Prognostic Factors and Response Duration in 419 MDS Treated with Erythropoietin±GCSF: The GFM Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 522-522 ◽  
Author(s):  
S. Park ◽  
C. Kelaidi ◽  
S. Grabar ◽  
O. Beyne-Rauzy ◽  
S. Cheze ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Predictive Factors ◽  
Response Rate ◽  
Response Duration ◽  
Response Rates ◽  
Multilineage Dysplasia ◽  
Major Response ◽  
Significant Difference ◽  
The Impact

Abstract Background: EPO and its derivative darbepoietin alfa (DAR) are important treatments of anemia in lower risk MDS. Prognostic factors of response and of its duration have been recently updated (Blood, 2005, 106, 803–11) and we reanalyzed them in a large series of patients (pts) treated in France and Belgium. Patients: 419 MDS pts were treated with EPO (≥30000UI/wk for at least 12 wks) or DAR (300μg/wk)± GCSF in 25 GFM centers between 1998 and 2006 (160 prospectively analyzed in 3 consecutive trials, and 259 retrospectively analyzed). Median follow-up was 54 months, median age: 73.5 years. WHO classification: RA (14%), RCMD (16%), 5q- syndrome (4%), RARS (21%) RCMD-RS (13%), RAEB-1 (22%), RAEB-2 (6%), and also 4%CMML (FAB); karyotype: 64% FAV, 16% INT, and 4% UNFAV (16% failure or not done). IPSS: 34% LOW, 40% INT-1, 8% INT-2, 2% HIGH (16% unavailable). 185, 126, 80 and 28 pts received EPO alone (alfa or beta), DAR, EPO+G and DAR+G respectively. Median pre-treatment EPO level was 76 UI/l (only 7% pts>500 UI/l). All pts had Hb<10g/dl and 54% required RBC transfusions (including 36% with >2 RBC units/month). Results: 63% pts responded (IWG criteria: 43%HI-E major and 20% HI-E minor), including 57%, 63%, 57%, 66%, 63% with EPO alfa alone, beta alone, EPO+G, DAR alone, DAR+G response (p=ns). Median response duration was 20 mos (range 3–74 mos), 25 and 14 mos for major and minor responses (p= 0.001). Relapse was associated with treatment discontinuation (45%), progression to higher grade MDS (12%) or AML (13%), but without evident cause in 30% cases. In univariate analysis, significantly higher response rates were observed in pts with <10% blasts (p= 0.002), low and INT-1 IPSS score (p=0.001), transfusion <2 RBC units/month (p<0.0001), EPO level<200UI/l (p<0.0001) whereas no significant difference in response rate were seen between RA (69%,) RCMD (72%), RARS (59%), RCMD-RS (71%), RAEB-1 (60%) and 5q- syndrome (52%), and between cytogenetic groups. The response rate in RARS and RCMD-RS was similar with EPO or DAR alone (62.5%), and EPO or DAR+G (60%). In multivariate analysis, EPO <200UI/l (p=0.008), transfusion requirement (p<0.0001) and IPSS (p=0.047) remained predictive factors of response. Longer response duration was significantly associated with blasts<10% (20 mos vs 8 mos for blasts>10%, p=0.007), major response (vs minor), IPSS low-INT-1 (median 22 mos vs 8 mos for INT-2/HIGH, p=0.001) and in pts with absence of multilineage dysplasia (24 mos vs 16 mos, p=0.01). In multivariate analysis, blasts <10% and major response remained predictive factors of longer response. Conclusions: EPO level <200UI/l, RBC transfusions <2 units/month were confirmed as major prognostic factors of response to EPO±G. Good response rates were seen in RAEB-1, and with EPO alone, in RARS and RCMD-RS. Multilineage dysplasia was not associated with lower response rates, but with shorter response duration. Other prognostic factors of shorter response duration were minor response (vs major), and blasts >10%. A case control study with pts of the International MDS risk Analysis Workshop, who received RBC transfusion alone, is in progress to evaluate the impact of EPO treatment on leukemia-free survival and overall survival, and its results will be presented.

Response Rates and Perceived Questionnaire Length in Mail Surveys

1979 ◽  
Vol 16 (3) ◽  
pp. 429-431 ◽  
Author(s):  
Terry L. Childers ◽  
O. C. Ferrell
Keyword(s):  
Interaction Effect ◽  
Response Rate ◽  
Mail Survey ◽  
Response Rates ◽  
Survey Response ◽  
Factorial Experiment ◽  
Mail Surveys ◽  
Survey Response Rate ◽  
Significant Difference ◽  
The Impact

A 2 × 2 factorial experiment was designed to test the impact on mail survey response rate resulting from variations in paper trim size and number of printed pages in the questionnaire. ANOVA findings suggest 8½ × 11″ paper trim size produces a better response rate than an 8½ × 14″ paper trim size. Use of a one-sheet (front and back) versus a two-sheet (front only) questionnaire did not cause a significant difference in response rate; a hypothesized interaction effect was not found to be statistically significant.

scholarly journals Retrospective Analysis of Prognostic Factors for Waldenström Macroglobulinemia: A Multicenter Cooperative Study in Japan

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5028-5028
Author(s):  
Akio Saito ◽  
Atsushi Isoda ◽  
Akihiko Yokohama ◽  
Hiroshi Handa ◽  
Norifumi Tsukamoto ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Pleural Effusion ◽  
Initial Treatment ◽  
Response Rate ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Japanese Patients ◽  
Western Countries ◽  
Significant Difference

Abstract Background: Analysis of prognostic factors and clinical trials of novel agents for Waldenstrӧm macroglobulinemia (WM) are ongoing in Western countries, but few studies of WM have been performed in Japan. As a step toward future investigations, we retrospectively analyzed clinical features and prognostic factors in Japanese patients with WM. Methods: We retrospectively analyzed clinical and laboratory characteristics, treatment and outcomes of 110 patients with WM, IgM-MGUS or lymphoplasmacytic lymphoma (LPL) diagnosed from January 2001 to March 2013 at 12 institutes. Overall survival (OS) was analyzed using Kaplan-Meier methods and survival was compared using log-rank testing. Several clinical characteristics at diagnosis were assessed by Cox regression for uni- and multivariate analysis for OS. Results: Median age at diagnosis was 69 (range, 41-96) years, 73.6% were male, 12.0% had an ECOG performance status 2-4 and 6.4% presented with B-symptoms. Hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia and cold agglutinin disease were shown in 9.1%, 4.5%, 1.8%, 4.5% and 2.7%, respectively. In 94 patients with available CT findings at diagnosis, lymphadenopathy, hepatosplenomegaly, pleural effusion, lung involvement, bone involvement and skin involvement were shown in 41.5%, 14.9%, 8.5%, 4.3%, 4.3% and 6.4%, respectively. Median serum monoclonal protein level was 2.62 g/dl (range, 0.70-9.35 g/dl). Symptomatic WM was present in 76 patients, asymptomatic WM in 23 and IgM-MGUS in 2 according to criteria of the Second International Workshop on WM. Seven patients showed IgG- or IgA-secreting LPL and 2 showed LPL without bone marrow infiltration. In patients with symptomatic WM, international prognostic scoring system for WM (ISSWM) was low in 9.2%, intermediate in 34.2%, high in 39.5% and unknown in 17.1%. Among patients with asymptomatic and symptomatic WM, watchful waiting was performed in 91.3% and 40.0%, respectively, with 61.9% and 36.7% remaining untreated, respectively. Median time to treatment from diagnosis of asymptomatic or symptomatic WM was 240 days (range, 3-1238 days) and 31 days (range, 0-2011 days), respectively. Oral alkylating agents were administered to 34.7% of patients with WM, 19.4% were treated with CHOP or CHOP-like regimen with or without rituximab, 8.2% received fludarabine mono- or combination therapy and 6.1% received rituximab monotherapy. Rituximab-containing therapy was administered as the initial treatment in 33.8% of patients who received treatment. Overall response rate (ORR) (complete + partial response rate) was 48.6%, and patients treated with rituximab-containing therapy displayed higher ORR (64.0%) compared to those with non-rituximab therapy (40.8%). Plasmapheresis was performed in 3.7% of patients. Three patients (2.7%) showed transformation to diffuse large B-cell lymphoma, and 7 (6.4%) developed second primary malignancies. Median follow-up was 38 months, 5-year OS rate for all patients was 74.9% (95% confidence interval (CI) 62.5-83.7) and rates for those with symptomatic WM, asymptomatic WM and other LPL were 66.0% (95%CI 50.6-77.6), 100% and 88.9% (95%CI 43.3-98.4), respectively. Significant differences in survival between risk groups of ISSWM in patients with symptomatic WM were not seen (5-year OS: high, 62.4%; intermediate, 64.3%; low, 75.0%; p=0.86). Although no significant difference in OS was observed compared to initial treatment (p=0.265), patients treated with rituximab during the observation period showed significantly prolonged OS compared to those treated without rituximab (5-year OS rates: 78.9% vs. 45.6%, p=0.036). In univariate analysis, age, pleural effusion, serum albumin, C-reactive protein and serum IgM levels were poor prognostic factors for OS. In multivariate analysis, age >65 years (hazard ratio (HR)=3.294; 95%CI 1.097-9.888, p=0.0336) and pleural effusion (HR=4.55; 95%CI 1.602-12.930, p=0.0045) were identified as significant prognostic factors for OS. Conclusion: Prognostic factors for WM in Western countries may not be applicable to Japanese patients. This study suggested presence of pleural effusion at diagnosis is associated with poor clinical outcomes. Further investigations including histopathological examinations and molecular analyses are required to elucidate prognostic factors in Japan. Disclosures No relevant conflicts of interest to declare.

Comparison of Four MANOVA Test Statistic for Pig Production in Delta State, Nigeria

2021 ◽  
Vol 6 (5) ◽  
pp. 43-49
Author(s):  
J. M. Aniesedo ◽  
C. N. Okoli
Keyword(s):  
Multivariate Analysis ◽  
Analysis Of Variance ◽  
Multivariate Normality ◽  
Secondary Source ◽  
Multivariate Analysis Of Variance ◽  
Test Statistic ◽  
Pig Production ◽  
Normality Test ◽  
Significant Difference ◽  
The Impact

This study used the multivariate analysis of variance (MANOVA) test statistic to examine the impact of three categories feed used in the production of pig in Delta State. The multivariate test statistic considered are the Pillai – Bartlett trace, Wilks’ Test Statistic, Roy’s Largest Root Test Statistic, and the Lawley- Hotelling (LH) Statistic. The objectives include to: evaluate the robustness of the four Multivariate Analysis of Variance test statistics to ensure that the best is employed in multivariate analysis to guarantee most useful result in pig production; determine the relatively efficient test statistic for pig production; and determine the test statistic that is consistent across the sample sizes. Secondary source of data collection was used to obtain the data required for the analysis. The outcome of the study showed that the obtained data was multivariate normally distributed based on the result of the asymmetry-based multivariate normality test and the multivariate normality test based on the kurtosis test which makes the data suitable parametric multivariate method such as multivariate analysis of variance (MANOVA). The results show that the Wilks and Roy tests found a significant difference for the intercept. While the Pillai and LH tests could not find any significance. The Roy test was also found to be significant for feed one, feed two, and feed three. The Wilks and Roy tests also turned out to be significant differences for the intercept. All test measures showed significance for feed one. The Wilks and Roy tests also showed a significant difference for feed two, while all test measures found a significance for feed one. Another result showed that none of the tests found significance for the interaction between feed one and two, while the Roy test found significance for the interaction between feed one and three, feed two and three and feed one, two and three. The performance of the test for evaluating the performance of feeds for pig production with/without considering interactions was found to be in the following order of magnitude: Roy, Wilks and Pilla = LH. This result implies that the Roy method, with or without consideration of the interaction, has a better performance of the test than the other methods considered in the study.

scholarly journals Colorectal Perforation in Patients with Connective Tissue Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Kiichi Sugimoto ◽  
Kazuhiro Sakamoto ◽  
Yu Okazawa ◽  
Rina Takahashi ◽  
Kosuke Mizukoshi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Odds Ratio ◽  
Colorectal Perforation ◽  
Fecal Peritonitis ◽  
Colonoscopic Examination ◽  
Cumulative Survival ◽  
Significant Difference

Purpose.The goal of this retrospective study was to identify prognostic factors associated with mortality after surgery for colorectal perforation among patients with connective tissue disease (CTD) and to review postoperative outcomes based on these prognostic factors.Methods.The subjects were 105 patients (CTD group: n=26, 24.8%; non-CTD group: n=79, 75.2%) who underwent surgery for colorectal perforation at our department. Cases with iatrogenic perforation due to colonoscopic examination were excluded from the study. We retrospectively investigated perioperative clinicopathological factors in patients undergoing surgery for colorectal perforation.Results.There were 7 patients (6.7%) who died within 28 days after surgery in all patients. In multivariate analysis, CTD and fecal peritonitis emerged as significant independent prognostic factors (p=0.005, odds ratio=12.39; p=0.04, odds ratio=7.10, respectively). There were 5 patients (19.2%) who died within 28 days after surgery in the CTD group. In multivariate analysis, fecal peritonitis emerged as a significant independent prognostic factor in the CTD group (p=0.03, odds ratio=31.96). The cumulative survival curve in the CTD group was significantly worse than that in the non-CTD group (p=0.006). An analysis based on the presence of fecal peritonitis indicated no significant difference in cumulative survival curves for patients without fecal peritonitis in the CTD and non-CTD groups (p=0.55) but a significant difference in these curves for patients with fecal peritonitis in the two groups (p<0.0001).Conclusions.This study demonstrated that cumulative survival in patients with CTD is significantly worse than that in patients without CTD after surgery for colorectal perforation.

scholarly journals Az ellenoldali csípőtáji törésig eltelt időt befolyásoló prognosztikai tényezők vizsgálata

2018 ◽  
Vol 159 (38) ◽  
pp. 1543-1547
Author(s):  
Krisztina Juhász ◽  
Imre Boncz ◽  
Péter Kanizsai ◽  
Andor Sebestyén
Keyword(s):  
Risk Factors ◽  
Prognostic Factors ◽  
Hip Fracture ◽  
Femoral Neck ◽  
Femoral Neck Fracture ◽  
Hip Fractures ◽  
Age Groups ◽  
Significant Difference ◽  
Neck Fracture ◽  
The Impact

Abstract: Introduction: Although several national studies reported on the risk factors for contralateral hip fracture, there are no data about the prognostic factors of the time until contralateral hip fractures. Aim: The aim of the study was to analyse the impact of different prognostic factors on the time until the development of contralateral fracture and to determine the incidence of contralateral hip fractures after femoral neck fractures. Method: Patients aged 60 years and over with contralateral hip fracture between 01 Jan 2000 and 31 Dec 2008 were identified among those who suffered their femoral neck fracture in Hungary in 2000. Risk factors as age, sex, comorbidities, type of fracture and surgery, place of living and hospitals providing treatment for primary fracture were analysed by one way ANOVA focusing on the time until the development of contralateral hip fracture. Results: 312 patients met the inclusion criteria. The incidence of contralateral hip fracture after femoral neck fracture ranged between 1.5% and 2.1%, the cumulative incidence was 8.24%. The mean time until the development of contralateral hip fracture was 1159.8 days. The incidence of contralateral hip fracture showed no significant deviation. Significantly shorter time (p = 0.010) was detected until the contralateral hip fracture in older patients with femoral neck fracture. Conclusions: The yearly incidence of contralateral hip fracture showed no significant difference by patients with femoral neck fracture over 60 years. The shorter time until the contralateral hip fracture by the older age groups highlights the need of elaboration of prevention strategies. Orv Hetil. 2018; 159(38): 1543–1547.

Exploring the Impact of E-mail and Postcard Prenotification on Response Rates to a Mail Survey in an Academic Setting

2008 ◽  
Vol 2 (1) ◽  
pp. 94-103
Author(s):  
Leslie A. McCallister ◽  
Bobette Otto
Keyword(s):  
Response Rate ◽  
Mail Survey ◽  
Response Rates ◽  
Impact Response ◽  
Full Time ◽  
Initial Mailing ◽  
Project Costs ◽  
The Impact ◽  
E Mail ◽  
Time Faculty

What techniques effectively and consistently impact response rates to a mail survey? No clear answer to this question exists, largely because variability in response rates occurs depending on the population of interest, questionnaire type, and procedures used by researchers. This article examines the impact of e-mail and postcard prenotification on response rates to a mail survey by using a population of university full-time faculty and staff. Comparisons were made among respondents who received a postcard prenotification, those who received an e-mail prenotification, and those who received no prenotification prior to the initial mailing of a questionnaire. Data show that e-mail prenotification had the largest impact on response rate, while postcard prenotification had the least impact. In addition, the use of e-mail prenotification reduced overall project costs (both time and money). We suggest that the uses and applicability of e-mail prenotification be further explored to examine both its initial and overall impact on response rate in populations utilizing an electronic environment.

A New Cytokine-Based Stratification Is Highly Predictive of Survivals in AML Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1412-1412
Author(s):  
Pierre Peterlin ◽  
Joelle Gaschet ◽  
Thierry Guillaume ◽  
Alice Garnier ◽  
Marion Eveillard ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Risk Stratification ◽  
Univariate Analysis ◽  
Standard Of Care ◽  
Healthy Controls ◽  
First Line ◽  
Serum Samples ◽  
Gm Csf ◽  
Significant Difference ◽  
The Impact

Introduction: Recently, a significant impact of the kinetics of Fms-like tyrosine kinase 3 ligand concentration (FLc) during induction (day[D]1 to D22) has been reported on survivals in first-line acute myeloid leukemia (AML) patients (pts) (Peterlin et al, 2019). Three different FLc profiles were disclosed i) sustained increase of FLc (FLI group, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, intermediate-risk) and iii) stagnation of low levels (&lt;1000 pg/mL, FLL group, high-risk). An update of this prospective monocentric study (www.ClinicalTrials.gov NCT02693899) is presented here evaluating also retrospectively the impact on outcomes of 6 other cytokine level profiles during induction. Methods: Between 05/2016 and 01/2018, 62 AML pts at diagnosis (median age 59 yo [29-71], &lt;60 yo n=33) eligible for first intensive induction were included and provided informed consent. They received standard of care first-line chemotherapy. Serum samples collected on D1, 8, 15 & 22 of induction were frozen-stored until performing ELISA for FL, TNFa, SCF, IL-1b, IL-6, IL-10, GM-CSF. Normal values were assessed in 5 healthy controls. Pts outcomes considered were relapse/leukemia-free (LFS) and overall (OS) survivals. Results: FLI, FLD and FLL profiles were observed for 26, 22 and 14 pts respectively. A total of 372 samples were assayed for the 6 other cytokines. Median concentrations at D1, D8, D15, D22 for these 6 cytokines were as follows, considering the whole cohort (and healthy donors): TNFa: 0.53, 0, 0, 0 (0); SCF: 5.91, 0, 0, 0 (3); IL-1b : 0, 0, 0, 0 (0); IL-6: 4.85, 16.28, 10.11, 7.1 (0), IL-10: 0, 0, 0, 0 (0) and GM-CSF:1.63, 1.8, 0.67, 1.34 (9.98). Median IL-6 and GM-CSF levels, compared to healthy controls, were respectively higher and lower during induction. No significant difference was observed in terms of median cytokine concentrations at any time when comparing the three FL sub-groups or FLI vs FLD pts. With a median follow-up of 28 months (range: 17-37), FLI and FLD pts show now similar 2-y LFS (62.9% vs 59%, p=0.63) and OS (69.2% vs 63.6%, p=0.70). FLL pts have a significantly higher rate of relapse (85,7% vs FLI 19,2% vs FLD 32%, p=0,0001). Comparing FLL vs FLI+FLD pts disclosed significantly different LFS (7.1% vs 61.1%, p&lt;0.001) but not OS (36.7% vs 66.6%, p=0.11). In univariate analysis, 2y LFS and OS were not affected by the concentration (&lt; or &gt; median) of the 7 cytokines studied except for LFS and GM-CSFc at D8 (p=0,04) and D15 (p=0,08), for LFS and FLc at D1 (p=0.06), D8 (p=0,03), D15 (p=0,04) and D22 (p=0,03) and for OS and GM-CSF at D15 (p=0.08). A significant association between LFS was observed with ELN 2017 risk stratification (2-y LFS: favorable: 68,1% vs intermediate: 48,1% vs unfavorable: 30,7%, p=0.03) but not OS (2 y: 77% vs 55,5% vs 46,1%, p=0.09). Multivariate analysis showed that no factor was independently associated with OS while LFS remained significantly associated with the FLc profile (FLL vs others, HR: 5.79. 95%CI: 2.48-13.53, p&lt;0.0001) and GM-CSF at D15 (HR: 0.45; 95%CI: 0.20-0.98, p=0.04) but not with ELN 2017 risk stratification (p=0.06). Cytokine levels were then assessed to try to better discriminate FLI and FLD pts. A significant higher IL-6 level at D22 was found in relapsed or deceased FLI/FLD pts (median:15,34 vs 5,42 pg/mL, p=0,04). FLI/FLD pts with low IL-6 at D22 (&lt; median, 15.5 pg/mL, n=35 vs n=14 with high level) had significant better 2y LFS and OS (74,2% vs 38,4%, p=0,005 and 77,1% vs 38,4%, p=0,009, respectively). A new prognostic risk-stratification could thus be proposed, i.e. FLI/FLD with IL-6 &lt;15.5 pg/mL (favorable), FLI/FLD with IL-6 &gt;15.5 pg/mL (intermediate) and FLL (unfavorable). This new classification was considered for a second multivariate analysis, showing that it is the strongest factor associated with OS (p=0.006, ELN p=0.03, FL profile p=0.04) and LFS (p&lt;0.0001, ELN p=0.005, GM-CSFc D15 p=0.03) (figure 1). Conclusion: This study confirms stagnation of low FLc during AML induction as a strong poor prognosis factor. Moreover, IL-6 levels at D22 further discriminate FLI/FLD pts. Thus, a new cytokine-based risk-stratification integrating FL kinetics and IL-6 levels during induction may help to better predict outcomes in first-line AML patients. These results need to be validated on a larger cohort of AML patients while anti-IL-6 therapy should be tested in combination with standard 3+7 chemotherapy. Figure 1 Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy; Astellas: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria.

Treatment of Myelodysplastic Syndromes with del 5q before the Lenalidomide Era: The GFM Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2678-2678 ◽  
Author(s):  
Charikleia Kelaidi ◽  
Sophie Park ◽  
Sabine Brechignac ◽  
Lionel Mannone ◽  
Norbert Vey ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Response Rate ◽  
Response Duration ◽  
Response Rates ◽  
Erythroid Response ◽  
Recent Introduction ◽  
Pre Treatment

Abstract Background: MDS with del 5q are characterized by profound anemia, which until the recent introduction of lenalidomide (N Engl J Med2005; 352: 549–57, J Clin Oncol2005;16S:5), was considered generally unresponsive to available treatments. In order to reevaluate the outcome of those patients in the pre-lenalidomide era, we analyzed response of anemia in MDS with del 5q treated with EPO ± G-CSF and thalidomide in previous GFM trials. Patients: MDS with del 5q included in 419 MDS treated with EPO or Darbepoetin (DAR) ± G-CSF by GFM centers (including 3 successive GFM trials: Blood2004; 104: 321–7; Blood2005;106 suppl 1: 712a; Br J Haematol2006;133: 513–9 and submitted to ASH 2006), and in 134 MDS treated with thalidomide in two successive GFM trials (Br J Haematol2005; 131: 609–18, and submitted to ASH 2006). Patients received at least 30,000 U/w of EPO or 300 mg/w of DAR and doses ranging from 50 to 800 mg/d of Thalidomide during at least 12 weeks. Results: 48 MDS with del 5q received EPO (or DAR) ± G-CSF, including 30 pts with del 5q alone, 9 with one and 9 with >1 additional cytogenetic abn; 21/48 had marrow blasts ≥5% (7 had >10%). 17 had the “5q- syndrome” according to WHO. Median pre-treatment EPO level was 287 UI/L (range 12–5,665), i.e. significantly more than in non del 5q cases (median 68, p<0.001). 22/48 pts (46%) had erythroid response, including 15 major and 7 minor (11 responses after EPO or DAR alone and 11 after EPO or DAR + G-CSF) vs. 64% in pts without del 5q (p=0.01) (p= 0.066 after adjustment for marrow blasts). The response rate was 52%, 55%, 22% and 33%, respectively in del 5q pts with the 5q- syndrome, one additional cytogenetic abn, >1 additional cytogenetic abn, and marrow blasts ≥5%. Response duration was significantly shorter in MDS with del 5q than in other MDS (mean 12 vs. 24 months, p=0.019) and in pts with 5q- syndrome vs. other MDS with marrow blasts <5% (mean 11vs. 24months, p=0.025). 20 pts with del 5q were treated with thalidomide. 6/20 had an erythroid response (30 %, including 3 major and 3 minor responses) vs. 29% of other MDS (p=NS) Conclusion: MDS with del 5q with ≤1 additional cytogenetic abn and no excess of marrow blasts may have erythroid response to EPO ± G-CSF but responses are generally very short, while response rates to thalidomide are low. Those results are clearly inferior to results obtained with lenalidomide in MDS with del 5q.

Comparison of the Predictive Value of MRD and PVA Score in Pediatric ALL.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1520-1520
Author(s):  
Anja Troeger ◽  
Gabriele Escherich ◽  
Udo zur Stadt ◽  
M. L Den Boer ◽  
Rob Pieters ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Correlation Coefficient ◽  
Predictive Value ◽  
Genetic Alterations ◽  
Relevant Parameter ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact

Abstract Early identification of patients (pts) at risk for relapse allows for development of risk-adapted treatment strategies, thus steadily improving the outcome in pediatric acute lymphoblastic leukemia (ALL). Besides classic prognostic factors such as age, initial leukocyte count (WBC), genetic alterations and the immune phenotype, the so called PVA Score, summarizing the in vitro resistance of blasts against prednisone, vincristine and asparaginase, has been applied for treatment stratification in the CoALL protocol, a German multicenter study for children with ALL. Over the past years it has become increasingly clear that the in vivo response to chemotherapy assessed by detection of residual malignant cells (MRD) by PCR technique can be predictive of prognosis. Here we compare for the first time the relevance of in vitro (PVA Score) and in vivo (MRD) treatment response in a large cohort of 275 children with ALL, age 1–17 years, uniformly treated according to the CoALL protocols 05–92 to 07–03. Children with B cell precursor ALL (BCP-ALL) and T-ALL were analyzed separately. Bone marrow samples of 160 children with BCP-ALL and of 115 T-ALL pts diagnosed between 1992–2005 were prospectively assessed for PVA Score at diagnosis and MRD levels at day (d) 15, 29 and 43 after informed consent was obtained from the parents or legal guardians at the time of enrolment. Of note, 7 of the BCP-ALL and 14 of the T-ALL pts with late morphological response were excluded from analysis. Overall median MRD levels in BCP-ALL pts (MRDd15: 6×10e-4; MRDd29: 2×10e-5) were one log lower than in T-ALL (MRDd15: 9×10e-3; MRDd29: 3×10e-4). We detected no association between PVA Score and MRD level in BCP-ALL (correlation coefficient: r=0.15; p=0.15) and only a weak correlation in T-ALL pts (correlation coefficient: r=0.43; p=0.0003). When assessing the impact of the PVA Score on relapse free survival (RFS), in BCP-ALL only score 3+4 (good response) vs. 8+9 (poor response) was prognostically relevant (RFS 0.86±0.05 vs. 0.59±0.12; p=0.03), whereas in T-ALL no significant difference between these subgroups was found (RFS 0.71±0.1 vs. 0.68±0.1; p=0.62). In multivariate analysis PVA Score 3+4 vs. 8+9 remained the most relevant parameter for RFS in BCP-ALL (p=0.05) when compared to age and initial WBC. However, MRD levels were of even higher predictive power, especially at later time points: MRD negativity at d29 in BCP-ALL identified pts with significantly superior RFS (RFS MRD neg.: 0.9±0.05 vs. pos.: 0.7±0.05; p=0.003) and low MRD levels indicated a favorable outcome in T-ALL (RFS MRD &lt;10e-3: 0.89±0.05 vs. MRD &gt;10e-3: 0.68±0.07; p=0.001). Moreover, both BCP-ALL and T-ALL pts characterized by MRD levels &gt;10e-3 on d43 exhibited a poor outcome (RFS BCP-ALL: 0.42±0.17; RFS T-ALL: 0.47±0.14). MRD remained an independent marker in multivariate analysis including initial WBC and age, both in BCP- (MRDd29: p=0.006; MRDd43: p=0.001) and T-ALL (MRDd29: p=0.003; MRDd43: p=0.015). By multivariate analysis, in T-ALL low MRD levels on d29 predicted superior RFS independently from the PVA Score (MRD: p=0.002 vs. PVA: p=0.09), whereas in BPC-ALL these parameters were not completely independent from each other at that early time point (MRD: p= 0.059 vs. PVA: p= 0.063) but became independent at d43 (MRD: p= 0.018 vs. PVA: p= 0.253). While the predictive value of the PVA Score was limited to BCP-ALL, MRD was an independent prognostic marker for both BCP- and T-ALL and reliably identified pts at low and high risk for relapse.

Impact of Pretransplant Cytogenetics and Marrow Remission Status on Outcome of Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Stem Cell Transplantation Conditioned with Busulfan and Fludarabine

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 341-341
Author(s):  
Ebru Koca ◽  
Rima M Saliba ◽  
Marcos De Lima ◽  
Uday Popat ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
Remission Status ◽  
The Impact ◽  
Acute Myeloid

Abstract BACKGROUND: The purpose of this study was to determine the impact of cytogenetics and remission status on outcome of allogeneic stem cell transplantation (alloSCT) conditioned with busulfan and fludarabine based regimens for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: We retrospectively collected data on all consecutive patients (pts) who received busulfan and fludarabine with alloSCT at MD Anderson Cancer Center for AML and MDS between January 2001 and December 2007. All pts received busulfan and fludarabine in myeloablative (busulfan 130 mg/m2 for 4 days and fludarabine 40 mg/m2 for 4 days) or reduced intensity doses. ATG was added to the regimen for unrelated and mismatched related donor transplants. Pts in first complete remission (CR) or advanced CR (2nd or 3rd CR) and also pts with morphologic remission but platelet count &lt;100,000/mcl (termed “marrow remission”) were included. Pts were divided into subgroups according to cytogenetic abnormalities based on the MRC, SWOG, CALGB, and the recently described Dana-Farber (DF) categorization systems. Cox’s regression analysis was used to evaluate the impact of the prognostic factors on overall survival (OS), progression free survival (PFS) and non-relapse mortality (NRM). The cumulative incidence of NRM was estimated considering progression of disease as a competing risk. RESULTS: 215 pts were included in the analysis with a median age 47 (range 13–69). Four pts were less than 18 years old and 117 (54%) were older than 45 years. Diagnoses were AML (n=176), MDS (n=14) and AML evolving from MDS (n=25). Disease status at alloSCT was; first CR (n=111), advanced CR (n=65) and marrow remission (n=39). Donors were matched related (n= 114), matched unrelated (n=86), 1 antigen mismatched related (n=7), or 1 antigen mismatched unrelated (n=6). Stem cell source was bone marrow (n=84) or peripheral blood (n=131). Median follow-up time of surviving pts was 36 months (range 1.6–85). The 3 years actuarial probabilities of OS and PFS were 59% and 51%, respectively. The 3 years cumulative incidence of NRM was 22%. On univariate analysis, adverse cytogenetics according to the DF scoring system (but not the MRC, SWOG and CALGB classifications) was associated with a significantly lower OS (HR=1.8, P=0.03) and PFS (HR=1.7, P=0.02). Three year PFSs for pts in CR with favorable, intermediate or adverse cytogenetics were 58%, 56% and 49%, respectively (Figure 1). In addition, pts in marrow remission compared to those who were in first or advanced CR with full platelet recovery prior to transplant had a significantly poorer OS (41 vs 63 % at 3 yrs, HR=2.1, P=0.01), and PFS (33 vs 55% at 3 yrs, HR=1.9, P=0.01). Outcomes were comparable for pts in first and advanced CR (Figure 2). AML evolving from MDS was a significant adverse risk factor for OS (HR=1.9, P=0.04) but not for PFS (HR=1.6, P=0.08). On multivariate analysis, pts had the highest mortality rate if they had both a marrow remission and adverse cytogenetics, classified according to the DF system (HR (OS)=3.4, P&lt;0.001; and HR (PFS)=3.2, P&lt;0.001). A diagnosis of AML evolving from MDS remained as a significant adverse factor for OS on multivariate analysis (HR=2.1; P=0.01). Significant adverse prognostic factors for NRM on univariate and multivariate analysis included alloSCT later than one year after diagnosis (HR=2; P= 0.02) and AML evolving from MDS (HR=2.6; P=0.01). There was no impact of cytogenetics on the rate of NRM. CONCLUSION: Cytogenetic characteristics and remission status before alloSCT correlate with transplantation outcome in MDS or AML pts conditioned with busulfan and fludarabine. This regimen with alloSCT produced improved outcomes compared to published results with standard chemotherapy for pts in the intermediate and high risk cytogenetic groups. Figure 1. PFS by DF cytogenetic scoring system for patients in first and advanced CR. Figure 1. PFS by DF cytogenetic scoring system for patients in first and advanced CR. Figure 2. PFS by remission status prior to transplant. Figure 2. PFS by remission status prior to transplant.

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