scholarly journals Anti-GD2 immunotherapy with the chimeric antibody ch14.18 for high-risk neuroblastoma

2020 ◽  
Vol 19 (3) ◽  
pp. 173-178
Author(s):  
T. V. Shamanskaya ◽  
N. A. Andreeva ◽  
D. T. Utalieva ◽  
D. Yu. Kachanov
Keyword(s):  
Monoclonal Antibodies ◽  
High Risk ◽  
Tumor Cells ◽  
Multimodal Therapy ◽  
Risk Groups ◽  
High Risk Group ◽  
Chimeric Antibody ◽  
High Dose ◽  
Term Survival ◽  
Hematopoietic Stem

Neuroblastoma is the most common extracranial solid tumor in children 0–14 years old. Current risk-adapted treatment programs are based on stratification of patient into three risk groups. 40–50% of patients are stratified into the high-risk group. The prognosis in high-risk patients remains poor (the probability of long-term survival is less than 50%), despite the use of aggressive multimodal therapy, including high-dose chemotherapy and autologous hematopoietic stem cell transplantation. In most cases tumor cells in neuroblastoma express disialoganglioside GD2, which is a possible target for immunotherapy. Over the past 30 years, GD2-directed chimeric monoclonal antibodies ch14.18 have been introduced into clinical practice. A number of clinical studies have shown an improvement in the prognosis in patients with high-risk neuroblastoma, when using monoclonal antibodies ch14.18, primarily due to the eradication of the minimal residual population of tumor cells resistant to standard chemotherapy. This literature review summarizes the international experience in the use of monoclonal antibodies ch14.18 from early phases of clinical trials to large randomized trials, which allowed immunotherapy to be considered as an important component of multimodal therapy for high-risk neuroblastoma. Future prospects for the use and place of immunotherapy in first-line therapy of high-risk neuroblastoma and in relapsed setting are considered.

scholarly journals Allogeneic Stem Cell Transplantation in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Christine Greil ◽  
Monika Engelhardt ◽  
Jürgen Finke ◽  
Ralph Wäsch
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Groups ◽  
High Dose ◽  
Term Survival ◽  
Hematopoietic Stem

The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.

scholarly journals Screening Circulating Tumor Cells as a Noninvasive Cancer Test in 3388 Individuals from High-Risk Groups (ICELLATE2)

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Juan Castro ◽  
Luis Sanchez ◽  
María Teresa Nuñez ◽  
Ming Lu ◽  
Tomas Castro ◽  
...  
Keyword(s):  
High Risk ◽  
Early Detection ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Symptoms ◽  
Risk Groups ◽  
Circulating Tumor Cell ◽  
High Risk Group ◽  
Screening Tests ◽  
Cancer Risk Factors

Cancer is known to spread up to 12 years before clinical symptoms occur, but few screening tests exist. Early detection would give the opportunity for early treatment, potentially improving prognosis. To this end, 3388 subjectively healthy individuals of age 45 to 80 who had been exposed to cancer risk factors were screened for the occurrence of circulating tumor cells in their blood. Presence of circulating tumor cells is a suspicious finding indicative of spreading cancer, since cancer metastasizes by way of the blood and offers the opportunities to (a) follow up the individual clinically based on established guidelines for early detection of cancer and (b) evaluate the cells further analytically. 107 individuals showed one or more circulating tumor cells in a 7.5 ml blood sample, which constitutes a positive circulating tumor cell test, based on the iCellate IsoPic™ laboratory test. That number compares favorably with the cancer incidence per 100,000 people/year that is 157.1 in Peru, given that a high-risk group of individuals was screened and that the screening results would be expected to correspond to an accumulated incidence of up to 12 years. The present findings therefore identify screening for circulating tumor cells as a promising new test.

High-risk Neuroblastoma: Poor Outcomes Despite Aggressive Multimodal Therapy

2021 ◽  
Vol 17 ◽  
Author(s):  
Adil Abdelhamed Abbas ◽  
Alaa Mohammed Noor Samkari
Keyword(s):  
High Risk ◽  
Multimodal Therapy ◽  
Treatment Strategies ◽  
Low Risk ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Clinical Behavior ◽  
Frequent Relapses ◽  
Recent Developments ◽  
Poor Outcomes

: Neuroblastoma (NBL) is a highly malignant embryonal tumor that originates from the primordial neural crest cells. NBL is the most common tumor in infants and the most common extracranial solid tumor in children. The tumor is more commonly diagnosed in children of 1-4 years of age. NBL is characterized by enigmatic clinical behavior that ranges from spontaneous regression to an aggressive clinical course leading to frequent relapses and death. Based on the likelihood of progression and relapse, the International Neuroblastoma Risk Group classification system categorized NBL into very low risk, low risk, intermediate risk, and high risk (HR) groups. HR NBL is defined based on the patient's age (> 18 months), disease metastasis, tumor histology, and MYCN gene amplification. HR NBL is diagnosed in nearly 40% of patients, mainly those > 18 months of age, and is associated with aggressive clinical behavior. Treatment strategies involve the use of intensive chemotherapy (CTR), surgical resection, high dose CTR with hematopoietic stem cell support, radiotherapy, biotherapy, and immunotherapy with Anti-ganglioside 2 monoclonal antibodies. Although HR NBL is now better characterized and aggressive multimodal therapy is applied, the outcomes of treatment are still poor, with overall survival and event-free survival of approximately 40% and 30% at 3-years, respectively. The short and long-term side effects of therapy are tremendous. HR NBL carries a high mortality rate accounting for nearly 15% of pediatric cancer deaths. However, most mortalities are attributed to the high frequency of disease relapse (50%) and disease reactiveness to therapy (20%). Newer treatment strategies are therefore urgently needed. Recent discoveries in the field of biology and molecular genetics of NBL have led to the identification of several targets that can improve the treatment results. In this review, we discuss the different aspects of the epidemiology, biology, clinical presentations, diagnosis, and treatment of HR NBL, in addition to the recent developments in the management of the disease.

scholarly journals The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia

Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2091-2097 ◽  
Author(s):  
J Cortes ◽  
SM O'Brien ◽  
S Pierce ◽  
MJ Keating ◽  
EJ Freireich ◽  
...  
Keyword(s):  
High Risk ◽  
Systemic Chemotherapy ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Relapse Rates

Although central nervous system (CNS) leukemic relapse is frequent in adult acute lymphocytic leukemia (ALL), the need for prophylaxis in different risk groups for CNS relapse, the value of high-dose systemic and intrathecal (IT) chemotherapy, and the timing of prophylaxis are not well defined. This analysis was conducted to investigate these questions and to assess the value of a risk-oriented CNS prophylaxis approach. We analyzed the incidence of CNS leukemia after initiation of therapy in patients treated on 4 consecutive trials for adult ALL including different CNS prophylactic modalities. The treatment groups included (1) the program preceeding the vincristine-Adriamycin- dexamethasone (VAD) regimen, with no CNS prophylaxis; (2) the VAD regimen with prophylaxis using high-dose systemic chemotherapy; (3) the modified VAD program with high-dose systemic chemotherapy to all patients and IT chemotherapy for high-risk patients after achieving complete remission; and (4) the hyperCVAD program with early high-dose systemic and IT chemotherapy starting during induction to all patients, with more IT injections (16IT) administered to the high-risk group for CNS relapse compared with the low-risk group (4IT). A total of 391 patients were included, 73 of whom were treated with preVAD, 112 with VAD, 114 with modified VAD, and 92 with hyperCVAD. The overall CNS relapse rates were 31%, 18%, 17%, and 3%, respectively for the 4 groups (P < .001). For the high-risk group for CNS relapse, they were 42%, 26%, 20%, and 2%, respectively (P < .001). The differences in CNS relapse rates in the low-risk group were not statistically significant. At 3 years, the overall CNS leukemia event-free rates were 48%, 76%, and 98%, respectively (P < .001). In the high-risk group, the CNS event- free rates were 38%, 66%, 75%, and 98%, respectively (P < .001); however, there was no difference in the low-risk group. We conclude that (1) high-dose systemic chemotherapy is a useful prophylactic measure; (2) early IT chemotherapy is necessary to reduce the incidence of CNS leukemia overall and in the high-risk group; and (3) a risk- oriented approach is appropriate to tailor the intensity of CNS prophylaxis.

scholarly journals Combination of NCCN Risk Stratification System and Pre-Transplant Minimal Residual Disease Levels for the Prognosis of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3434-3434
Author(s):  
Yahan Li ◽  
Xue Sun ◽  
Xin Wang ◽  
Xiaosheng Fang
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Poor Prognosis ◽  
Residual Disease ◽  
Risk Groups ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Risk Stratification Tool ◽  
Prognosis Group

Abstract Background Numerous studies have confirmed that National Comprehensive Cancer Network (NCCN) risk stratification or pre-transplant minimal residual disease (MRD) levels can predict the risk of recurrence and survival after transplantation. But it is unclear whether combining these two parameters can more accurately predict prognosis. Methods We retrospectively analyzed 85 patients with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and constructed a new risk stratification tool combining NCCN risk stratification and pre-MRD levels. All patients were grouped by NCCN risk stratification (favorable/intermediate prognosis and poor prognosis group), pre-MRD levels (MRD (-) group (&lt;0.1%) and MRD (+) group (≥0.1%)) and a combination of the above (low, intermediate and high risk groups), and graft-versus-host disease (GVHD) and prognosis were compared between groups. Results Relative to the favorable/intermediate prognosis group, OS and RFS were poorer in the poor prognosis group (71% vs 82%, P= .156; 60% vs 74%, P= .101) and CIR (29% vs 20%, P= .229) and NRM (23% vs 14%, P= .200) were better. The incidence of aGVHD and cGVHD was slightly lower in the favorable/intermediate prognosis group than in the poor prognosis group (38% vs 46%, P= .415; 10% vs 11%, P=. 572). Relative to the MRD (+) group, the MRD (-) group had significantly better OS and RFS (89% vs 59%, P= .002; 79% vs 50%, P= .003), lower CIR and NRM (15.1% vs 37.5%, P= .011; 11.3% vs 28%, P= .040), and a lower incidence of cGVHD (6% vs 19%, P= .022). The new risk stratification tool stratified patients into low, intermediate and high risk groups. Patients in the high-risk group had the highest incidence of aGVHD and cGVHD (42% vs 35% vs 53%, P= .606; 6% vs 11% vs 20%, P= .157). The difference in cGVHD between the low- and high-risk groups was significant (P= .038). Three-year OS was 93.9%, 70% and 60% (P= .011) and RFS was 85%, 62% and 46.7% (P= .009) for low-, intermediate- and high-risk patients, respectively. The differences in OS and RFS between the low- and intermediate-risk groups were statistically significant (P= .010; P= .025), as were the differences in OS and RFS between the low- and high-risk groups (P= .001; P= .001). Patients in the high-risk group had the highest CIR and NRM relative to those in the low- and intermediate-risk groups (9% vs 32% vs 33.3%, P= .027; 6% vs 24.3% vs 26.7%; P= .059). The differences in CIR (P= .012) and NRM (P= .028) were statistically significant in both the low-risk and intermediate-risk groups, as well as in the low- and high-risk groups (CIR: P= .028; NRM: P= .021). Multivariate analysis indicated that time to ANC recovery, time from diagnosis to transplantation, and novel risk stratification were independent prognostic factors. Conclusions Both pre-MRD levels and NCCN risk stratification predict AML prognosis after allo-HSCT, and combining the two can more accurately predict post-transplant prognosis. Disclosures No relevant conflicts of interest to declare.

MD Anderson Scoring System (MDACC) Predicts Outcomes After Hematopoietic Stem Cell Transplantation (HSCT) Better Than Other Prognostic Classifications In MDS

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3340-3340
Author(s):  
Piyanuch Kongtim ◽  
Uday R Popat ◽  
Marcos de Lima ◽  
Guillermo Garcia-Manero ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Risk Group ◽  
Univariate Analysis ◽  
Scoring Systems ◽  
Risk Groups ◽  
High Risk Group ◽  
Risk Scores ◽  
Hematopoietic Stem ◽  
Very High

Abstract MDS is a heterogeneous group of hematopoietic stem cell disorders. Various prognostic models have been established to categorize patients with MDS including the International Prognostic Scoring System (IPSS), the Revised-IPSS (r-IPSS) and MDACC Scoring System. In this analysis, we compared those three classification schemas for their outcome predictability after HSCT. We analyzed 291 MDS patients with a median age of 55 (interquartile range (IQR) 47-60.7 years) who underwent HSCT between January 2001 and December 2011. Histology by WHO classification included RA/RARS 48 (16.5%), RCMD 28 (9.6%), RAEB-1 59 (20.2%), RAEB-2 63 (21.7%), MDS unclassified 67 (23%), and CMML 26 (9%). Of 291, 117 patients (40.2%) had therapy related MDS (t-MDS). Conditioning regimen was myeloablative in 201 patients (69.1%) and reduced intensity in 90 patients (30.9%). Donors were matched related (MRD), matched unrelated (MUD), mismatched (MMD) in 131 (45%), 114 (39.2%) and 46 (15.8%) patients respectively. Risk categorization was performed by IPSS, r-IPSS and MDACC scoring systems at the time of diagnosis. IPSS, r-IPSS and MDACC scoring systems could be assessed in 239 (82.1%), 241 (82.8%) and 231 (79.4%) patients respectively. The median follow up time of 109 survivors was 45 months. The median time from diagnosis to HSCT was 7.3 months (IQR 4.6-12.4 months). Three-year overall survival (OS) was 38.1% (95%CI 32.3-43.9) with 3-year event free survival (EFS) of 34.2% (95%CI 28.4-40). Cumulative relapse incidence (RI) at 3-year was 28.8% (95%CI 23.3-34.5). Cumulative incidence of treatment related mortality (TRM) at 3 year post-transplant was 27.9% (95%CI 22.6-33.6). In univariate analysis, IPSS and r-IPSS were able to differentiate 2 risk groups for OS and EFS. High risk group per IPSS and very high risk group per r-IPSS had lower OS with hazard ratio (HR) of 2.4 to 3.1, lower EFS with HR of 2.2 to 2.7. While IPSS could not predict RI, very high risk group by r-IPSS had higher RI with HR of 3.6 compared with lower risk groups. Both IPSS and r-IPSS did not identify different risk groups for TRM. On the other hand, MDACC scoring system was able to identify 4 different risk groups for EFS and OS in univariate analysis. Three-year OS was 68%, 46.1%, 30.3% and 11.4% for patients with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 respectively (p<0.001) (figure1). Three-year EFS with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 was 61.7%, 40.8%, 28.1% and 7.4% respectively (p<0.001). For RI and TRM, only MDACC risk scores of ≥9 was associated with poor outcomes with 3-year RI of 38.9% and 3-year TRM of 41.7% compared with 13.3% and 15.5% in risk scores of 0-4 (p=0.01 and p=0.01 respectively). In multivariate analysis, MDACC score, matched unrelated and mismatched donors were associated with inferior OS (table1). As a summary, MDACC risk scoring system for MDS better differentiates prognostic groups than IPSS or r-IPSS. Considering the high frequency of t-MDS among transplanted MDS patients, we propose that MDACC scoring system should be used for prognostic classification for hematopoietic transplantation. Disclosures: No relevant conflicts of interest to declare.

Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma

Cancer ◽  
2006 ◽  
Vol 106 (11) ◽  
pp. 2327-2336 ◽  
Author(s):  
Emer O. Hanrahan ◽  
Kristine Broglio ◽  
Deborah Frye ◽  
Aman U. Buzdar ◽  
Richard L. Theriault ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Breast Carcinoma ◽  
Randomized Trial ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Primary Breast Carcinoma ◽  
Hematopoietic Stem ◽  
Stem Cell Support ◽  
Cell Support

scholarly journals Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 374
Author(s):  
Simon Bailey ◽  
Nicolas André ◽  
Lorenza Gandola ◽  
Maura Massimino ◽  
Stefan Rutkowski ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
High Risk ◽  
Disease Risk ◽  
Risk Groups ◽  
Randomised Clinical Trial ◽  
Paediatric Oncology ◽  
High Dose ◽  
The Status ◽  
Risk Patients

Medulloblastoma patients receive adapted therapies stratified according to their risk-profile. Favourable, standard, and high disease-risk groups are each defined by the status of clinical and pathological risk factors, alongside an evolving repertoire of diagnostic and prognostic biomarkers. Medulloblastoma clinical trials in Europe are coordinated by the International Society for Paediatric Oncology (SIOP-Europe) brain tumour group. Favourable and standard-risk patients are eligible for the SIOP-PNET5-MB clinical trial protocol. In contrast, therapies for high-risk disease worldwide have, to date, encompassed a range of different treatment philosophies, with no clear consensus on approach. Higher radiotherapy doses are typically deployed, delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, trials to date in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international biomarker-driven, randomised, clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens. The HR-MB patient population is molecularly and clinically defined, and upfront assessments incorporate a standardised central review of molecular pathology, radiology, and radiotherapy quality assurance. Secondary objectives include the assessment of (i) novel therapies within an upfront ‘window’ and (ii) therapy-associated neuropsychology, toxicity, and late effects, alongside (iii) the collection of materials for comprehensive integrated studies of biological determinants within the SIOP-HR-MB cohort.

scholarly journals Establishment of an immune-related gene pairs model to predict colon adenocarcinoma prognosis

2020 ◽  
Author(s):  
Jihang Luo ◽  
Puyu Liu ◽  
Leibo Wang ◽  
Yi Huang ◽  
Yuanyan Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Risk Group ◽  
Colon Adenocarcinoma ◽  
Risk Groups ◽  
High Risk Group ◽  
Related Gene ◽  
Immune Genes ◽  
Gene Pairs ◽  
Immune Related Gene

Abstract Background Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma(COAD) is the main pathological type of colon cancer. There is a lot of evidence describing the correlation between the prognosis of COAD and the immune system. The objective of the current study was the development of a robust prognostic immune-related gene pairs (IRGPs) model for estimating overall survival of COAD. Methods The gene expression profiles and clinical information of patients with colon adenocarcinoma come from TCGA and GEO databases and are divided into training and validation cohorts. Immune genes were selected which show significantly association with prognosis. Results Among 1647 immune genes, a 17 IRGPs model was built which was significantly associated with OS in the training cohort. In the training and validation data set, the IRGPs model divided patients into high-risk groups and low-risk groups, and the prognosis of the high-risk group was significantly worse( P <0.001). Univariate and multivariate Cox proportional hazard analysis confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways in high-risk groups were up-regulated. T cells regulatory and Macrophage M0 were significantly highly expressed in the high-risk group. Conclusion We successfully constructed an IRGPs model that can predict the prognosis of COAD, which provides new insights into the treatment strategy of COAD.

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