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1.
Al-Kali A Konoplev S Lin E Kadia T Faderl S Ravandi F Ayoubi M Brandt M Cortes JE Kantarjian H Borthakur G 《Haematologica》2012,97(2):235-240
Background
The hypocellular variant of acute myeloid leukemia accounts for less than 10% of all cases of adult acute myeloid leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute myeloid leukemia differs from that of non-hypocellular acute myeloid leukemia.Design and Methods
We retrospectively analyzed all the cases reported to be hypocellular acute myeloid leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases.Results
One hundred twenty-three (9%) patients were identified: patients with hypocellular acute myeloid leukemia were older than those with non-hypocellular acute myeloid leukemia (P=0.009) and more frequently presented with cytopenias (P<0.001). Forty-one patients with hypocellular acute myeloid leukemia had an antecedent hematologic disorder and 11 patients had received prior chemo-radiotherapy for non-hematopoietic neoplasms. On multivariate analysis, overall survival, remission duration and event-free survival were comparable to those of other patients with acute myeloid leukemia.Conclusions
The outcome of hypocellular acute myeloid leukemia does not differ from that of non-hypocellular acute myeloid leukemia. 相似文献2.
Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia 总被引:12,自引:3,他引:12 下载免费PDF全文
Kantarjian H Gandhi V Cortes J Verstovsek S Du M Garcia-Manero G Giles F Faderl S O'Brien S Jeha S Davis J Shaked Z Craig A Keating M Plunkett W Freireich EJ 《Blood》2003,102(7):2379-2386
In a phase 2 study, 62 patients with relapsed and refractory acute myeloid leukemia (AML; n = 31), myelodysplastic syndrome (MDS; n = 8), chronic myeloid leukemia in blastic phase (CMLBP; n = 11), and acute lymphocytic leukemia (ALL; n = 12) received 40 mg/m2 clofarabine intravenously over 1 hour daily for 5 days, every 3 to 6 weeks. Twenty patients (32%) achieved complete response (CR), 1 had a partial response (PR), and 9 (15%) achieved CR but without platelet recovery (CRp), for an overall response rate of 48%. In AML, responses were noted in 2 (18%) of 11 patients in first salvage with short first CR (= 12 months), in 7 (87%) of 8 patients with longer first CR, and in 8 (67%) of 12 patients in second or subsequent salvage. Responses were observed in 4 of 8 patients with high-risk MDS (50%), in 7 (64%) of 11 with CML-BP, and in 2 (17%) of 12 with ALL. Severe reversible liver dysfunction was noted in 15% to 25%. After the first clofarabine infusion, responders accumulated more clofarabine triphosphate in blasts compared with nonresponders (median 18 vs 10 microM; P =.03). This increased only in responders (median, 1.8-fold; P =.008) after the second clofarabine infusion. In summary, clofarabine is active in acute leukemias and MDS; cellular pharmacokinetics may have prognostic significance. 相似文献
3.
Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia 总被引:10,自引:6,他引:10 下载免费PDF全文
Kantarjian HM O'Brien S Cortes JE Giralt SA Rios MB Shan J Giles FJ Thomas DA Faderl S De Lima M Garcia-Manero G Champlin R Arlinghaus R Talpaz M 《Blood》2002,100(5):1590-1595
Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD. 相似文献
4.
Considerable progress has been made in the treatment of acute and chronic leukemias. Remission rates are generally high and cure rates of up to 80% can be achieved in children with acute lymphoblastic leukemia (ALL). However, in many patients the disease will ultimately recur. In most if not all of these patients, relapse is thought to result from subclinical levels of residual leukemia, termed minimal residual disease (MRD). Therefore, the study of MRD holds a significant potential to understand the biology of relapse and remission and to design new therapies to improve the cure rate of patients. A major goal of these studies is to be able and identify patients at a defined risk of relapse which can lead to risk-adapted therapy approaches. Laboratory assays such as polymerase chain reaction (PCR) and multicolor flow cytometry are sensitive enough to detect one leukemic cell in up to 104-105 normal cells and have become ideal tools to monitor MRD. Especially PCR has been used extensively. Although a wealth of data has been generated, some questions remain as to the impact of monitoring MRD on clinical outcome and are the object of this review. 相似文献
5.
Mattiuzzi GN Kantarjian H O'Brien S Kontoyiannis DP Giles F Zhou X Lim J Bekele BN Faderl S Cortes J Pierce S Leitz GJ Raad I Estey E 《Cancer》2004,100(3):568-573
BACKGROUND: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS: Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS: One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with i.v. ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of i.v. ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS: Despite its theoretic advantages, the authors found no evidence that i.v. ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole. 相似文献
6.
Verstovsek S Giles FJ O'Brien S Faderl S Kantarjian HM Keating MJ Albitar M 《Leukemia research》2004,28(7):707-711
We measured telomerase activity (TA) in bone marrow samples from 214 patients with CLL and correlated it with patients' characteristics and survival. In >50% of cases (126/214; 59%) no detectable TA was found. There was no difference in TA between previously treated (n = 153) and untreated (n = 61) patients (P = 0.4), or patients with various Rai (0-IV) stages (P = 0.85). TA correlated significantly with white blood cell and lymphocyte count (P = 0.02 and 0.01, respectively) but not with bone marrow cellularity, beta2-microglobulin (beta2M), or other patient characteristics. Patients who had no TA had slightly lower beta2M and lower lymphocyte counts (P = 0.5 and 0.04, respectively) as compared with patients with detectable TA. However, there was no correlation between TA and survival. This data suggests that TA may not play a significant role in the clinical behavior of CLL. 相似文献
7.
Faderl S Hochhaus A Hughes T 《Hematology / Oncology Clinics of North America》2004,18(3):657-70, ix-x
Detection and monitoring of minimal residual disease has become one of the most prevalent topics in chronic myeloid leukemia(CML) therapy. The goal of early detection of residual disease is to allow timely therapeutic intervention before overt relapse of therapy resistant disease occurs. The most powerful tool to serve this purpose is polymerase chain reaction (PCR). Major improvements in assay techniques have advanced PCR from a purely qualitative test with considerable variability of test results to a real-time quantitative assay with far more reproducible results than were possible before. At the same time, treatment of CML has changed dramatically since the introduction of imatinib. Integration of therapy and molecular assays such as PCR, in addition to a profound understanding of the pathophysiology of CML, has assumed even more importance. Quantitative PCR testing has become the standard monitoring strategy for patients undergoing stem cell transplantation.Although correlations have been established between positive test results and probability of relapse, no absolute guidelines for monitoring exist, especially for patients treated with imatinib. 相似文献
8.
Tsimberidou A Cortes J Thomas D Garcia-Manero G Verstovsek S Faderl S Albitar M Kantarjian H Estey E Giles FJ 《Leukemia research》2003,27(10):893-897
Clinical resistance to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia (AML) is associated with blast multidrug resistance (MDR) phenotype. A Phase II study of Mylotarg, fludarabine, ara-C and the MDR-modifier, cyclosporine (CSA) (MFAC) was conducted in 32 patients with primary resistant (11, 34%) or relapsed (21, 66%) AML. Nine (28%) patients obtained complete remission (CR), two (6%) CR with incomplete platelet recovery. Overall median survival was 5.3 months, 12-month survival rate 19%. Fourteen patients (44%) developed grade 3/4 hyperbilirubinemia; six (18%) grade 3/4 hepatic transaminitis; three (9%) hepatic veno-occlusive disease (VOD). CSA inclusion in gemtuzumab ozogamicin-based regimens is feasible. MFAC is an effective regimen for refractory AML. 相似文献
9.
Clinical relevance of VEGF receptors 1 and 2 in patients with chronic myelogenous leukemia 总被引:5,自引:0,他引:5
Verstovsek S Lunin S Kantarjian H Manshouri T Faderl S Cortes J Giles F Albitar M 《Leukemia research》2003,27(7):661-669
Vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML) and high vascular endothelial growth factor (VEGF) levels correlate with worse survival. We analyzed the significance of VEGF-receptor 1 (VEGF-R1) and VEGF-R2 levels in bone marrow samples from 170 CML patients (137 chronic, 24 accelerated, and 9 blastic phase). Median VEGF-R1 and VEGF-R2 levels were 4.66 and 2-fold, respectively, that in normal control samples. Receptor levels did not correlate with disease phase or other host and disease features examined. Chronic phase CML patients with increased VEGF-R2 levels had significantly inferior survival than patients without receptor up-regulation (P=0.009). Patients in accelerated/blastic phase CML with elevated VEGF-R2 expression had marginally worse survival (P=0.05). In contrast, high VEGF-R1 levels did not correlate with a specific CML phase, characteristic, or outcome. Our findings support VEGF-R2 over-expression as an independent prognostic indicator for shortened survival in patients with CML. 相似文献
10.
Kantarjian HM O'Brien S Cortes JE Shan J Giles FJ Rios MB Faderl SH Wierda WG Ferrajoli A Verstovsek S Keating MJ Freireich EJ Talpaz M 《Cancer》2003,97(4):1033-1041