scholarly journals Pharmacokinetics and Tolerability of Etoposide in Newly Diagnosed Lymphoma Patients with Hepatic Impairment

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4445-4445
Author(s):  
Catherine Lai ◽  
Diane Cole ◽  
Nicole Lucas ◽  
Seth M. Steinberg ◽  
Brigitte C Widemann ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Dose Reduction ◽  
Hepatic Impairment ◽  
Conflicts Of Interest ◽  
Aggressive Lymphoma ◽  
P Value ◽  
Newly Diagnosed ◽  
Aggressive Lymphomas ◽  
Significant Difference ◽  
Elevated Bilirubin

Abstract Background: The addition of etoposide to chemotherapy regimens (e.g.- CHOEP and EPOCH) may be beneficial for the treatment of aggressive lymphomas. Previous studies have shown decreased clearance of etoposide in hepatic impairment leading to a dose reduction or removal of drug. Total clearance of etoposide does not change significantly in patients with elevated bilirubin. However, free (or unbound) etoposide levels are a more accurate measurement of drug clearance (Stewart el al. Changes in the Clearance of Total and Unbound Etoposide in Patients with Liver Dysfunction. J Clin Oncol. 1990 Nov;8(11):1874-9.). No studies have analyzed etoposide pharmacokinetics and clinical toxicity in lymphoma patients with hepatic impairment. Methods: Patients with newly diagnosed aggressive lymphoma received 1 to 8 cycles of DA-EPOCH +/-R at the NCI. Of 56 pts studied, 48 had normal and 8 had elevated bilirubin (median 3.4mg/dL, range 1.4-22.5mg/dL). All patients received full dose etoposide at 200mg/m2 over 96-hours on cycle 1. Blood samples were collected at 0, 22 and 96 hours after infusion began. Results: There was no significant difference between free etoposide clearance (Cl) and the free etoposide concentration (Css) in patients with elevated versus normal bilirubin (see table below). In all patients, irrespective of bilirubin, there was no significant correlation between free etoposide Cl, free etoposide Css and creatinine clearance (CrCl) or age. Neutropenia and thrombocytopenia was higher in patients with elevated bilirubin. Complete response (CR) was achieved in 75% (6/8) versus 85% (41/48) and PR in 0% (0/8) vs 4% (2/48) of patients with elevated vs normal bilirubin. Conclusions: Etoposide pharmacokinetics were not altered in patients with abnormal versus normal hepatic function. Although there was an increase in hematologic toxicities, there was no difference in Css or Cl of etoposide. Importantly, there were no significant differences in febrile neutropenia or grade 3/4 toxicities. The toxicity difference is likely attributed to other drugs. Response rates were similar between the 2 groups. Our results do not support the empiric dose reduction of etoposide in patients with aggressive lymphomas receiving potentially curative treatment. Table Results Elevated Bilirubin Normal Bilirubin p-value Median age (yrs) 39 (17-59) 54 (20-75) 0.15 IPI (int hi/hi risk) 75% (6/8) 23% (11/48) 0.0070 ANC nadir < 500/mm3 (C1) 100% (8/8) 54% (26/48) 0.017 PLT nadir < 25x103/mm3 (C1) 38% (3/8) 4% (2/48) 0.017 Febrile Neutropenia (C1) 13% (1/8) 13% (6/48) 1.00 G3/4 GI and neuro tox (C1) 38% (3/8) 13% (6/48) 0.11 Median free etoposide clearance on C1 (ml/min/m2) 724 (438-1413) 663 (199-1148) 0.40 Median free etoposide concentration on C1 (μM) 0.082 (0.044-0.135) 0.089 (0.052-0.298) 0.44 Disclosures No relevant conflicts of interest to declare.

A Better Mobilization Regimen for Newly Diagnosed Multiple Myeloma Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4051-4051
Author(s):  
Ahmed Y Abuabdou ◽  
Eric R Rosenbaum ◽  
Saad Usmani ◽  
Bart Barlogie ◽  
Michele Cottler-Fox
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Optimal Number ◽  
P Value ◽  
Newly Diagnosed ◽  
The Poor ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Minimum Number ◽  
Poor Mobilizer

Abstract Abstract 4051 Introduction: What constitutes an acceptable mobilization regimen for collecting CD34+ cells depends on whether the goal of collection is to obtain a minimum number versus optimal number of cells. When treating patients with high-risk myeloma it may be important to obtain an optimal number. Here we compare retrospectively our earlier mobilization regimen, VTD-PACE, with MVTD-PACE in newly diagnosed, previously untreated multiple myeloma patients. Materials and Methods : We reviewed data for all patients who collected hematopoietic progenitor cells on Total Therapy protocols TT3a/TT3b with VTD-PACE (n=394) from February 2004 to September 2008 (138 females and 256 males, median age 59y; range 31–75), and on TT4/TT5 with MVTD-PACE (n=188) from August 2008 to May 2011 (78 females and 110 males, median age 61y, range 30–76). Based on their predicted first day collection with a large volume leukapheresis (30L processed), using our center's predictive formula (Blood 2010; 116(21):1182a), patients were stratified into 4 mobilizer types: poor (<2×106 CD34+ cells/kg), intermediate (≥2 to 10×106), good (>10 to 20×106) and excellent (>20×106). Variables examined included number of CD34+ cells/μl blood on day 1 and day 2 of collection (we have a minimum 2 day collection requirement), number of collection days to reach our minimum goal of 20×106 CD34+ cells/kg, and total CD34+ cells/kg collected for both chemotherapy groups. Variables for both groups stratified by mobilizer type were compared using two-tailed student's t-tests, except for the poor mobilizer group, where population size was too small for formal statistical analyses (VTD-PACE n=7, MVTD-PACE n=4), although averages were calculated. Results : There was no significant difference between VTD-PACE and MVTD-PACE for CD34+ cells/μl blood on day 1 of collection among the excellent [mean 368.9 (n=184) vs. 434.6 x106 (n=92); p-value 0.07], good [mean 138.6 (n=102) vs. 128.6 x106 (n=40); p-value 0.19], and intermediate [mean 60.1 (n=100) vs. 55.9 x106 (n=52); p-value 0.39] groups. A statistically significant difference between VTD-PACE and MVTD-PACE was found for CD34+ cells/μl blood on day 2 of collection for excellent mobilizers [mean 333.8 (n=184) vs. 460 ×106 (n=92); p-value <0.001], but not for the good [mean 165.7 (n=102) vs. 189.5×106 (n=40); p-value 0.21] and intermediate [mean 80.1 (n=101) vs. 102.3 ×106 (n=52); p-value 0.07] groups. When CD34+ cell/kg collection totals with VTD-PACE and MVTD-PACE were compared, a significant difference was seen for the intermediate mobilizer group only [mean 23.6 (n=101) vs. 26.3 ×106 (n=52); p-value 0.03]. For the poor mobilizer group, VTD-PACE had an average CD34+ cells/μl blood of 13.5×106 for day 1 of collection and 17.0 ×106 for day 2, with a total of 14.5×106 CD34+cells/kg collected; while MVTD-PACE had an average of 13.2×106 CD34+ cells/μl blood for day 1 of collection, 24.9×106 for day 2, with a total of 24.2×106CD34+ cells/kg collected. The number of collection days was similar between VTD-PACE and MVTD-PACE in the excellent mobilization group (2 days), but was slightly more for VTD-PACE compared to MVTD-PACE for the good (2.1 vs. 2 days), intermediate (3.2 vs. 2.9 days), and poor (6.1 vs. 5.8 days) groups. Conclusion : Both regimens allow more than minimum collections, but MVTD-PACE provides a higher peak number of CD34+ cells/μl blood, resulting in a slightly lower mean number of days of collection than VTD-PACE to reach an optimal collection. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Retrospective Study on Prephase Therapy Prior to Definitive Multiagent Chemotherapy in Aggressive Lymphomas

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2981-2981
Author(s):  
Luis E Malpica Castillo ◽  
Jonathan Galeotti ◽  
Natalie S Grover ◽  
Xianming Tan ◽  
Stephen Clark ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Dose Reduction ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Preventive Strategy ◽  
Bulky Disease ◽  
Aggressive Lymphomas ◽  
Significant Difference ◽  
Multiagent Chemotherapy ◽  
Ecog Ps

Abstract Background : Diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) are aggressive lymphomas that evolve rapidly and are fatal if untreated. Most treatment-related toxicities occur during the initial phase of therapy, particularly in the elderly and in patients with a high disease burden. Prephase therapy is used as a preventive strategy prior to definitive multiagent chemotherapy to ameliorate the development of toxicity, such as febrile neutropenia, tumor lysis syndrome, deterioration in performance status, and death. While this approach is often implemented, there are few data supporting when to initiate a prephase regimen, or whether this approach will be effective. We present data from our experience at the University of North Carolina Cancer Hospital. Methods : We conducted a retrospective analysis of patients (pts) diagnosed with DLBCL and BL between January 2016 and December 2017. Pts were divided into 'prephase' (PP) and 'non-prephase' (NPP) groups. The PP group received either prednisone (P) alone at 60 mg/kg oral daily from day -6 to day -1, or in combination with vincristine (V) 1 mg intravenously on day -6 (VP regimen), cyclophosphamide 200 mg/m2 on day -6 (CP regimen), or all three drugs (CVP regimen). Multiagent chemotherapy was given at day 0. Both groups were evaluated until day 30. ECOG performance status (PS), grade 3-4 cytopenias, absolute neutrophil count (ANC) and platelet nadirs, time to ANC and platelet recovery, episodes of febrile neutropenia, hospitalization and emergency (ER) visits, and next cycle dose reduction or delay, were compared in both groups. Results : Ninety-two pts (DLBCL n=82, and BL n=10) were identified. Clinical characteristics are shown in Table 1. Twenty-two pts received PP therapy (vs. NPP n=70). Median age at diagnosis was 59 years and 61 years for PP and NPP group, respectively. Female predominance was observed in both groups (PP 59% and NPP 54%). Poor baseline ECOG PS was significantly different between the PP and NPP group (median score 2 vs. 0, p<0.001). Stage III-IV and bulky disease were more common in the PP group, although this was not statistically significant. Oral prednisone was the most common prephase therapy used (P n=17, VP n=1, CP n=1, CVP n=3). All regimens were well tolerated. Definitive chemotherapy regimens and outcomes are summarized in Table 2. The PP group had a significant improvement in PS from a median PS of 2 at baseline to a median PS of 1 (p<0.001) by day 14. The NPP group did not have a significant change in PS. In a subgroup analysis, both pts older than 60 years with any PS (n=10, p=0.027), and pts 60 years or younger with a PS of 2 or more (n=6, p=0.023) had a significant improvement in PS after prephase therapy. PP pts had a shorter time for ANC and platelet count recovery than NPP pts (ANC 4 vs. 8 days, p=0.013; platelet 4 vs. 9 days, p=0.023). The platelet nadir was significantly lower in the PP (80 x 109 plt/L) compared to the NPP group (150 x 109 plt/L) (p=0.025). There was no significant difference in the episodes of febrile neutropenia. Conclusions : Prephase therapy significantly improved PS by day 14 of definitive multiagent chemotherapy at first cycle. The overall improvement in PS was primarily caused by improvements in 2 groups: pts older than 60 years, and pts 60 years or younger with poor PS (ECOG PS 2 or more). This is consistent with who we would expect to benefit the most from prephase therapy. Patients who received prephase therapy had a significant reduction in the length of their ANC nadir, although, interestingly, the rate of febrile neutropenia was low in both arms. The length of the platelet nadir was also significantly reduced in the PP group. Conversely, the depth of platelet nadir was significantly lower in the PP group, which may be a reflection of more aggressive disease in this group. The prephase group trended towards a reduction in the number of hospital admissions, ER visits, and next cycle dose reduction or delays, but these did not reach statistical significance. Based on these results, we will implement a provider reminder to consider prephase therapy when using multiagent chemotherapy in pts with aggressive lymphomas older than 60 years, or pts <60 with PS of 2 or greater. Disclosures Grover: Seattle Genetics: Consultancy. Dittus:Seattle Genetics: Consultancy.

scholarly journals Effect of Ranibizumab Treatment in Cases of Choroidal Neovascular Membranes Secondary to Pathological Myopia versus Age-Related Macular Degeneration

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M S Abdaltawab ◽  
Z F Ismail ◽  
W M A Ebeid ◽  
S M Fawzy
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
P Value ◽  
Newly Diagnosed ◽  
Pathological Myopia ◽  
Age Related ◽  
Significant Difference ◽  
The Mean

Abstract Aim of the Work The aim of this work is to compare the response of treatment with ranibizumab in terms of visual acuity in cases of CNV secondary to pathological myopia versus CNV secondary to age-related macular degeneration. Methods This prospective, comparative study included ten eyes newly diagnosed as having CNV secondary to pathological myopia, and 10 eyes newly diagnosed as having subfoveal active CNV secondary to AMD. All patients had 3 monthly intravitreal Injections of 0.50 mg (in 0.05 ml of solution) ranibizumab with monthly evaluation of best corrected visual acuity (BCVA) by Landolt C chart, and also calculated in Logarithm of Minimum Angle of Resolution (Log MAR). Results pretreatment there was no significant difference between the two groups as the mean VA (Log Mar) was 1.31 ± 0.2 in AMD group and 1.17 ± 0.3 in MCNV group of P value = 0.431 and also post three IVI of ranibizumab showed no significant difference between the two groups as the mean VA (Log Mar) was 1.22 ± 0.2 for AMD and 1.22 ± 0.5 for MCNV of P value = 0.635. Conclusion there was no significant difference in BCVA between AMD and MCNV groups after three intravitreal injections of ranibizumab.

Hodgkin Lymphoma Outcomes: Can We Expect Ethnic Parity in a Hispanic Prevalent Population?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4056-4056
Author(s):  
Michelle Janania Martinez ◽  
Prathibha Surapaneni ◽  
Juan F Garza ◽  
Tyler W Snedden ◽  
Snegha Ananth ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Relative Survival ◽  
Complete Response ◽  
Statistical Testing ◽  
P Value ◽  
Hispanic Population ◽  
Significant Difference ◽  
The Mean

BACKGROUND It is estimated that 8110 persons will be diagnosed with Hodgkin Lymphoma (HL) in the US during 2019, but the advent of new treatment options has increased the cure rate to at least 80%. It has been reported that the rates of HL are lower in the adolescent and young adult (AYA) Hispanic population but significantly higher in the Hispanic population older than 65. The relative survival estimates are stated to be similar between AYA Hispanics (HI) and non-Hispanics (NH) but for ages 65-84, HI have a significantly higher mortality rate. Pediatric studies have suggested that ethnicity plays a role in outcomes in patients with HL but there is limited data in the adult population. There is an unmet need in the field, where dossiers on underrepresented ethnic minorities need to be carefully considered and compared to existing data. Therefore, our study aims to compare survival outcomes in Hispanics vs Non-Hispanics with HL, who were treated at the only NCI designated cancer center of South Texas. To our knowledge this is the largest cohort of HL patients from a single academic institution that serves primarily Hispanics. METHODS We located and retrospectively analyzed a total of 616 patients with diagnosis of Lymphoma (HL and NHL) by International Classification of Diseases (ICD) codes and identified 116 cases of HL; all the patients received care at UT Health San Antonio, between 2008-2018. Key variables for each patient included age, gender, race/ethnicity, comorbidities, insurance status, stage, BM and extranodal involvement, treatment received, outcome at 3 and 5 years and vitality status in 2018. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. The study was approved by the local Institutional Review Board. The findings will be available to patients, funders and medical community through traditional publishing and social media. RESULTS We identified 116 patients with HL, of which 73 were HI (63%), 43 NH (36%) and 1 not specified (1%). In regard to race, 92% identified as Caucasian, 4% as African American, 3% other and 1% Asian. The median age at diagnosis was 37.4, (SD 15.13). There were 49 females (42%) and 67 males (58%). The most common funding source was commercial insurance N=54 (47%), followed by a hospital payment plan N=30 (26%), Medicare N=16 (14%), unfunded N=13 (11%) and Medicaid N=3 (2%). Most prevalent co-morbidities were HTN N=28 (24%) and diabetes mellitus N= 23(20%); 50% of patients had no co-morbidities (N=63).At diagnosis ECOG of 0-1 was seen in 108 patients (93%); 8 were Stage I (7%), 39 stage II (33%), 32 stage III (28%), and 37 stage IV (32%). EBV was positive in 26 patients (22%). There were 15 patients that were HIV positive (13%), 54% with CD4 count <200, and 12 (75%) on antiretroviral therapy at diagnosis. Median PFS was 853.85 days (SD 912.92). We excluded patients who were lost to follow up or had not reached 3/5 years. At 3 year follow up there was: complete response in 37 HI (74%) vs 22 NH (92%); disease progression in 8 (16%) vs 0 (0%); death in 5 (10%) vs 2 (8%), respectively (p-value= 0.094). At 5 year follow up there was: complete response in 30 HI (77%) vs 17 NH (90%); progressive disease in 2 (5%) vs 0 (0); death 7 (18%) vs 2 (11%), respectively (p-value = 0.619). At the end of 2018, 41 HI (84%) were alive compared to 22 NH (88%) [p-value 0.74]. CONCLUSION Within the limitations of sample size, our study demonstrates that in the prevalently Hispanic population of our institution, HI patients with HL have no statistically significant difference in outcome when compared to NH patients. Disclosures No relevant conflicts of interest to declare.

Pharmacokinetic and Pharmacodynamic Evaluation of a Biosimilar Rituximab in Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP (Rituximab, Cyclophosphamide, Adriamycin, Vincristine, Prednisolone).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4491-4491 ◽  
Author(s):  
Auro Viswabandya ◽  
P.V. Prashanthi ◽  
C. Nirmala Raju ◽  
Reena Rajsekhar ◽  
Vikram Mathews ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
Fixed Dose ◽  
P Value ◽  
Newly Diagnosed ◽  
Blood Samples ◽  
Significant Difference ◽  
Post Infusion ◽  
Multi Center Study

Abstract Addition of rituximab (375 mg/m2) to CHOP has been shown to improve survival in patients with DLBCL. However there is limited data on the pharmacokinetics (PK) and pharmacodynamics (PD) of this drug in this condition. We have evaluated the PK and PD of a biosimilar rituximab (Reditux®, Dr. Reddy’s Laboratories Ltd, Hyderabad, India) in 17 patients with newly diagnosed DLBCL treated at a single center with R-CHOP as part of a multi-center study undertaken to assess the safety and efficacy of this drug. R-CHOP (rituximab-375mg/m2; cyclophopsphamide-750mg/m2; adriamycin-50mg/m2; vincristine-1.4mg/m2 on day 1 and prednisolone-60mg/m2 on days 1 to 5) was given every 3 weeks for a total of 6 cycles. Blood samples for measurement of rituximab were collected just prior to start of infusion and 10min, 24, 72, 192 and 360 hours post-infusion for all patients during cycle 1 and in 6 patients during cycle 6 also. Additional samples were collected pre- and 10 minutes post-infusion after cycles 2, 3, 4, 5 and 6. Plasma rituximab levels were quantified using an immunoassay (sensitivity: 1ug/ml). B-lymphocyte counts were measured in peripheral blood samples taken from all patients at the beginning of each cycle. All patients were evaluated for clinical and radiological response after the 2nd, 4th and 6th cycles. Patients, mean age: 52 years (range:31–71) had disease in the following stages: stage II: 5, stage III: 7, stage IV: 5. Twelve out of 17 patients achieved complete remission while 5 had partial response (NCI criteria). At a mean follow-up of 5 months (range: 3–8), 3 patients had relapse of the disease. The arithmetic mean ±SD of PK parameters of Rituximab during cycle 1 were as follows: T½(hrs): 167±63; Cmax(ug/ml): 186±49; Cmin(ug/ml): 22.4±12.84; AUC0-∞ (ug.hrs/ml): 28162±11227) and Cl/F (ml/kg/hr): 23.8±10.8. These data are comparable with values previously reported for rituximab in other conditions. Though a 2–7 fold inter-individual variation was noted among these patients, there was no significant difference in these parameters between those in whom the disease relapsed as opposed to those who maintained remission. Among the 6 patients in whom data was available for the 1st and 6th cycles (table), there was significant reduction in Cl/F with associated increase in Cmax and AUC in the 6th cycle as compared to the 1st cycle. In 16 patients for whom the data was available, pre-treatment mean B lymphocyte count which was 121/ul (range:1.5–410.5) dropped to a mean of 9.9/ul (range:0.3–62.3) after the first cycle and remained in that range for the rest of treatment period. These data show that even with a 3-weekly regimen, therapeutic trough levels (25 μg/ml) of rituximab was observed across all cycles. In fact, the changing PK parameters of the drug with progressive cycles of R-CHOP suggest that fixed-dose regimens may not be the optimal way to administer this drug. Parameter Cycle1 (n=6) Cycle 6 (n=6) p value T ½ (hours) 200 386 0.0481 Cmax (μg/ml) 203 279 0.0556 Cmin (360Hr) 24.71 82.16 0.0028 AUC0- ∞ (μg.hrs/ml) 31167 92240 0.0049 Cl/F(ml/kg/hr) 20.5 7.6 0.0030

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

The Impact of Distance to Treatment Center on the Outcome of AML

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4742-4742 ◽  
Author(s):  
Bruno C. Medeiros ◽  
Tamara J. Dunn ◽  
Holbrook E Kohrt ◽  
Steven Coutre ◽  
Jason Gotlib ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
Adverse Outcomes ◽  
Treatment Center ◽  
P Value ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Impact

Abstract Abstract 4742 Introduction While the distance patients travel to a treatment center (DTC) adversely impacts survival of patients with trauma, cardiac, or neurological disorders, as well as certain solid tumors, less is known of its influence in acute myeloid leukemia (AML). Care for patients with AML involves frequent emergent and urgent management, often complicating primary therapy provided in distant tertiary referral centers. We therefore hypothesized that increased DTC has a negative impact on outcome. We tested this hypothesis by assessing the effect of DTC on survival of patients with AML receiving care at a single institution. Patients and Methods Within the Stanford Leukemia Database, we identified 884 consecutive adult patients between 1993 and 2009 meeting the following criteria: age >=18, newly diagnosed AML (excluding APL), clinical management at Stanford University Medical Center (SUMC), and verified residence location available for DTC determination. Of these, 571 were deemed fit by the admitting physician to receive myelosuppressive induction chemotherapy. DTC was calculated by straight-line journey distance between home address at the time of diagnosis and treatment center. Results The median age for the entire cohort is 55 years and 322 patients (36%) are older than 60 years of age. Median survival for the entire cohort was 14.0 months. DTC was not univariately associated with outcome as a continuous variable. When testing for a critical DTC threshold impacting outcomes across the entire cohort, we found a significant correlation between longer DTC and adverse outcomes, shorter DTC was associated with lower OS. Patients living within 20 miles of SUMC had a worse median overall survival (10.4 months versus 15.0 months, HR 1.23, corrected p-value 0.02). However, when adjusted for administration of induction chemotherapy (p<0.0001), age at presentation (p<0.0001) and karyotype at diagnosis (CBF vs other; p-value- 0.92), the negative impact of DTC was lost (p=0.08). Conclusion After accounting for confounding factors, DTC has no significant impact on the outcome of newly diagnosed AML patients receiving care at our institution. Unlike non-hematologic malignancies, distance to treatment center likely does not adversely influence outcomes for patients with AML. Disclosures: No relevant conflicts of interest to declare.

A Meta-Analysis of CAG (cytarabine, aclarubicin, G-CSF) Regimen for the Treatment of 1045 Patients with Leukemia in China and Japan,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3638-3638
Author(s):  
Guoqing Wei ◽  
Wanmao Ni ◽  
Dicky Chiao ◽  
He Huang ◽  
Zhen Cai ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Fixed Effects ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Early Death ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
China And Japan ◽  
Better Than

Abstract Abstract 3638 Background: CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of AML and MDS. This study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in acute leukemia (AL) and MDS pts. Methods: The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages between January 1995 and December 2010. Eligible studies were relevant clinical trials on AL and MDS pts treated with CAG regimen. Complete remission (CR) rates and odds ratio (OR) were compared through a meta-analysis using a random-effects or fixed-effects model. Results: 37 trials with a total of 1045 AL and MDS pts were included for analysis. Among the 1045 pts treated with CAG, 819 pts were AML, 215 pts were de novo MDS or transformed AML (MDS/tAML), 6 pts were ALL, and 5 pts were biphenotypic acute leukemia (BAL). The AML CR rate of CAG from 29 studies was 58.0% (95% CI, 53.1%-62.7%). The MDS/t-AML CR rate from 12 studies was 45.7% (95% CI, 39.0%-52.4%). The AML CR rate was significantly better than that of MDS /tAML (Q=8.072, p<0.01). Among 819 AML pts, 327 pts were newly diagnosed, 370 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 122 pts. Interestingly, no significant difference in CR rates was noted between the newly diagnosed (57.0%, 95% CI 51.5%-62.3%) and R/R AML pts (60.1%, 95% CI 50.5%-68.9%) (Q=0.312, p>0.05). The CR rate for the 367 elderly AML pts was 52% (95% CI 51.5%-62.3%). The CR rate was also significantly higher in pts with favorable (64.5%, 95% CI 38.8%-83.9%) and intermediate (69.6%, 95% CI 60.4%-77.5%) cytogenetics than those with unfavorable one (29.5%, 95% CI 19.7%-41.8%) (p<0.05). There were 7 trials that compared the CR rates of CAG regimen with those of other induction regimens in AML pts. Surprisingly, the CR rate of CAG was significantly higher than those of other induction regimens (OR 2.425, 95% CI, 1.515–3.880). CAG regimens were well tolerated with cardiotoxicity in 0.42% cases (4/954) and early death occurred in 4.40% cases (44/1000). Conclusions: CAG regimen induced significantly higher CR rates in AML than in MDS pts. The CR rates of CAG regimen was significantly better than those of other induction regimens in AML pts. This regimen was well tolerated with low cardiotoxicity and early death rate. Disclosures: No relevant conflicts of interest to declare.

CAG (cytarabine, aclarubicin, G-CSF) Regimen Is Effective and Well Tolerated in 367 Elderly Patients with AML in China and Japan: A Meta-Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4290-4290
Author(s):  
Guoqing Wei ◽  
Delong Liu
Keyword(s):  
Elderly Patients ◽  
Fixed Effects ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Current Therapy ◽  
Newly Diagnosed ◽  
Fixed Effects Model ◽  
Elderly Aml ◽  
Significant Difference ◽  
China And Japan

Abstract Abstract 4290 Background: Current therapy is still unsatisfactory in elderly patients (pts) with acute myeloid leukemia (AML). CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of elderly AML pts. The aim of this study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in elderly AML pts. Methods: The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages from January 1995 to December 2010. Eligible studies were relevant clinical trials of elderly AML pts treated with CAG regimen. Complete remission (CR) rate, odds ratio (OR) and 95% confidence intervals (CIs) of chemotherapy were compared through a meta-analysis using a random-effects or fixed-effects model. Results: 19 trials with a total of 367 elderly AML pts were identified and included for analysis. Among the 367 AML pts treated with CAG, 266 pts were newly diagnosed AML, 54 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 47 pts. The CR rate for the 367 elderly AML pts was 52.0% (95% CI 46.8%-57.2%). Interestingly, no significant difference in CR rates was noted between the newly diagnosed (54.7%, 95% CI 48.6%-60.7%) and R/R AML pts (45.7%, 95% CI 32.4%-59.6%) (Q=1.332, p=0.248). Three studies compared the CR rates of elderly AML pts according to the karyotype. The CR rate was significantly higher in pts with intermediate (72.4%, 95% CI 58.0%-83.3%) cytogenetics than those with unfavorable one (35.7%, 95% CI 18.7%-57.2%) (Q=7.803, p=0.005). These elderly AML pts tolerated CAG well with low cardiotoxicity (0.73%, 2/273) and ED (8.48%, 29/342). Conclusions: CAG regimen induced high CR rates in elderly pts with new and relapsed/ refractory AML. This regimen was well tolerated with low cardiotoxicity and early death rate. Disclosures: No relevant conflicts of interest to declare.

Revisiting the Role of the Stat Laboratory: Is It Safe to Perform Activated Clotting Time Determinations (ACTs) Out of the Operating Room

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4256-4256
Author(s):  
Michael Plietz ◽  
Aaron Leifer ◽  
Vilma Padilla ◽  
Carole Pineda ◽  
Khrishan Naraine ◽  
...  
Keyword(s):  
Half Life ◽  
Conflicts Of Interest ◽  
P Value ◽  
Clotting Time ◽  
Heparin Group ◽  
Platelet Factor ◽  
Activated Clotting Time ◽  
Significant Difference ◽  
Stat Laboratory ◽  
Over Time

Abstract Abstract 4256 Background: Activated clotting time (ACT) is determined during cardiac procedures in order to assess the level of anti-coagulation. There are three main anticoagulants used during cardiac procedures:heparin, angiomax and Plavix. Heparin is often used in the cardiac OR for major procedures and is neutralized, over time, by platelet factor 4(PF4). Angiomax, bivalirudin, has a quick onset of action, but a much shorter half-life when compared to Heparin. Plavix, clopidogrel, irreversibly inhibits platelets from clotting and is used on patients in need of anticoagulation for an extended period of time. The purpose of this study was to evaluate the stability of ACT results over time utilizing different coagulation regimens. If the ACT value remains stable over time, this would enable us to remove the device from the OR and place it in a stat laboratory. Methods: ACTs were determined by the ISTAT (Abbott), a hand held point of care device, using kaolin activated cartridges. A single blood sample was obtained and was evaluated at intervals of 0, 5, 10, 15, and 20 minutes. In addition, temperature, age, body surface area and platelet count of patient were recorded. The time 0 specimen was used to determine the patients ACT and interval testing was performed on the remnant. Results: 36 samples representing 22 patients had ACT tests performed using the ISTAT. There was no significant change from 0 to 20 minutes over the entire dada set. However, when divided into different anti-clotting agents there were significant changes. Patients who had only taken Angiomax had a significant difference within the first 5 minutes (p value=.0094). Patients taking Angiomax and Plavix together had no change in ACT values at 20 minutes. Patients on Heparin alone demonstrated a loss of ACT stability at 10 minutes with values both increasing and decreasing. Conclusions: Patients on Angiomax alone demonstrated a significant difference in ACT value within the first 5 minutes and all intervals thereafter. Based on Angiomax short half-life the ACT should be performed as soon as possible. The ACT values in patients taking both Angiomax and Plavix achieved steady state throughout the 20 minutes and had little if any decrease in value. The results for the Heparin group were unreliable at 10 minutes. As a result of these findings, performing an ACT outside the OR is feasible assuming the test can be performed by 10 minutes. Disclosures: No relevant conflicts of interest to declare.

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