Outcome of Patients with Newly Diagnosed Diffuse Large B-Cell Non-Hodgkin Lymphomas (DLBCL) Receiving Initial Therapy in Hospital Compared with An Out-Patient Setting

Abstract Abstract 4944 Background: DLBCL is the most common form of aggressive non-Hodgkin lymphoma (NHL). Despite its aggressive nature, the majority of patients are diagnosed and managed in an out-patient setting and only minority of patients require hospital admission, for symptom control or management of associated co-morbid conditions. The outcomes of patients admitted to hospital with newly diagnosed DLBCL, though presumed to be inferior to patients managed in an outpatient setting, due to advanced disease or poorer performance status is presently unknown. The aims of this study were to identify predictors of treatment location (in-patient vs. out-patient), and assess the survival of patients according to treatment location (in-hospital or out-patient). Methods: Retrospective chart review over 5 years (January 2005 to December 2009) of newly diagnosed patients with DLBCL in Winnipeg, Canada. These patients were treated either in a teaching hospital, at Health Sciences Center, or in the out-patient setting, at CancerCare Manitoba. Clinical predictors of treatment setting were analyzed using multivariable logistic regression. Survival at one and three years was assessed with Kaplan-Meier statistics. Results: We included140 patients (46 in-patients and 96 outpatients). The mean age of the in-patient population was 68.3 (SD 14.2); while for the out-patient group it was 65.2 (SD 15.3). The in-patient group was comprised of 47.8% female, with the outpatient having 52.1%. Fifty percent of the in-patient group came from a rural residence, while only 28.1% of the out-patient group was from a rural residence. Of the in-patient group 21.7% had a favorable IPI (0-2), compared with 70.8% of the out-patient population. Of the 46 in-patients, 28 (60.9%) received R-CHOP, compared with 69 (71.9%) from the out-patient group. Four (8.7%) in-patients received an alternate form of chemotherapy (e.g. R-CVP), compared with 18 (18.8%) outpatients. Fourteen (30.4%) in-patients received no chemotherapy, compared with 9 (9.4%) in the out-patient group. Patients with an IPI of 3 or higher at diagnosis were significantly more likely to require hospital admission for initial treatment [Odds ratio (OR) = 8.43; (95% CI 2.55–19.30), p-value <0.01]. Patients living in rural setting were more likely to be hospitalized compared to those who resided in Winnipeg [OR = 2.34; (95% CI 0.86–6.46), p-value = 0.04]. Overall survival at one and three year was 50.0% and 38.8% for the in-patient group, compared with 85.3% and 69.3 for the out-patient group (p<0.01). In a subgroup of patients who received R-CHOP, survival for in-patients compared with out-patients was 71.4%% vs. 89.7%% at one year, and 57.7% vs. 76.8% (p=0.03) at three years respectively. Survival of in-patients with a low IPI (0-2) that completed R-CHOP (six cycles) therapy was 100% at one year, compared with 97.7% in the out-patient group (p=0.10). Survival of in-patients with high IPI (≥3) that completed R-CHOP was 68.2% at one year, compared to 66.7% in the out-patient group (p=0.51). Conclusions: The overall survival of patients with DLBCL that require hospital admission to receive their first cycle of chemotherapy is inferior to patients who can be treated in the out-patient setting. Observed differences in survival may relate to the decreased administration of chemotherapy among in-patients, which may further relate to patient co-morbidity and functional status. Among patients who receive a full course of chemotherapy, the location of treatment initiation does not appear to impact survival. Factors found to be associated with in-patient treatment initiation include high IPI and rural status. Initial in-patient treatment is not a necessarily associated with poor prognosis if a complete course of chemotherapy can be delivered and to better inform prognosis, further studies are needed to predict which patients will ultimately not be able to tolerate a full course of chemotherapy and thus be at high risk for death. Disclosures: Rubinger: Roche Canada: Consultancy.

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ATIM-35. THE ASSOCIATIONS BETWEEN TOTAL LYMPHOCYTE COUNTS AFTER CONCOMITANT CHEMORADIATION WITH OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.034 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi9-vi9

Author(s):

Stephen Ahn ◽

Jae-Sung Park ◽

Yong Kil Hong ◽

Seung Ho Yang ◽

Sin-Soo Jeun

Keyword(s):

Overall Survival ◽

Complete Blood Count ◽

Malignant Tumors ◽

P Value ◽

Newly Diagnosed ◽

Total Lymphocyte ◽

Concomitant Chemoradiation ◽

Newly Diagnosed Glioblastoma ◽

The Relationship

Abstract Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary’s Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1,742 versus 1,319 cells/mm3, P-value < 0.001). Patients with TLC < 1,200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1,200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC < 1,200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 – 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.

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Combining Proteomics and Gene Expression Profiling Identifies Proteins/Genes Associated with Short Overall Survival in Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.197.197 ◽

2012 ◽

Vol 120 (21) ◽

pp. 197-197

Author(s):

Ricky D Edmondson ◽

Shweta S. Chavan ◽

Christoph Heuck ◽

Bart Barlogie

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Multivariate Analyses ◽

Rank Test ◽

P Value ◽

Newly Diagnosed ◽

Training Set ◽

Test Set ◽

Log Rank Test ◽

Test Sets

Abstract Abstract 197 We and others have used gene expression profiling to classify multiple myeloma into high and low risk groups; here, we report the first combined GEP and proteomics study of a large number of baseline samples (n=85) of highly enriched tumor cells from patients with newly diagnosed myeloma. Peptide expression levels from MS data on CD138-selected plasma cells from a discovery set of 85 patients with newly diagnosed myeloma were used to identify proteins that were linked to short survival (OS < 3 years vs OS ≥ 3 years). The proteomics dataset consisted of intensity values for 11,006 peptides (representing 2,155 proteins), where intensity is the quantitative measure of peptide abundance; Peptide intensities were normalized by Z score transformation and significance analysis of microarray (SAM) was applied resulting in the identification 24 peptides as differentially expressed between the two groups (OS < 3 years vs OS ≥ 3 years), with fold change ≥1.5 and FDR <5%. The 24 peptides mapped to 19 unique proteins, and all were present at higher levels in the group with shorter overall survival than in the group with longer overall survival. An independent SAM analysis with parameters identical to the proteomics analysis (fold change ≥1.5; FDR <5%) was performed with the Affymetrix U133Plus2 microarray chip based expression data. This analysis identified 151 probe sets that were differentially expressed between the two groups; 144 probe sets were present at higher levels and seven at lower levels in the group with shorter overall survival. Comparing the SAM analyses of proteomics and GEP data, we identified nine probe sets, corresponding to seven genes, with increased levels of both protein and mRNA in the short lived group. In order to validate these findings from the discovery experiment we used GEP data from a randomized subset of the TT3 patient population as a training set for determining the optimal cut-points for each of the nine probe sets. Thus, TT3 population was randomized into two sub-populations for the training set (two-thirds of the population; n=294) and test set (one-third of the population; n=147); the Total Therapy 2 (TT2) patient population was used as an additional test set (n=441). A running log rank test was performed on the training set for each of the nine probe sets to determine its optimal gene expression cut-point. The cut-points derived from the training set were then applied to TT3 and TT2 test sets to investigate survival differences for the groups separated by the optimal cutpoint for each probe. The overall survival of the groups was visualized using the method of Kaplan and Meier, and a P-value was calculated (based on log-rank test) to determine whether there was a statistically significant difference in survival between the two groups (P ≤0.05). We performed univariate regression analysis using Cox proportional hazard model with the nine probe sets as variables on the TT3 test set. To identify which of the genes corresponding to these nine probes had an independent prognostic value, we performed a multivariate stepwise Cox regression analysis. wherein CACYBP, FABP5, and IQGAP2 retained significance after competing with the remaining probe sets in the analysis. CACYBP had the highest hazard ratio (HR 2.70, P-value 0.01). We then performed the univariate and multivariate analyses on the TT2 test set where CACYBP, CORO1A, ENO1, and STMN1 were selected by the multivariate analysis, and CACYBP had the highest hazard ratio (HR 1.93, P-value 0.004). CACYBP was the only gene selected by multivariate analyses of both test sets. Disclosures: No relevant conflicts of interest to declare.

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Prognosis of gastric cancer (GC) patients with positive peritoneal cytology.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.41 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 41-41

Author(s):

Hironori Shiozaki ◽

Elena Elimova ◽

Rebecca Slack ◽

Hsiang-Chun Chen ◽

Gregg A Staerkel ◽

...

Keyword(s):

Overall Survival ◽

Diagnostic Laparoscopy ◽

Cox Model ◽

Peritoneal Metastases ◽

Patient Treatment ◽

Cancer Center ◽

Peritoneal Cytology ◽

Term Survival ◽

Risk Of Death ◽

One Year

41 Background: Laparoscopic staging of patients with GC can disclose peritoneal metastases. Although this finding is associated with a poor prognosis, some patients achieve a long-term survival. In an attempt to provide explanation we compared the overall survival (OS) of patients with GC peritoneal metastases from two settings: cytology positive only (Cy+) and grossly positive (Gross+). Methods: 146 GC patients with peritoneal metastases were identified between 2000 and 2014. Cox-model regression was used for overall survival (OS) analyses. Results: Patient/treatment characteristics were as follows: males (66%), good ECOG scores (0-1; 89%), metastases confirmed by a diagnostic laparoscopy (84%), poorly differentiated histology(92%), received chemotherapy (89%), received chemoradiation (22%), and received surgery (10%). The median follow-up time for all patients was 12.9 months and median OS was 15 months. Patients with Gross+ were at higher risk of death compared to Cy+ patients (50% vs. 83%1-year OS, respectively). Only diagnostic laparoscopy and metastasis type (Gross+ vs. Cy+) were significant in both univariate and multivariate OS models. With both factors in the same model, patients with Gross+ were more than twice as likely to die when compared to those with Cy+ (HR=2.23; p=0.001) while patients having a diagnostic laparoscopy were half as likely to die (HR=0.52; p=0.01). Conclusions: The one-year OS of patients with Cy+ peritoneal metastases is significantly longer than those with Gross+ findings. As such, novel strategies for Cy+ patients may further prolong their survival. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI).

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Presence of Extrachromosomal DNA (ecDNA) Impacts Both Progression Free and Overall Survival and Is an Independent Poor Prognostic Marker in Multiple Myeloma

Blood ◽

10.1182/blood-2021-151647 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 461-461

Author(s):

Parth Shah ◽

Anil Aktas-Samur ◽

Mariateresa Fulciniti ◽

Raphael Szalat ◽

Masood A. Shammas ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Board Of Directors ◽

Copy Number ◽

Research Funding ◽

P Value ◽

Newly Diagnosed ◽

Extrachromosomal Dna ◽

Publicly Traded ◽

Advisory Committees

Abstract Background Focal amplifications and rearrangements drive tumor growth and evolution in cancer. Focally amplified regions often involve the juxtaposition of rearranged segments of DNA from distinct chromosomal loci into a single amplified region and nearly half of these regions can be explained by circular, extrachromosomal DNA (ecDNA) formation. Cancer-associated ecDNA shows a unique circular placing ecDNA at the interface of cancer genomics and epigenetics. As formation of ecDNA represents a manifestation of genomic instability, we have investigated presence and prognostic impact of ecDNA in multiple myeloma (MM). Methods Whole genome (WGS) and transcriptome (RNAseq) sequencing data from CD138 purified MM cells from 191 uniformly-treated newly diagnosed MM patients were used for this analysis. Copy number variants (CNV), single nucleotide variants (SNV) and structural variants (SV) were identified on all WGS samples using Facets, Mutect2 and Manta. Seed data from these CNV results was passed to the AmpliconArchitect tool to determine presence of focally amplified and rearranged segments of DNA. Seed CNV thresholds were set for a minimum CNV size of 100kb and a copy number of equal or greater to 5. Extrachromosomal calls were then annotated using the Amplicon Classifier to determine the presence of ecDNA. Multivariate survival analysis was performed after segregating samples into the conventional myeloma risk classifications including translocations, copy number alterations, ISS, age and mutations associated with risk. Differential expression analysis was performed on transcriptomic data using DEseq2. Results We identified 6.8% of the newly diagnosed patients with ecDNA, 12.5% with complex non-cyclic DNA amplifications and 10.1% with linear amplifications. ecDNA and complex events were targeting MM dependent genes, including MYC/PVT1, IRF4 as well as known driver genes such as CDYL and TRAF2. We further evaluated association between ecDNA, complex rearrangements, linear amplification and patients with none of these amplification types and found that patients with ecDNA had significantly poor PFS (median PFS 22 months vs. 41 months) and OS (median OS 41 months vs. 105 months). Patients having ecDNA in their MM cells did not show any significant enrichment for known translocations, double hit or TP53 mutations. In a multivariate model including ecDNA and all other known MM risk features, ecDNA was found to be an independent predictor of progression free survival.(HR 2.6, CI: 1.26 -5.6, p=0.0082) and overall survival (HR 7.94 CI:3.5-17.9 p < 0.0001). Patients with ecDNA have higher mutational load probability(8798 vs 6982, effect size = 0.64 , probability is 91.1). However, this was not reflected in heterogeneity by using MATH score. We found that patients with ecDNA are likely to have BRAF mutations (OR= 25.07 [2.57 - 330 95% CI], p value = 0.002), however overall RAS/RAF pathway mutations were similar to other patients. Patients with ecDNA showed fragile DNA with more breaks (median segments 197 vs. 125.5, p value = 0.001). Although ecDNA is defined as copy number gain with fragments having 5 or more copies, overall genomic gain between ecDNA and other patients were similar. However, overall genomic loss in patients with ecDNA were higher than others (7% vs. 4.2%, p = 0.06). By differential gene expression analysis we noted 98 differentially expressed genes in MM cells with ecDNA. The downregulated geneset involved pathways responsible for cell death as well as the RAS pathway. Interestingly, CD38 was upregulated in the ecDNA dataset suggesting greater potential for CD38 targeting therapies in these patients. Conclusions ecDNA, as an unique marker of perturbed genomic integrity, is observed in a subset of patients and is an independent prognostic marker in newly diagnosed MM patients. As patients with ecDNA are not fully captured by other risk features its incorporation in an expanded definition of a high risk group of multiple myeloma should be investigated. Future studies will endeavor to explore the biological mechanism through which ecDNA are formed and influences outcomes in myeloma. Figure 1 Figure 1. Disclosures Richardson: Sanofi: Consultancy; GlaxoSmithKline: Consultancy; Karyopharm: Consultancy, Research Funding; AstraZeneca: Consultancy; AbbVie: Consultancy; Oncopeptides: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy; Protocol Intelligence: Consultancy; Celgene/BMS: Consultancy, Research Funding; Secura Bio: Consultancy; Regeneron: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Perrot: Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria. Thakurta: Oxford University: Other: Visiting Professor; BMS: Current Employment, Current equity holder in publicly-traded company. Anderson: Gilead: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Munshi: Legend: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Adaptive Biotechnology: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Celgene: Consultancy; Pfizer: Consultancy.

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The Chronic Kidney Disease-Epidemiology Collaboration-Cystatin C (CKD-EPI-CysC) Equation Has an Independent Prognostic Value for Overall Survival in Newly-Diagnosed Patients with Symptomatic Multiple Myeloma: Comparison with 3 Other Equations for GFR Estimation

Blood ◽

10.1182/blood.v120.21.1849.1849 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1849-1849

Author(s):

Meletios A Dimopoulos ◽

Efstathios Kastritis ◽

Eirini Katodritou ◽

Anastasia Pouli ◽

Eurydiki Michalis ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Cystatin C ◽

Prognostic Value ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

P Value ◽

Newly Diagnosed ◽

Number Of Patients ◽

Ckd Stage

Abstract Abstract 1849 Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The estimation of glomerular filtration rate (GFR) is based on equations that use serum creatinine (sCr) as a marker of RI (i.e. MDRD or CKD-EPI). The IMWG has recommended the use of the MDRD formula for the estimation of GFR in MM patients with stabilized sCr, while the classification of RI is based on the 5 stages of the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). However, the equations based on sCr are imprecise and thus novel markers of renal injury have been used in patients with renal damage, including cystatin-C (CysC). CysC is considered as a more sensitive marker of GFR than sCr. Recently, the CKD-EPI investigators have reported that a combined sCr-CysC (CKD-EPI-sCr-CysC) equation correlated better with GFR than equations based on either of these markers alone (CKD-EPI or CKD-EPI-CysC; Inker et al, NEJM 2012;367:20–9). Although cysC has been reported by our group to be elevated in MM patients, the CKD-EPI equations and their value on MM patients' survival have never been evaluated. Therefore, we studied 220 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years) and 16% had sCr ≥2 mg/dl. Serum CysC was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). Serum CysC was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, CKD-EPI, CKD-EPI-CysC and CKD-EPI-sCr-CysC equations were 63.45 ml/min/1.73m2, 68.13 ml/min/1.73m2, 68.11 ml/min/1.73 m2, and 64.87 ml/min/1.73 m2, respectively (p<0.01). Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 39.5% for MDRD vs. 42.2% for CKD-EPI vs. 43.1% for CKD-EPI-CysC vs. 45% for CKD-EPI-sCr-CysC (p<0.01; see also the table). Concordance for CKD stage allocation for the 4 equations of estimating eGFR was 97% for MDRD vs. CKD-EPI, 60% for MDRD vs. CKD-EPI-CysC and 84% for MDRD vs. CKD-EPI-sCr-CysC. A significant correlation was found between ISS stage and all studied equations (p<0.01 for all). The median overall survival (OS) for all patients was 52 months. In the univariate analysis per CKD stage, the 4 equations could predict for OS (the higher CKD stage had poorer survival) with the following significance: MDRD (p=0.057), CKD-EPI (p=0.01), CKD-EPI-CysC (p<0.0001), and CKD-EPI-sCr-CysC (p=0.006). When we tested the 4 equations as continuous variables, all had prognostic value for OS but the CKD-EPI-CysC had the strongest prognostic value (p<0.0001 and Wald=24.0 vs. p<0.0001 and Wald=19.7 for CKD-EPI-sCr-CysC, p=0.003 and Wald=8.9 for CKD-EPI and p=0.005 and Wald=7.7 for MDRD). In the multivariate analysis, that included ISS stage, LDH ≥300 U/l and eGFR for each different equation (as a continuous variable) only eGFR that included CysC but not sCr (CKD-EPI-CysC and not CKD-EPI-sCr-CysC) had independent significance (p=0.013) along with high LDH (p=0.029). Our data suggest that the CKD-EPI-sCr-CysC equation for the estimation of GFR detects more MM patients with stage 3–5 RI than the MDRD, CKD-EPI or CKD-EPI-CysC equations. However, CKD-EPI-CysC was the only equation that could predict for OS, possibly due to the very strong correlation of CysC with ISS (as myeloma cells produce CysC also). The confirmation of these data will lead to the broader use of equations based on CysC (CKD-EPI-CysC with or without sCr) for the evaluation of RI in patients with MM, as it has been suggested for patients with several other renal disorders. Table. Evaluation of Renal Function Stage by Different Equations CKD stage MDRD equation CKD-EPI equation CKD-EPI-CysC equation CKD-EPI-sCr-CysC equation p-value 1 60 (27%) 57 (26%) 67 (30%) 44 (20%) 2 73 (33%) 70 (32%) 58 (26%) 77 (35% Friedman-test 3 53 (24%) 55 (25%) 57 (26%) 62 (28%) p<0.01 4 21 (9.5%) 25 (11%) 27 (12%) 24 (11%) 5 13 (6%) 13 (6%) 11 (5%) 13 (6%) Disclosures: No relevant conflicts of interest to declare.

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Thiotepa-Based Conditioning for Allogeneic Stem Cell Transplantation (allo-HSCT) in Acute Lymphoblastic Leukaemia (ALL) - a Survey from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v126.23.4316.4316 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4316-4316

Author(s):

Sandra Eder ◽

Eric Beohou ◽

Myriam Labopin ◽

Jaime Sanz ◽

Jürgen Finke ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Working Party ◽

Disease Status ◽

P Value ◽

Unrelated Donor ◽

Free Survival ◽

One Year

Abstract Background Thiotepa is an alkylating compound with an effective antineoplastic activity that was used in the past mainly for solid tumors and lymphoma, partially due to its ability to penetrate the blood-brain-barrier. Moreover, beside its myelosupressive activities, thiotepa has immunosuppressive properties making it an attractive agent to be used in the conditioning pre-transplantation. In the current retrospective registry study, we analyzed thiotepa-based conditioning regimen for allo-HSCT in adult patients with ALL using the EBMT ALWP database. Methods Inclusion criteria were: adults with de novo or secondary ALL who underwent first allo-HSCT between 2000 and July 2014 with a thiotepa-based regimen. Donors were either HLA-matched siblings or matched unrelated donors. Haploidentical and cord blood transplantations were excluded as well as patients who received a previous allo-HSCT. Results A total of 323 patients with adult ALL were identified. Median age was 43 years (range, 18 - 76); 59% were males and 41% females. Disease status at allo-HSCT was CR1 in 48.9%, CR2 in 21.7%, CR3 in 6.2% and 23.2% of the patients had an active disease at time of transplant. Transplantation was performed from a HLA-matched sibling (49.8%) or a matched unrelated donor (51.2%). Sixty-five per cent of patients received a myeloablative and 35% a reduced-intensity conditioning regimen, respectively. Stem cell source was peripheral blood stem cells in 84% of the transplants, while 16% received bone marrow grafts. Neutrophil engraftment (defined as >0.5x109/L) was 98% with a median day of 15 (range, 2 - 41). Platelets engraftment (defined as >20x109/L) was 92% with a median day of 14 (range, 7 - 98). Incidence of acute GvHD (Grade> II) was 26.6%, while chronic GvHD occurred in 35.9% at one year (24.6% with extensive disease). With a median follow-up of 16.8 months, the non-relapse mortality was 12.4% and 25.3% at 100 days and one year, respectively. Relapse incidence at 1 year was 33.3%.The one-year leukemia-free survival and overall survival incidences were 57% and 66%. Table 1 shows the outcome according to donor and disease status at time of allo-HSCT. When looking for conditioning regimen more precisely, comparing thiotepa / busulfan ± melphalan (n=213) to thiotepa / other (n=110), higher relapse incidence at one year (34.9% vs 30.3%, p=0.016) and lower leukemia-free survival (38.8% vs 45.9%, p=0.0203), respectively were observed, without difference in non-relapse mortality (23.8% vs 26.3 %, n.s.) and overall-survival (59.6% vs 51.1%, p=0.109). Conclusion This large survey suggests that TTP-based conditioning therapy in adult ALL is feasible and effective, with main outcomes being comparable to literature published results achieved with other regimens. Table 1. Donor LFS,1 year p-value OS,1 year p-value Relapse,100 days Relapse,1 year p-value NRM,100 days NRM,1 year p-value HLA-matchedsibling 49% 0.0262 62% 0.0133 13.1% 31.9% 0.4641 8.7% 18.3% 0.0042 matchedunrelateddonor 33% 46% 15.2% 34.7% 16.2% 32.1% Table 2. Disease status at allo-HSCT LFS,1 year p-value OS,1 year p-value Relapse,100 days Relapse,1 year p-value NRM,100 days NRM,1 year p-value CR1 49% <0.0001 68% <0.0001 6.4% 27.5% 0.0028 7.6% 22.6% 0.1859 CR2+ 33% 40% 21.5% 39% 17% 27.8% Disclosures Mohty: Riemser: Honoraria, Research Funding.

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A Multi Center Trial of hyperCVAD+Rituxan in Patients with Newly Diagnosed Mantle Cell Lymphoma.

Blood ◽

10.1182/blood.v110.11.387.387 ◽

2007 ◽

Vol 110 (11) ◽

pp. 387-387 ◽

Cited By ~ 31

Author(s):

Elliot M. Epner ◽

Joseph Unger ◽

Thomas Miller ◽

Lisa Rimzsa ◽

Catherine Spier ◽

...

Keyword(s):

Overall Survival ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Newly Diagnosed ◽

Survival Estimate ◽

Free Survival ◽

Mantle Cell ◽

Md Anderson ◽

One Year

Abstract BACKGROUND: A Phase II Study multinstitutional study by the lymphoma group within the Southwest Oncology Group (SWOG 0213) was performed to determine the 1 year progression free survival of patients with newly diagnosed mantle cell lymphoma (MCL). Previously, this regimen was utilized in a similar group of newly diagnosed MCL patients in a single institution study by Romaguera et al (JCO200523:7013) at the MD Anderson Cancer Center. They reported a 97% response rate, a 87% CR rate, and a 3 year failure free survival rate of 73%. PATIENTS AND METHODS: This study was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Newly diagnosed MCL patients under age 70 with adequate organ function and measurable disease were eligible. All cases were histologically confirmed. RESULTS: 49 eligible patients were enrolled. There was one probable treatment-related death due to colitis. Grade 4 hematologic toxicity was reported for 87% of patients. 40 patients have been evaluated for response. 3 patients had inadequate assessment and are assumed to be non-responders.16 patients (40%) had complete responses, 7 patients (18%) had unconfirmed complete responses, and 12 patients (30%) had partial responses for an overall response rate was of 88% (35/40; 95% CI, 73%–96%). Median follow-up among patients still alive is 1.6 years (range: 0.3–4.1 years). The progression-free survival estimate at 1-year is 89% (95% CI: 80%–98%) and at 2 years is 64% (95% CI: 46%–82%). The overall survival estimate at 1 year is 91% (95% CI: 82%–99%) and at 2 years is 76% (95% CI: 60%–91%). 13 of the 49 eligible patients have progressed or died. One year overall survival was 91% and one year progression free survival is 89%. Two year PFS is 63% (95% CI: 46%–82%). Two year OS is 76% (95% CI: 60%–91%). The 1-year progression-free survival estimate is 89% (95% CI: 80%–98%). The 1-year overall survival estimate is 91% (95% CI: 82%–99%). The overall response rate was 88% (35/40; 95% CI, 73%–96%). CONCLUSIONS: The hyperCVAD + rituximab regimen is active as reported in MCL with a one year progression free survival of 89%. However, similar to the reported MD Anderson experience, this regimen is toxic and a continuous pattern of relapse over time is observed.

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Presence of PD-1 Expressing T Cells Predicts for Inferior Overall Survival in Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.1785.1785 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1785-1785 ◽

Cited By ~ 2

Author(s):

Gasmi Billel ◽

Eric L Smith ◽

Ahmet Dogan ◽

Meier Hsu ◽

Sean Devlin ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

T Cells ◽

T Cell ◽

Research Funding ◽

P Value ◽

Newly Diagnosed ◽

Cell Infiltrate ◽

Cell Exhaustion

Abstract Background: Programmed cell death 1 (PD-1) protein downregulates T cell activation and is related to immune tolerance. PDL1 up regulation, T cell infiltration, and T cell exhaustion are features, which suggest susceptibility to PD-1 blockade antibodies. Blockade of PD-1 or its ligand PD-L1 has shown promising responses in several malignancies. Although little clinical activity has been seen in patients with relapsed multiple myeloma (MM), the role of the PD-1 pathway and T cell exhaustion in newly diagnosed MM has not been explored. Objective: To determine whether T-cell infiltrate or expression of PD-1 correlates with clinical features and prognosis among patients with newly diagnosed multiple myeloma. Methods: We screened a clinically annotated database of 341 patients seen at MSKCC between 1998 and 2012 that had Multiple Myeloma, received a bone marrow transplant and were consented to a biospecimen research protocol for availability of pre-treatment bone marrow specimens. A total of 64 bone marrow biopsy specimens were identified. Immunohistochemistry (IHC) was performed in formalin-fixed paraffin-embedded specimens using an anti human CD3 monoclonal antibody (mAb) (Dako, Clone F7.2.38) and an anti human PD-1 mAb (Cell Marque, catalog #315M-95). CD3 and PD1 IHC staining were graded as negative (<5% for CD3, < 1% for PD1), or positive (≥5% for CD3, ≥1% for PD1). Correlative analyses were performed between CD3/PD1 expression and clinical outcome using the following parameters: International Staging System (ISS), cytogenetic risk, progression free survival (PFS), overall survival (OS), and response to treatment. Groups were compared by Fisher's exact test. OS and PFS were assessed by Cox regression and estimated by Kaplan-Meier methods. Results: 23 specimens (36%) were CD3 positive and 10 specimens (16%) were PD-1 positive. All PD-1 positive specimens were CD3 positive. 41 specimens (64%) were CD3 negative (<5%) and PD1 negative (<1%). Based on these results, specimens were divided into three groups: Exhausted T-cell infiltrate (CD3+/PD1+), non exhausted T-cell infiltrate (CD3+/PD1-) and no T-Cell infiltrate (CD3-/PD1-). In the exhausted T-cell infiltrate group 30% of patients had ISS stage 3 and 40% had high risk cytogenetics. In the non-exhausted T-cell group 15% of patients had ISS stage 3 and 15% high cytogenetic risk. In the no T-cell infiltrate group 10% had ISS stage 3 disease and 22% high cytogenetic risk. These proportions were not significantly different across the 3 groups. Median OS from 1st auto infusion was 7 years while median PFS was 2.3 years. On univariate analysis, there was no significant difference in PFS between the 3 groups. The presence of CD3 and PD1 T-cells were significantly associated with OS (p-value = 0.04). Median OS from 1st auto infusion was 43 months for the exhausted T-Cell infiltrate group followed by 83 months for the no T-Cell infiltrate group. The non exhausted T-cell group had the highest OS, median not reached; OS by 7-years was 75%. Cytogenetic risk at diagnosis was significantly associated with OS (p-value = 0.03). In a multivariable model, CD3/PD1 staining continued to trend toward an association with OS (p-value = 0.08) and cytogenetic risk remained significant (p-value = 0.05). Conclusions: The presence of T-cells with PD-1 expression was not associated with higher risk disease at MM diagnosis based on cytogenetics and ISS stage. The presence of PD-1 expressing CD3+ T cells trends toward an association with poorer overall survival in newly diagnosed MM, especially compared to non exhausted T-cell infiltrate, suggesting the possibility that T cell exhaustion represents a novel high risk disease characteristic. Further investigation is necessary to assess if the presence of CD3+PD-1+ T cells is an independent prognostic feature in newly diagnosed MM. Figure 1. Overall survival by CD3/PD1 Staining in 64 newly diagnosed myeloma patients. Figure 1. Overall survival by CD3/PD1 Staining in 64 newly diagnosed myeloma patients. Disclosures Giralt: JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding. Landgren:International Myeloma Foundation: Research Funding; Onyx: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Medscape: Honoraria; Bristol-Myers Squibb: Honoraria; Medscape: Consultancy; BMJ Publishing: Consultancy; Celgene: Honoraria; Onyx: Honoraria; BMJ Publishing: Honoraria; Onyx: Research Funding. Hassoun:Novartis: Consultancy; Takeda: Research Funding; Celgene: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Lesokhin:Genentech: Research Funding; Aduro: Consultancy; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Efranat: Consultancy.

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Assessment of the impact of the Hospital Anxiety and Depression Scale on the initiation of treatment in newly diagnosed cancer patients in a safety-net hospital.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.31_suppl.250 ◽

2017 ◽

Vol 35 (31_suppl) ◽

pp. 250-250

Author(s):

Daulath Singh ◽

Annapoorna Singh ◽

Punita Grover ◽

Mahathi Indaram ◽

Nikki Malomo ◽

...

Keyword(s):

Cancer Patients ◽

Poisson Regression ◽

Treatment Initiation ◽

Depression Scale ◽

Anxiety And Depression ◽

P Value ◽

Newly Diagnosed ◽

Hospital Anxiety ◽

Poisson Regression Analysis ◽

The Impact

250 Background: Distress is a universal symptom in oncologic patients which negatively impact the quality of life and survival. It interferes with the ability to cope with the diagnosis and is a risk factor for non-adherence with treatment. The Hospital Anxiety and Depression Scale (HADS), is used at our institution for distress screening. The aim of our study is to assess the impact of distress, measured by the HADS score, on initiation of treatment in newly diagnosed cancer patients. Methods: We conducted a retrospective chart review of patients with a new diagnosis of cancer, between March 1st, 2014 and December 31st, 2015; who had been evaluated for distress at their first oncology clinic visit. We included only patients who were treated with chemotherapy or chemoradiation, with curative intent. Poisson regression analysis was conducted to investigate the relationship between HADS to treatment initiation while including age, sex, race, insurance status, cancer type, and stage as covariates in the model. Results: A total of 101 patients met the inclusion criteria. The mean age was 54 years, 63% were female and 37% were male. The majority were Caucasians (53%), followed by African-Americans (36%). 56% of the population had Medicaid, and 26% had Medicare and private insurance. The most common cancers were – breast (30%), gastrointestinal (20%), gynecologic (15%) and lung (11%). 64% received chemotherapy and 36% were treated with chemoradiation. We grouped patients into 3 categories based on the HADS score – category 1 with score ≤7 (28%), category 2 with score 8-10 (17%) and category 3 with score ≥11 (55%). The median time to treatment initiation was 28 days. Multivariate Poisson regression analysis did not show any correlation between the HADS score and treatment initiation. Subscales analyses showed that higher depression scores correlate with a delay in treatment initiation (p-value 0.01), while the anxiety scores had no influence (p-value 0.57). Conclusions: In our study, the initial total HADS score did not affect the treatment initiation. Interestingly, depression had an influence on the initiation of treatment in newly diagnosed cancer patients.

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The prognosis of NF1 mutations in newly diagnosed AML: A single-center retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18525 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18525-e18525

Author(s):

Mohammad Telfah ◽

Haitham Abdelhakim ◽

Nicole Balmaceda ◽

Eyad Gharaibeh ◽

Andrew K. Godwin ◽

...

Keyword(s):

Overall Survival ◽

Retrospective Study ◽

Categorical Variables ◽

Rank Test ◽

P Value ◽

Newly Diagnosed ◽

Single Center ◽

Wild Type ◽

Recurrent Mutations ◽

Baseline Characteristics

e18525 Background: Several recurrent genetic mutations have been described in acute myeloid leukemia (AML), which have both prognostic and therapeutic implications. Recurrent mutations in the Neurofibromin 1 ( NF1) gene are reported in 1-5 % of AML patients; however, there are limited data regarding its prognostic implications. Here, we report the outcomes for patients with newly diagnosed AML with a somatic NF1 mutation at our center. Methods: A retrospective chart review included patients with newly diagnosed AML at KUMC from 01/2016 through 09/2018. All patients had targeted next-generation sequencing (NGS) at diagnosis. Baseline characteristics were compared between patients with NF1 mutations and those who were wild-type using Fisher’s exact test for categorical variables, and the Wilcoxon rank-sum test for continuous variables. The primary outcome was overall survival (OS), which was measured from the time of diagnosis to the time of death from any cause. A stepwise Cox proportional-hazard model was used to adjust for potential confounders. Results: Data on 110 patients were included. Out of the 110 patients, 15 (13.6%) had a delectable NF1 mutation, while 95 (86.4%) patients were NF1 wild-type. The baseline characteristics of the two groups are displayed below. Median OS for patients with an NF1 mutation was 7.3 months, while it was 18.4 months for patients with NF1 wild-type, Log-rank test p-value 0.02. After adjusting for potential confounders, including age, ELN risk category, induction regimen, presence of other mutations such as TP53, the hazard of death remained significantly higher for patients with NF1 mutations, HR 2.4, CI (1.05-5.6), p-value 0.04. Conclusions: In this single-center retrospective study, the presence of a NF1 mutation was associated with worse overall survival in patients with newly diagnosis AML. [Table: see text]

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