphoma may overcome the poor prognosis associated with a positive FDG-PET scan before transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2008Akihide Yoshimi A positive scan in pretransplantation fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be associated with a poor prognosis in patients with lymphoma undergoing high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). For those with a positive FDG-PET scan, treatment that includes allogeneic stem cell transplantation (allo-SCT) may be an alternative. However, it is uncertain whether allo-SCT can overcome a poor prognosis. Therefore, we conducted a retrospective analysis of 14 patients with lymphoma who had undergone FDG-PET scan within one month before allo-SCT at our institution. Eleven patients were FDG-PET-positive and three were negative. With a median follow-up of 17 months (range: 6,44) after allo-SCT, the cumulative incidence of progression was 29.3% in FDG-PET-positive patients and 0% in the FDG-PET-negative patients. Four of the 11 patients who had post-transplantation FDG-PET showed FDG-avid lesions on the first post-transplantation scan. In two of the four, regression of the lesions was observed during the scheduled reduction of immunosuppressant without donor lymphocyte infusion and remained without progression at the last follow-up (34 and 8 months). Durable responses after allo-SCT, at least with conventional conditioning regimens, can be expected in patients with FDG-PET-positive lesions before transplantation. Thus, conventional allo-SCT could be an attractive modality compared to ASCT for patients with positive FDG-PET after the completion of conventional salvage chemotherapy, and particularly for patients with T and NK-cell lymphomas. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Phase II study of pentostatin in advanced T-cell lymphoid malignanciesCANCER, Issue 2 2004Update of an M. D. Anderson Cancer Center series Abstract BACKGROUND The goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T-cell lymphoid malignancies. METHODS Patients were eligible if they had biopsy-proven T-cell lymphoma or leukemia and failure to respond to previous therapy or an expected complete response rate to conventional therapy of < 20%. Pentostatin was administered at an initial dose of 3.75 or 5.0 mg/m2 by intravenous bolus daily over a consecutive 3-day period every 3 weeks. RESULTS Forty-two of 44 patients enrolled in the study were evaluable. The median age of the patients was 62 years (range, 38,86 years). Patients received a median of 3 previous therapies (range, 0,10 previous therapies). Of these patients, 32 (76%) had mycosis fungoides/Sézary syndrome and 10 patients (24%) had other T-cell leukemias or lymphomas. The overall response rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17 patients [40.5%]). Durable responses were observed mainly in patients with Sézary syndrome or peripheral T-cell lymphoma. The median follow-up period for surviving patients was 20 months (range, 1,83+ months). The median duration of response was 4.3 months (range, 1,61 months). The most common toxicities were neutropenia, nausea, and CD4 suppression. A transient early ,flare' of disease was observed in some responders. CONCLUSIONS At these doses, pentostatin was reasonably well tolerated and is an effective drug for the treatment of T-cell lymphomas. Cancer 2004;100:342,9. © 2003 American Cancer Society. [source] Current management of adult idiopathic thrombocytopenic purpura in practice: a cohort study of 201 patients from a single center,INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2004J. Zimmer Summary To define usefulness and response to therapy and outcome in adults with idiopathic thrombocytopenic purpura (ITP) in clinical practice. We retrospectively reviewed a cohort of 201 consecutive patients with ITP, diagnosed between 1985 and 1994. In particular, we analyzed the therapies used, their response rates, prognostic indicators of response and outcome. In 62 patients, with minor bleeding episodes and a mean (±SD) platelet count of 88 ± 23 × 109/l, no treatment was used and chronic ITP was diagnosed in 59%. A total of 139 patients, with bleeding episodes in 71.2% cases and a mean platelet count of 20 ± 13 × 109/l, received at least one treatment. Three patients died (1.5% of the series). Corticosteroids were used in 118 patients, with an initial response rate of 82.2% and a long-term complete response (CR) of only 22.9%. Intravenous immunoglobulin was used in 26 patients, with an initial transient response in more than 60%. A splenectomy was performed in 55 patients, with an initial response rate of 92.5% and a long-term CR in 60%. Young age and prior response to corticosteroids were significant predictors of a durable response to splenectomy. Danazol was given in 37 patients, with a favorable response in 73% of cases. Our results illustrate the guidelines of the American Society of Hematology. Patients with moderate thrombocytopenia do not require treatment. In severe cases, splenectomy is the only treatment giving durable cures in a significant proportion of patients. Despite frequent chronicity, ITP is life-threatening only in a minor subset of patients. [source] Cutaneous melanoma: available therapy for metastatic diseaseDERMATOLOGIC THERAPY, Issue 1 2006Ahmad A. Tarhini ABSTRACT:, Survival of melanoma varies widely by stage, from a potentially highly curable disease when detected in early stages, to a disease with dismal prognosis when it reaches advanced inoperable stages. Stage IV melanoma defines distant metastasis and continues to comprise an ominous prognosis, with a median survival of 6,9 months. Currently, there is no therapeutic agent known to prolong survival in patients with metastatic melanoma. Therapeutic approaches studied in metastatic melanoma include chemotherapy, biochemotherapy, nonspecific immune adjuvants, cancer-specific vaccines, cytokines, monoclonal antibodies, and specific immunostimulants. Chemotherapy with single-agent dacarbazine is the only United States Food and Drug Administration (US-FDA)-approved chemotherapy agent for metastatic melanoma. Immunological approaches have yielded the only newly US-FDA-approved agent for metastatic disease in 30 years, high-dose bolus IL-2, based on durable responses in some patients with metastatic melanoma, but with associated high toxicity rate and cost. A number of novel therapeutic agents are undergoing active clinical investigation. [source] Novel agents to override imatinib resistance mechanismsDRUG DEVELOPMENT RESEARCH, Issue 7 2008Asumi Yokota Abstract Chronic myelogenous leukemia (CML) is a disorder of hematopoietic stem cells that results from the Philadelphia chromosome (Ph) created through translocation of human chromosomes 9 and 22. The resulting Bcr-Abl fusion protein has constitutively high tyrosine kinase activity that causes transformation of hematopoietic stem cells. Imatinib mesylate (IM) was developed as a specific Bcr-Abl kinase inhibitor and is efficacious in treating Ph-chromosome-positive (Ph+) leukemias such as CML and Ph+ acute lymphoblastic leukemia (ALL). Within a few years of its introduction to the clinic, IM has dramatically altered the first-line therapy for CML. Although most newly diagnosed CML patients in the chronic phase (CP) achieved durable responses when treated with IM, resistance to IM has become a major problem in patients with advanced-stage disease. The most important mechanism of IM resistance are point mutations within the Abl kinase domain; therefore, there is an urgent need for novel agents that can inhibit mutated Bcr-Abl. In this review, we describe novel Bcr-Abl tyrosine kinase inhibitors, the so-called "Super Gleevec" inhibitors. Drug Dev Res 69:398,406, 2008. © 2008 Wiley-Liss, Inc. [source] The current status of targeted therapy for non-small cell lung cancerINTERNAL MEDICINE JOURNAL, Issue 9 2010H. Francis Abstract Lung cancer accounts for more cancer-related deaths than any other malignancy in Australia and worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers and is associated with a 5-year survival of only 15%. Treatment with platinum-based doublets in the first-line setting and single agent chemotherapy in the second-line setting has improved survival and quality of life in patients with NSCLC. However, the benefits associated with chemotherapy are modest and serve to stress the need for novel therapeutic approaches. In the last decade a range of targeted therapies has been evaluated in NSCLC. Dramatic and often durable responses were seen in patients treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib particularly in females, non-smokers, patients of East Asian ethnicity and those with adenocarcinomas , a group subsequently found to be enriched for tumours with activating EGFR mutations. Large randomized phase III trials have since established a role for EGFR TKI in the second- and third-line setting as well as a potential role for the monoclonal antibodies bevacizumab and cetuximab, directed at vascular endothelial growth factor and EGFR, respectively, in the combination with chemotherapy in the first-line setting. Recently it has been shown that patients with EGFR mutations may benefit from gefitinib in the first-line setting. Other promising agents under evaluation are inhibitors of the insulin-like growth factor-1 receptor and inhibitors of recently described ALK gene rearrangements. [source] Clinical value of minor responses after 4 doses of rituximab in Waldenström macroglobulinaemia: a follow-up of the Eastern Cooperative Oncology Group E3A98 trialBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Morie A. Gertz Summary Waldenström macroglobulinaemia is a low-grade, lymphoplasmacytic lymphoma that is responsive to rituximab. We report the role of a minor response in predicting overall outcomes. We extended follow-up of a previously described cohort (n = 69) treated with 4 weekly doses of rituximab and observed durable responses (median time to progression, 30 months; 5-year survival rate, 66%). Patients achieving a minor response [25,50% immunoglobulin M (IgM) reduction] appeared to do as well as those achieving an objective response (>50% IgM reduction), which suggests that more aggressive or intensive therapy for minor responders is not required. Future studies of Waldenström macroglobulinaemia should report minor responses because they are associated with clinically meaningful benefits. This trial was registered at http://www.clinicaltrials.gov as #NCT00005609. [source] Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemiaCANCER, Issue 13 2009Alfonso Quintás-Cardama MD Abstract BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure. METHODS: To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall, 72% of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42% of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCR-ABL mutations. CONCLUSIONS: The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance. Cancer 2009. © 2009 American Cancer Society. [source] | ||||||||||