scholarly journals TARC before ASCT Is Highly Predictive of Outcome in Patients with Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL) after First-Line Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3009-3009 ◽  
Author(s):  
Simonetta Viviani ◽  
Francesco Spina ◽  
Arabella Mazzocchi ◽  
Maria Galbiati ◽  
Flavio Crippa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Conflicts Of Interest ◽  
Cox Model ◽  
Univariate Analysis ◽  
Salvage Chemotherapy ◽  
New Drugs ◽  
Rank Test ◽  
High Dose ◽  
Bulky Disease

Abstract Background: Second-line salvage chemotherapy(CT) followed by high-dose (HD) CT and autologous stem cells reinfusion (ASCT) is standard treatment forR/R HL patients, although long-term cure can be achieved in only half of them, depending on risk factors. Chemosensitivity to salvage CT before ASCT, mainly represented by a negative PET scan, is highly predictive of a favorable outcome. The availability of new markers of prognosis, like the measurement of the serum chemokineTARC, could help identifying those patients who may require further treatment, i.e. new drugs like Brentuximab Vedotin or Nivolumab or Pembrolizumab, before ASCT, in order to achieve a durable remission.Therefore we planned to prospectively evaluate the prognostic role of serum TARC levels collected at different time points in cHL R/R patients. Methods: Serum TARC levels were measured by commercially available ELISA test kits (R & D Systems, Minneapolis, USA) in 41 patients treated with IGEV (ifosfamide, gemcitabine, vinorelbine, prednisone) salvage CT, followed by myeloablative B(F)EAM (carmustine, (fotemustine), etoposide, cytosine arabinoside, melphalan) + ASCT at Istituto Nazionale Tumori of Milan, Italy, from January 2007 to December 2013. The 99th centile of TARC distribution in a group of 156 independent healthy subjects corresponding to 800 pg/mL, was considered as cut-off value discriminating between normal and abnormal TARC values. TARC evaluation was performed before starting salvage CT(T0), after the first IGEV cycle (T1) and before ASCT (T-preASCT). The Wilcoxon Mann Whitney test was used to analyze TARC as a function of patient and disease characteristics and PET results. Kaplan-Meyer curves and log-rank test were used to assess differences in PFS according to TARC levels. Cox model was used for multivariate analysis. Results: Main patient characteristics at relapse/progression were as follows: males/females: 19/22, median age: 31 years (range,19-69), B symptoms: 34%, bulky disease: 27%, stage III/IV: 39%, extra nodal involvement: 34%, refractory vs relapsed < 12 months vs relapsed ≥ 12 months: 49% vs 34% vs 17%. Median (IQ range) T0, T1 and T-preASCT were: 1856 (8801-9983) pg/mL, 1148 (544-2532) pg/mL and 829 (454-1725) pg/mL, respectively. Patients with bulky disease had higher median T0 than their counterpart (3241 vs 1462 pg/mL; p=.016). Median T-preASCT was significantly higher in patients with refractory disease compared to relapse < or ≥ 12 months (1100 vs 595, vs 548 pg/mL, p=.027). A positive PET was recorded in 57.5% of patients after 2 IGEV cycles and in 32% before ASCT. Forty-one percent of patients needed ≥ 2 salvage CT before ASCT and 63% had ≥ 2 risk factors. At each time point, median TARC values were significantly higher in PET-2 positive patients compared to their counterpart (T0: 3238 vs 1310; T1: 1866 vs 624; T-preASCT: 908 vs 544; pg/mL). Median (IQ range)T-preASCT levels were significantly higher in patients with a positive PET before ASCT:1091 (596-10578) pg/mL compared to those with a negative one: 651 (447-964) pg/mL. After a median follow-up of 65 months, 5-year PFS and OS (95% CI) were 70 (57-88)% and 84 (72-98)%, respectively. In univariate analysis T-preASCT > 2000 pg/mL, PET-2, PET-preASCT, ≥ 2 risk factors and ≥ 2 salvage CT lines significantly affected PFS. In multivariate analysis only T-preASCT > 2000 pg/mL was significantly associated with a poor PFS (HR 6.65, CI95% 1.12-39.35, p=0.036) as shown in Figure 1. Conclusions: Results of this single institution prospective study suggest that a cheap and easy to perform test, like serum TARC levels measurement before ASCT, may help to ameliorate the identification of those patients at risk of failing ASCT, for whom anticipated use of new active drugs, like anti-CD30 immunoconjugates and/or anti-PD1 blockers, should be explored, in order to improve the cure rate of ASCT. Figure 1 PFS according to TARC levels Figure 1. PFS according to TARC levels Disclosures No relevant conflicts of interest to declare.

scholarly journals The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Lin Gui ◽  
Fei Wang ◽  
Jinning Shi ◽  
Baoan Chen
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Survival Time ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Rank Test ◽  
Newly Diagnosed

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR&lt;3.61) or high NLR group (NLR≥3.61), low MLR group (MLR&lt;0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR&lt; 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB&lt;100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB&lt;100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis. Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR Disclosures No relevant conflicts of interest to declare.

Absence of High-Dose Consolidation Courses and Low Numbers of Allogeneic HSCTs Did Not Affect Overall Optimistic Results in B-Cell Precursor Ph-Negative Adult ALL Patients Treated By Non-Intensive but Non-Interruptive ALL-2009 Protocol: Data of the Russian ALL Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2497-2497
Author(s):  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey Sokolov ◽  
Galina Kliasova ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Risk Groups ◽  
High Dose ◽  
Late Response ◽  
Allogeneic Hsct ◽  
Blast Cells

Abstract Introduction It is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Patients and Methods The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L>100). No central MRD monitoring was performed. Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC <30, EGIL BII-III, LDH < 2N; no late CR; t(4;11)-negative), 56,5% (n=95) - in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis. Results CR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%). Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d, PRD resistance) age (>30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant. Conclusions Our data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Effect of metastasis surgery on overall survival in patients (pts) with advanced soft tissue sarcoma (ASTS): A subanalysis of the PALSAR trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10035-10035
Author(s):  
Nuria Kotecki ◽  
Binh Bui Nguyen ◽  
Jean-Yves Blay ◽  
Simone Mathoulin-Pelissier ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Liver Metastasis ◽  
Cox Model ◽  
Performance Status ◽  
Univariate Analysis ◽  
High Dose ◽  
Line Treatment ◽  
Primary Location

10035 Background: The role of surgery in pts with ASTS remains controversial. We have conducted an exploratory retrospective analysis of the role of metastasis surgery in ASTS pts receiving 1st-line chemotherapy (CT). Methods: The database includes all pts enrolled in PALSAR-1 and PALSAR-2 trials [Fayette 2009; Bui-Nguyen 2011], treated with dose-intensified MAID or high-dose CT with peripheral blood stem cells support as 1st-line treatment of ASTS. In our analysis, the primary endpoint is overall survival (OS). Log-ranks are used for univariate analysis and Cox model for multivariate analysis. Impact of treatments had been evaluated after adjustment to confounders (Cox Model). Confounders were defined as parameters with significantly different distribution in pts who underwent metastasis surgery and those who did not (p<0.05) and significantly associated with OS (p<0.05). Results: The database consists of 410 pts (160 in PALSAR-1 and 248 in PALSAR-2) with a median age of 43. Among them, 77 patients (18%) underwent metastasis surgery. At the end of the treatment, 61 pts experienced complete response (CR), 45 with CT alone and 16 with metastasis surgery and CT. The median follow-up was 29 months. The median OS was 35.7 months (29.9-41.5). The following parameters are associated with longer OS in univariate analysis: primary location (p=0.0001), performance status (p=0.010) and absence of liver metastasis (p=0.001). We identified 4 factors associated with metastasis surgery (n=76): limb/trunk primaries, young age, absence of liver metastasis and absence of progression of the target lesions after 4 cycles. The sole identified confounder was primary location. In multivariate analysis the 2 categories of patients experiencing significant longer OS are those with CR without surgery (HR=2.2, [1.7-5.8], p=0.0001) and those with CR following metastasis surgery (HR=3.8, [2.3-6.2], p=0.0001). Conclusions: Among the pts with ASTS receiving poly-CT as 1st-line treatment, the OS of pts experiencing CR with or without metastasis surgery appears similar. Metastatis surgery without CR does not offer significant OS advantage.

Pretransplatation PET as Major Prognostic Discriminant in IGEV (ifosfamide, gemcitabine, vinorelbine and prednisone) Treated Patients with Relapsed/Refractory Hodgkin's Lymphoma (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3707-3707
Author(s):  
Rita Mazza ◽  
Stefano Luminari ◽  
Massimo Magagnoli ◽  
Michele Spina ◽  
Teodoro Chisesi ◽  
...  
Keyword(s):  
Complete Remission ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Response To Therapy ◽  
High Dose ◽  
Bulky Disease ◽  
The Impact

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

Multiple Extranodal Involvements; Significant Risk Factor of Relapse In Peripheral T-Cell Lymphoma, Not Otherwise Specified

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4887-4887
Author(s):  
Kazuya Sato ◽  
Yoshihiro Torimoto ◽  
Yutaka Kohgo ◽  
Takashi Fukuhara
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Primary Treatment ◽  
Extranodal Involvement ◽  
Peripheral T Cell Lymphoma ◽  
Bulky Disease ◽  
Not Otherwise Specified

Abstract Abstract 4887 Background: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) comprises clinically and histopathologically a heterogeneous group of predominantly nodal diseases which do not fit into definition of any other identified subtype of PTCLs. Most of cases are advanced diseases and characterized by aggressive behavior and very poor prognosis. Although several risk factors for response and survival in PTCL-NOS have been reported, little information is available for the incidence and risk factors of relapse after complete response (CR) achievement. Further analyses of the relapse will give valuable information for effective therapeutic strategies for PTCL-NOS. The aim of this study is to evaluate the incidence and risk factors of the relapse in PTCL-NOS patients. Methods: We retrospectively reviewed 107 patients with PTCL-NOS diagnosed by The 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in Hokkaido Hematology Study Group, which includes 30 hematology/oncology or pediatrics departments of 23 institutes, from January 2002 to December 2009. We further investigated the incidence, clinical backgrounds, and risk factors of relapse of the PTCL-NOS patients. Response to treatment was assessed by international workshop to standardize response criteria for non-Hodgkin's lymphomas (Cheson BD et al. J Clin Oncol. 1999). Overall survival (OS) curves were estimated using Kaplan-Meier method and compared by log-rank test. The association between clinical factors and relapse rate was evaluated in univariate analysis by the chi-squared test. Factors independently associated with relapse or OS were identified in multivariate analysis by logistic regression model or Cox proportional hazards model, respectively. Results: The median follow-up of the patients was 24 months (range 1–95). The sample population included 70 males and 37 females with a median age of 67 years (range 9–94). Chemotherapy (ChT) was selected in 90% (96/107) patients as the primary treatment. CHOP-lile regemens were chosen in 91% (86/96) patients as the primary ChT. The estimated 5 year-OS of all the patients was 35%. 48 (52%) patients achieved CR after primary treatment in the evaluable 92 patients, and were futher analyzed. Relapse was occured in 46% (22/48) patients with a median remission duration of 9 months (range 2–51). Multiple or diffuse extranodal relapses were presented in 64% (14/22) patients. Only 5 (24%) paitients achived 2nd CR in the 21 relapsed patients recived salvage ChT. Survaval of patients with relapse was significantly shorter than that without relapse (5 year-estimated OS 32% vs 100%, p<0.0001). Factors of high relapse rates at diagnosis were as follows; central nervous system involvement (100%), extranodal involvement sites>1 (87%), gastrointestinal involvement (80%), bulky disease (67%), bone marrow (BM) involvement (67%), high (H) and high-intermediate (HI) risk groups of International Prognositic Index (IPI) (63%). In addition, relapse rate of the patients showing FDG-uptake by PET after primary treatment was 100%. In univariate analysis, extranodal involvement sites at diagnosis >1 (p=0.022), H and HI risk groups of IPI at diagnosis (p=0.021), FDG-uptake by PET after primary treatment (p=0.043) were identified as risk factors of relapse. Age, clinical stage, B-sympton, perfomance status, BM imvolvement, bulky disease, high LDH level, risk groups of prognositic index for PTCL-U (PIT), and regemen or dose-reduction of primary treatment were not significant indicators for relapse in univariate analysis. In multivariate analysis, extranodal involvement sites at diagnosis >1 was identified as an independent risk factor not only for relapse (relative risk 26.0; 95% CI 1.115–605.9; p=0.043) but also for OS (relative risk 10.8; 95% CI 1.1466–80.13; p=0.02). Conclusions: Almost half of PTCL-NOS patients who achieved CR after primary treatment will relapse and the prognosis is poor. Multiple extranodal involvements at diagnosis will be a predictive factor of relapse and survival. These findings warrant further studies regarding specific treatment approaches for PTCL-NOS patients with multiple extranodal involvements to inhibit the relapse. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

2020 ◽  
pp. 1-6
Author(s):  
Baoan Chen ◽  
Lin Gin ◽  
Jinning Shi ◽  
Wei Zhang ◽  
Wenjing Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Cox Regression ◽  
Survival Curve ◽  
Univariate Analysis ◽  
Evaluation Criteria ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Early Evaluation

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: A total of 60 patients with MM who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University and Zhongda Hospital Affiliated to Southeast University from August 2011 to March 2020 were retrospectively analysed. According to NLR, MLR, PLR, the patients were divided into the low NLR group (NLR < 3.61) or high NLR group (NLR ≥ 3.61), low MLR group (MLR < 0.33) or high MLR group (MLR ≥ 0.33), low PLR group (PLR < 129.78) and high PLR group (PLR ≥ 129.78). Overall survival (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of the patients was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin(β2-MG), lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR ≥ 129.78, HGB < 100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR ≥ 129.78, HGB < 100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis.

Germline Polymorphisms Provide Strong Prognostic Information in Intermediate Risk Acute Myeloblastic Leukemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 398-398
Author(s):  
Alvaro Urbano-Ispizua ◽  
Salut Brunet ◽  
Mariano Monzo ◽  
Granada Perea ◽  
Alfons Navarro ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Rank Test ◽  
P Value ◽  
Risk Category ◽  
High Dose ◽  
Intermediate Risk ◽  
Prognostic Information ◽  
Prognostic Variables ◽  
Increased Risk

Abstract In this study we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways (GSTT1, SULT1C2, CD-EX, TOP2A, SXR-1, SXR-2), DNA repair (XPD, XPA, XPG, ERCC1), angiogenesis (VEGF-1, VEGF-2), and multidrug resistance (MDR1-1, MDR1-2) predict clinical outcome in patients with AML. Two hundred adult patients ≤60 year-old with primary AML (M3 excluded), enrolled in the AML-99 protocol of the CETLAM group between November-98 and July-03, have been studied. Induction therapy consisted of idarubicin, intermediate dose ara-C (IDAC) and VP16. Intensification included mitoxantrone and IDAC. Patients were following treated with high-dose ara-C or transplantation depending on the risk category. According to the MRC cytogenetic classification, 32 patients had a favourable karyotype, 23 had abnormalities indicating poor prognosis, and 110 patients were included in the intermediate prognosis (IP) group. We focused on IP group patients with the aim of improving its prognostic stratification. The characteristics considered were: age (<50 years vs ≥50), WBC (≤20x109/l vs >20x109/l), FAB classification, MLL rearrangement, internal tandem duplication of FLT3 (ITD-FLT3), induction courses to achieve complete remission (CR) (1 vs 2), and germline polymorphisms of the above-mentioned genes. Prognostic variables in the univariate analysis (Kaplan-Meier method) with a p value ≤0.2 (log-rank test) were included for the multivariate analysis (proportional hazard method). Of the 110 patients included in the IP group, 86 (78%) achieved a CR, 11 (10%) were chemoresistant and 13 (12%) died during induction. After a median follow-up of alive patients of 24 months (range 5–64), overall survival was of 31% at 5 years. In the multivariate analysis, adverse prognostic variables for survival were polymorphism of XPA (RR=3.4; p=0.02) and of MDR1-1 (RR=2.1; p=0.02), and WBC >20x109/l (RR=2.1; p=0.02). Increased risk of relapse was associated with polymorphism of SULT1C2 (RR 4.1; p=0.004), ITD-FLT3 (RR 3.3; p=0.003), VEGF2 (RR 2.8; p=0.04) and MDR1-1 (RR 2.4; p=0.02). Finally, in the multivariate analysis for refractoriness to chemotherapy, XPA polymorphism was the only independent factor increasing the risk (RR=14; p=0.02). In conclusion, germline polymorphisms, which can easily be analyzed from DNA of peripheral blood, have independent prognostic value in intermediate risk AML.

Super (S)-Beam for Advanced and Refractory Multiple Myeloma (ARMM)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4800-4800
Author(s):  
Sarah Waheed ◽  
Bijay Nair ◽  
Yazan Alsayed ◽  
Monica Grazziutti ◽  
Elias J. Anaissie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Proliferation Index ◽  
Rank Test ◽  
High Dose ◽  
Significance Level ◽  
Risk Parameters

Abstract Abstract 4800 Background: Despite availability of novel agents, many MM patients still relapse and require salvage interventions. In the Arkansas program, we have attempted to procure initially sufficient hematopoietic precursor cells, for use in high-dose therapy salvage regimens once phase I-II trials have been exhausted. We are reporting on the efficacy in terms of response rate, EFS and OS of ARMM patients receiving S-BEAM. Patients and Methods: S-BEAM comprised standard BEAM (carmustine 300 mg/m2 on day 1, etoposide 200 mg/m2 days 1–4, cytarabine 400 mg/m2 days 1–4, melphalan 140 mg/m2 on day 5) with the addition of cisplatin (10-12.5mg/m2/d CI × 5d), bortezomib (1.3-1.5mg/m2 on days 1 + 4), thalidomide (100-200mg/d for 5 days) or lenalidomide (25-100mg/d for 5 days), DEX (40-100mg/d for 5 days) plus rapamycin (3mg d1, 1mg d2-5). Statistical methods included Cox regression modeling using significance level 0.05 and Kaplan-Meier methodology for all figures. Comparisons within figures were made using the log-rank test. Results: The characteristics of 147 patients treated included prior transplant (Tx) in 67% (2Tx, 29%; =>3Tx, 11%), and prior exposure and resistance in virtually all patients (92%) to bortezomib, thalidomide, lenalidomide applied in VTD, VRD or with chemotherapy VTD-PACE. Pre-S-BEAM high-risk features included low albumin (<3.5g/dL; 66%) high B2M (>=3.5mg/L; 32%), high LDH (>=ULN; 44%), and presence of cytogenetic abnormalities (CA) in 70%. Clinical outcomes included at least PR in 62% including 48% with n-CR and 29% with CR. Two-year estimates of EFS and OS were 29% and 33%; TRM within 60 days was 3%. At 4 years, 23% remain alive and 15% event-free. Independently significant variables affecting both OS and EFS adversely included, in a model without GEP, high B2M (>5.5mg/L), high LDH (>=ULN), low hemoglobin (<10g/dL) and CA, whereas achieving PR improved survival. Based on R2-driven independent adverse variables, B2M, LDH and CA were linked to poor outcomes, with 1-year estimates of OS/EFS of 83%/69% with 0, 63%/52% with 1, 25%/9% with 2, and 13%/0% with more than 2 high-risk parameters. Gene expression profiling (GEP)-defined high-risk was present in 55% (70 genes, R70) and in 47% (80 genes, R80); delTP53 was noted in 21% and Proliferation Index (PI) score >=10 in 42%. When GEP data were included in a subset of 103 patients, high-risk designation, high LDH and age >=65 were identified on the basis of highest R2 values (49% for OS, 41% for EFS). Among 28 patients lacking any of these 3 features, 1-year OS/EFS was 83%/67%, with 1 variable (n=36) 53%/38%, with 2 (n=31) 22%/6% and with 3 (n=8) 0%/0% (both P<0.001). Applying a cut-off of 2 adverse variables, the 60 patients with 2 or fewer enjoyed 2-year OS of 49% and EFS of 48%, as opposed to 7% and 4%, respectively, among the remaining 36 patients with more than 2 risk features. Conclusion: S-BEAM provides effective salvage therapy in ARMM with 60-day TRM of 3% and prognostic factor-dependent survival expectation. We are currently evaluating S-BEAM earlier in the disease course, with PAC-MED as induction prior to and as consolidation after S-BEAM in high-risk myeloma. Overall survival by number of non-GEP risk factors (B2M, LDH, CA), selected based on maximum R2 value (38% for OS, 33% for EFS) Overall survival by number of risk factors (age, LDH, GEP high-risk), selected based on maximum R2 values (49% for OS, 41% for EFS) Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Conditioning Regimens Do Not Offer a Survival Advantage to Myeloma Patients Receiving Allogeneic Stem Cell Hematopoietic Transplantation: A Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC) Registry Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4113-4113
Author(s):  
Yvan Beaussant ◽  
Etienne Daguindau ◽  
Aurore Vivot ◽  
Mohamad Mothy ◽  
Herve Avet-Loiseau ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
New Drugs ◽  
Rank Test ◽  
Reduced Intensity Conditioning ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Abstract 4113 Purpose: Despite the raise of major new drugs in the management of multiple myeloma (MM), it is still an incurable disease and allogeneic stem cell transplantation (alloSCT) is currently the sole potential curative therapy mediated by a graft-versus-myeloma (GVM) effect. For over ten years, reduced intensity conditioning regimens (RIC) in alloSCT has been developed to maintain the GVM effect and to decrease the high transplanted related mortality (TRM) associated with myeloablative conditioning (MAC) in myeloma patients. Yet, as numerous studies have assessed RIC alloSCT versus autologous SCT, only few data provides a comparison between RIC and MAC for MM in large series. Our study aims to compare RIC and MAC alloSCT for MM on a large retrospective French cohort. Methods: We report a retrospective multicenter study based on the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry, evaluating the outcome of patients undergoing alloSCT for MM. Between 1995 and 2009, 811 patients allografted for MM were registered. Data concerning disease characteristics and the allograft procedure were screened using the French Promise® database; computerized discrepancy errors and data verification of every single file ensure data quality, important missing data were directly retrieved in each centre. We assign the type of conditioning regimen for each patient according to the registry's data reported by the local physician and check this information according to the following rules. We consider as myeloablative (MAC) all regimens containing > 8 mg/kg oral busulfan, > 600 cGY TBI, ≥ 200 mg/kg cyclophosphamide or combinations as BEAM like regimens. All other chemotherapy combinations with or without TBI are defined as RIC regimens generally including fludarabine. Patients were excluded when major data or conditioning information were not available; 566 patients (70% of the entire cohort) were finally eligible for analysis, 478 RIC and 88 MAC. Chi-squared test and T-test were used for comparisons. Survival analyses (Overall survival, OS; progression-free survival, PFS) are made using the Kaplan-Meier curve and log rank test. Multivariate analysis is made using the Cox proportional hazards model. Results: The RIC and MAC populations were statistically different regarding age (respectively 53 versus 46 years, p<.0001), number of prior transplant (> 1 prior transplant in 94% RIC versus 77% MAC, p<.0001), time to transplantation (<12 months after diagnosis in 22% RIC versus 38% MAC, p=.001) and stem cell source (peripheral blood 84% RIC versus 52% MAC, p<.0001, and bone marrow 10% RIC versus 45% MAC, p<.0001). The 2-year OS is 69.5% after RIC and 79.9% after MAC (p<.0001); 5-year OS is 49.7% after RIC and 60.2% after MAC (p<.0001, fig.1). The 2 year PFS is 49.3% and 70.1% and 5-year PFS is 29.6% and 40.8% after RIC and MAC respectively (p<.0001, fig.2). Factors associated with better OS and PFS in multivariate analysis are the following in the whole cohort: < 12 months between diagnosis and alloSCT (p=.0078 and p=.0037, respectively); disease status at transplantation (at least partial response, p=.0409 and p=.0026); no or limited acute graft-versus-host disease (GvHD) (p<.0001 and p=.0094) and presence of chronic GvHD (p<.0001 and p<.0001). On multivariate analysis, the intensity of conditioning regimen (RIC vs MAC) do not appear statistically significant for OS (p = 0.64) and PFS (p = 0.17). For patients transplanted between 2006 and 2009, neither high risk-cytogenetic nor bortezomib use before transplantation seems to affect the outcome in multivariate analysis. Conclusions: In the French practice, MAC regimens have had more limited indications due to their higher toxicity. This study suggests that the outcome after MAC-alloSCT is comparable to that after RIC-alloSCT with a trend to a better OS in the late follow-up (after 5 years) after MAC. The aspect of flattening in the survival curves suggests that the anti-tumoral action of the conditioning regimen remains essential on the anti-myeloma effect after alloSCT and that should be considered in the transplantation procedure. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk Factor Analysis for Infection after Medial Open Wedge High Tibial Osteotomy

2021 ◽  
Vol 10 (8) ◽  
pp. 1727
Author(s):  
Ta-Wei Liu ◽  
Chih-Hao Chiu ◽  
Alvin Chao-Yu Chen ◽  
Shih-Sheng Chang ◽  
Yi-Sheng Chan
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Multivariate Analysis ◽  
High Tibial Osteotomy ◽  
Univariate Analysis ◽  
Arthroscopic Surgery ◽  
Underlying Disease ◽  
Tibial Osteotomy ◽  
Open Wedge ◽  
Wedge High Tibial Osteotomy

Background: Medial open wedge high tibial osteotomy (MOWHTO) is a well-established treatment for osteoarthritis of the medial tibiofemoral compartment. Surgical site infection (SSI) after MOWHTO is a devastating complication that may require further surgery. In this study, we aimed to identify the risk factors for infection after MOWHTO over 1 to 4 years of follow-up. Methods: Fifty-nine patients who underwent MOWHTO combined with knee arthroscopic surgery were included in this prospective study. Artificial bone grafts were used in all cases. Possible risk factors, including sex, age, body mass index (BMI), underlying disease, hospitalization length, correction angle, and surgery time, were recorded. Both univariate and multivariate analysis were used. Results: A total of 59 patients who underwent 61 operations were included. Eleven patients (18.0%) were reported to have SSI. Univariate analysis showed that smoking and diabetes mellitus were positively associated with SSI. Multivariate analysis showed that smoking and age were positively associated with SSI. Three patients (4.9%) were reported to suffer from deep SSI, requiring surgical debridement, all of whom were male smokers. Conclusion: Smoking, diabetes mellitus, and old age were identified to be possible risk factors of SSI after MOWHTO. These findings are common risk factors of SSI after orthopedic surgery according to the literature. Patient selection should be performed cautiously, and postoperative prognosis for MOWHTO should be carefully explained to patients who smoke.

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