Assessment of the prognostic impact of serum level of soluble cluster of differentiation (sCD155) in newly diagnosed Low grade cell Non Hodgjen Lymphoma in Adult Egyptian patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohamed Osman Azzazi ◽  
Hany Mohamed Abd-Allah Hegab ◽  
Nermeen Adel Nabih Abd El-Ghafar ◽  
Mary Gamal Nageb Melek ◽  
Dina Mostafa Fahmy Ahmed
Keyword(s):  
Prognostic Factors ◽  
University Hospital ◽  
Low Grade ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Remission Status ◽  
Poor Predictor ◽  
Significant Difference ◽  
Egyptian Patients ◽  
Cluster Of Differentiation

Abstract Background CD155-dependent signals not only influenced net tumor growth but also responsiveness to immune checkpoint therapies. Thus, blocking CD155 could be a rational strategy to improve current immunotherapeutic Aim of the work To assess CD155 in newly diagnosed Low grade B non Hodgkin Lymphomas as prognostic marker for remission Patients and methods CD 155 measured by Ellisa at the time of diagnosis of 50 patients newly diagnosed low grade B non Hodgjen Lymphomas and the remission status followed up prospectively at 3 and 6 months in hematology unit at Ain Shams University Hospital Results there were high statistically significant difference between CD155 level and cytogenetic risk and Eligibility for auto transplantation, there were statistically significant difference between CD155 level and B symptoms, there were high statistically significant difference between CD155 level and Radiology stage, BM infiltation, protocol after 3months, There were high statistically significant difference between CD155 level and Radiology stage, BM infiltration, CBC after 6 months There were high statistically significant difference between CD155 level and non Remission and CD155 had Sensitivity88.46% and Specificity75% as poor predictor of remission Conclusion The CD155 level is prognostic factors for remission in Low grade B non Hodgkin Lymphomas as high CD155 level is poor prognostic factors for response and remission with Sensitivity 88.46%and Specificity75. %

Clinicopathological Features, Prognostic Factors, Survival Trends, and Treatment of Malignant Ovarian Germ Cell Tumors: A SEER Database Analysis

2021 ◽  
Vol 44 (4) ◽  
pp. 145-152
Author(s):  
Hualei Guo ◽  
Hao Chen ◽  
Wenhui Wang ◽  
Lingna Chen
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Proportional Hazards ◽  
Germ Cell Tumors ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
Seer Database ◽  
Survival Times ◽  
Survival Curves ◽  
Significant Difference

Objective: The aim of this study was to investigate the clinicopathological prognostic factors of malignant ovarian germ cell tumors (MOGCT) and evaluate the survival trends of MOGCT by histotype. Methods: We extracted data on 1,963 MOGCT cases diagnosed between 2000 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database and the histological classification of MOGCT, including 5 categories: dysgerminoma, embryonal carcinoma (EC), yolk sac tumor, malignant teratoma, and mixed germ cell tumor. We examined overall and disease-specific survival of the 5 histological types. Kaplan-Meier and Cox proportional hazards regression models were used to estimate survival curves and prognostic factors. We also estimated survival curves of MOGCT according to different treatments. Results: There was a significant difference in prognosis among different histological classifications. Age, histotype, grade, SEER stage, and surgery were independent prognostic factors for survival of patients with MOGCT. For all histotypes, 1-, 3-, and 5-year survival rate estimates were >85%, except for EC, which had the worst outcomes at 1 year (55.6%), 3 years (44.4%), and 5 years (33.3%). In the distant SEER stage, both chemotherapy and surgery were associated with improved survival outcomes compared with surgery- and chemotherapy-only groups. Conclusions: Dysgerminoma patients had the most favorable outcomes, whereas EC patients had the worst survival. A young age, low grade, and surgery were all significant predictors for improved survival. In contrast, a distant SEER stage was a risk factor for poor survival. Chemotherapy combined with surgery contributed to longer survival times of patients with MOGCT in the distant SEER stage.

Prognostic Factors for Outcome of Patients Undergoing Allogeneic HSCT from Unrelated and Related Donors for AML and MDS: A Retrospective Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1147-1147
Author(s):  
Thorsten Graef ◽  
Matthias Vaupel ◽  
Roland Fenk ◽  
Leilani Ruf ◽  
Fabian Zohren ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Prognostic Impact ◽  
Allogeneic Hsct ◽  
Remission Status ◽  
Unrelated Donors ◽  
One Year

Abstract PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for many patients with myeloid leukemia, especially in refractory or relapsed disease. To determine prognostic factors that correlate with outcomes after HSCT in adults with AML and MDS we analysed several clinical and haematological parameters. PATIENTS AND METHODS: In this unicenter retrospective study, we studied 120 adults who received allogeneic HSCT for AML (n=88) or MDS (n=32) between 1993 and 2003. The median age was 44 years (range 21–72), included were 59 male and 61 female patients. 42% of the patients were transplanted in first complete remission (CR1), 17% were transplanted in CR after salvage therapy and 41% were in relapse or refractory to induction or salvage therapy. The grafts consisted in 88 cases (73%) of PBSCT and in 32 cases of bone marrow, in 34% unrelated donors were used. The medium number of infused CD34+ cells was 5.51x106/kg. As conditioning regimen standard myeloablative therapies without (53%) or with (25%) TBI, or a non-myeloablative regimen including TBI (22%) were used. The prognostic impact for several groups with different clinical and hematological parameters were assessed by univariate and multivariate analyses using the Cox regression model. RESULTS: One-year and three-year probabilities of overall survival (OS) were 52% (48% to 57%) and 38% (36% to 43%). In univariate analysis, remission status and cGvHD were significantly associated with OS (CR vs. non-CR p=0.00001; cGvHD vs. non-cGvHD p=0.00001). Median OS for patients who underwent transplantation in CR were 2374 vs 180 days and for chronic GvHD 2374 vs 294 days. One-year and three-year probabilities of relapse were 30% (31% to 17%) and 31% (34% to 24%). CR, cGvHD and ablative regimens resulted in a lower relapse rate (p=0.00001; p=0.0002, p=0.028). One-year and three-year probabilities of transplant-related mortality (TRM) were 27% (28% to 30%) and 34% (32% to 40%). Extensive cGvHD, transplantion before 1997 and unrelated donor were significantly associated with higher TRM (p=0.03; p=0.04; p=0.03). Multivariate analysis was performed to test for the prognostic role of those factors that had achived a p-value of 0.25 or less in the Log-Rank test. For OS, sex, donor, tbi, remission status, and cGvHD and time from diagnosis to transplantation were included. For a better OS and lower RR especially the remission status and the occurrence of cGvHD were significant prognostic factors for the outcome after allogeneic transplantation (OS: p=0.0001, p=0.001; RR: p=0.0001, p= 0.001); sex and time from diagnosis to transplantation were also predictive for a better OS (p=0.007, p= 0.045) and the use of non-tbi based regimens resulted in a lower RR (p=0.006); for TRM, transplantions before 1997 and unrelated donors were detect as significant prognostic factors (p=0.027, p=0.033). CONCLUSION: Remission status at transplantation and the occurrence of cGvHD are the major prognostic factors for the outcome after allogeneic HSCT in AML and MDS. We therefore conclude that allogeneic stem cell transplantation should be performed early in haematological remission in patients with high-risk AML and MDS, if a suitable donor is available.

Efficacy of Yttrium-90 Zevalin Outside of Clinical Trials: Preliminary Results of a Retrospective Bi-Center Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5015-5015
Author(s):  
Francesco Cicone ◽  
Francesco Scopinaro ◽  
Sebastien Baechler ◽  
Nicolas Ketterer ◽  
Franz Buchegger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Setting ◽  
Patient Population ◽  
Statistical Significance ◽  
University Hospital ◽  
Low Grade ◽  
Number Of Patients ◽  
Significant Difference ◽  
Routine Clinical Setting

Abstract Background and Aim: Due to limited data regarding the efficacy of Radioimmunotherapy with 90Y-Zevalin (RIT-Z) outside of controlled clinical trials, we carried out a biinstitutional, international retrospective study to assess the efficacy of RIT-Z in a routine clinical setting. The relationship between the number of previous therapies and outcomes as well as the response to the last therapy was assessed. Possible differences in outcomes for patients treated in the two different centers were also analyzed. Materials and Methods: Forty-three consecutive patients treated at the University Hospital of Lausanne (CHUV, Switzerland) and at S. Andrea University Hospital of Rome (Italy) were evaluated, none of which had been previously included in clinical trials. Only 31 patients entered the final analysis: patients lost at follow up, undergoing autologous transplantation (ASCT), or treated within the last 3 months were excluded. Efficacy of therapy was evaluated in terms of Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Treatment (TTNT). Survival curves were obtained with the Kaplan- Meier method (statistical significance = p<0.05). Results: Characteristics of the patient population are listed in Table 1. Although 50% of the patients had aggressive histologies, patients treated at S. Andrea had slightly more favorable features than those treated at CHUV. Fourteen patients (45%) had received at least 4 previous treatments, and all had received Rituximab. Fourteen patients (45%) had not responded to the last therapy, while 6 (19%), all treated at S.Andrea, were considered disease-free at the time of RIT-Z, which was administered for consolidation. Median follow up time was 20 months (11.5 vs. 25 months for S.Andrea and CHUV, respectively). Median PFS and TTNT were similar. After achieving a partial response, 2 patients were referred to Rituximab maintenance after RIT-Z and remain progression-free. Median OS was still not attained. Although not statistically significant, a trend towards better outcomes for S. Andrea patients was found. In comparing patients with indolent and aggressive lymphoma, only PFS was found to be significantly different (median PFS: 10 vs. 5 months, p<0.05). In patients with <4 and ≥ 4 previous therapies, twenty month OS was 88% vs. 53.6% (p=0.02), respectively; median TTNT was 22 vs. 5 months (p=0.013), while differences in PFS did not attain statistical significance. The duration of response in non-responders to their last therapy was shorter than in responders: 20-month OS- 44% vs. 94% (p=0.0015), median PFS and TTNT- 3.5 vs. 15 months (p=0.0002) and 4 vs. 15 months (p=0.0001), respectively. Median PFS and TTNT after RIT-Z did not differ from those found after the last therapy. A significant difference in outcomes for heavily pretreated or refractory patients was found in those with low grade follicular lymphoma. Conclusions: Poorer outcomes were found in our patient population treated in a routine clinical setting compared to those enrolled in clinical trials. This may be related to greater heterogeneity of our study cohort which included more patients with unfavorable conditions (e.g. aggressive NHL, ≥4 treatment courses including rituximab in all, and ASCT in 25%). Our results suggest that the best benefit may be expected with RIT-Z either for consolidation or relatively earlier in the course of NHL treatment. Table 1. Total CHUV S. Andrea Population Analyzed (72%) Number of patients 43 23 20 31 Median Age 61 63 58,5 62 Aggressive Histology (FL grade 3 or DLBCL) 18 (41,8%) 8 (34,7%) 10 (50%) 11 (35,5%) Indolent Histology (FL grade 1 or 2) (%) 25 (58,2%) 15 (65,3%) 10 (50%) 20 (64,5%) Patients with ≥4 previous treatments 19 (44,2%) 12 (52,1%) 7 (35%) 14 (45,2%) Patients with previous ASCT 11 (25,6%) 6 (26%) 5 (25%) 8 (25%)

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Clinical Significance of Immunohistochemical Markers of Diffuse Large B-Cell Lymphoma In the Rituximab Era.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1800-1800
Author(s):  
Miyuki Hayama ◽  
Masataka Okamoto ◽  
Yuki Hagiwara ◽  
Ken Tanae ◽  
Mika Kohri ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Combination Chemotherapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Survival Ratio ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 1800 Rituximab combination chemotherapy has significantly improved the treatment outcome of diffuse large B-cell lymphoma (DLBCL). Therefore, the prognostic factors of DLBCL in the rituximab era are different from previously reported prognostic factors. Biological prognostic markers have been analyzed to help understand the biologic basis of treatment outcome. Hans, et al. reported that patients with non-germinal center B-cell like (GCB)-type DLBCL had a significantly poorer prognosis than those with GCB-type DLBCL in the pre-rituximab era. In patients who received rituximab combination chemotherapy, there is a report that did not find a difference in survival ratio between those with GCB DLBCL or non-GCB DLBCL. On the other hand, there was a report that found a difference in survival ratio between patients with GCB DLBCL and those with non-GCB DLBCL. In the present study, we compared the prognostic factors of DLBCL between patients who received CHOP-like chemotherapy and those who received rituximab combined with CHOP-like therapy. The subjects were 204 DLBCL patients who underwent rituximab + CHOP-like therapy and in whom markers could be analyzed. We evaluated CD5, CD10, BCL2, BCL6, and MUM1 expression by immunohistochemistry. One hundred forty-six DLBCL patients who underwent CHOP-like therapy were assumed as historical controls. The median age was 52 years in both groups. In the R-CHOP-like and CHOP-like groups, patients with stage III or IV disease comprised 75% and 67%, respectively, patients with performance status3a2 comprised 28% and 20%, respectively, and patients with serum LDH >normal comprised 60% and 77%, respectively. There were no significant differences in clinical characteristics between the CHOP-like group and R-CHOP-like group. BCL2 was positive in 85(63%) of the 134 patients who received the R-CHOP-like regimen and in 66 (46%) of the 142 patients who received the CHOP-like regimen. When the 202 patients who received the R-CHOP-like regimen were divided into the GCB group and the non-GCB group, the GCB group consisted of 92 patients (46%) and the non-GCB group consisted of 110 patients. The relationships between immunohistological markers and outcome among the patients with DLBCL who received CHOP-like therapy were studied. CD5, CD10, and BCL6 had no prognostic impact on 5-year overall survival (OS) and progression-free survival (PFS) rates. When the patients were divided into the GCB DLBCL and non-GCB DLBCL groups, the 5-year OS of the GCB group was 78% and that of the non-GCB group was 57% (p<0.05). The 5-year PFS of the GCB group was 73% and that of the non-GCB group was 52% (p<0.05). The 5-year OS rate of the BCL2-positive and -negative groups was 61% and 74%, respectively (p<0.05). The 5-year PFS rate of the BCL2-positive and -negative groups was 55% and 70%, respectively (p<0.05). Thus, among patients who received the CHOP-like regimen, the BCL2-positive group showed significantly poorer prognosis than the BCL2-negative group. Next, the effect of rituximab with chemotherapy was examined. CD5, CD10, BCL2, BCL6, and MUM-1 had no prognostic impact on 5-year OS and PFS rates. When the patients were divided into the GCB DLBCL (n=92) and non-GCB DLBCL (n=110) groups, the 5-year OS of the GCB group was 74% and that of the non-GCB group was 75%, showing no significant difference. The 5-year PFS of the GCB group was 71% and the 5-year PFS of the non-GCB group was 69%, showing no significant difference. In the rituximab era, BCL2, MUM1 and non-GCB were not prognostic factors. As to reports on patients with DLBCL who received rituximab combination chemotherapy, there was a report in which the cases were separated into the GCB-type DLBCL and non-GCB-type DLBCL groups and compared. Fu, et al. reported that the survival of patients with GCB-type DLBCL was still superior to that of patients with non-GCB-type DLBCL in the rituximab era. However, other reports did not find a difference in survival ratio between those with GCB-type DLBCL or non-GCB-type DLBCL. In conclusion, the finding of improved OS and PFS with the addition of rituximab indicates that new biomarkers should be studied. Disclosures: No relevant conflicts of interest to declare.

ABCA3 Expression Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3946-3946 ◽  
Author(s):  
Antony Ceraulo ◽  
Aminetou Mint-Mohamed ◽  
Delphine Maucort-Boulch ◽  
Etienne Paubelle ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Relapse Rate ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Gemtuzumab Ozogamicin ◽  
Small Sample ◽  
Control Group ◽  
Prognostic Impact ◽  
Significant Difference

Abstract Background. The ATP binding cassette transporter 3 (ABCA3) has been recently found to induce a significant reduction in cytotoxicity following exposure to anthracyclines, mitoxantrone, etoposide, Ara-C, vincristine, and rituximab. ABCA3 acts through the modulation of multivesicular bodies (MVB) and contributes to drug sequestration in late endosomal organelles, i.e. MVB and lysosomes. Studies having investigated the prognostic impact of ABCA3 expression in AML have yielded conflicting results as ABCA3 expression has both been reported to exert unfavorable or neutral effects on patient outcomes. In addition, the small sample size of these studies precluded the use of multivariate analyses. Methods. Our goal was to investigate the prognostic impact of ABCA3 expression in adult patients with AML treated with IC with or without gemtuzumab ozogamicin (GO). To this end we investigated the relationship between ABCA3 expression and EFS in a representative series of 221 AML homogeneously treated in the ALFA-0701 trial. qRTPCR amplification of conserved ABCA3 mRNA sequences, as identified with FasterDB database, was performed with GUS and ABL as reference genes. Primer sets were complementary to conserved ABCA3 exons 6-7 and exon 19-20 junctions. Patients were given a 3+7 induction course without (control group, n=110) or with fractionated intravenous GO (n=111) (Castaigne S, Lancet 2012; 379:1508-1516). Results. Among the 278 randomized patients, 221 had available bone-marrow diagnostic samples with high-quality RNA. The same benefits associated with GO were observed in the 221 patients from the present study as in the entire trial population. Overall, median age, CR rate, relapse rate, median follow-up, 3-years EFS were 62.1 years, 76.5%, 66%, 47.45 months, 28±3%, respectively. There was no significant difference in the level of ABCA3 expression between responders and non-responders. In the 169 responders, ABCA3 expression at diagnosis was more than 3-fold higher in the 111 remitters who subsequently relapsed than in the 58 patients who remained in persistent CR (p=0.033). The level of ABCA3 expression was significantly lower in ELN favorable group than in intermediate and adverse risk AML (p= 0.004) and negatively correlated with CD33 expression (R=-0.272, p<10-4). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±3 vs 45±7 % p=0.002). Multivariate analysis identified age, treatment arm, and ELN risk group as independent prognostic factors for EFS. In the control group, there was no significant association between ABCA3 expression and CR rate, relapse rate, and EFS. In the 111 patients within the GO arm, there was no significant difference in the level of ABCA3 expression between responders and non-responder whereas in the 89 responders, ABCA3 expression at diagnosis was more than 7-fold higher in the 53 remitters who subsequently relapsed than in the 36 patients who remained in persistent CR (p=0.006). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±5 vs 64±9 % p=0.0002). Multivariate analysis identified ABCA3 expression, cytogenetics, CD33 expression, and ECOG as independent prognostic factors for EFS (Figure 1). Conclusion. WhileABCB1 has been previously found to attenuate GO-induced cytotoxicity in AML cells (Walter RB, Blood 2003; 102:1466-1473), present results indicate that higher ABCA3 expression independently predicts poor outcome in AML patients treated with fractionated GO and intensive chemotherapy (IC). GO is an anti-CD33 antibody carrying a toxic calicheamicin derivative that, after hydrolytic release within lysosomal vesicles, induces DNA strand breaks, apoptosis, and cell death. Whether the clinical effect of ABCA3 expression relies on the modulation of CD33 internalization, calicheamicin release or combination thereof is under investigation. Finally our results encourage inhibiting ABCA3, such as with indomethacin, in order to overcome drug resistance in AML treated with GO-IC. Figure 1 Figure 1. Disclosures Thomas: Pfizer: Consultancy.

Maximum tumor dimension and tumor volume as prognostic factors in patients with newly diagnosed localized Ewing sarcoma (ES)- a report from the Children’s Oncology Group (COG).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11529-11529
Author(s):  
Leo Mascarenhas ◽  
Allen Buxton ◽  
Steven G. DuBois ◽  
Dian Wang ◽  
Nadia N. Laack ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prognostic Factors ◽  
Tumor Size ◽  
Tumor Volume ◽  
Cox Model ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Increased Risk ◽  
Significant Difference

11529 Background: Maximum tumor dimension > 8 cm. and large tumor volume have been reported to be adverse prognostic factors in patients with ES but have not been prospectively evaluated in the context of a phase 3 clinical trial with interval compressed chemotherapy. Methods: COG AEWS1031 (NCT01231906) was a randomized phase 3 clinical trial comparing interval compressed chemotherapy regimens in patients with newly diagnosed localized ES of bone and soft tissue. A correlative objective of AEWS1031 was to evaluate tumor size and volume as prognostic factors. Institution-reported dimensions of the primary tumor from baseline imaging were prospectively collected. For inclusion in this analysis, patients had to have at least 1 tumor dimension reported for tumor size analyses and dimensions in 3 axes for tumor volume analyses. Maximum dimension was dichotomized as less than vs. > / = 8cm. Tumor volume was dichotomized as less than vs. > / = 200 mL. Event-free (EFS) and overall survival (OS) from enrollment were calculated using Kaplan-Meier methods and compared between groups using a two-sided log-rank test. Hazard ratios (HR) and confidence intervals (CI) were calculated using the Cox model. Results: The 5-year EFS and OS of the 629 eligible patients was 78% (95% CI: 75-81%) and 87% (95% CI: 84-90%) respectively and there was no significant difference in both EFS and OS between the randomized interval compressed chemotherapy arms of AEWS1031. 590 of 629 (94%) patients were evaluable for maximum tumor dimension and 307 (52%) had tumors > / = 8 cm. Patients with tumors > / = 8 cm were at significantly increased risk for EFS events (p = 0.016) with estimated 5-year EFS of 73.7% (95% CI: 68.1 vs.78.4%) vs. 82.9% (95% CI 77.7-87.1%) for patients with tumors < 8 cm [HR: 1.53 (1.08-2.17)]. For tumor volume, 586 of 629 patients (93%) were evaluable and 180 (31%) had tumors > / = 200 mL. Patients with tumor volume > / = 200 mL were at significantly increased risk for EFS events (p = 0.003) with estimated 5-year EFS of 70% (95% CI: 62.3-76.4%) vs. 81.6% (95% CI: 77.2-85.2%) for patients with tumors < 200 mL [HR: 1.69 (1.2-2.39)]. Conclusions: Maximum tumor dimension and tumor volume as defined are both prognostic in patients with newly diagnosed localized ES treated with interval compressed chemotherapy. Clinical trial information: NCT01231906 .

scholarly journals Additive Value of Dynamic FDOPA PET/CT for Glioma Grading

2021 ◽  
Vol 8 ◽  
Author(s):  
Antoine Girard ◽  
Pierre-Jean Le Reste ◽  
Alice Metais ◽  
Nibras Chaboub ◽  
Anne Devillers ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Kinetic Parameters ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Time To Peak ◽  
Positron Emission ◽  
Pet Ct ◽  
Significant Difference

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas.Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC).Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min−1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP).Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.

scholarly journals Lymphocyte Doubling Time As A Key Prognostic Factor To Predict Time To First Treatment In Early-Stage Chronic Lymphocytic Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Fortunato Morabito ◽  
Giovanni Tripepi ◽  
Riccardo Moia ◽  
Anna Grazia Recchia ◽  
Paola Boggione ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Doubling Time ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Prognostic Role ◽  
Mutational Status ◽  
Binet Stage ◽  
Time To First Treatment

The prognostic role of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was recognized more than three decades ago when the neoplastic clone’s biology was almost unknown. LDT was defined as the time needed for the peripheral blood lymphocyte count to double the of the initial observed value. Herein, the LDT prognostic value for time to first treatment (TTFT) was explored in our prospective O-CLL cohort and validated in in two additional CLL cohorts. Specifically, newly diagnosed Binet stage A CLL patients from 40 Italian Institutions, representative of the whole country, were prospectively enrolled into the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540). Two independent cohorts of newly diagnosed CLL patients recruited respectively at the Division of Hematology in Novara, Italy, and at the Hospital Clinic in Barcelona, Spain, were utilized as validation cohorts. In the training cohort, TTFT of patients with LDT &gt;12 months was significantly longer related to those with a shorter LDT. At Cox multivariate regression model, LDT ≤ 12 months maintained a significant independent relationship with shorter TTFT along with IGHV unmutated (IGHVunmut) status, 11q and 17p deletions, elevated β2M, Rai stage I-II, and NOTCH1 mutations. Based on these statistics, two regression models were constructed including the same prognostic factors with or without the LDT. The model with the LTD provided a significantly better data fitting (χ2 = 8.25, P=0.0041). The risk prediction developed including LDT had better prognostic accuracy than those without LDT. Moreover, the Harrell’C index for the scores including LDT were higher than those without LDT, although the accepted 0.70 threshold exceeded in both cases. These findings were also confirmed when the same analysis was carried out according to TTFT’s explained variation. When data were further analyzed based on the combination between LDT and IGHV mutational status in the training and validation cohorts, IGHVunmut and LDT&gt;12months group showed a predominant prognostic role over IGHVmut LTD ≤ 12 months (P=0.006) in the O-CLL validation cohort. However, this predominance was of borden-line significance (P=0.06) in the Barcelona group, while the significant prognostic impact was definitely lost in the Novara group. Overall, in this study, we demonstrated that LDT could be re-utilized together with the more sophisticated prognostic factors to manage the follow-up plans for Binet stage A CLL patients.

scholarly journals Prognostic Impact of Bone Marrow Erythropoiesis on Newly Diagnosed Plasma Cell Myeloma: A Single Institutional Analyses

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5579-5579
Author(s):  
Daniel E Ezekwudo ◽  
Rohit Singh ◽  
Bolanle Gbadamosi ◽  
Mark Micale ◽  
Ishmael Jaiyesimi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Outcome ◽  
Plasma Cell ◽  
Prognostic Impact ◽  
Plasma Cell Myeloma ◽  
Newly Diagnosed ◽  
Bone Marrow Biopsies ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Impact

Abstract Introduction: In plasma cell myeloma (PCM), tumor burden and activity plays an important role in diagnosis and prognosis (e.g. circulating plasma cells), however very little attention has been directed to the impact of the non-plasma cell component of the bone marrow. The presence of anemia has been used to distinguish PCM from smoldering myeloma; however this can be a non-specific finding as there are many potential causes of anemia besides PCM. We sought to determine if the level of erythropoiesis in bone marrow biopsies may be a more reliable prognostic factor. In the study herein, we assessed the level of bone marrow erythropoiesis in patients with newly diagnosed PCM, and compared those findings with cytogenetic results (CGs), other prognostic factors and overall clinical outcome. We hypothesized that patients with adequate erythropoiesis (AEp) are likely to have favorable cytogenetics and better outcome compared to those with decreased erythropoiesis (DEp). Methods: We retrospectively reviewed pathology database for bone marrow biopsies in patients with diagnosis of plasma cell myeloma (PCM) at Beaumont Hospital, an academic community center from 2012 and 2014. Biopsy cases without anemia were excluded. A total of 91 patients with plasma cell myeloma and anemia were identified. Each biopsy was re-examined to determine the level of erythropoiesis. The level of erythropoiesis was calculated by multiplying erythroid fraction (obtained from M:E ratio) with non-plasma cell bone marrow cellularity. Cases were separated into AEp and DEp using an erythroid compartment cut-off of 7.5% based on already established data. Kaplan-Meier analysis was used to compare survival between groups. Results: Demographic distribution of studied patients were 46 (50.1%) white, 39 (43%) African Americans and 6 (6.6%) others. Out of 91 cases analyzed, 38 (42%) had AEp whereas 53 (58%) had DEp. Among those with AEp, 23 (62%) had favorable CGs (defined as those without t (4, 14), t (14, 16), t (14, 20) or 17 p deletion); 15 (38%) had unfavorable CGs. Among those with DEp, 14 (26%) had favorable CGs whereas 39 (74%) had unfavorable cytogenetics. The vast majority of patients with favorable CGs were alive whether they had AEp (87%) or DEp (79%), thus CGs remained significant even after controlling for erythroid compartment (p = 0.03). Overall, those with AEp were noted to have significantly lower β-2 microglobulin (AEp median =2.42 mg/dL, DEp median = 4.50 mg/dL, p = 0.02). Kaplan-Meier analysis showed a significant difference in survival curves among the four groups (AEp with favorable CGs, AEp with unfavorable CGs, DEp with favorable CGs, DEp with unfavorable CGs, p<.0001). While the two groups with favorable CGs showed no significant difference (p=.6050), the two groups with unfavorable CGs did (p=.0027). Conclusion: Our findings suggest that patients with PCM and anemia are not a homogenous population. Assessment of the erythroid compartment in these patients reveals a population with AEp that has more favorable CGs and lower β-2 microglobulin than patients with DEp. Despite this finding, patients with favorable CGs had a favorable clinical outcome whether they had AEp or not, indicating that current therapies can overcome differences in erythropoiesis in that group. For patients with unfavorable CGs, however, those with AEp had superior survival outcome compared to those with DEp, indicating that there may be some prognostic or diagnostic utility to assessing erythropoiesis in patients who meet current criteria for PCM, and possibly, incorporating erythropoietic activity into diagnostic/prognostic schema. Disclosures No relevant conflicts of interest to declare.

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