Independent Risk Factor For Event-free Survival Research Articles

Clinical Outcomes of Elderly Patients with Advanced-Stage Classic Hodgkin Lymphoma Who Received an ABVD Regimen: A Multi-Center Retrospective Study in Japan (HORIZON study)

Clinical Outcomes of Elderly Patients with Advanced-Stage Classic Hodgkin Lymphoma Who Received an ABVD Regimen: A Multi-Center Retrospective Study in Japan (HORIZON study)

Clinical manifestations of Langerhans cell histiocytosis with multisystem involvement in 53 children

Objective: To analyze the clinical characteristics and long-term outcome of Langerhans cell histiocytosis with multisystem involvement (MS-LCH) in children, and to evaluate the efficacy of modified DAL-HX83/90 protocol. Methods: This retrospective study included 53 patients with MS-LCH admitted to the Department of Pediatric Hematology and Oncology, First Affiliated Hospital of Zhengzhou University from January 2011 to May 2019. Modified DAL-HX83/90 protocol was used in all patients as an initial treatment. The patients were divided into the group with (RO+) or without (RO-) risk organ involvement. The RO+group was further divided into two groups, as RO+Ⅰ group (lung involvement only) and RO+Ⅱ group (extra-pulmonary, with or without lung involvement). The clinical characteristics and the long-term outcome were summarized. Event-free survival (EFS) and overall survival (OS) curves were analyzed with Kaplan-Meier method. Univariate and multivariate analysis of prognostic factors including age, sex, risk organ involvement and response to 6-week induction were analyzed with Log-Rank test and Cox proportional hazards models. Results: Among the 53 children with MS-LCH, 34 were male and 19 were female. The age of onset was 21 months (3 months-13 years). There 22 were in RO+group, with 12 in RO+Ⅰ group and 10 in RO+Ⅱ group, and 31 in RO-group. The follow-up period was 51 (12-144) months. The overall response rate of 6-week induction was 89% (47/53), and the recurrence rate was 30% (16/53). The 5-year EFS and OS were (67±6) % and (83±5) %, respectively. Univariate analysis showed that the 5-year EFS and OS of patients who responded well to 6-week induction chemotherapy were significantly higher than those who had no response ((76±6) % vs. 0, (88±4) % vs. (41±22) %, χ2 = 34.743, 10.608, both P<0.05). The 5-year EFS and OS of RO-group were significantly higher than that of RO+group ((80±7) % vs. (49±10) %, (93±4) % vs. (70±10) %, χ2=6.022, 4.793, both P<0.05). And the 5-year EFS of RO+Ⅰ group was significantly higher than that of RO+Ⅱ group ((83±10) % vs. (10±9) %, χ2=9.501, P=0.002). While age and sex were not significantly associated with 5-year EFS and OS (all P>0.05). Cox proportional hazard regression model showed that response to 6-week induction chemotherapy was the independent risk factor for EFS (HR=13.114, 95%CI 3.759-45.742, P<0.01) and OS (HR=7.748, 95%CI 1.542-38.920, P=0.013). Conclusions: Most of the children without risk organ involvement treated with modified DAL-HX83/90 protocol could achieve long-term survival. However, the children involved liver, spleen, or hematopoietic system had a high risk of disease progression and recurrence.

Radiation therapy is an important factor to improve survival in pediatric patients with head and neck rhabdomyosarcoma by enhancing local control: a historical cohort study from a single center

BackgroundThe purpose of this study is to analyze the influence of radiation therapy on survival in a historical cohort of 56 pediatric patients with head and neck rhabdomyosarcoma.MethodsA historical cohort of 56 pediatric patients with head and neck rhabdomyosarcoma from June 1st, 2013 to June 30th, 2019 was chosen. Clinical data and follow up results were collected including all diagnosis, treatment and prognosis information. Overall survival (OS) and event free survival (EFS) as time-to-event distributions were estimated with Kaplan-Meier method, and univariate analysis was performed with log rank test to detect differences between groups. Multivariate analysis was performed to explore the risk factors for survival with Cox proportional hazard model.ResultsThe media follow up time of all 56 patients was 31.8 months (range 3.5–74.6 months). There were 26 events during follow up, including 14 disease progressions and 12 relapses. The estimated 5-year OS of all patients was 69.9%, and the estimated 5-year EFS was 48.8%. Patients with radiation therapy as a component of the initial treatment plan had better 5-year OS and EFS compared with those without radiation therapy (OS 80.3% vs. 49.7%, p = 0.003 and EFS 63.9% vs. 21.9%, p < 0.001). In patients with events, those who received salvage radiation therapy had better 5-year OS compared with those who didn’t (OS 66.0% vs. 31.2%, p = 0.033). On multivariate analysis, tumor size > 5 cm and non-initial radiation therapy were independent risk factors for OS in all patients, non-initial radiation therapy was an independent risk factor for EFS in all patients, and tumor size > 5 cm was an independent risk factor for OS in patients with events.ConclusionsRadiation therapy as a component of initial treatment can improve the OS and EFS in pediatric head and neck rhabdomyosarcoma patients by enhancing local control, and non-initial radiation therapy is an independent risk factor for OS and EFS. Salvage radiation therapy still can improve OS in patients with disease progression and relapse. Tumor size > 5 cm is an independent risk factor for OS in pediatric HNRMS patients with or without disease progression/relapse.

Prognostic significance of the PANK family expression in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogenous hematological malignancy and its prognostication depends on the genetic mutation and expression profile of each patient. Pantothenate kinase (PANK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. It has four isoforms encoded by PANK1-4, respectively. Whether the expression of the PANK family has prognostic significance in AML remains unclear. We screened The Cancer Genome Atlas database for AML patients with complete PANK1-4 expression data. Eighty-four AML patients met the criteria and were included in this study. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations were described. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. Patients with high PANK2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than patients with low PANK2 expression (P=0.007, P=0.016, respectively), whereas patients with high PANK4 expression had shorter EFS and OS than patients with low PANK4 expression (P=0.022, P=0.015, respectively). Multivariate analysis confirmed that high PANK4 expression was an independent risk factor for EFS and OS (both P<0.05). Our study suggested that high PANK2 expression might have favorable effects on AML, while high PANK4 expression was indicative of poor prognosis.

High IFITM3 expression predicts adverse prognosis in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignancy caused by the uncontrolled and dysregulated clonal expansion of abnormal myeloid primordial cells. In general, the prognosis of AML remains poor despite new discoveries in its pathogenesis and treatment. It is crucial to find early and sensitive biomarkers and continue to explore active targeted treatments. Interferon-induced transmembrane protein (IFITM) family is an important part of the interferon signaling pathway and participate in the regulation of immune cell signaling, adhesion, cancer, and liver cell migration. However, the clinical and prognostic value of the IFITM family in AML has rarely been studied. We screened The Cancer Genome Atlas database and found 155 AML patients with IFITM family (IFITM1-5) expression data. In patients who only received chemotherapy, those with high IFITM3 expression had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expression (all P < 0.05). Multivariate analysis demonstrated that high IFITM3 expression was an independent risk factor for EFS and OS in patients only received chemotherapy (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, all IFITM members had no impact on either EFS or OS. In conclusion, our study elucidated that high IFITM3 expression could be an adverse prognostic factor for AML, whose effect might be overcome by allo-HSCT.

Enhanced expressions of FHL2 and iASPP predict poor prognosis in acute myeloid leukemia.

iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study. Patients with high expressions of FHL2 and iASPP had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expressions (P = 0.005, P = 0.003, respectively). Univariate analysis indicated that high expressions of FHL2 or iASPP were unfavorable for EFS and OS (all P < 0.05), while multivariate analysis confirmed that high FHL2 expression was an independent risk factor for EFS and OS (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, EFS and OS were not significantly different between FHL2 or iASPP high- and low-expression groups. Our results suggested that high expressions of FHL2 and iASPP were poor prognostic factors for AML, but the prognostic effect might be overcome by allo-HSCT.

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age ≥60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count ≥50×10⁹/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P< 0.001). Multivariate analysis suggested that allo-HSCT and NPM1 mutations were independent favorable prognostic factors for EFS and OS (all P< 0.05), WBC count ≥50×10⁹/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT.