scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation (allo HSCT) in Patients with IPSS Low or Intermediate-1 Myelodysplastic Syndrome (MDS): A Prospective Multicenter Phase II Study Based on Donor Availability By the GFM & SFGM-TC "MDS-ALLO-Risk"

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1842-1842
Author(s):  
Marie Sebert ◽  
Cendrine Chaffaut ◽  
Sylvain Thepot ◽  
Corentin Orvain ◽  
Thomas Cluzeau ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Research Funding ◽  
Low Risk ◽  
Donor Group ◽  
Hematopoietic Stem ◽  
The Past ◽  
Group A ◽  
Group B

Abstract Background: Allo HSCT is a potentially curative treatment in MDS which, in higher risk (IPSS high and int 2) MDS demonstrated an overall survival (OS) advantage over conventional treatment (especially HMAs) in retrospective (Koreth et al., JCO 2013) and prospective (Robin et al. leukemia 2015) studies. Retrospective studies, on the other hand, suggested no OS advantage for allo HSCT in lower risk MDS (IPSS low and int 1), except possibly in the "poorest" lower risk MDS subsets, as classified by the WPSS (Alessandrino et al. AMJH 2013) However, about 25% of lower risk MDS patients are reclassified as higher risk by the R-IPSS and a proportion of other lower risk MDS can also harbor some higher risk features that compromise their outcome. MDS-ALLO-RISK trial (clinicaltrial.gov NCT02757989), was designed to assess outcome of lower risk MDS patients with some high-risk features after HLA-matched donor HSCT. Method: The primary objective of this study was to demonstrate an OS improvement in lower risk MDS patients with some high risk features with a donor compared with those without a donor (with a 3 year OS of 70% versus 40%, respectively) . Inclusion criteria were: IPSS low or int1 MDS with at least one of the following characteristics: 1) R-IPSS intermediate or higher 2) RBC transfusion dependent anemia and failure to two or more treatments (including EPO, Lenalidomide or HMA ); 3) platelets < 20 G/L requiring transfusions 4) ANC < 0.5 G/L with severe infection 5) no contra indication to allo HSCT 6) age <70 years 7) HLA identical donor (sibling or 10/10 unrelated) 105 inclusions were planned: 62 in group with a donor (group A) and 43 in group without a donor (group B). Recruitment began in June 2016 and stopped in March 2021 due to futility on the interim analysis. Median follow-up was 20 months. Data cut off analysis was June 2021. Results: 79 patients were included, 64 in group A and 15 in group B. Median age was 62.4 (IQR: 58-65) years in group A and 66 (IQR: 60.5-68) years in group B. Patients in group A were more frequently males (73 vs 40%, p=0.029), WHO was CMML in 8 (10%), MDS-SLD in 5 (8%), MDS-MLD in 9 (11%), MDS-EB1 in 41 (52%), MDS-RS in 12 (15%), unclassified in 4 (6%) without significant differences between the two groups. IPSS /IPSS-R was similar in both groups: IPSS low in 10% (11% in group A and 7% in group B) and Int-1 in 90%. IPSS-R: very low risk (6% vs 0%); low risk (25% vs 27%); intermediate (50% vs 47%); high (19% vs 27%); no very high risk. Among the 64 patients with a donor, 58 (92%) received HSCT, 2 died before HSCT; 2 had progressive disease and 2 are planned for HSCT. Transplanted patients received reduced intensity conditioning regimen with busulfan 6.4mg/kg, fludarabine 150mg/m2 and ATG (rabbit antithymocyte globulin therapy, grafalon®) 30mg/kg and cyclosporine-mycophenolate mofetil as GVHD prophylaxis. In group A, 21/64 had died, including 13 died from a non-relapse cause. In group B, 4/15 patients had died, 3 from MDS progression and one from CNS bleeding. Three-year OS was 60% (95%CI: 46.9-76.8) in group A and 64.2% (41.3-99.6) in group B (p=NS). At the time of analysis, 20 and 5 patients had progressed/relapsed in group A and B respectively. with a cumulative incidence of relapse/progression (from inclusion) of 27.4% (IC95%: 15;39.8) in group A and 41.7% (IC95%:9.2;74.2) in group B (p=0.71). Among the 58 transplanted patients, 11 (19%) died without disease progression, including one death from a solid tumor. 3 years non-relapse mortality in transplanted patients was 23.4% (IC95%:9.7;37). 3 years Incidence of grade 2 to 4 acute GVHD was 40.8% and 3 years chronic GVHD was 24.9%. Conclusion: In this, to our knowledge, first prospective study in IPSS lower risk patients with some unfavorable clinical or biological features, HLA identical donor (sibling or 10/10 unrelated) HSCT yielded a 3-year OS of 60%. Non relapse mortality was however 23%, and OS somewhat lower than expected (70% at 3 years) and similar to that observed in patients without a donor. Long-term follow-up is needed to better define subgroups of IPSS lower risk MDS that may benefit from allo HSCT. Disclosures Sebert: Abbvie: Consultancy; BMS: Consultancy. Cluzeau: Pfizer: Other: travel, accommodations, expenses; Astellas: Speakers Bureau; Amgen: Speakers Bureau; Agios: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Speakers Bureau; Takeda: Other: travel, accommodations, expenses; Jazz Pharma: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Speakers Bureau. Loschi: AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Servier: Ended employment in the past 24 months, Honoraria; MSD: Honoraria. Huynh: Jazz Pharmaceuticals: Honoraria. Ades: ABBVIE: Honoraria; NOVARTIS: Honoraria; CELGENE/BMS: Honoraria; CELGENE: Research Funding; JAZZ: Honoraria, Research Funding; TAKEDA: Honoraria. Fenaux: JAZZ: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Robin: NEOVII MEDAC NOVARTIS: Research Funding.

Should Hematopoietic Stem Cell Transplantation in First Complete Remission Be Restricted to High-Risk Patients in Childhood Acute Myeloid Leukemia?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1094-1094
Author(s):  
Hideki Muramatsu ◽  
Nobuhiro Nishio ◽  
Asahito Hama ◽  
Hiroshi Yagasaki ◽  
Yoshiyuki Takahashi ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group A ◽  
Group B ◽  
First Complete Remission

Abstract Hematopoietic stem cell transplantation (HSCT) has been used as an effective consolidation therapy for children with acute myeloid leukemia (AML) in first complete remission (CR). Although it is effective in relapse prevention, often it causes severe late sequelae, such as short stature and infertility. There is a recent trend to restrict the use of HSCT in first CR for high-risk patients. However, there is no study comparing which strategy is better, risk-adapted or general recommendation for HSCT in AML children in first CR. In our institutes, all such children in first CR were recommended either allogeneic or autologous HSCT until 1997. After 1998, patients were classified into three risk-groups. Low-risk patients (t(8;21) and inv(16)) were not recommended to undergo HSCT. High-risk patients (−7, 5q-, Ph1, t(16;21) and remission failure) were recommended to undergo HSCT. Intermediate-risk (other karyotypes) patients received HSCT in first CR if a suitable donor was available. In this study, we retrospectively compared the prognosis of 66 patients who were diagnosed with de novo AML between 1991 and 1997 (group A; n=37) and between 1998 and 2003 (group B; n=29). AML with Down syndrome and AML-M3 were excluded. The median (range) age was five (0–15) years. FAB classifications were M0 (n = 1), M1 (n = 10), M2 (n = 22), M4 (n = 6), M4E (n = 5), M5 (n = 14), M6 (n = 0), and M7 (n = 8). Chromosome analysis data were t(8;21) (n = 18), inv(16) (n = 4), 11q23 (n = 10), other abnormalities (n = 14), normal karyotype (n = 14), and unknown (n = 6). Induction chemotherapy comprised VP-16, cytarabine, and mitoxantrone. Sixty-three of 66 patients (95.5%) achieved CR. HSCT in first CR was done in 24 patients (64.9%) in group A and seven patients (24.1%) in group B (p = 0.0044). Age, sex, WBC count at diagnosis, FAB classification and chromosomal abnormalities did not differ between the two groups. Fourteen (five in group A and nine in group B) patients relapsed. Six (three in group A and three in group B) of them were salvaged by HSCT. Both 5-year event-free survival (EFS) and overall survival (OS) were statistically higher in group A than in group B (5-year EFS: 83.8 ± 6.1% versus 62.1 ± 9.0%, p = 0.0404; 5-year OS: 91.6 ± 4.7% versus 71.6 ± 8.5%, p = 0.0364). Although intensified chemotherapy without HSCT for low-risk AML patients is desirable to avoid the late complications of HSCT, our analysis showed that the introduction of risk-stratified treatment strategy significantly worsened the chances of EFS and OS. Our risk stratification based on chromosomal abnormalities only may be insufficient to identify low-risk AML children. Development of more sophisticated risk classification, including molecular markers, may be required to identify true low-risk patients who should avoid HSCT in first CR.

Second Report of Clinical Significance of sFas for DLBCL Treated with CHOP and New Analysis of sFas for DLBCL Treated with R-CHOP.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1570-1570
Author(s):  
Hisashi Tsurumi ◽  
Takeshi Hara ◽  
Jun-ichi Kitagawa ◽  
Naoe Goto ◽  
Nobuhiro Kanemura ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Factor ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Significant Prognostic Factor ◽  
Chop Regimen ◽  
Number Of Patients ◽  
Group A ◽  
Sfas Level ◽  
Group B

Abstract Introduction: We have previously reported serum concentration of sFas predict a clinical outcome of patients with DLBCL. Here, we added the number of patients and confirmed that a high serum sFas level was associated with unfavorable prognosis of patients with DLBCL. Patients and methods: We used a prospective, consecutive entry design, and the study protocol was approved by the Institution’s Review Board. Between October 1995 and September 2002 previously untreated 132 patients with DLBCL (Group A: patients treated without rituximab) and between December 2002 and March 2007 previously untreated 75 patients with DLBCL (Group B: patients treated with rituximab) confirmed by biopsy participated in this study. We considered eligible for this study all patients with histologically confirmed diagnosis of DLBCL, according to the Working-Formulation and the WHO classification. Serum sFas was determined using ELISA. Patients were assigned to receive eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin) -COP therapy before September 2002. The patients who had been registered after October, 2002 received the R-CHOP or R-THP-COP therapy. A serum sFas level of 3.0ng /ml was used as the cut-off value in this study. All follow-up data were updated on March 1, 2007. Results: In Group A: 132 patients were enrolled in this category (82 males, 50 females, age; 14 to 92 years, median; 66 years). IPI scoring was available in all patients; accordingly 18.2% patients were classified as low risk, 25.8% as low-intermediate; 32.6% as high-intermediate, and 23.5% as high risk. Overall, the CR rate was 73.5%; PRs were observed in 7.6% and failures in 18.9%. The CR rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 51.1% and 81.6%, respectively (P<0.0005). The 5-year OS rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 19.8% and 61.9%, respectively (P<0.0001). In Group B: 75 patients were enrolled in this category (42 males, 33 females, age; 24 to 88 years, median; 69 years). IPI scoring was as follows; 22.6% patients were classified as low risk, 26.6% as low-intermediate; 21.3% as high-intermediate, and 29.3% as high risk. Overall, the CR rate was 72.0%; PRs were observed in 22.7% and failures in 5.3%. The CR rates for patients with a sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 65.6% and 76.7%, respectively (NS). The 2-year OS rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 54.7% and 92.2, respectively (P<0.01). Multivariate analysis using the proportional hazards model revealed that sFas concentration significantly correlated with overall survival in both group A and B (p<0.05). Discussion: The IPI is now considered as the most reliable index. After introduction of rituximab to treat for B cell lymphoma, the change of the prognostic factor is expected. In this examination, initially, we could confirm that sFas was an important prognostic factor for DLBCL in the patients who are treated with CHOP regimen as a result of extending the period of surveillance. In addition, we could show that sFas is a useful prognostic factor for DLBCL in the patients who are treated with R-CHOP regimen, too. Conclusion: Serum sFas is a significant prognostic factor for DLBCL and a useful tool for selecting the appropriate therapeutic strategy in patients with DLBCL.

Outcome Of Patients (pts) With Low and Intermediate-1 Risk Myelodysplastic Syndrome (MDS) After Hypomethylating Agent (HMA) Failure

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 388-388 ◽  
Author(s):  
Elias Jabbour ◽  
Guillermo Garcia-Manero ◽  
Lianchun Xiao ◽  
Al Ali Najla ◽  
Asmita Mishra ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Lower Risk ◽  
Research Funding ◽  
Complete Response ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Cancer Center ◽  
Primary Resistance ◽  
High Risk Disease

Abstract Background HMA are standard of care in pts with high-risk MDS and commonly used in pts with lower risk. Pts with high-risk disease post HMA failure have a poor prognosis with a median survival of 4-6 months. The prognosis of pts with low and intermediate-1 risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure is not known. Aims To assess outcome of pts with low and intermediate-1 risk disease post HMA failure that might benefit from specific strategies or investigational agents. Methods Data from 423 pts with low (n= 141, 33%) and intermediate-1 risk disease (n=282, 67%) by IPSS score treated with HMA at MD Anderson Cancer Center (MDACC; n=144) and Moffitt Cancer Center (MCC; n=279) between 2000 and 2011 were analyzed. Results Median age was 69 years. 294 (69%) pts had a diploid cytogenetic analysis. 63 (15%) pts had therapy-related MDS. 282 (67%) pts received azacitidine, 87 (21%) decitabine, and 54 (12%) both. Median number of cycles of HMA administered was 6 (range, 1-64) for a median duration of therapy of 7 months (range, 1- 74). Best response to HMA was complete response (CR) in 39 (9%) pts, partial response (PR) in 13 (3%), a bone marrow CR in 6 (1%), and hematologic improvement (HI) in 90 (21%) pts. Pts had discontinued HMA because of primary resistance in 198 (47%) pts, loss of response in 141 pts (33%), intolerance in 13 pts (3%) and other reasons in 71 pts (17%). At the time of HMA failure, 81 (19%) pts transformed into acute myeloid leukemia (AML). Of the 302 remaining pts evaluable by IPSS, 67 (22%) pts were of low-risk, 158 (53%) of intermediate-1 risk, 48 (16%) of intermediate-2 risk, and 29 (9%) of high-risk disease. By the revised IPSS (R-IPSS), the percentage of pts with low, very low, intermediate, high, and very high risk disease were 11%, 29%, 30%, 20%, and 10%, respectively. By the MDACC global prognostic scoring system (MDGPSS) 18%, 35%, 29%, and 18%, of the pts were of low-risk, intermediate-1, intermediate-2, and high-risk disease, respectively. After a median follow-up of 16 months from HMA failure, 117 (28%) pts remained alive. The median overall survival (OS) was 15 months (95% CI: 12-18) with estimated 1- and 3-year OS rates of 55% and 27%, respectively. Both, the R-IPSS and the MDGPSS were predictive of survival post HMA failure (Table 1 ). Conclusion In the largest cohort of lower risk MDS pts treated with HMA, the outcome after HMA failure is poor. Treatment of those patients remains an unmet medical need. OS is a reasonable primary endpoint for clinical studies targeting this population. Disclosures: Lancet: Celgene: Research Funding. Sekeres:Celgene: Consultancy; Amgen: Consultancy. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.

Clinical “MUTATOME” Of Myelodysplastic Syndrome; Comparison To Primary Acute Myelogenous Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 518-518 ◽  
Author(s):  
Hideki Makishima ◽  
Thomas LaFramboise ◽  
Bartlomiej P Przychodzen ◽  
Kenichi Yoshida ◽  
Matthew Ruffalo ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Research Funding ◽  
Somatic Mutations ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Clonal Architecture ◽  
Ras Family ◽  
Definition Of ◽  
The Impact

Abstract Chromosomal aberrations and somatic mutations constitute key elements of the pathogenesis of myelodysplastic syndromes (MDS), a clonal hematologic malignancy characterized by cytopenias, a dysplastic bone marrow and propensity to clonal evolution. Next generation sequencing (NGS) enables definition of somatic mutational patterns and clonal architecture as a discovery platform, and for clinical applications. We systematically applied NGS to 707 cases of MDS and MDS-related disorders. 205 cases (low-risk MDS: N=78, high-risk MDS: N=42, MDS/MPN: N=48 and sAML: N=37) were tested by whole exome sequencing (WES). For validation in an additional 502 patients (low-risk MDS: N=192, high-risk MDS: N=104, MDS/MPN: N=111 and sAML: N=95), targeted deep NGS was applied for 60 index genes which were most commonly affected in the cohort analyzed by WES. For NGS data analysis a statistical pipeline was developed to focus on: i) identification of the most relevant somatic mutations, and ii) minimization of false positive results. We studied serial samples from 21 exemplary informative patients. We also compared somatic mutational patterns to those seen in primary AML TCGA cohort (N=201). Given the size of the cohort, there was, for example, a 87% chance of seeing mutations at a frequency of 1% and a 98% of seeing those with a frequency of 2%. While focusing on the most common events, we observed 1117 somatic mutations in 199 genes. The 88 genes mutated mutated in >1% of cases with MDS carried 388 mutations in MDS+sAML (2.5/case), 128 in MDS/MPN (2.7/case) and 398 in pAML (2.0/case). The average number of mutations per case increased during progression (2.2 in lower-risk, 2.8 in higher-risk MDS, 3.4 in sAML). In MDS, the 30 most frequently affected genes were present at least once in 70% of patients. The 30 most frequently mutated genes in MDS/MPN were mutated in 82% of patients. Individual mutations were also sub-grouped according to their function. When we compared three MDS subcategories (lower-risk, higher-risk MDS and sAML) in a cross-sectional view, RTK family, RAS family, IDH family and cohesin family mutations were more frequently detected in the sAML group than in the MDS group. In contrast, the frequency of the DNMT family, TET2 and ASXL family gene mutations did not increase in frequency in the sAML cohort. In addition to better definition of mutational patterns of known genes, we have also defined new mutations, including in the RNA helicase family and the BRCC3pathway. Clonal architecture analysis indicates that mutations of TET2, DNMT3A, ASXL1, and U2AF1 most likely represent ancestral/originator events, while those of the IDH family, RTK family and cohesin family are typical secondary events. Establishment of mutational patterns may improve the precision of morphologically-based diagnosis. The comparison between MDS-related diseases (MDS+sAML) and pAML revealed a notably different mutational pattern suggestive of a distinct molecular derivation of these two disease groups. While RTK, IDH family and NPM1 mutations were more frequently observed in the pAML cohort, mutations of SF3B1 and SRSF2, were more common in MDS+sAML. With regard to the connections between individual mutation combinations, RTK mutations were strongly associated with DNMT, but not with RAS family mutations in the pAML cohort, while the mutual association between TET2 and PRC2 family, cohesin family and RUNX1were encountered in the MDS+sAML cohort. Individual mutations may have prognostic significance, including having an impact on survival, either within the entire cohort or within specific subgroups. In the combined MDS cohort, TP53 family mutations were associated with a poor prognosis (HR; 3.65, 95%CI; 1.90-7.01, P<.0001) by univariate analysis. Similar results were found for mutations in TCF4(HR; 7.98, 95%CI; 1.58-10.1, P<.0007). Such an individual approach does not allow for assessment of the impact of less common mutational events. In conclusion, our study continues to indicate the power of NGS in the molecular analysis of MDS. MDS and related disorders show a great deal of pathogenetic molecular overlap, consistent with their morphologic and clinical pictures, but also distinct molecular differences in mutational patterns. Some of the specific mutations are pathognomonic for specific subtypes while some may convey a prognostic rather than discriminatory value. Disclosures: Makishima: Scott Hamilton CARES grant: Research Funding; AA & MDS international foundation: Research Funding. Polprasert:MDS foundation: Research Funding.

Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 534-534
Author(s):  
Natasha Catherine Edwin ◽  
Jesse Keller ◽  
Suhong Luo ◽  
Kenneth R Carson ◽  
Brian F. Gage ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Discriminative Ability ◽  
Blood Institute ◽  
C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

Validation of a genomic classifier (ColoPrint) for predicting outcome in the T3-MSS subgroup of stage II colon cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3510-3510 ◽  
Author(s):  
Ramon Salazar ◽  
Josep Tabernero ◽  
Victor Moreno ◽  
Ulrich Nitsche ◽  
Thomas Bachleitner-Hofmann ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Lower Risk ◽  
Low Risk ◽  
Stage Ii ◽  
Disease Relapse ◽  
Risk Of Disease

3510 Background: Adjuvant therapy for stage II patients is recommended for patients with high risk features, especially with T4 tumors. Adjuvant therapy is not indicated for patients with MSI-H status who are considered of being at low risk of disease relapse. However, this leaves the majority of patients with an undetermined risk. ColoPrint is an 18-gene expression classifier that identifies early-stage colon cancer patients at higher risk of disease relapse. Methods: ColoPrint was developed using whole genome expression data and was validated in public datasets (n=322) and independent patient cohorts from 5 European hospitals. Tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 70 months) for patients were available and the ColoPrint index was determined using validated diagnostic arrays. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) and the subset of patients who were T3/ MSS (n=227). Results: In the analysis of all stage II patients, ColoPrint classified two-third of stage II patients as being at lower risk. The 3-year Relapse-Free-Survial (RFS) RFS was 91% for Low Risk and 74% for patients at higher risk with a HR of 2.9 (p=0.001). Clinicopathological parameters from the ASCO recommendations (T4, perforation, <12 LN assessed, and/ or high grade) or NCCN guidelines (ASCO factors plus angio-lymphatic invasion) did not predict a differential outcome for high risk patients (p< 0.20). In the subgroup of patients with T3 and MSS phenotype, ColoPrint classified 61% of patients at lower risk with a 3-year RFS of 91% (86-96%) and 39% of patients at higher risk with a 3-year RFS of 73% (63-83%) (p=0.002). No clinical parameter was significantly prognostic in this subgroup. Conclusions: ColoPrint combined with established clinicopathological factors and MSI, significantly improves prognostic accuracy, thereby facilitating the identification of patients at higher risk who might be considered for additional treatment.

Real-World Treatments and Thrombotic Events in Polycythemia Vera Patients: A Retrospective Analysis between 2018-2019 in US Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Srdan Verstovsek ◽  
Ariel Han ◽  
Karin Chun Hayes ◽  
Tracy Woody ◽  
Frank Valone ◽  
...  
Keyword(s):  
High Risk ◽  
Real World ◽  
Blood Cells ◽  
Initial Treatment ◽  
Research Funding ◽  
Treatment Initiation ◽  
Low Risk ◽  
High Risk Patients ◽  
Risk Patients

BACKGROUND Polycythemia Vera (PV) is a rare myeloproliferative neoplasm associated with an increased production of red blood cells, white blood cells, and platelets. Most frequent treatment includes phlebotomy, hydroxyurea, interferon, and ruxolitinib. Current NCCN guideline recommends managing HCT levels to below 45%. The objective of this study was to determine real-world standards of care and patient characteristics, and to observe how treatment decisions vary by HCT level and thrombosis risk. METHODOLOGY We conducted a retrospective study using Symphony Health's longitudinal transactional healthcare claims database that includes prescription, medical and hospital claims across &gt; 4,900 US payers representing 86% of US lives. Eligible patients had at least one ICD-10 diagnosis code for PV and at least one of the treatments including phlebotomy, hydroxyurea, busulfan, interferon, and ruxolitinib between Jan 1, 2018 and Dec 31, 2019 (index period). For eligible patients, all prior treatment history initiated as far back as January 2010 was used to report therapy changes. Patients were also required to have at least one PV diagnosis within a year of treatment initiation and at least 2 HCT lab results during the index period. PV treatment changes and characteristics were studied. RESULTS Out of 28,306 patients with PV, 4,264 patients had HCT lab data for 2 years (index period). Median duration of follow-up was 854 days (range 98-3,373days). Patient therapy duration was from 1 to 9 years. Median patient age was 65 (range 11-94), with 1,451 (34%) patients aged less than 60, 2,813 (66%) 60 years or older, and a substantial male predominance (62% vs 38%). 1,247 (29%) patients were classified as Low Risk (age&lt; 60 with no TE history) and 3,017 (71%) patients as High Risk. Within the High-Risk group, 2,224 (52%) were age&gt;60 without prior TE, 204 (5%) were age&lt;60 with prior TE and 589 (14%) were age&gt;60 with prior TE. For Low Risk patients' initial treatment was phlebotomy alone (85%) and a total of 73% of all Low Risk patients remained on phlebotomy alone. For High Risk patients' initial treatment was phlebotomy alone (60%) and 43% all of High-Risk patients remained on phlebotomy alone (Figure 1). The median HCT prior to treatment initiation was 52.9% and 48% during treatment. 936 (22%) patients achieved NCCN treatment guidelines with HCT levels always remaining under 45%, and 1,226 (29%) patients had HCT levels controlled between 45% and 50%. However, 2,102 (49%) patients had some or all HCT levels&gt; 50% (Figure 2). With the most recent lab test, 2,180 (51%) of patients still had HCTs above 45% and 804 (19%) were still above 50%. In a sub-cohort of 653 High Risk patients with a prior TE and up to 5 years of follow up, 236 (36%) had at least one other TE; for the 1,774 High Risk patients who did not have the history of thrombosis, 161(9%) had at least one TE (Table 2). The most common TE since treatment began in patients with prior TE were deep vein thrombosis (n= 92 patients, 14%) and stroke (n= 95 patients, 15%). Among High Risk patients (n=397) who had another thrombotic event, 180 (45%) were treated by phlebotomy only and never switched to any other therapies. CONCLUSIONS Despite currently available treatments in US, patients' HCT level after treatment were higher than recommended as per guidelines. Failure to maintain HCT less than 45% increases the risk of future thrombotic events as shown by 36% of patients with prior TE experiencing another TE within the next 5 years. Disclosures Verstovsek: Sierra Oncology: Consultancy, Research Funding; ItalPharma: Research Funding; Blueprint Medicines Corp: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Incyte Corporation: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; PharmaEssentia: Research Funding; Genentech: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; CTI Biopharma Corp: Research Funding. Han:Protagonist Therapeutics: Consultancy. Chun Hayes:Protagonist: Consultancy. Woody:Protagonist: Current Employment. Valone:Protagonist: Current Employment. Gupta:Protagonist: Current Employment.

Prospective Feasibility Analysis of Reduced Intensity Conditioning Regimens (RIC) for Hematopoietic Stem Cell Transplantation (HSCT) in Elderly Patients with AML and MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2892-2892 ◽  
Author(s):  
Raoul Tibes ◽  
Marcos de Lima ◽  
Elihu Estey ◽  
Sherry Pierce ◽  
Richard Champlin ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Donor Group ◽  
Potential Donor ◽  
No Donor ◽  
Significant Group ◽  
Hematopoietic Stem ◽  
Younger Age ◽  
Group A ◽  
Group B ◽  
Selection Factors

Abstract Introduction and Methods: RIC HSCT has become a therapeutic option for elderly patients (pts) with AML and MDS in 1st CR (CR1). However the overall applicability of this procedure in such pts has not been assessed. To do so we wrote a protocol stipulating that all pts age &gt; 50 with AML would be seen by a transplant service consult at first MDACC presentation. A donor search would be initiated and all pts with a matched sibling, or unrelated donor would receive RIC HSCT in 1st CR using a Fludarabine/Melphalan conditioning regimen. Results: 99 of 257 pts undergoing induction therapy from 2001–2003 achieved a CR (39%). BMT consulted on 62 of the 99 (63%), and 25 of the 62 (40%) had a potential donor (20 sibling, 5 unrelated). 14 pts received a HSCT in CR1 (14% of CR1 pts, 5 % of all pts; 13 sibling, 1 unrelated). Survival (OS) and relapse-free survival (RFS) were each worse in non-consulted pts (group A) than in consulted pts (p =0.009 for S, medians of 28 and 66 weeks; p =0.019 for RFS, with medians of 20 vs. 36 weeks). This may have reflected the worse performance status of Group A pts (ECOG-PS 3,4 in 19% vs. 5%). Consulted pts without a donor (group B) did worse than consulted pts with donor (groups C+D [OS 49 vs. 124 wks (p=0.03); RFS 23 vs. 52 wks (p=0.016)]. Transplanted pts in CR1 (group C) did better than the remainder of consulted pts (groups B+D) and OS (p=0.023) and RFS (p&lt;0.001) were not reached at 86 wks median f/u. Median time to HSCT was 17 weeks and transplant-related mortality zero. Among pts with donors in CR1 transplanted pts did better [RFS: p=0.001; OS: p=0.156]. The primary reason for not receiving a HSCT in CR1 pts with potential donor (Group D) was disease relapse in 81%. Significant group differences included: younger age of consulted pts (p=0.01); younger age of consulted pts with donor (p=0.03); younger age of transplanted pts (p =.01), less frequent −5/−7 (p=0.02) but more frequent 11Q abnormalities (p =0.007) in the donor and transplant group. Group A B C D E Overall CR/no Consult CR/consult/no donor CR/consult/donor/HSCT CR/consult/donor/no HSCT No CR *median in wks; #miscellaneous/complex karyotype/insufficient metaphases, nr=not reached N= 37 37 14 11 158 RFS* 28 20 23 nr 24 na OS* 24 28 49 nr 100 13 Follow up* 66 59 66 86 73 60 Median Age 65 68 65 57 60 67 %AHD 49 46 54 43 36 65 AML/MDS 216/41 30/7 28/9 12/2 9/2 137/21 cyto:+8, −5,−7 162 20 26 3 5 108 cyto:# 79 16 10 6 5 42 cyto:11q 16 1 1 5 1 8 To adjust for selection and time to transplant biases, transplanted pts were matched with controls from the consult no-donor group (B) with each control having an RFS time at least as long as the interval from CR date to transplant date in their transplanted pairmate. The improved RFS in the transplant group persisted but was no longer statistically significant (p=0.197). Conclusion: RIC HSCT in selected elderly CR1 pts improved OS and RFS, likely due to the graft-versus-leukemia effect. However, transplant efficacy could also be due to younger age, better cytogenetics, less comorbidity, lead-time bias or unknown selection factors. The performance of RIC HSCT in only 14% of elderly pts in CR1 and only 5% of elderly pts raises questions about the general applicability of this procedure, since most pts die before receiving a HSCT or do not enter CR1.

Antibiotic Prophylaxis Before Dental Procedures Can Reduce ONJ Incidence.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3613-3613 ◽  
Author(s):  
Vittorio Montefusco ◽  
Francesca Gay ◽  
Francesco Spina ◽  
Maria Teresa Ambrosini ◽  
Massimo Maniezzo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zoledronic Acid ◽  
High Risk ◽  
Antibiotic Prophylaxis ◽  
Low Risk ◽  
Dental Procedure ◽  
Dental Procedures ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Osteonecrosis of the jaw (ONJ) is a frequent complication in bisphosphonate-treated multiple myeloma (MM) patients. The pathogenesis is unclear, and major risk factors are duration of bisphosphonate treatment and dental procedures. The histology of osteonecrotic bone shows osteomyelitis and inflammatory infiltrates, and, in most cases, presence of Actynomycetes. Since dental procedures are a major risk factor for ONJ development and oral microflora can be involved in the pathogenesis of the disease, we conducted a retrospective observational trial comparing ONJ occurrence and related risk factors in two groups of MM patients, who received zoledronic acid treatment at two Italian hematological centres. In one centre all patients systematically received as antibiotic prophylaxis amoxicillin-clavulanate 1 gm bid or levofloxacin 500 mg once a day starting from one day before to 3 days after any dental procedure (group A, 52 patients), while in the other centre patients did not receive any prophylaxis (group B, 61 patients). Dental procedures were categorized according to their invasivity and their supposed probability to cause ONJ. Extractions, implants, and professional cleanings were considered at high risk, while fillings were considered low risk procedures. Thirty-three group A patients (63%) and 32 group B patients (52%) received high risk procedures; 4 group A patients (8%) and 5 group B patients (8%) received low risk procedures, while 15 (29%) and 24 (39%) patients, respectively, had a denture. The duration of zoledronic acid exposure differed significantly between the two groups, with a median of 26 months for A patients and 12 months for B patients (p&lt;0.0001). In group A no cases of ONJ were observed, while in group B 8 cases (13%) of ONJ were diagnosed, with a significant difference between the two groups (p=0.007). There was a temporal correlation between dental procedure and ONJ, with a median time of 60 days (range 37–990). The relative risk of ONJ after a dental procedure was 4.8 (p=0.01). The pooled analysis of the two groups showed that age, sex, transplant procedure, and thalidomide therapy did not correlate with ONJ. In both groups the presence of dentures was not associated with ONJ. While in group B incidence of ONJ is consistent with data reported in the literature, which range between 7% and 11%, group A patients had an unexpected low occurrence of this complication, despite a significantly longer exposure to zoledronic acid. This finding suggests a possible role of antibiotic prophylaxis in protecting from ONJ after dental procedures. Further, our observation, along with the correlation between dental procedures and ONJ development, can contribute to the proposal of a comprehensive model of ONJ pathogenesis: trauma of the alveolar bone modified by bisphosphonates induces a bacterial translocation with a subsequent induction of infection, inflammation and necrosis. In this perspective, since antibiotic prophylaxis is a simple and low cost precaution, it’s reasonable to propose it as part of standard care to zoledronic acid treated MM patients before any dental procedure.

Minimal Residual Disease (MRD) in Childhood Acute Lymphoblastic Leukemia (ALL). Correlation with Prognostic Factors and Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4848-4848
Author(s):  
Anna Paisiou ◽  
Georgios Paterakis ◽  
Nikolaos Tsagarakis ◽  
Nektaria Kentrou ◽  
Vassilios Papadakis ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Time ◽  
Residual Disease ◽  
Childhood All ◽  
Time Points ◽  
Standardized Treatment ◽  
Group A ◽  
Group B ◽  
Time Point

Abstract Aim: The aim of this study was the prospective evaluation of MRD during childhood ALL therapy and its correlation with specific prognostic criteria of ALL-BFM 95 protocol and with patient outcome. Patients/Methods: 127 children (49 girls) with ALL were studied during the period 1999–2008. The median age at diagnosis was 9,32 years (range, 0,6–16,48). All patients were diagnosed in the same center and treated uniformly with the ALL-BFM 95 protocol, modified in two therapeutic branches, medium and high risk, as we have published previously. We used three or five colours’ flow cytometric panels for MRD quantification at sequential standardized treatment time-points: at day 15 of induction (T1), at day 33 (T2) of induction, before consolidation (T3), before re-induction (T4), before maintenance (T5), at maintenance completion (T6). Additionally for the high risk patients, 6 more determinations before each consolidation treatment cycle were performed. The median follow-up time was 48,4 months (range, 1,7–110,3). For statistical analysis, descriptive statistics and Kaplan-Meier were used. Results: Immunophenotypical analysis resulted in 119 patients with ALL of B-origin and 8 of T-origin. Median WBC at diagnosis was 10×109/lt, while extra-BM infiltration was found in 9 children. According to ALL-BFM 95 protocol’s criteria: 40 patients were fulfilling the criteria of the standard risk (SR), 61 of medium (MR) and 26 of high risk (HR), respectively, and therapeutically were divided into two groups: A (101 patients, SR+MR) and B (26 patients, HR). MRD was detected in: 59/123 patients at treatment time-point (T1) (39/59 from group A, of which 26/39 with high MRD levels, and 20/59 from group B, all with high MRD levels). In time-point (T2), disease was detected in 19/124: 5/19 from group A (3/5 high MRD levels), 14/19 from group B (11/14 high MRD levels). At treatment-point (T3), 3/127 had detectable disease (all from group B). None of the patients of group A had minimal residual disease at the following time-points, while only 2 patients of group B had persistent presence of MRD. In total, 14/127 children relapsed (4/SR, 2/MR, 8/HR), with significant levels of MRD in 7 (6/7 HR) and 4 (all HR) patients, at time-point (T1) and (T2), respectively. Among all, 114 children survived (CR1: 110, CR2: 4), while 13 children died (9/disease, 4/therapy-related toxicity). Conclusions: Our results suggest that MRD detection in continuous standardized treatment time-points of childhood ALL correlates with shorter disease free (DFS) and overall survival (OS), however in our cohort there was no sufficient evidence of MRD independency as prognostic factor (cox-regression analysis) compared to the classical prognostic criteria of the ALL-BFM 95. The enlargement of the group of patients and the expansion of the follow-up period will lead to more reliable conclusions.

Sign in / Sign up

Export Citation Format

Share Document