Safety and Long-Term Efficacy of Maintenance Therapy with Alternating Azacytidine (AZA) and Lenalidomide (Len) Cycles in Elderly (≥ 60) Fit Patients (Pts) with Poor Prognosis AML in First Complete Remission (CR) After LIA Induction. A Phase II Multicentric GOELAMS Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3787-3787
Author(s):  
Mathilde Hunault ◽  
Nathalie Maillard ◽  
Aline Tanguy-Schmidt ◽  
Chantal Himberlin ◽  
Bachra Choufi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Maintenance Therapy ◽  
Poor Prognosis ◽  
Conflicts Of Interest ◽  
Time Interval ◽  
Conventional Chemotherapy ◽  
Poor Risk ◽  
The Impact

Abstract In elderly pts, the prognosis of AML associated with poor risk cytogenetics or secondary to either MDS or previous cancer is so bad that only supportive care or investigational studies are usually recommended. Fit patients may achieve CR after conventional induction, but early relapse appears to be nearly inescapable whatever classical consolidation or maintenance therapy is used. Therefore, the GOELAMS investigated the impact of a maintenance using two agents mainly used in MDS, ie AZA and Len. Between March 2011 and February 2013, 117 pts from 27 centers (median age 69 yrs; 60-80) with previously untreated poor prognosis AML were included. Poor Risk factors were either preceding MDS (n=52), previous cancer (n=37) or centrally reviewed (IL) poor risk cytogenetics (n=83) defined as complex karyotype (≥3 abnormalities, n=65), monosomal karyotypes (n=54), del or - 5 (n=61) or 7 (n=44), 3q abnormality (n=9) or MLL rearrangement except for t(9;11) (n=5). Median WBC was 2.9 G/L (0.5-160), 7 pts had WBC ≥ 30 G/L. Induction chemotherapy included Lomustine 200 mg/m² po d1, Idarubicine 8 mg/m²/d (d1-5), Cytarabine 100mg/m²/d CI (d1-7). Patients in CR received 12 maintenance cycles alternating every 28 days AZA (sc 75 mg/m²/d1-7) and Len (10mg/d1-21), which started if PMN and platelets were >1 G/L and 100 G/L respectively. After d42, subsequent cycles were reduced to 50 mg/m²/d and 5 mg/d. GCSF was allowed in case of PMN < 0.5 G/L after 7 days or febrile neutropenia. At the end of induction, CR was achieved in 56% (65 pts) without any predictive factor, 9% died from infection (n=6), cerebral hemorrhage (n=1) or MOF (n=4) and 35% (41pts including 5 CRp) failed to achieve CR. The 12 planned maintenance courses could be given to 21 pts (32%) (median: 6). Few toxicities were observed. AZA courses were slightly more toxic than Len courses (table 1). Table 1.AZA courses %Len courses %Gr 3/4 neutropenia46.8/ 27.339.7 /17.6Antibiotics for fever at home6.97Hospitalization for febrile neutropenia0.52.7RBC transfusions55.4Gr 3 Thrombopenia2016Platelets transfusion8.67.9Interval between courses > 35 days26.118.4Median time interval between courses31 d28 dCourses with doses reductions9.621.6 Maintenance courses were interrupted because of relapse (n= 34, 77%), alloSCT (n=4 %), count error (n=1 %) or toxicities (n =5, 11%) occurring after Len (depression, vascular purpura and pseudomembranous diarrhea, sudden death, all during cycle 1) or after Aza (atrial fibrillation and cardiac dysfunction). Twenty Gr3/4 AE were reported among 441 cycles (0.56%/courses). Median follow-up for survivors was 38 mo (26-47). Median OS was 10 mo, with 21% 2y OS. Median CR duration was 7 mo (1-30). Impact of prognostic factors on DFS is shown table 2. Within poor risk factors, Cytogenetic abnormalities appeared as even poorer than previous MDS or cancer. Table 2.CR %CR NDFS median moP VALUE1y DFS %2y DFS %All patients56657.941.512.3Age ≥ 7058.3288.6 vs 7.746.417.9WBC ≥ 3.3 G/L48.1267.0 vs12.423.111.5Previous MDS51.92713.8 vs 6.4.0551.922.2MDS only68.41316.8 vs 6.4.00869.230.8Previous cancer54207.5 vs 7.9355Cancer only80812.4 vs 7.755012.5Poor cytogenetic53445.1 vs 15.3.0429.56.8Complex caryotype49.2324.8 vs 12.9.012259.4Monosomal caryotype50274.6 vs 12.9.00218.57.4Chromosome 5 abnormality52.5325 vs 13.8.00218.86.3Chromosome 7 abnormality54.5243.6 vs 12.00120.84.23q55.6510.4 vs 7.740017p deletion48.5165.0 vs 10.52512.5MLL8043.4 vs 8.4250poor cytogenetic + MDS42.997.7 vs 7.944.422poor cytogenetic + cancer46.774.8 vs 7.928.90poor cytogenetic + cancer + MDS71.453.4 vs 8.4200cancer + MDS00---Poor cytogenetic only rev aza57.5236.3 vs 12.9.05521.74.3Poor cytogenetic only SA255436.430.220.9 In the previous GOELAMS SA2 trial, 78 pts with poor risk cytogenetics without secondary leukemia received the same LIA induction followed in CR by maintenance therapy with 6 mini-reinductions (Ida 10mg/m² d1, cytarabine 50 mg/m²x2/d d1-5) and 6MP-MTX for 2years. In the present study, the DFS of the group of pts with poor risk cytogenetics without previous cancer or MDS is very similar. This alternating azacitidine/lenalidomide maintenance improved DFS and OS of pts without poor risk cytogenetics (median 15.7 and 24 mo). In this setting, it could be randomly compared to conventional chemotherapy maintenance. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Maintenance Therapy With Alternating Azacytidine and Lenalidomide Cycles In Elderly (≥ 60) Fit Patients (Pts) With Poor Prognosis AML In First Complete Remission (CR) After Lia Induction. A Phase II Multicentric Goelams Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2691-2691 ◽  
Author(s):  
Mathilde Hunault-Berger ◽  
Edouard Randriamalala ◽  
Aline Schmidt-Tanguy ◽  
Chantal Himberlin ◽  
Bachra Choufi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Maintenance Therapy ◽  
Poor Prognosis ◽  
Conflicts Of Interest ◽  
Multiorgan Failure ◽  
Single Agent ◽  
Early Death ◽  
Poor Risk ◽  
Obvious Benefit ◽  
Preparative Regimen

Abstract The prognosis of poor risk AML in elderly pts justifies either supportive care only or investigational studies without obvious benefit of post-remission chemotherapies. A phase I study has demonstrated that the combination of azacitidine and lenalidomide is well-tolerated in AML with efficacy superior to that of single-agent therapy in higher-risk MDS (Sekeres JCO2010). The GOELAMS group investigated the efficacy of 12 maintenance cycles alternating monthly azacitidine (sc 75 mg/m²/d1-7) and lenalidomide (10mg/d1-21) every 28 days for pts in CR and compared the results to previous SA2002 and BGMT95 prospective trials which shared the same LIA induction followed by chemotherapy-based maintenance. Between 3/2011 and 2/2013, 117 pts from 27 centers (median age 69 yrs; 60-80, 9 pts ≥ 75) with previously untreated poor prognosis AML were included. Risk factors allowing inclusion were either: i) centrally reviewed (IL) poor risk cytogenetics (n=83) defined as complex karyotype (≥3 abnormalities), monosomal karyotype, t(6;9), del or – 5 or 7, and EVI1 or MLL rearrangement except for t(9;11); ii) preceding MDS (n=52) or iii) secondary leukemia occurring after previous cancer (n=37). Median WBC was 2.9 G/L (0.5-160), 19 pts had WBC > 30 G/L. Induction chemotherapy included lomustine 200 mg/m² po d1, Idarabucine 8 mg/m²/d (d1-5), cytarabine 100mg/m²/d CI (d1-7) and G-CSF (d15 to recovery). At the end of induction, CR (excluding CRp) was achieved in 56% (65 pts), 9% died from infection (n=6), cerebral hemorrhage (n=1) or multiorgan failure (n=4) and 35% (41pts) failed to achieve CR. Despite a trend towards a higher CR rate in pts without previous MDS (59% vs 48% CR), CR was not related to any of the risk factors studied. Median follow-up for survivors is 16 months (3-25). Monthly alternating azacitidine-lenalidomide maintenance therapy was started in 65 pts. Except for 1 pt who died during cycle1 of lenalidomide without any obvious explanation, tolerance was good. Median nadir of neutrophils and platelets was 1 and 96 G/L respectively. Grade 3/4 adverse events occurred in 6% of cycles and were due to infection, haemorrhage, hepatitis or fatigue (3%, 1%, 0.5%, 0.5% of cycles respectively). Median CR duration was 4.5 mo (1-23) and 40 pts relapsed. Allogeneic SCT with non myelo-ablative preparative regimen was performed in 4 pts less than 70 years in CR1: 1 is alive in relapse, 2 died of GVH and 1 is in continuous CR. Pts achieving CR had a median OS of 13 mo (95% CI 7.3-18.6), 54% being alive at 1 year and 15% at 2y. In refractory pts, the median OS was 7 mo (95% CI 2.8-11.2) with 32% alive at 1 year (P = 0.0001). OS and DFS reported in the current trial and compared to historical controls are described below: induction results are similar to those observed in the 128 poor risk cytogenetic pts of the previous SA2002/BGMT trials treated with the same LIA induction (CR 58%, early death 15%, failure 27%) but who received maintenance therapy with 6 mini-reinductions (Ida 10mg/m² d1, cytarabine 50 mg/m²x2/d d1-5) and 6MP-MTX for 2years. No significant survival benefit was observed compared to pts with poor risk cytogenetics treated with chemotherapy maintenance in our previous trials. However, pts included in this trial have probably an even worse prognostic than those included in the GOELAMSSA2/BGMT95 trial which excluded AML secondary to MDS and previous cancers. This type of alternating azacitidine/lenalidomide maintenance improves OS and DFS of pts without poor risk cytogenetics (median DFS not reached and 19 mo) and could be randomly compared with conventional chemotherapy maintenance in AML secondary to MDS or cancer but also in older pts with intermediate risk cytogenetics.Median (95% CI)6mo1y2yOS maintenance aza-rev (117)9 mo (7.5-10.5)70%41%17%OS 2002/BGMT95 (128)6 mo (4.1-7.8)54%32%21%DFS maintenance aza-Rev (65)10 mo (2.5-17.4)61%49%8%DFS 2002/BGMT95 (74)9 mo (6.0-11.9)63%43%26%OS poor risk cytogenetic (83) vs other (33)8 mo vs NR P=0.000162% vs 83%27% vs 70%10% vs 60%OS previous cancer (37) vs no cancer (80)9 mo vs 9 mo68% vs 73%44% vs 40%24% vs 17%OS previous MDS (52) vs no MDS(64)12 mo vs 7 mo P=0.00177% vs 65%58% vs 26%27% vs 12%DFS poor risk cytogenetic (44) vs other (20)6 mo vs 19 mo P=0.00748% vs 84%33% vs 67%11% vs 28%DFS previous cancer (20) vs no K(45)8 mo vs 8 mo80% vs 61%46% vs 47%0% vs 13%DFS previous MDS (27) vs no MDS(38)15 mo vs 6 mo, P=0.0874% vs 48%59% vs 32%12% vs 0% Disclosures: No relevant conflicts of interest to declare.

Bortezomib Induction Followed by ASCT in Patients with Multiple Myeloma: Achievement of Response After Induction and Achieving CR Post-ASCT Are Both Important Prognostic Markers

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1866-1866
Author(s):  
Min Kyoung Kim ◽  
Chang-Ki Min ◽  
Myung Soo Hyun ◽  
Kihyun Kim ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Induction Treatment ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival

Abstract Abstract 1866 Background: In multiple myeloma (MM), the association between the response to induction before autologous stem cell transplantation (ASCT) and long-term outcome is less clear but the situation may change with the introduction of novel agents. We therefore assessed the clinical relevance of response of bortezomib induction treatment or post-ASCT response for patients who received bortezomib-combined induction chemotherapy followed by ASCT. Methods: We retrospectively assessed 183 MM patients who received bortezomib-containing induction therapy (BTZ-IT) followed by ASCT in 24 institutions throughout Korea between 2003 and 2010. Records of these patients were reviewed using the Korean Myeloma Registry database (www.myeloma.or.kr). Each institution was requested to reconfirm the data using additional case report forms. Patients who had overt MM based on International Myeloma Working Group diagnostic criteria were selected. Results: One-hundred seventy eight patients were eligible. Their median age was 56 years (range, 28–69 years) and 96 (53.9%) were male. Forty nine (27.5%) received bortezomib as front-line therapy and 129 (72.5%) as second-line treatment. All patients underwent ASCT and 22 (12.4%) were treated with tandem ASCT. Ninety-seven (54.5%) patients were treated with maintenance therapy after ASCT. After BTZ-IT, the response rates in this selected series of patients were 37.6% CR, 12.4% VGPR, 41.0% PR, 7.3% SD and 1.7% PD (Figure 1A, 1B, 1C); the corresponding post-ASCT rates were 69.2% CR, 14.0% VGPR, 11.0% PR, 2.9% SD and 2.9% PD. At a median follow-up of 46.6 months, the 3-year overall survival (OS) and event-free survival (EFS) rates were 70.0% and 31.9%, respectively. Multivariate analysis showed that factors independently predictive of OS and EFS included achievement of BTZ-IT response °Ã PR (P=0.025 and P=0.014, respectively) and the treatment with maintenance therapy (P=0.048 and P=0.001, respectively). Post-ASCT CR vs. °Â VGPR was also an independent prognostic factor for OS and EFS (P=0.0001 and P=0.002, respectively). Conclusion: At least PR to BTZ-IT and CR after ASCT were predictive of survival. These findings suggest that patients who responded to BTZ-IT may benefit from ASCT due to an enhanced quality of response. Maintenance therapy can also affect patient outcomes. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Five-year Follow-up of Transobturator Sling: 152 Cases with the Same Surgeon

2018 ◽  
Vol 40 (10) ◽  
pp. 614-619
Author(s):  
Mucio Diniz ◽  
Luisa Diniz ◽  
Gustavo Lopes da Silva ◽  
Agnaldo Filho ◽  
Zilma Reis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Urinary Incontinence ◽  
Short Form ◽  
Transobturator Sling ◽  
Logistic Regression Models ◽  
International Consultation ◽  
Surgical Failure ◽  
The Impact

Objective To evaluate the long-term subjective cure rate of the transobturator sling, including an analysis of the risk factors and of the impact of increased surgical experience on the results. Methods A retrospective cohort study of women who underwent transobturator sling surgery from 2005 to 2011 was conducted. Patients were evaluated by a telephone survey using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and by subjective questions regarding satisfaction. An ICIQ-SF score of 0 was considered a cure. The crude and adjusted odds ratios and 95% confidence intervals were estimated in univariate and multivariate logistic regression models to identify risk factors for surgical failure. Differences with p < 0.05 were considered significant. Results In total, 152 (70.6%) patients answered the questionnaire. The median follow-up period was 87 months. The urodynamic diagnosis was stress urinary incontinence in 144 patients (94.7%), and mixed urinary incontinence in 8 (5.3%) patients. Complications occurred in 25 (16%) patients. The ICQ-SF results indicated that 99 (65.10%) patients could be considered cured (ICIQ-SF score = 0). Regarding the degree of satisfaction, 101 (66%) considered themselves cured, 43 (28%) considered themselves improved, 7 (4.6%) considered themselves unchanged, and one reported worsening of the incontinence. After the univariate and multivariate analyses, the primary risk factor for surgical failure was the presence of urgency (p < 0.001). Conclusion The transobturator sling is effective, with a low rate of complications and a high long-term satisfaction rate. The risk factors for failure were the presence of urgency and patient age. The increased experience of the surgeon was not a factor that influenced the rate of complications.

Acute Splenic Sequestration In a Newborn Cohort with Sickle Cell Anemia (SCA): Predictive Factors and Impact on Disease Severity

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 263-263 ◽  
Author(s):  
Cécile Arnaud ◽  
Annie Kamdem ◽  
Lena Coïc ◽  
Nadia Médejel ◽  
Emmanuelle Lesprit ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Severity ◽  
Predictive Factors ◽  
G6pd Deficiency ◽  
Conflicts Of Interest ◽  
Blood Parameters ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 263 Early occurrence of dactylitis, severe anemia and leukocytosis have been identified as risk factors for adverse outcome in children with SCA (Miller NEJM 2000), but the impact of acute splenic sequestrations (ASS) on disease severity has not yet been reported. The goal of this study was to define the predictive factors of ASS and to evaluate if this complication was a risk factor for disease severity. Methods. SS patients of the newborn cohort, seen at our SCA Center in Créteil before 3 months of age and older than 2 years at the last visit (n=197), were included in this study. Alpha and beta genotypes, and G6PD activity were determined. Blood parameters were recorded at steady state during the second year of life. ASS was defined as an Hb-decrease of ≥20% associated with a spleen-increase ≥2cm. Vaso-occlusive crises (VOC) requiring hospitalizations and acute chest syndromes (ACS) were recorded. The yearly rates of VOC and ACS were calculated for the entire follow-up and for the period before any intensification (transfusion program, hydroxyurea or SCT). Results. Median follow-up was 7.9 yr (range 2–24), providing 1820 patient-years. Alpha-Thal was present in 70/162 (43.2%); beta-haplotypes, available in 140 patients, were Car/Car in 62 (44.3%), Ben/Ben in 35 (25%), Sen/Sen in 7 (5%), and others in 34 (25.7%). G6PD deficiency was present in 24/171 (14%). At baseline, mean (SD) blood parameters were: Hb: 8g1/dL (1.2); Ht: 24.6% (3.9); MCV: 79.2 fL(8.3); HbF: 15.7% (8.2); LDH: 919 UI/L (369) and reticulocytes: 296 (114); WBC: 14.3 (5.2), neutrophils 5.8 (3.1) × 109/L. Among the 197 SS-patients, 64 (32%) experienced their first ASS at the median age of 2.0 yr (range 0.1–12.9) and 36/64 recurred. ASS occurred before 1 yr of age in 10 (5%) and before 2 yr in 33/197 (17%). Splenectomy was performed in 24 of them at the median age of 5.1 yr (range 2.7–12.9). The KM-estimated cumulative risk of ASS occurrence at age 7 was 32% (95%CI: 25–39%). The Cox-regression analysis showed that gender, G6PD deficiency, beta haplotypes were not risk factors whereas alpha-Thal significantly increased the risk of ASS occurrence (HR: 1.9, 95% CI:1.1-3.3, p=0.021). Among blood parameters, multivariate Cox analysis retained low platelet (HR: 1.4 per 1×107/L decrease; 95%CI:1.1-1.8, p=0.014) and high reticulocyte counts (HR=2.0 per 1×107/L increase; 95%CI:1.6-2.6) as independent significant predictive factors for ASS. Comparison of patients with or without ASS history showed no significant difference in the rate of ACS but significantly higher rates of VOC during the entire follow-up (0.68±0.58 vs 0.47±0.55; p=0.014) and in the number of hospitalizations (1.64±0.83 vs 1.29±0.92; p=0.01) in patients with ASS history. Rates of VOC before intensification were 1.1±0.7 and even 2.2±2.0 in those having experienced ASS before age 1 vs 0.6±0.7 (p=0.001) in those with no ASS history. Conclusion. Results from this study in a newborn cohort show that ASS are more frequent in patients with alpha-Thal and are associated with a higher rate of VOC. Splenectomy is usually recommended in case or recurrent ASS; however, our previous results show that geno-identical SCT can cure 95%SCA children and partly restore splenic function. We suggest that this procedure be proposed to those with available donor before considering total splenectomy. Disclosures: No relevant conflicts of interest to declare.

SF3B1, NOTCH1 and TP53 Mutations Do Not Affect the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Chronic Lymphocytic Leukemia (CLL): 6-Year Follow-up of the Gcllsg CLL3X Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 966-966 ◽  
Author(s):  
Peter Dreger ◽  
Andrea Schnaiter ◽  
Marianna Rossi ◽  
Peter Paschka ◽  
Andreas Bühler ◽  
...  
Keyword(s):  
Research Funding ◽  
Direct Sequencing ◽  
Reference Laboratory ◽  
Hematopoietic Stem ◽  
Tp53 Mutations ◽  
Poor Risk ◽  
The Impact ◽  
Notch1 Mutations

Abstract Abstract 966 PURPOSE of this analysis was to provide long-term follow-up of the GCLLSG CLL3X trial which aimed at evaluating reduced-intensity HSCT in patients with poor-risk CLL, and to compare the impact of the newly identified risk factors SF3B1 and NOTCH1 mutations on the outcome of HSCT with that of established prognostic factors, such as TP53 abnormalities. PATIENTS AND METHODS: CLL3X included 100 patients with poor-risk CLL (median age 53 (27-65) years), of whom 90 patients were allografted with blood stem cells from related (40%) or unrelated donors (60%). 24% had refractory CLL at HSCT, and 13% received in-vivo T cell depletion (TCD) with alemtuzumab during conditioning. All genetic studies were performed in the Ulm central reference laboratory of the GCLLSG. Genomic aberrations and IGHV mutation status were analyzed by FlSH and direct sequencing as previously described. NOTCH1 was studied by direct sequencing of a PCR fragment from the PEST domain (exon 34, chr9:139,390,619-139,391,290). SF3B1 (exons 13–16) and TP53 (exons 4–10) were analyzed by DHPLC (WAVE® 3500HT, Transgenomic Inc) with subsequent sequencing of aberrant fragments, if needed after subcloning. RESULTS: With a median follow-up of 6.0 (0.6-10.8) years, 6-year overall survival (OS) of all 100 patients enrolled was 53%. The 90 allografted patients had a 6-year OS and event-free survival (EFS) of 58% and 38%, respectively. Of 28 patients who were relapse-free and MRD-negative 12 months after HSCT, only 3 subsequently experienced clinical disease recurrence at 2.8, 5.0, and 9.0 years post transplant, and 24 (86%) remained MRD-negative throughout the whole follow-up. SF3B1, NOTCH1, and TP53 mutational status could be obtained each in 80/100 patients, and 17p FISH results were available in 82/100 patients. SF3B1 abnormalities were found in 26%, NOTCH1 abnormalities in 14%, and TP53 mutations in 30% of patients; whereas 17p- was detected in 20% of patients with diagnostic material available. Whilst SF3B1 and NOTCH1 mutations were mutually exclusive, 29% of patients with TP53 mutations also had an SF3B1 or NOTCH1 abnormality, and 46% of TP53-mutated patients had a concomitant 17p deletion. By univariate comparisons, we did not find significant survival differences between SF3B1-mutated, NOTCH1-mutated and SF3B1+NOTCH1 wild-type patients (Figure). Multivariate analysis using Cox regression modeling did not show a significant impact of SF3B1, NOTCH1, and TP53 (TP53mut and/or 17p-) abnormalities on OS and EFS (Hazard ratios (HRs) of SF3B1mut 0.82, 95%CI 0.35–1.97 and 0.64, 95%CI 0.32–1.31; HRs of NOTCH1mut 0.69, 95%CI 0.22–2.12 and 0.73, 95%CI 0.29–1.81; HRs of TP53abn 0.99, 95%CI 0.42–2.32 and 0.61, 95%CI 0.31–1.21). In contrast, TCD and refractory disease at HSCT retained their adverse impact on OS and EFS as already observed in an earlier analysis at a follow-up time of 3.8 years (Blood Oct 7, 2010). CONCLUSIONS: HSCT can provide long-term EFS in approximately 40% of patients with poor-risk CLL. Patients who are in MRD-negative remission one year after HSCT have a >80% probability of durably remaining in this status. Long-term disease control does not appear to be affected by the presence of SF3B1, NOTCH1, and TP53 abnormalities, suggesting that HSCT can overcome the treatment resistance found to be associated with this abnormality. Disclosures: Hallek: Roche: Consultancy, Honoraria, Research Funding. Stilgenbauer:Roche: Consultancy, Honoraria, Research Funding.

scholarly journals MO1049PROGRESSION OF CHRONIC KIDNEY DISEASE AND LONG-TERM MORTALITY IN PATIENTS HOSPITALIZED WITH TRICUSPID REGURGITATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Saban Elitok ◽  
Anja Haase-Fielitz ◽  
Martin Ernst ◽  
Michael Haase
Keyword(s):  
Risk Factors ◽  
Hemoglobin Concentration ◽  
Ckd Progression ◽  
Survival Status ◽  
Independent Risk Factors ◽  
Index Hospital ◽  
The Impact ◽  
Long Term Mortality

Abstract Background and Aims Uremic toxins negatively affect the cardiovascular system resulting in significant morbidity and mortality. However, independent risk factors for chronic kidney disease (CKD) and that of worsening CKD have not been studied in patients with tricuspid regurgitation (TR), yet. Accordingly, in this study, we aimed to assess independent risk factors for the development of progressive CKD in patients with TR. Also, the impact of progressive CKD on long-term mortality was evaluated. Method This retrospective, single-center study comprised 444 consecutive patients with TR who were hospitalized between January 2010 and June 2017. We excluded patients with CKD stage 5. Demographic data, comorbidities, type of admission, medication, echocardiographic and laboratory parameters, and survival status were obtained from patient medical record from index hospital admission through discharge. For at least three years, serum creatinine concentrations and survival status were collected from outpatient medical record. We identified independent risk factors for CKD progression. Also, we assessed the impact of CKD progression and other variables on 3-year mortality using multivariable logistic regression analysis. For analysis of 3-year mortality, we grouped patients according to different combinations of their TR grade and presence or absence of CKD progression. Results Stage of CKD at hospital admission (odds ratio 0.34 [95% confidence interval 0.24-0.50], p &lt; 0.001), baseline hemoglobin concentration (OR 0.72 [95% CI 0.57-0.92], p=0.006) and presence of diabetes type 2 (OR 1.81 [95% CI 1.08-3.03], p=0.024) were identified as independent risk factors for CKD progression. Progression of CKD during follow-up (OR 2.16 [95% CI 1.31-3.57], p=0.003), grade of TR and mitral regurgitation during index hospital stay and hemoglobin concentration at baseline were independent risk factors for 3-year mortality. Combination of TR grade and status of CKD progression showed a stepwise pattern for 3-year mortality (Figure 1). Patients with TR 1 and CKD progression had a similar 3-year mortality as patients with TR 2 or 3 but no CKD progression. In patients with TR 1, risk for 3-year mortality doubled if CKD progression occurred (OR 2.49 [95% CI 1.38-4.47], p=0.002). Conclusion Although retrospective studies cannot imply causal relationship, based on study findings, kidney follow-up especially in patients with mild TR may be advisable. If CKD progression can be prevented in patients with TR and if such kidney protection may reduce long-term mortality may be objective of future studies.

Synergistic Effect of Hypokalemia and Atrial Fibrillation on Prognosis in Patients with Stroke after Intravenous Thrombolysis

2021 ◽  
Vol 18 ◽  
Author(s):  
Li-Min Wei ◽  
Cheng-Ye Zhou ◽  
Wang-Qian Ge ◽  
Jia-Sheng Huang
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Poor Prognosis ◽  
Intravenous Thrombolysis ◽  
Interactive Effects ◽  
Modified Rankin Scale ◽  
Early Neurological Deterioration ◽  
Near Term ◽  
The Impact

Background: The association between atrial fibrillation (AF) and the prognosis of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) is debated. Hypokalemia is highly prevalent in patients with AF. We aimed to investigate the effect of hypokalemia and AF on the prognosis of AIS patients following IVT. Method: AIS patients undergoing IVT were enrolled and divided into four groups: normokalemia and non-AF, normokalemia and AF, hypokalemia and non-AF, hypokalemia and AF. Logistic regression was applied to analyze the impact of hypokalemia, AF, and their combination on the prognosis of patients. Results: The analysis included 567 patients, 184 with 3-month poor prognosis (modified Rankin Scale score of 3-6). Following adjustment of risk factors, hypokalemia and AF increased the risks for 3-month poor prognosis (adjusted Odds Ratios (aOR) = 4.97; 95% confidence interval (CI), 1.99–12.44, P =.001), early neurological deterioration (END) (aOR=7.98; 95% CI, 3.55–17.95, P <.001), 1-year poor prognosis (aOR=5.05; 95% CI, 1.99–12.81, P =.001), 1-year all-cause death (aOR =6.95; 95% CI, 2.35–20.56, P <.001). Patients with normokalemia and AF merely increased the risk of 1-year all-cause death (aOR=2.69; 95% CI, 1.10–6.61, P=.013). Patients with hypokalemia and non-AF were not associated with any poor prognosis. There were combined and interactive effects of hypokalemia with AF on the 3-month poor prognosis (P for interaction =.039) and END (P for interaction=.005). Conclusion: Hypokalemia and AF synergistically increased the risk of near-term poor prognosis, END, long-term poor prognosis, and all-cause death of AIS patients following IVT.

scholarly journals Allogeneic Hematopoietic Transplantation in Patients with CLL: Results of a Large Disease-Specific Risk Factor Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3209-3209
Author(s):  
Johannes Schetelig ◽  
Liesbeth de Wreede ◽  
Michel van Gelder ◽  
Niels Smedegaard Andersen ◽  
Carol Moreno ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Disease Control ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Risk Profile ◽  
Poor Risk ◽  
History Of ◽  
The Impact

Abstract Objectives: For medically-fit young patients with high-risk chronic lymphocytic leukemia (CLL) BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. We hypothesized that given the choice between these drugs and transplantation in future only patients with a low risk of treatment failure will be selected for alloHCT. Therefore, we searched for risk factors for 2-year non-relapse mortality (NRM) and 5-year event-free survival (EFS) after alloHCT, the latter as a surrogate for long-term disease-control. Methods: Data from patients with CLL who had received a first alloHCT from a HLA-identical sibling (SIB) or unrelated donor between 2000 and 2011 were updated in an EBMT data quality initiative. Multivariable Cox regression models were fitted to assess the impact of baseline risk factors for NRM and EFS. Results: Data on 694 patients were included into the analysis. The median age of the cohort of patients was 55 years (19 years to 74 years). Seventy-nine percent of patients had a Karnofsky performance status of 90% or higher. A disease history of less than two years was reported in 20% of patients and 44% of patients had a disease history of more than 5 years. The median number of pretreatments was 3 (range, 0-15). Eleven percent of patients had received a previous autologous HCT. Only 9% of patients had never received purine-analogs (PA) during their treatment history. Sixty-three percent of patients had either PA-refractory disease or relapse within 24 months from the last PA-containing chemotherapy at the time of HCT. A deletion 17p had been diagnosed in 28% of patients in this cohort. Information on PA-sensitivity, early relapse after autologous transplantation or PA-combination therapy and del(17p)/TP53 is used to select patients for allogeneic HCT according to the EBMT 2007 consensus. EBMT consensus criteria were met in 76% of evaluable patients. Overall, the majority of patients analyzed in this subset of all registered patients had high-risk CLL. For the whole cohort 2-year NRM was 28% (95%-CI, 24% to 32%). The baseline risk factors age, Karnofsky performance status, donor type, and donor-recipient sex mismatch had a significant impact on 2-year-NRM. With the help of these risk factors the outcome of good risk and poor risk reference patients was predicted whose linear predictors were close to the 10th and the 90th percentile of all patients in the dataset. The good risk male reference patient has an age of 45 years, a Karnofsky performance index of 100%, is in partial remission at HCT and has a matched related male donor. The poor risk male reference patient has 55 years of age a Karnofsky performance index of 80%, SD/PD at HCT, and a matched unrelated female donor. The female reference patients had the same characteristics, apart from the donor sex. Two-year-NRM was predicted to be 11% (12%) for male (female) patients with a favorable risk compared to 40% (32%) with a poor risk profile (see Figure). The same approach was used to analyze risk factors for long-term disease control. Five-year-EFS was 37% (95%-CI, 33% to 41%) for all patients. Age, Karnofsky performance status, history of an autologous HCT, remission status, and donor-recipient sex mismatch had a significant impact. The model-based prediction of 5-year EFS was 54% (64%) for a male (female) patient with a favorable risk profile compared to 15% (30%) with a poor risk profile. Current knowledge suggests that allogeneic HCT can overcome the negative prognostic impact of high risk cytogenetic abnormalities, especially of a deletion(17p) or TP53 -mutation. Even in this large cohort we observed only a trend for a lower incidence of relapse/progression in patients without deletion(17p) CLL within the first two years after HCT with translated into a trend for better EFS at that time. The impact on long-term disease-control and mortality was even smaller. Conclusion: Information on predicted 2-year-NRM and 5-year-EFS for good and poor risk reference patients derived from a large CLL dataset may be instrumental to select patients for future alloHCT. Model-based prediction of non-relapse mortality and relapse/progression. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Covid-19 In Man: A Very Dangerous Affair.

2021 ◽  
Vol 21 ◽  
Author(s):  
Giuseppe Lisco ◽  
Vito A. Giagulli ◽  
Giovanni De Pergola ◽  
Anna De Tullio ◽  
Edoardo Guastamacchia ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Metabolic Diseases ◽  
Systemic Disease ◽  
Public Health Issue ◽  
Immune System Dysfunction ◽  
Data Support ◽  
Systemic Spread ◽  
The Impact

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.

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