Home About us Contact
|
Home About us Contact | ||
|
|
||
Hematologic Response (hematologic + response)
Selected AbstractsEffect of First Treatment with Aminobisphosphonates Pamidronate and Ibandronate on Circulating Lymphocyte SubpopulationsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2000Martin Pecherstorfer Abstract Up to 60% of patients receiving their first infusion of the bisphosphonate pamidronate experience an acute-phase reaction. In this study, we used flow cytometry to determine the effects of pamidronate treatment on circulating lymphocyte subpopulations, and we investigated whether pamidronate and ibandronate treatment affect lymphocyte subpopulations differently. Twenty patients received a pamidronate infusion, 20 patients received intravenously injected ibandronate, and 10 controls received a clodronate infusion. Pamidronate treatment was followed by a significant increase in median body temperature at the 10-hour measurement and a significant decrease in counts of circulating lymphocytes, natural killer cells, T cells, and CD4+ and CD8+ T-cell subsets. Ibandronate treatment did not affect median body temperature, and it was associated at the 10-hour measurement with maximum increases in total lymphocyte count, B cells, T cells, and CD4+ and CD8+ T-cell subsets. Thus, there is a substantial difference in the hematologic response to initial treatments with pamidronate and ibandronate. Clodronate treatment did not induce changes in body temperature or significantly affect the number of circulating T cells and NK cells. The reduction in lymphocyte subsets after initial pamidronate therapy might be mediated by the release of tumor necrosis factor ,, whose source in the acute-phase reaction could be T cells. [source] Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Angela Dispenzieri We evaluated the capability of soluble cardiac biomarkers to predict tolerability and outcomes of IMiD-containing treatments among 106 patients treated on clinical trials. Baseline elevations in troponin T (TnT) and N-terminal brain naturietic protein (NT-proBNP) predicted for an inability to tolerate IMiD-based regimens. The best predictors for early attrition during cycle 1 were TnT , 0.07 ,g/L and NT-proBNP , 11,939 ng/L. NT-proBNP-response underperformed TnT-response as a predictor for overall survival (OS), but both predicted for early protocol attrition. Despite hematologic response, IMiD-treated patients were at higher risk for NT-proBNP rises and early drug discontinuation than a control population but not for early death. These observations prompt two questions: (1) does IMiD-based therapy lead to increased fluid retention and/or cardiac toxicity and (2) is an NT-proBNP-driven cardiac response system valid in IMiD-treated amyloidosis patients? Recognition of potential drug-induced cardiac toxicity is important so that increased cardiac surveillance and drug dose-adjustment or discontinuation may be implemented. Am. J. Hematol. 85:757-759, 2010. © 2010 Wiley-Liss, Inc. [source] Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Michael B. Lilly Dasatinib 70 mg twice daily is indicated for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) intolerant or resistant to imatinib. In patients with chronic-phase chronic myelogenous leukemia, once-daily dosing has similar efficacy with improved safety, compared with twice-daily dosing. A phase 3 study (n = 611) assessed the efficacy and safety of dasatinib 140 mg once daily versus 70 mg twice-daily in patients with advanced phase chronic myelogenous leukemia or Ph+ ALL resistant or intolerant to imatinib. Here, results from the Ph+ ALL subset (n = 84) with a 2-year follow-up are reported. Patients were randomly assigned to receive dasatinib either 140 mg once daily (n = 40) or 70 mg twice daily (n = 44). The rate of confirmed major hematologic response with once-daily dosing (38%) was similar to that with twice-daily dosing (32%). The rate of major cytogenetic response with once-daily dosing (70%) was higher than that with twice-daily dosing (52%). Compared with the twice-daily schedule, the once-daily schedule had longer progression-free survival (median, 3.0 months versus 4.0 months, respectively) and shorter overall survival (median, 9.1 months versus 6.5 months, respectively). Overall safety profiles were similar between two groups, with nonhematologic adverse events being mostly grade 1 or 2. Pleural effusion was less frequent with once-daily dosing than with twice-daily dosing (all grades, 18% versus 32%). Notably, none of the differences between the two schedules was statistically significant. Compared with the 70 mg twice daily, dasatinib 140 mg once daily had similar overall efficacy and safety in patients with imatinib-resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier: NCT00123487). Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Dyspnea secondary to pulmonary hematopoiesis as presenting symptom of myelofibrosis with myeloid metaplasiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2006Elisa Rumi Abstract We report a case of a patient with myelofibrosis with myeloid metaplasia (MMM) who presented with progressive dyspnea of unexplained origin. Splenomegaly, blood smear, and bone marrow findings allowed diagnosis of MMM. High-resolution CT chest scan revealed diffuse septal thickening, while echocardiography and electrocardiogram showed no indirect evidence of pulmonary hypertension. Finally, lung biopsy revealed irregularly distributed interstitial fibrosis with islands of erythroblasts, immature granulocytic elements, and dysplastic megakaryocytes, allowing diagnosis of pulmonary extramedullary hematopoiesis (EMH). The patient received hydroxyurea as cytoreductive agent, obtaining a good hematologic response and an improvement of dyspnea. Note that, in this patient, dyspnea was the first clinical symptom of MMM; the dyspnea was not associated with pulmonary hypertension and improved following cytoreductive treatment. This case points to the importance of suspecting pulmonary EMH when unexplained progressive dyspnea occurs in a patient with MMM. Early recognition of pulmonary EMH may prevent PH and favor a better response to therapy. Am. J. Hematol. 81:124,127, 2006. © 2006 Wiley-Liss, Inc. [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] Treatment of chronic myeloid leukemia in the imatinib eraCANCER, Issue 6 2007Perspective from a developing country Abstract BACKGROUND There is paucity of data from developing countries on the efficacy and safety of imatinib mesylate in chronic myeloid leukemia (CML). The primary objective of this study was to document complete and partial cytogenetic responses to imatinib in all phases of CML. Secondary objectives included evaluations of complete hematologic response, safety, time to progression, and survival. METHODS Two hundred seventy-five patients in all phases of CML who received treatment with imatinib from January 2001 to December 2005 were included in the study. All patients had on bone marrow or BCR-ABL positive in peripheral blood by polymerase chain reaction. RESULTS After a median follow-up of 18 months, major cytogenetic responses (Ph <35%) in chronic phase (CP), accelerated phase (AP), and blastic phase (BP) were documented in 61%, 57%, and 28% of patients, respectively. A complete cytogenetic response was observed in 39.4%, 35.7%, and 14.3% of patients in CP, AP, and BP, respectively; and a complete hematologic response was observed in 90%, 86%, and 30%, respectively. The median time to progression at 18 months was 91% in CP and 68% in AP. The overall survivals in CP, AP, and BP at 18 months was 92%, 74%, and 38%, respectively. CONCLUSIONS Impressive hematologic, cytogenetic, and molecular responses to imatinib were observed, similar to the responses reported in patients from Western countries. Patients had good compliance, toxicity was limited, and overall quality of life was improved markedly. The results indicated that the biology of CML is not different in patients from developing countries. Cancer 2007 © 2007 American Cancer Society. [source] Results of decitabine (5-aza-2,deoxycytidine) therapy in 130 patients with chronic myelogenous leukemiaCANCER, Issue 3 2003Hagop M. Kantarjian M.D. Abstract BACKGROUND General and site-specific DNA methylation is associated with tumor progression and resistance in several cancers, including chronic myelogenous leukemia (CML). Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML. METHODS One hundred and thirty patients with CML were treated: 123 with Philadelphia chromosome (Ph)-positive CML (64 blastic, 51 accelerated, 8 chronic) and 7 with Ph-negative CML. Decitabine was given at 100 mg/m2 over 6 hours every 12 hours × 5 days (1000 mg/m2 per course) in the first 13 patients, 75 mg/m2 in the subsequent 33 patients, and 50 mg/m2 in the remaining 84 patients. RESULTS A total of 552 courses were given to the 130 patients. Only four patients (3%) died during the first course from myelosuppressive complications (three patients) or progressive disease (one patient). Of 64 patients in the CML blastic phase, 18 patients (28%) achieved objective responses. Of these 18 patients, 6 achieved complete hematologic responses (CHR), 2 achieved partial hematologic responses (PHR), 7 achieved hematologic improvements (HI), and 3 returned to the second chronic phase (second CP). Five patients (8%) had cytogenetic responses. Among 51 patients in the accelerated phase, 28 patients (55%) achieved objective responses (12 CHR, 10 PHR, 3 HI, and 3 second CP). Seven patients (14%) had cytogenetic responses. Among eight patients treated in the chronic phase, five (63%) had objective responses. Of seven patients treated for Ph-negative CML, four (57%) had objective responses. There was no evidence of a dose-response effect. The estimated 3-year survival rate was less than 5% in the blastic phase and 27% in the accelerated phase. The only significant toxicity reported was severe myelosuppression, which was delayed, prolonged, and dose dependent. With decitabine 50,75 mg/m2, the median time to granulocyte recovery above 0.5 × 109/L was about 4 weeks. Myelosuppression-associated complications included febrile episodes in 37% and documented infections in 34%. CONCLUSIONS Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases. Cancer 2003;98:522,8. © 2003 American Cancer Society. DOI 10.1002/cncr.11543 [source] | ||||||||||