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.

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.

Pacmed Salvage Therapy for Advanced High-Risk Multiple Myeloma (AHRMM)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1969-1969
Author(s):  
Yazan Alsayed ◽  
Sarah Waheed ◽  
Jackie Szymonifka ◽  
Bijay Nair ◽  
Saad Usmani ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Large Cell ◽  
Novel Agents ◽  
Tumor Control ◽  
High Dose ◽  
Logrank Test ◽  
Baseline Characteristics

Abstract Abstract 1969 Background: High-risk MM remains a very difficult clinical challenge despite advances in therapy for the majority of patients who have benefited from the use of high-dose therapies and novel agents. Recognizing that MM from the outset represents a genomically highly complex malignancy with even further accelerated acquisition of mutations with every further relapse, we have tried to develop multi-agent combinations employing drugs with efficacy in other high-grade tumors such as large cell lymphomas and incorporated novel agents as well. Patients and Methods: Eighty-four patients with AHRMM were given PACMED comprising cisplatin (15-25mg/m2 CI × 3d), cytarabine (1.0-1.5g/m2/d × 3), cyclophosphamide (1.0-1.5g/m2/d CI × 3), mesna (1.0-1.5g/m2/d CI × 3), etoposide (0.3-0.5g/m2/d × 3) and DEX (40-100mg/d × 3); additional agents included bortezomib (1.0-1.6mg/m2 on days 1 + 4), thalidomide (100-200mg/d × 4d) or lenalidomide (25-100mg/d × 4) and rapamycin (3mg d 1, 1mg d 2–4) with or without HPC boost. Statistical methods included Cox regression modeling for OS and EFS, along with Kaplan-Meier methodology for survival and cumulative incidence plots. Survival comparisons were made using the logrank test. Results: Baseline characteristics included age >=65 in 18%, B2M >=3.5mg/L in 68% and >5.5mg/L in 38%, CRP >=8mg/L in 60%, LDH >=ULN in 57%, and cytogenetic abnormalities (CA) in 62%. Gene expression profiling (GEP)-defined high-risk (70 genes, R70; 80 genes, R80) was present in 80% and 71%; PR (Proliferation), MF and MS subtypes were present in 44%, 27% and 14%. Prior transplants (Tx) had been given to 96%, including 40% who received 2Tx, 25% with 3Tx and 14% with >3Tx. PR was achieved by 29%, including 14% n-CR and 8% CR. 1-year estimates of OS and EFS were low at 13% and 8%, and median durations were 5 and 3 months. Increased age and high LDH were the only baseline characteristics adversely affecting both OS and EFS. The 29 patients with neither of these risk factors experienced 1-yr OS/EFS rates of 31%/17%; the corresponding values with 1 risk factor (n=47) were 5%/4% and with both risk factors (n=8) 0%/0%. Conclusion: Single cycle PACMED provides only transient tumor control in this heavily pretreated population with 80% displaying GEP-defined high-risk and 62% CA, as a manifestation of end-stage MM. We are currently evaluating repeated cycles of PACMED earlier in the disease course in high-risk MM, in the context of a Super-BEAM transplant regimen. 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.

Multiple Myeloma In Patients Under 40 Years Old Is Associated With High-Risk Features and Worse Outcomes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5359-5359 ◽  
Author(s):  
Caitlin L. Costello
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Young Patients ◽  
Age At Diagnosis ◽  
Cancer Center ◽  
Common Disease ◽  
High Dose

Background The median age of patients diagnosed with multiple myeloma (MM) is approximately 70 years old. It is an uncommon malignancy in persons younger than 40 years, representing only 2% of all patients diagnosed with MM. It has been suggested that young patients may present with more aggressive and less common disease features, frequently delaying the initial diagnosis and thereby affecting outcomes. With this background, we explored the outcome of young MM patients presenting to our institution over the past thirteen years. Methods We performed a retrospective review of a cohort of 236 patients with MM who received treatment for active MM at the University of California, San Diego Moores Cancer Center between January 2000 and July 2013.  The demographics and disease features of patients up to 40 years of age at diagnosis were analyzed using descriptive statistics. The survival outcomes of these young patients were compared with the remainder of the cohort using the Kaplan-Meier method. Results Nineteen (6.5%) out of the 236 patients with MM were ²40 years of age at diagnosis, with a median age of 35.5 years old. The median follow-up of this group of young patients was 42 months (range 5-92). The patient and disease characteristics are outlined in Table 1. Seven young patients (37%) had MM with no heavy chain component, including light chain only secreting or non-secretory disease.  Seven patients (37%) had a non-IgG paraprotein. Nine (56%) patients presented with extramedullary plasmacytomas. Two (10%) patients had plasma cell leukemia. All patients received at least one treatment regimen that included a novel agent. Fifteen patients (79%) had received high-dose therapy, and four patients (21%) underwent allogeneic stem cell transplantation (SCT) after at least one prior autologous SCT. The 5-year and 7-year overall survival (OS) from diagnosis was 51.7% and 28%, respectively, and the median OS was 60.7 months. In contrast, the median OS of patients ≥41 years old at diagnosis was 78.6 months (p=0.15, figure 1). Conclusion In this single center study with long follow up, we demonstrate that patients diagnosed with MM ²40 years of age exhibit several high-risk features and frequently present with advanced stage disease. Despite the use of novel agents in this population, there is a statistical trend towards a worse outcome with an 18-month difference in median overall survival when compared to older patients with MM. More aggressive treatment strategies are needed to improve survival in this young patient population. Disclosures: No relevant conflicts of interest to declare.

Does chemotherapy work in reversal of malignant obstruction due to gastric cancer?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21676-e21676
Author(s):  
Vanessa Montes Santos ◽  
Renata Gondim Meira Velame Azevedo ◽  
Rossana Veronica Mendoza Lopez ◽  
Paulo Marcelo Hoff ◽  
Jorge Sabbaga ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Metastatic Gastric Cancer ◽  
Rank Test ◽  
Anticholinergic Drugs ◽  
Significance Level ◽  
Malignant Obstruction ◽  
Kaplan Meier ◽  
Clinical Measures

e21676 Background: Malignant obstruction (MO) is a common complication in patients with gastric cancer. Although palliative chemotherapy has already shown beneficial for overall survival in advanced cases, its value for MO reversal is still unknown. Methods: Inthis retrospective study we analyzed all consecutive patients with metastatic gastric cancer admitted with MO at the Instituto do Câncer do Estado de São Paulo (ICESP) from 2008 to 2016. The primary and secondary endpoints were overall survival and obstruction reversal rate respectively. Clinical measures other than chemotherapy and alimentary pause included the use of octreotide 0.1 mg, 3 times a day, steroids, antiemetics and anticholinergic drugs. Survival curves were calculated by Kaplan-Meier and log-rank test was used to compare them. The Cox regression model was used to evaluate risk factors for overall survival and the hazard ratio (HR) was calculated with its respective 95% confidence intervals. The analysis was performed in SPSS v.18 for Windows statistical software, and the significance level was 5%. Results: One hundred and eighteen(118)patients were included. Median overall survival was 11.2 months and survival time after the MO was 3.6 months for the whole group. Median time of use of octreotide was 3 days. Reversal of obstruction was seen in 16 of 36 patients (38.4%) in which chemotherapy was used and only in 22 of the 92 patients (24%) treated with exclusive clinical measures. In spite of these figures a significant better overall survival (p 0.002) was achieved in the group of patients that reached obstruction reversal without chemotherapy (13.6 months vs. 11.6 months for the clinical treatment group). Conclusions: This study suggests that chemotherapy even when reversing MO, has no impact in patients overall survival. These finding is particularly relevant for cost contingency in settings with limited resources. .

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 Cancer survival among children and adolescents at a state referral hospital in southeastern Brazil

2013 ◽  
Vol 13 (4) ◽  
pp. 335-344
Author(s):  
Glaucia Perini Zouain-Figueiredo ◽  
Eliana Zandonade ◽  
Maria Helena Costa Amorim
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Survival Rate ◽  
Children And Adolescents ◽  
Cox Regression ◽  
Referral Hospital ◽  
Cns Tumors ◽  
Southeastern Brazil ◽  
Rank Test ◽  
Adolescent Cancer

OBJECTIVES: to analyze the patient characteristics and evaluate overall survival, survival according to demographic variables, the most common tumor groups and subgroups, the stages of disease, and risk factors after at least 5 years among children and adolescents with cancer who were admitted to a state referral hospital between 2000 and 2005. METHODS: the Kaplan-Meier method was employed to estimate survival. The survival curves were compared using the log-rank test. The Cox regression model was used to estimate the effect of independent variables. RESULTS: a total of 571 new cases were registered. The most frequent cancer groups were leukemia (34%), lymphoma (18%), and central nervous system (CNS) tumors (15%).The overall survival rate was 59%. The risk factors associated with lower survival were an age of more than 4 years or less than 1 year, the presence of CNS tumors, and non-localized disease. CONCLUSION: although this was not a populationbased study, it provides important epidemiological information about a state where population data on childhood and adolescent cancer are scarce and where hospital-based data do not exist. The survival rate found here should serve as a framework for future improvements, helping to guide policymakers focused on pediatric oncology in the state.

Analysis of Risk Factors for Overall Survival at 5 Years in 96 Patients after Allogeneic Hematopoietic Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4669-4669
Author(s):  
Jiahua Ding ◽  
Jiahua Ding
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Blood Type ◽  
Hematopoietic Stem

Abstract Abstract 4669 The aim was to analyze the risk factors for overall surrival at 5 years in 96 patients undergoing allogeneic hematopoietic stem cell transplantation by retrospec- tive analysis. 11 clinical parameters were selected for univariate analysis by using a Cox regression: age, sex, morbid rate, HLA locus, donor type, donor-recipient blood type, conditioning regimen, aGVHD, HC, VOD and IP. Factors significant at the 0.1 level on univariate analysis were evaluated by multivariate analysis by a Cox regres- sion. The cumulative incidence of aGVHD and patients survival rate were calculated by the method of Kaplan and Meier. 95 patients achieved sustained donor engraftment except one patients not. The median time of leukocyte engraftment was 13 days. The incidence rates of grades I∼IV acute GVHD was 43.75%.one of grades I aGVHD was 11.46%,gradesIIaGVHD was 19.79%,grades III∼‡WaGVHD was 12.50%. Ten patients relapsed and 38 dead,the overall survival at 5 years was 60.42%. The COX method analysis showed that aGVHD and disease states at transplant significantly im- proved OS. In conclusions, The key to improve the outcome of allo-HSCT is to red- uce the incidence and severity of aGVHD, meanwhile selecting the suitable disease state of CR1 at transplantation to treat the patients in advanced refractory and recure- nt situation. Disclosures: No relevant conflicts of interest to declare.

Prognostic Relevance of Dose-Density of DHAP-Reinduction Therapy in Relapsed HL: An Analysis of the German Hodgkin-Study Group (GHSG)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 552-552
Author(s):  
Stephanie Sasse ◽  
Magdalena Alram ◽  
Horst Mueller ◽  
Lenka Smardova ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
High Dose ◽  
Time Interval ◽  
Cycle Duration ◽  
Cox Regression Analysis ◽  
Prognostic Relevance

Abstract Abstract 552 Purpose: Only about 50% of relapsed Hodgkin Lymphoma (HL) patients achieve long-term remission with intensive reinduction therapy followed by high-dose-chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Response to reinduction treatment indicates chemosensitivity and is predictive for the outcome. An important determinant for the efficacy of reinduction therapy was thought to be dose-density. Based on this hypothesis, we aimed at increasing dose density of DHAP (dexamethasone, high-dose cytarabine, cisplatinum) in the HDR2 trial for patients with relapsed HL by shortening the cycle interval from 21 to 14 days. This was feasible after the introduction of G-CSF and consecutive reduction of neutropenia. However, the prognostic relevance of dose-density of DHAP or any other regimen in relapsed HL has never been proven. Therefore we performed a retrospective analysis of patients treated in the HDR2-trial with regard to time interval of DHAP courses and outcome. Patients and methods: In the HDR2 trial, patients with relapsed HL initially received two courses of DHAP. Those patients without disease progression after DHAP were randomized to proceed to HDCT with BEAM and ASCT or to receive additional sequential high-dose reinduction chemotherapy before BEAM and ASCT (Josting et al, JCO 2010). DHAP cycle interval was defined as the time interval between day 1 of the first course and start of the second DHAP course. Kaplan-Meier and Cox regression analysis were used to estimate the prognostic value of the DHAP cycle interval on progression-free survival (PFS) and overall survival (OS) after relapse. Mean differences of DHAP cycle intervals depending on thrombocytopenia were tested using a t-test for independent groups. The level of significance was set to P < 0.05. Results: From a total of 284 HL-patients included, 269 patients were evaluable for this analysis. The median age was 36 years, 36% of the patients analyzed were female, 53% had advanced-stage disease at diagnosis of relapse, and 13% had received >1 previous chemotherapy. Median time from initial diagnosis to relapse was 44.3 months. Only 15% of the HL patients received the second DHAP course within the recommended time interval of 14 days; in 39% the DHAP course interval was 21 days or longer. Cox regression analysis showed a significant association between the length of the DHAP cycle interval and PFS (p= 0.012). This was confirmed (p=0.035) even after adjustment for established prognostic factors including early or multiple relapses, stage III or IV at relapse, and anemia at relapse (Josting et al., 2002). In addition, overall survival was also significant as determined in the multivariate analysis (p=0.003). Patients who received the second DHAP course on day 21 or later had a significantly lower PFS and OS than those patients who proceeded with the second course before day 21 (3-year PFS 58% vs. 73%, p= 0.027; 3-year OS 76% vs. 87%, p = 0.016, respectively). Grade 4 thrombocytopenia occurred frequently (30%, grade 3/4 = 60%) and contributed significantly to the duration of the cycle. The mean DHAP cycle interval was longer for patients with grade 4 thrombocytopenia (20.9 days) than for patients with grade 0–3 thrombocytopenia (19.3 days, p= 0.028). Both PFS and OS were significantly reduced compared to those patients who did not develop thrombocytopenia grade 4 (3-year PFS 58% vs 70%, p= 0.029; 3-year OS 71% vs 88%, p= 0.002). Conclusion This is the first analysis showing that dose density of DHAP reinduction therapy is a significant and relevant prognostic factor with regard to PFS and OS of relapsed HL patients. Based on these findings, we recommend minimized cycle duration during reinduction therapy for relapsed HL patients in clinical routine. Furthermore, thrombocytopenia is a frequent and also significant factor which contributes to prolonged DHAP course intervals, and has a negative impact on PFS and OS. These findings support the investigation of thrombopoietin analogues during DHAP reinduction in relapsed HL patients in order to maintain dose density. Disclosures: No relevant conflicts of interest to declare.

scholarly journals 312 Female sex independently predicts adjuvant immunotherapeutic benefit from CTLA4 immune checkpoint inhibition

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A339-A339
Author(s):  
Ahmad Tarhini ◽  
Ni Kang ◽  
Sandra Lee ◽  
F Stephen Hodi ◽  
Gary Cohen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Efficacy ◽  
Significant Interaction ◽  
Cox Regression ◽  
Performance Status ◽  
Phase Iii ◽  
High Dose ◽  
List Type ◽  
Female Sex ◽  
Interaction Term

BackgroundSex differences in tumor immunity and response to immunotherapy were shown in murine models and descriptive analyses from recent clinical trials. Female sex hormones have been implicated in melanoma development and response to systemic therapy. We hypothesized a gender difference in response to adjuvant immunotherapy with ipilimumab (3 or 10 mg/kg; ipi3 or ipi10) versus high dose IFNα (HDI) as tested in the E1609 trial.MethodsE1609 demonstrated significant overall survival (OS) benefit with ipi3 versus HDI.1 We investigated treatment efficacy between ipi and HDI in the subgroups by sex (female, male), age (< 55 or ≥55), stage at study entry (IIIB, IIIC, M1a/1b), ECOG performance status (PS 0, 1), ulceration (yes, no), primary tumor (known, unknown), number of lymph nodes involved (0, 1, 2–3, 4+). Forest plots were created to compare OS and RFS with ipi3 vs. HDI and ipi10 vs. HDI using the concurrently randomized ITT populations. For the estimated HRs, 95% confidence intervals were created for all subgroups.ResultsThe subgroups of female, stage IIIC, PS=1, ulcerated, in-transit without lymph node involvement demonstrated significant improvement in overall survival (OS) and/or relapse free survival (RFS) with ipi3 versus HDI as summarized in table 1. Female sex was significant for both OS and RFS and was further explored. In investigating RFS with ipi3 versus HDI, a multivariate Cox regression model including sex, treatment and interaction term of sex*treatment, indicated a significant interaction between sex and treatment (P = 0.026). Including sex, PS (0 vs. 1), age (<55 vs. 55+), ulceration (yes vs. no), stage (IIIB, IIIC, M1a, M1b), treatment and interaction term of sex*treatment, indicated a significant interaction between sex and treatment (P = 0.024). While similar trends were seen, no significant interactions between sex and treatment effect were found in the OS multivariate analysis or in the comparison of ipi10 versus HDI. When exploring age, in the univariate analyses in the ipi3 versus HDI comparison older women appeared to drive most of the difference (age ≥55: OS, P=0.02 and RFS, P=0.08; differences non-significant for women <55). Table 1.Abstract 312 Table 1Treatment efficacy between ipi3 and HDI by subgroupConclusionsFemale sex was independently associated with RFS adjuvant immunotherapeutic benefit from ipi3, supporting a potentially important role for female related factors in the immune response against melanoma, and these warrant further investigation.Trial RegistrationNCT01274338Ethics ApprovalThe study protocol was approved by the institutional review board (IRB) of each participating institution and conducted in accordance with Good Clinical Practice guidelines as defined by the International Conference on Harmonisation. This study was monitored by the ECOG-ACRIN DataSafety Monitoring Committee and the NCI.ConsentAll patients provided IRB-approved written informed consent.ReferenceTarhini AA, Lee SJ, Hodi FS, Rao UNM, Cohen GI, Hamid O, Hutchins LF, Sosman JA, Kluger HM, Eroglu Z, Koon HB, Lawrence DP, Kendra KL, Minor DR, Lee CB, Albertini MR, Flaherty LE, Petrella TM, Streicher H, Sondak VK, Kirkwood JM. Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: North American Intergroup E1609. J Clin Oncol. 2020 Feb 20;38(6):567–575. PMID: 31880964.

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