Outcomes with Autologous (Auto) and Allogeneic (Allo) Stem Cell Transplantation (SCT) for Relapsed/Refractory Follicular Lymphoma (FL) in the Post-Rituximab Era: A Comparative Analysis From the National Comprehensive Cancer Network (NCCN) Non-Hodgkin's Lymphoma (NHL) Outcomes Database Project,

Abstract Abstract 4112 Background: AutoSCT and AlloSCT have both been shown to be effective for the treatment of relapsed/refractory FL. However, outcomes with either modality are not well defined in the post-rituximab era, especially regarding autoSCT. The NCCN NHL Outcomes Database was utilized to examine survival for FL patients (pts) refractory or relapsed after rituximab-based therapy who underwent subsequent autoSCT or alloSCT. Further, prognostic factors were investigated. Methods: The NCCN NHL Outcomes Database is a prospective cohort study collecting comprehensive clinical, treatment, and outcomes data for NHL pts at 7 participating NCCN centers. Among all NHL pts in the database (n=5,395), 1,670 had FL, of whom 240 had SCT during the study observation period of 1/1/00 to 12/31/09 (follow-up through May 2011). Pts were excluded if they 1) did not have relapsed/refractory FL (n=13) or 2) had not received prior rituximab (n=11). In total, 216 pts (autoSCT n=158, alloSCT n=58) were included for analysis. Median follow-up was 2.9 years. Univariate Cox proportional hazards regression was used to assess associations of prognostic factors within each type of SCT for overall survival (OS) and failure free survival (FFS). OS was defined as years from SCT to death; FFS was defined as relapse, transformation, disease progression, or death. Variables with a p <0.20 were entered into a multivariate Cox model within each type of SCT. In a similar fashion, Cox regression was used to assess OS and FFS between type of SCT. Results: There were several notable differences in pt and disease characteristics between SCT modalities. Pts who received autoSCT were significantly older at initial FL diagnosis compared with alloSCT (median 51 vs 46 years, p=0.002) and older at time of SCT (median 55 vs 51 years, p=0.005). However, median time from initial FL diagnosis to SCT was shorter for alloSCT vs autoSCT (3.3 vs 4.1 years, p=0.02). AlloSCT pts received a median of 4 prior therapies vs 3 for the autoSCT cohort (p<0.001). Further, pts who had alloSCT had a higher proportion of resistant disease at time of SCT than autoSCT pts (19% vs 7%, p=0.01), while autoSCT pts were more likely to have grade 3 FL compared with alloSCT (36% vs 9%, p=0.001). There were no comparative differences among gender, race, stage at SCT or performance status. 59% of alloSCT pts had a matched-sibling donor, while 42% had an unrelated donor. The most common conditioning regimens for autoSCT were CBV 50%, BEAM 30%, and TBI-based 16%, while for alloSCT were Flu/Mel 31%, TBI-based 28% (Flu-TBI or Cy-TBI), and Bu/Flu 24%. The cumulative rate of relapse, progression, and/or transformation was 33% for autoSCT pts compared with 16% for alloSCT (p=0.01), while the overall non-relapse mortality (NRM) rate for alloSCT was 33% vs 10% for autoSCT (p<0.0001). There was no difference in FFS between type of SCT (p=0.30) with 3-year FFS of 55% (95%CI 46%-63%) for autoSCT vs 56% (95%CI 42%-70%) for alloSCT (Figure 1). However, OS was significantly different between type of SCT (p<0.001); the 3-year OS was 85% (95%CI 79%-91%) for autoSCT compared with 64% (95%CI 50%-77%) for alloSCT (Figure 2). Factors that predicted survival on univariate analysis for pts who had autoSCT were increasing age (continuous variable, years) and >3 prior therapies, while age > 50 years and resistant disease status at SCT predicted survival for alloSCT. Further, these factors remained significant on Cox regression multivariate analysis (Table 1). Additionally, multivariate analysis including all SCT pts (n=216) was performed to compare survival between autoSCT and alloSCT. After adjusting for age, number of prior therapies, and disease status, alloSCT still showed increased risk of death compared with autoSCT (HR 2.2, 95%CI 1.2–4.1, p=0.01); no significant difference was noted for FFS (p=0.72). Conclusion: To our knowledge, this represents the largest analysis of autoSCT and alloSCT among FL pts relapsed/refractory s/p prior rituximab. Within this multicenter prospective cohort analysis, we identified prognostic factors that predicted survival within autoSCT and alloSCT cohorts. Furthermore, autoSCT and alloSCT were associated with comparable FFS, however including adjustment for competing prognostic factors, OS was improved among pts who had autoSCT. Based on these data, we conclude that autoSCT remains a viable therapy for relapsed/refractory FL in the post-rituximab era. Disclosures: No relevant conflicts of interest to declare.

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The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518775044 ◽

2018 ◽

Vol 33 (6) ◽

pp. 385-393 ◽

Cited By ~ 3

Author(s):

Jakub Kazmierski ◽

Chaido Messini-Zachou ◽

Mara Gkioka ◽

Magda Tsolaki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cox Regression ◽

Symptomatic Treatment ◽

Risk Of Death ◽

Increased Risk ◽

Functional Assessments ◽

The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

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Association of Perioperative Risk Factors and Cumulative Duration of Low Bispectral Index with Intermediate-term Mortality after Cardiac Surgery in the B-Unaware Trial

Anesthesiology ◽

10.1097/aln.0b013e3181d5e0a3 ◽

2010 ◽

Vol 112 (5) ◽

pp. 1116-1127 ◽

Cited By ~ 117

Author(s):

Miklos D. Kertai ◽

Nirvik Pal ◽

Ben J. A. Palanca ◽

Nan Lin ◽

Sylvia A. Searleman ◽

...

Keyword(s):

Cardiac Surgery ◽

Bispectral Index ◽

Cox Regression ◽

Medical Center ◽

Discriminative Ability ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk ◽

Significant Difference ◽

Cumulative Duration

Background Current data suggest that mortality after noncardiac surgery may be associated with persistent hypotension and the cumulative duration of low processed electroencephalogram-based bispectral index (BIS). This study assessed the relationships among cumulative duration of low BIS (BIS < 45), intermediate-term mortality, and anesthetic dose after cardiac surgery. Methods The authors studied 460 patients (mean age, 63.0 +/- 13.1 yr; 287 men) who underwent cardiac surgery between September 2005 and October 2006 at Washington University Medical Center, St Louis, Missouri. By using multivariable Cox regression analysis, perioperative factors were evaluated for their potential association with intermediate-term all-cause mortality. Results A total of 82 patients (17.8%) died during a median follow-up of 3 yr (interquartile range, 2.7-3.3 yr). Comparing patients who died with those who survived, there was no statistically significant difference in the relationship between end-tidal anesthetic gas concentrations during the anesthetic maintenance phase and the BIS. Cumulative duration of low BIS was independently associated with intermediate-term mortality. The 1.29 adjusted hazard ratio (95% CI, 1.12-1.49) for intermediate-term mortality with cumulative duration of low BIS translated into a 29% increased risk of death for every cumulative hour spent with a BIS less than 45. The final multivariable Cox regression model showed a good discriminative ability (c-index of 0.78). Conclusions This study found an association between cumulative duration of low BIS and mortality in the setting of cardiac surgery. Notably, this association was independent of both volatile anesthetic concentration and duration of anesthesia, suggesting that intermediate-term mortality after cardiac surgery was not causally related to excessive anesthetic dose.

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The association of tissue doppler E/e' ratio with poor survival is modified by gender and is attenuated with advanced age

European Heart Journal ◽

10.1093/eurheartj/ehab724.012 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

Y Wasserstrum ◽

R Gilead ◽

R Kuperstein ◽

S Ben-Zekry ◽

O Vatury ◽

...

Keyword(s):

Cox Regression ◽

Mitral Annulus ◽

Tissue Doppler ◽

Outcome Data ◽

Poor Survival ◽

Age And Gender ◽

Risk Of Death ◽

Increased Risk ◽

And Gender

Abstract Introduction Contemporary guidelines recommend a universal cutoff of 14 for the ratio between early mitral flow wave and early diastolic mitral annulus velocity measured by tissue doppler (E/e' ratio). While age-dependent normal E/e' values have been suggested, outcome data is lacking. Purpose We sought to evaluate the modification effect of age and gender on the prognostic value of the E/e' ratio. Methods Consecutive patients who underwent echocardiographic evaluation between 2009 and 2021 (N=104,315) in a single tertiary cardiovascular center. Patients with left or right ventricular dysfunction, any significant valvular disease, structural heart disease or evidence of pulmonary hypertension were excluded. Cancer and mortality data were available for all subjects from national registries. Patients with a metastatic malignancy at baseline or during follow up were excluded. Cox regression models were applied. Results Overall, 44,541 patients were included in the final analysis. Mean age was 55±17, 59% were male and 63% of the exams were performed in an outpatient setting. An elevated E/e' ratio above 14 was documented in 2,598 (7%) patients. During a median follow-up of 5.7 (IQR 2.8–9.1) years, 5,015 (11.3%) patients died. Kaplan Meier survival analysis demonstrated that the cumulative probability of death at 6 years was 23.4% (21.6–25.3) among patients with elevated E/e' ratio compared with 9.7% (9.3–10.0) among patients with E/e'<14 (p Log rank <0.001). This difference was less significant as age progressed (figure 1). Multivariate cox-regression model yielded consistent results such that an elevated E/e' ratio was associated with 2.66-fold increased risk of death during follow up (95% CI 2.44–2.89, p<0.001), and there was a decline in the increased risk and significant as age advanced in both genders (figure 2). Interaction analysis was significant for both gender and age such the association of elevated E/e' ratio with poor survival was more significant among men compared with women and among young vs. older subjects. Among women, elevated E/e' was associated with 2.4-fold increased risk of death versus 2.7-fold increased risk among men. Similarly, the hazard ratio for death associated with elevated E/e' was 2.29 (95% CI 1.74–3.02), 1.8 (95% CI 1.5–2.1), 1.13 (95% CI 0.97–1.31) and 1.07 (95% CI 0.92–1.25) for the age groups of <60, 60–70, 70–80 and >80, respectively. In a sensitivity analysis, similar findings were seen in when excluding patients with mild hypertrophy (maximal wall thickness >12mm) and without any mitral annulus calcification. Conclusion In apparently normal hearts, an elevated E/e' ratio is independently associated with increased mortality. This association is more pronounced among men and is attenuated with increased age. This study supports the need for gender-specific and age-specified outcome data with respect to measures of diastolic dysfunction. FUNDunding Acknowledgement Type of funding sources: None. Survival by age and gender groups E/e' >14 and mortality by age and gender

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Impact of Plasma Potassium Normalization on Short‐Term Mortality in Patients With Hypertension and Hyperkalemia

Journal of the American Heart Association ◽

10.1161/jaha.120.017087 ◽

2020 ◽

Vol 9 (24) ◽

Author(s):

Maria Lukács Krogager ◽

Peter Søgaard ◽

Christian Torp‐Pedersen ◽

Henrik Bøggild ◽

Gunnar Gislason ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Cox Regression ◽

Reference Group ◽

Multivariable Analysis ◽

Plasma Potassium ◽

Cardiovascular Death ◽

Risk Of Death ◽

Increased Risk ◽

Short Term Mortality

Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow‐up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (hyperkalemia) within 100 days of combination antihypertensive therapy initiation. A second potassium was measured 6 to 100 days after the episode of hyperkalemia. All‐cause mortality within 90 days of the second potassium measurement was assessed using Cox regression. Mortality was examined for 8 predefined potassium intervals derived from the second measurement: 2.2 to 2.9 mmol/L (n=37), 3.0 to 3.4 mmol/L (n=184), 3.5 to 3.7 mmol/L (n=325), 3.8 to 4.0 mmol/L (n=791), 4.1 to 4.6 mmol/L (n=3533, reference), 4.7 to 5.0 mmol/L (n=1786), 5.1 to 5.5 mmol/L (n=720), and 5.6 to 7.8 mmol/L (n=244). Ninety‐day mortality in the 8 strata was 37.8%, 21.2%, 14.5%, 9.6%, 6.3%, 6.2%, 10.0%, and 16.4%, respectively. The multivariable analysis showed that patients with concentrations >5.5 mmol/L after an episode of hyperkalemia had increased mortality risk compared with the reference (hazard ratio [HR], 2.27; 95% CI, 1.60–3.20; P <0.001). Potassium intervals 3.5 to 3.7 mmol/L and 3.8 to 4.0 mmol/L were also associated with increased risk of death (HR, 1.71; 95% CI, 1.23–2.37; P <0.001; HR, 1.36; 95% CI, 1.04–1.76; P <0.001, respectively) compared with the reference group. We observed a trend toward increased risk of death within the interval 5.1 to 5.5 mmol/L (HR, 1.29; 95% CI, 0.98–1.69). Potassium concentrations <4.1 mmol/L and >5.0 mmol/L were associated with increased risk of cardiovascular death. Conclusions Overcorrection of hyperkalemia to levels <4.1 mmol/L was frequent and associated with increased all‐cause and cardiovascular mortality. Potassium concentrations >5.5 mmol/L were also associated with an increased all‐cause and cardiovascular mortality.

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Prognostic implication of KIT mutations in melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9049 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9049-9049

Author(s):

Katherine G. Roth ◽

Emily C. Zabor ◽

Marta N. Colgan ◽

Jedd D. Wolchok ◽

Paul B. Chapman ◽

...

Keyword(s):

Cox Regression ◽

Chi Square ◽

Risk Of Death ◽

Disease Characteristics ◽

Kaplan Meier ◽

Increased Risk ◽

History Of ◽

Genetic Subgroup ◽

Prognostic Implications

9049 Background: The natural history of BRAF and NRAS mutant (mut) melanoma (mel) has been described, but prognostic implications of KIT mut mel have not. Methods: We performed a single-center retrospective review of 180 patients (pts) enriched for mucosal, acral or chronic sun-damaged skin (CSD) mel and screened for KIT, BRAF, and NRAS mut from 4/07 - 4/10 as a part of a phase II imatinib study. Pt/disease characteristics were compared using the Kruskal-Wallis or Chi-square tests. Factors associated with outcomes were assessed by Kaplan-Meier methods and multivariable Cox regression. Results: Median age, 63.7 years; 54.4% male. Primary site: 40% mucosal, 29% acral, 22% CSD, 9% others. Mut rate: 18% KIT, 16% BRAF, 14% NRAS, 52% wild-type (wt). Pathologic subtype differed by genetic subgroup (p<.001) while age, gender, and stage did not (all p>0.05). 18/26 (69%) KIT mut pts received imatinib in the metastatic (met) setting; 6/18 received > 1 other KIT inhibitor. 3/25 (12%) BRAF mut pts received vemurafenib. 8/27 (30%) KIT mut, 4/27 (15%) BRAF mut, 6/20 (30%) NRAS mut, and 6/20 (30%) wt pts received ipilimumab. 149/180 (83%) pts developed mets at a median of 2.15 years (95% CI: 1.72, 2.72). Median follow-up (FU) of pts not developing mets was 3.91 yrs (range: 0.25, 14.34). Older age (HR: 1.02, 95% CI: 1.00, 1.03) and pathologic subtype (mucosal vs CSD HR: 1.70, 95% CI: 1.02, 2.84; non-CSD/unknown vs CSD HR: 2.05, 95% CI: 1.00, 4.21) were associated with increased risk of mets but not with time from mets to death. Of 149 pts who progressed, 123 (83%) died during FU. Median time from met to death was 1.21 years (95% CI: 0.91, 1.67). Median FU from time of mets among those alive at last FU was 2.53 yrs (range: 0.06, 6.85). Mut status including KIT mut was not associated with time to first met or time from met to death. Pts who received ipilimumab from time of first distant met had reduced risk of death (HR: 0.55, 95% CI: 0.36, 0.87) independent of mut status. No impact was observed with KIT inhibition. Conclusions: KIT mut status is not an independent predictor of time to mets or survival in pts with mets. Ipilimumab improved pt outcomes regardless of mut status. The lack of impact of KIT inhibitors is likely due to the heterogeneity of KIT mut in mel but does not preclude efficacy in appropriately selected pts.

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Abstract P85: Are Myocardial Bridges Associated With Increased Risk of Death or Myocardial Infarction?

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_1.ap85 ◽

2011 ◽

Vol 4 (suppl_1) ◽

Author(s):

Mouaz H Al-Mallah ◽

Kamal Kassem ◽

Owais Khawaja ◽

Thomas Song ◽

Chad Poopat ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Prognostic Value ◽

Cox Regression ◽

Study Cohort ◽

Risk Of Death ◽

Increased Risk ◽

Artery Disease

Background: Myocardial bridging (MB) is frequently seen on coronary CT angiography (CCTA). However, there has been conflicting data on the prognostic value of MB. The aim of this analysis is to determine the prognostic value of MB in patients without obstructive coronary artery disease (CAD) (<50 diameter stenosis). Methods: We included patients with no known prior coronary artery disease (CAD) who underwent CCTA for various clincial reasons. Patients with obstructive CAD on CCTA were excluded. The study cohort was followed for all cause mortality or myocardial infarction (MI) (median follow-up 1.7 years). Group comparisons were made between patients with patients with or without MB. Results: A total of 715 patients were included in this analysis of which 68 patients had MB (10%). 73% of the bridges were in the mid LAD and 22% had bridging in the distal LAD. 48% of the study cohort had normal coronaries, while 52% had evidence of non obstructive CAD. There were no differences in the baseline characteristics, symptomatic status or prevalence of non obstructive CAD between the two groups (all p>0.5). After a median follow-up duration of 1.7 years, 23 patients died and 10 patients experienced myocardial infarction. There were no statistically significant differences in the rate of death/MI between the two groups (figure). Using multivariable Cox regression, the presence of MB was not associated with increased risk for death/MI (Adjusted HR 0.4, 95% confidence interval 0.1 -2.8, p=0.34) Conclusions: In patients with non-obstructive CAD, MB is not associated with increased risk for all cause death or MI.

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Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors

Journal of the American Society of Nephrology ◽

10.1681/asn.2021040548 ◽

2021 ◽

pp. ASN.2021040548

Author(s):

Hassan N. Ibrahim ◽

Dina N. Murad ◽

Sean A. Hebert ◽

Horacio E. Adrogue ◽

Hana Nguyen ◽

...

Keyword(s):

Kidney Failure ◽

Cox Regression ◽

Disease Risk ◽

Absolute Risk ◽

Kidney Donors ◽

Risk Of Death ◽

Increased Risk ◽

Time Varying Covariates ◽

Baseline Covariates

BackgroundObesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation.MethodsWe compared mortality, diabetes, hypertension, proteinuria, reduced eGFR and its trajectory, and the development of kidney failure in 8583 kidney donors, according to body mass index (BMI). The study included 6822 individuals with a BMI of <30 kg/m2, 1338 with a BMI of 30–34.9 kg/m2, and 423 with a BMI of ≥35 kg/m2. We used Cox regression models, adjusting for baseline covariates only, and models adjusting for postdonation diabetes, hypertension, and kidney failure as time-varying covariates.ResultsObese donors were more likely than nonobese donors to develop diabetes, hypertension, and proteinuria. The increase in eGFR in obese versus nonobese donors was significantly higher in the first 10 years (3.5 ml/min per 1.73m2 per year versus 2.4 ml/min per 1.73m2 per year; P<0.001), but comparable thereafter. At a mean±SD follow-up of 19.3±10.3 years after donation, 31 (0.5%) nonobese and 12 (0.7%) obese donors developed ESKD. Of the 12 patients with ESKD in obese donors, 10 occurred in 1445 White donors who were related to the recipient (0.9%). Risk of death in obese donors was not significantly increased compared with nonobese donors.ConclusionsObesity in kidney donors, as in nondonors, is associated with increased risk of developing diabetes and hypertension. The absolute risk of ESKD is small and the risk of death is comparable to that of nonobese donors.

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Prognostic Factors for Myelodysplastic Syndrome in the Veteran Population: Single Institution Experience.

Blood ◽

10.1182/blood.v110.11.4622.4622 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4622-4622

Author(s):

Michael Axelson ◽

Shirisha Reddy ◽

Crystal Lumby ◽

Sue Sivess-Franks ◽

Jonathan Dowell ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Blood Transfusion ◽

Cox Regression ◽

Medical Center ◽

Univariate Analysis ◽

Single Institution ◽

Number Of Patients

Abstract Background: Myelodyplastic syndrome (MDS) is the disease of the elderly and increasingly common in the veteran population. Here we report a single institution experience with MDS at the Dallas VA Medical Center. Patients and Method: From a period of 1998–2007, eighty three pts were identified out of which 54 pts had bone marrow (BM) biopsy proven diagnosis of MDS. Overall survival (OS) analysis with dependent variables (Age at diagnosis, IPSS Score, WHO morphologic diagnosis, number of blood and platelet transfusions required, Hb level, ANC, cytogenetics, blast percentage, BM cellularity at diagnosis) were conducted by selection method “foreward” and only these significant variables were used in the Cox regression for multivariate analysis. Methods of Kaplan and Meier were used to generate OS curves. Results: The median age of diagnosis was 74 yrs with a median follow up time of 12.5 months. The WHO morphologic subtype was RA/RARS (n=13), Del5q (n=1), RCMD/RCMDRS (n=34), RAEB1 (n=3), RAEB2 (n=1), missing (n=2). The distribution of IPSS score was 0 (n=25); 0.5 (n=15); 1.0 (n=8), 1.5 (n=4), missing (n=2). Five pts had treatment related MDS and 3 pts transformed to AML. One patient had concurrent MGUS and one patient developed multiple myeloma. At diagnosis, 23 pts had a hemoglobin (Hb) value of less than 10g/dl. Only 4 pts had ANC less than 500; sixteen pts had ANC 500–1800 and 34 pts had normal counts. A majority of pts had normal cytogenetics (n=37), 5 pts had good risk, 5 pts had intermediate risk and 7 pts had poor risk cytogenetics. Six pts had hypocellular (<30%) BM at diagnosis whereas 16 pts had a hypercellular marrow (> 50%). Only 4 pts had more than 5% blast in the BM. Twenty nine pts eventually became blood transfusion dependent and 12 pts needed platelet transfusion at some point. Thirty six pts were treated with erythropoietin (with or without neupogen) and 13 pts received some type of disease modifying therapy (5-azacytidine/lenalidomide/ATG/clinical trial). The mean survival time was 106 months. Median survival was not reached at the time of analysis. In the univariate analysis, IPSS score (p=0.003), No. of blood transfusions (p=0.028), cytogenetics (p=0.0001) and blast percentage (p=0.0015), were statistically significant. BM cellularity (p=0.06) and Hb level (p=0.09) showed a trend towards significance. On multivariate analysis, Hb greater than 10 (HR 0.08; p=0.011), abnormal cytogenetics (HR 4.2; p=0.001), BM Blast > 5% (p=0.026) and BM cellularity < 30% (HR 4.6; p=0.033) emerged as the significant predictors of overall survival. IPSS score or Blood transfusion requirement did not pan out to be significant. Conclusion: MDS in the veteran population may be different from general population and may have unique predictors of survival. A larger number of patients and longer duration of follow up is required to further evaluate these prognostic factors.

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Ten Year Follow up Analysis of the OSHO Phase III Trial (AML 96) Comparing Different Application Modes of AraC in Patients below 60 Years with Acute Myeloid Leukemia (AML): No Impact of AraCApplication Mode on Remission Rate, Toxicity, Disease-Free Survival or Overall Survival

Blood ◽

10.1182/blood.v112.11.2966.2966 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2966-2966

Author(s):

Cornelia Becker ◽

Rainer Krahl ◽

Antje Schulze ◽

Georg Maschmeyer ◽

Christian Junghanß ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Cox Regression ◽

Disease Free Survival ◽

Phase Iii ◽

High Dose ◽

Event Free Survival ◽

Free Survival ◽

Significant Difference

Abstract Clinical trials on different cytarabine doses for treatment of AML provide evidence of a dose response effect, but also for increase toxicity after high dose AraC (HDAC). Pharmacokinetic measurements of cytarabine-triphosphate (AraC-CTP), which is the most relevant cytotoxic metabolite of AraC, have revealed its formation in leukemic cells to be saturated with infusion rates above 250 mg/m2/h, this being significantly lower than used in HDAC schedules. Methods: Based on a pharmacological model and encouraging results of a phase II study we conducted a prospective randomized multicenter clinical trial comparing the effects of two different application modes of AraC in patients up to 60 years with untreated newly diagnosed AML. Patients were randomized to receive AraC at two different infusion rates (IR) during induction and consolidation treatment: arm A/experimental: 1 × 2 g/m2/d AraC over 8 hours (IR 250 mg/m2/h) arm B/standard: 2 × 1 g/m2/d AraC over 3 hours (IR 333 mg/m2/h). Induction and first consolidation consisted of AraC (days 1, 3, 5, 7) in combination with an anthracycline (Idarubicine 12 mg/m2 or Mitoxantrone 10 mg/m2, days 1–3). The final dosage points (AraC day 7 and anthracycline day 3) were excluded from the second consolidation. The third consolidation consisted of either allogeneic or autologous stem cell transplantation or of chemotherapy identical to second consolidation. Results: From 02/97 to 04/02 419 patients were enrolled in the study. The present analysis is based on 361 eligible and evaluable patients with a median follow up of 7 years. CR was reached in 249/361 (69%; 95%CI: 65%–74%) patients. No statistically significant differences were detected between arms A and B with regard to CR-rate (69% vs 69%) or early death rate (11% vs 8%). Hematological recovery of median white blood cell count (WBC) > 109/l and median platelets (plt) > 50 × 109/l revealed no difference between arms A and B after induction (WBC day 22 vs 22, p=0,68; plt day 25 vs 26, p=0,41) and consolidation (WBC day 28 vs 27, p=0,07; plt day 42 vs 40, p= 0,58). The event free survival (EFS) after 5 years is 0,25 ± 0,03 % for all patients with an overall survival of 0,31 ± 0,03 % after 5 years. For the purposes of analysis, the 83 transplant patients (23 allogeneic MRD, 14 allogeneic MUD and 46 autologous) were censored at time of transplant. No statistically significant difference between arms A and B in regard to EFS (0,25 ± 0,04 vs 0,25 ± 0,04, p=0,99), relapse incidence (0,63 ± 0,06 vs 0,60 ± 0,06, p=0,89), overall survival (0,32 ± 0,04 vs 0,30 ± 0,04, p=0,44) and therapy associated mortality (0,18 ± 0,04 vs 0,17 ± 0,03, p=0,95) were detectable after adjustment of prognostic factors. An analysis of risk factors by multivariate cox regression model confirmed cytogenetics at diagnosis to be the most important risk factor for CR rate (p<10−6) and for EFS (p<10−6). Other significant prognostic factors for EFS evaluated in the multivariate analysis were de novo vs secondary AML (p=0,0001), WBC (continuous) (p=0,001), LDH (>1–4 × vs other ULN) (p=0,008) and FAB classification (FAB M0,6,7 vs FAB M1,2,4,5) (p=0,0005). EFS after 5 years shows a significant correlation to cytogenetics (p<10−6) with 0,71±0,1, 0,27±0,05, 0,20±0,06 and 0,03±0,03 for favorable, normal, other and unfavorable cytogenetic karyotype, respectively. Conclusion: We conclude that the application of AraC at the presumptive saturating infusion rate of 250 mg/m2/h results in comparable remission rates, toxicity, event free survival and overall survival as compared to the standard IR with 333 mg/m2/h.

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Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma: A Retrospective Study of the Geltamo Group (1994-2011)

Blood ◽

10.1182/blood.v124.21.3980.3980 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3980-3980

Author(s):

Ana García-Noblejas ◽

Eulogio Conde ◽

Alejandro Martín ◽

María Jesús Vidal ◽

Rafael Rojas ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Cell Lymphoma ◽

Disease Status ◽

Line Treatment ◽

First Line ◽

Kaplan Meier ◽

Mantle Cell ◽

First Line Treatment

Abstract INTRODUCTION Autologous stem cell transplantation (ASCT) is one of the current treatment options for first-line treatment of mantle cell lymphoma (MCL) in young and fit patients in first complete response (CR). Nevertheless its role in less than CR, after intensive chemotherapy schemas or as consolidation after salvage regimens has not been established. AIM To analyze the impact of patient and treatment characteristics on outcome of MCL patients treated with ASCT. METHODS Retrospective analysis of MCL patients treated with ASCT and registered in the GELTAMO database from 1994 to 2011. An outcome up-date was performed on December 2013. The study was approved by local ethical committees. Statistical analysis was performed using SPSS 15.0. RESULTS Two hundred and forty eight patients were registered from the GELTAMO database. Patients’characteristics : median age was 55 years old (range 21-70 y), 70% male. One hundred and fifty eight patients (68%) were transplanted in CR, 125 were in first CR (79% of all CR) and 33 in second or third CR (21%). Fifty two patients (22%) were transplanted in first partial response and 15 (6%) with chemosensitivity disease after relapse. Only 8 patients (3%) were transplanted with refractory disease. Response : forty-eight out of 75 patients (64%) without CR at ASCT converted to CR after transplant. Survival: Sixteen percent of patients were lost to follow-up one year after transplantation. Median follow-up for alive patients was 47 months (range 0-245 months). Progression free survival for patients transplanted in first CR was 45 months (CI95%: 33-56 months), for patients transplanted in first partial response (PR) was 28 months (CI95%: 15-21months) and for patients transplanted in other response was 19 months (CI95%: 12-26 months). In the whole series, median overall survival (OS) from transplantation was 69 months (CI95% 51-87 months) and for those patients transplanted in first CR was 98 months (CI95% 67-130 months). When patients without CR before transplant are analyzed separately, those who achieved CR after transplantation have better PFS (38 vs 10 months, p<0.001) and OS (74 vs 16 months, p<0.001) than others. Treatment related mortality was 4%. We analyzed the variables that could be associated with PFS and OS. We considered age (≤60 vs >60), ECOG (<2, ≥2), IPI (<2, ≥2), status at transplant (1st CR vs others), conditioning with TBI and HDAC in first line treatment. In univariate analysis, ECOG (p=0.04) and status at transplant (p=0.01) were the variables associated with PFS. For OS, the same variables resulted significant (p<0.001 and p=0.07, respectively) and also, HDAC emerged as significant variable associated with outcome. (p=0.05). In multivariate analysis, ECOG and status at transplant remained as independent prognostic factors for PFS while ECOG and HDAC in first line had impact for OS, see Table 1. Table 1. Variables identified as independent prognostic factors for PFS and OS in multivariate analysis. PFS OS p RR (95% CI) p RR ECOG 0.01 3.6 (1.3-9.9) 0.04 4.5 (1.6-12.5) Status at trasplant 0.03 1.4 (1-2) 0.09 (ns) ---- HDAC at 1st line 0.7 (ns) ---- 0.014 0.5 (0.3-0.8) Afterwards, a survival analysis for PFS and OS was performed according to have received high dose AraC (HDAC) in first line treatment or not and disease status (DS) before ASCT (Table 2). Table 2. Survival analysis according to have received HDAC in 1st line treatment and disease status (DS) before ASCT DS before ASCT N Firts line treatment N PFS (CI95%)(Kaplan Meier) p OS (CI95%)(Kaplan Meier) p 1st CR 125 No HDAC 52 37 (22-51) 0.13 64 (37-91) 0.01 HDAC 72 56 (33-78) No reached 1st PR 52 No HDAC 35 33 (3-63) 0.59 61 (0-126) 0.9 HDAC 17 27 (18-37) 69 (46-92) ≠1st CR/PR 51 No HDAC 46 20 (13-27) 0.16 35 (5-66) 0.9 HDAC 5 11 (7-16) No reached CONCLUSION This retrospective study reproduces previous results published about the role of ASCT in MCL: ASCT consolidation in first CR induces high survival rates with a median PFS of 45 months and median OS of 98 months. Patients without CR after ASCT had a significant inferior outcome. ECOG < 2 and status at transplantation are crucial for PFS and first line treatment with AraC improves significantly OS, particularly in patients with first CR. Disclosures No relevant conflicts of interest to declare.

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