Excellent Survival Outcomes of Pediatric Patients With Acute Myeloid Leukemia Treated With the MASPORE 2006 Protocol

PurposeTo determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time.Patients and MethodsSixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia–Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients.ResultsSignificant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014).ConclusionOutcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate.     

Validation of a Molecular Risk Score for Prognosis of Patients With Acute Promyelocytic Leukemia Treated With All-trans Retinoic Acid and Chemotherapy-containing Regimens

IntroductionAlthough treatment of acute promyelocytic leukemia (APL) has evolved dramatically during the past decades, especially with the introduction of all-trans retinoic acid, risk stratification remains an important issue. To date, relapse risk can be predicted by leukocyte and platelet counts only. In the present report, we present a validation study on 3 candidate genes and a newly developed molecular risk score for APL in 2 independent patient cohorts.Patients and MethodsAn integrative risk score combining the expression levels of BAALC, ERG, and WT1 was calculated for 79 de novo APL patients from the original cohort and 76 de novo APL patients from a validation cohort. Gene expression analysis was executed the same for both cohorts, and the results regarding the effect on patient outcomes were compared.ResultsThe expression levels of BAALC, ERG, and WT1 were similar in both cohorts compared with the healthy controls. The relapse and survival rates were not different between the low- and high-risk patients according to the Sanz score. However, application of the molecular risk score on the validation cohort distinctly discriminated patients according to their risk of relapse and death just as in the original APL cohort, although single gene analyses could not reproduce the negative prognostic impact.ConclusionThe analysis clearly validated the prognostic effect of the integrative risk score on the outcome in APL patients. The value was further empowered because the single gene analyses did not show similar results. Whether the integrative risk score retains its prognostic power in the chemotherapy-free setting should be investigated further.     

急性早幼粒细胞白血病合并出血的临床分析

目的：研究急性早幼粒细胞白血病(APL)合并出血的临床特征和全反式维甲酸(ATRA)对APL早期出血的影响。方法：回顾性总结110例APL患者的临床特点和实验室检查结果；并比较ATRA治疗与传统化疗的疗效。结果：110例患者合并出血56例(50.9％)，早期出血死亡12例(10.9％)。早期出血死亡的危险因素有：高白血病细胞(＞1×109／L)，低血小板(＞30×109／L)，低纤维蛋白原(＜1.5 g／L)，高龄(＞50岁)，血红蛋白(＜10 g／L)。ATRA治疗组早期出血死亡率，血小板<30×109／L、纤维蛋白原＜1.0 g／L的时间，以及输注血制品次数均明显减少。结论：APL出血发生率较高；ATRA治疗明显减少早期出血死亡率，提高了APL的缓解治愈率。     

Outcome of a Real-Life Population of Patients With Acute Promyelocytic Leukemia Treated According to the PETHEMA Guidelines: The Polish Adult Leukemia Group (PALG) Experience

BackgroundAcute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population.Patients and MethodsWe analyzed 283 unselected APL patients treated in 20 Polish hospitals between 2005 and 2017. All patients were intended to be treated with PETHEMA (Programa Español para el Tratamiento de las Hemopatías Malignas) protocols based on all-trans retinoic acid plus chemotherapy.ResultsThe probability of overall survival at 4 years was 67%, while event-free survival was 64%. The early death (ED) rate was 20.1% (n = 57), while 3.5% (n = 10) patients died before induction therapy was started. The main causes of ED included hemorrhage (45.6%), infections (17.5%), and differentiation syndrome (14.5%). Of 273 treated patients, 214 (78.4%) experienced hematologic morphologic remission, 2 (0.7%) were found to have resistant disease, 47 (17.2%) could not be evaluated for response because of ED, and in 6 (3.7%) no data concerning the response were available. Multivariate analyses showed that predictors of ED and overall survival were Eastern Cooperative Oncology Group performance status > 2, age > 60 years, and all types of bleeding episodes that occurred before starting therapy, while an additional predictor of event-free survival was high white blood cell count (> 10 10⁹/L).ConclusionED remains a major problem in APL patients, especially in a real-life population. Shortening of the time between the initial contact with a health care professional, and all-trans retinoic acid administration and the use of appropriate supportive care could improve the outcome of unselected APL population, mainly by reducing the ED rate.     

WT1 Expression in Peripheral Blood at Diagnosis and During the Course of Early Consolidation Treatment Correlates With Survival in Patients With Intermediate and Poor-Risk Acute Myeloid Leukemia

BackgroundUp to 55% of non-APL acute myeloid leukemias (AML) lack a molecular target suitable for standardized disease monitoring. We aimed to evaluate the prognostic significance of WT1 gene expression at early stages of intensive treatment.Patients and MethodsA total of 106 consecutive patients with intermediate and high-risk AML who had WT1 expression at diagnosis >500 copies/10⁴ ABL and who achieved remission after 1 to 2 cycles of induction treatment were analyzed. WT1 expression was measured in peripheral blood using a standardized European LeukemiaNet method. Overexpression was defined as >50 copies/10⁴ ABL. The median follow-up was 30 months.ResultsPatients with normal versus high WT1 expression after 2 cycles of chemotherapy had overall survival (OS) at 3 years of 66% versus 41% (P = .01); event-free survival (EFS) 45% versus 22% (P = .01). Prognostic significance of WT1 expression after 2 cycles of treatment was maintained in the group of patients treated with chemotherapy alone without hematopoietic stem cell transplantation in first line treatment (OS 70% vs. 36%, P = .02; EFS 35% vs. 0%, P = .03). Significant prognostic factors for EFS on multivariate analysis were the achievement of molecular remission (<50 copies of WT1) at any time during treatment (hazard ratio [HR] 0.47, P = .04) and increased WT1 expression after 2 cycles of chemotherapy (HR 2.0, P = .03).ConclusionIncreased WT1 expression after 2 cycles of chemotherapy is a negative prognostic factor for survival. WT1 remains a valuable molecular marker in AML without any leukemia-specific mutation, especially if next generation sequencing and/or digital polymerase chain reaction are not routinely available.     

Factors Affecting Survival in Patients with Colorectal Cancer in Shiraz,Iran

Background: Colorectal cancer (CRC) is the third most common cancer in the world, and the fourth in Iran in both genders. The aim of this study was to find predictive factors for CRC survival. Materials and Methods: Medical records of 570 patients referred to the radiotherapy oncology department of Shiraz Namazi hospital from 2005 to 2010 were retrospectively analysed. Data were collected by reviewing medical records, and by telephone interviews with patients. Survival analysis was performed using the Cox’s regression model with survival probability estimated with Kaplan-Meier curve. The log-rank test was used to compare survival between strata. Data was analyzed with Stata 12. Results: The five-year survival rate and the mean survival time after cancer diagnosis were 58.5% and 67±1.4 months. On multivariate analysis, age of diagnosis, disease stage and primary tumor site‚ lymphovascular invasion and type of treatment (in colon cancer) were significant factors for survival. Conclusions: Age of diagnosis and type of treatment (adjuvant therapy in patients with colon cancer) were two modifiable factors related to survival of CRC patients. Therefore earlier diagnosis might help increase survival.     

Prognostic Prediction Model for Second Allogeneic Stem-Cell Transplantation in Patients With Relapsed Acute Myeloid Leukemia: Single-Center Report

Purpose

To identify factors affecting survival outcomes and to develop a prognostic model for second allogeneic stem-cell transplantation (allo-SCT2) for relapsed acute myeloid leukemia (AML) after the first autologous or allogeneic stem-cell transplantation.

Real-life Outcomes on Acute Promyelocytic Leukemia in Brazil – Early Deaths Are Still a Problem

Introduction

Although a considerable improvement in survival of patients with acute promyelocytic leukemia (APL) has been seen over the past decades, real-life outcomes seem to be worse than those reported by prospective studies. We aim to describe clinical characteristics and outcomes of adult patients diagnosed with APL in an academic hospital from the University of Sao Paulo.

Improvement of Early Death in Acute Promyelocytic Leukemia: A Population-Based Analysis

BackgroundEarly death is a major factor of treatment failure in acute promyelocytic leukemia (APL), however, the recent trends in the incidence of early death based on the population-level are not clear. Hence, this study is aimed at describing the incidence, recent trends, causes and characteristics of early death in APL based on the real world.Materials and MethodsAPL patients diagnosed from 1986 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) dataset were enrolled, and categorized based on gender, age, year of diagnosis, race, marital status, resident county and socioeconomic status (SES). The risk factors for all-cause and acute myelocytic leukemia (AML) specific early death were determined by univariate and multivariate logistic regression analyses, and stratified analysis was conducted by age.ResultsOverall, 3212 APL patients were included in analysis between 1986 and 2015, of which a total of 683 (21.3%) patients were noted for early death. Significant differences were recognized for patient distribution by age, year of diagnosis, marital status, and SES. The early death rate of APL patients diagnosed during 2006-2015 was significantly lower than that of the early stage, but this trend was not evident in juvenile patients. At the same time, older age, and lower SES score were independent risk factors for early death in the multivariate analysis.ConclusionWe established that the early death trend in APL has decreased over the past few years, but the early death rate remains high, especially in older patients and those with lower SES.     

急性早幼粒细胞白血病患者白细胞介素6测定与意义分析

本文用IL-6依赖细胞株MH60-BSF2检测12例患者血清与白血病细胞内IL-6活性。结果发现正常对照血清IL-6平均<10U/ml,白细胞内IL-6活性多数测不到(仅1例为5U/2×10~5)。APL患者治疗前期、中期(白细胞增殖期)及后期(缓解期)血清IL-6活性分别为36.06±15.72U/ml、41.5±/5.0U/ml和22.12±12.02U/ml:治疗中期似有升高(P>0.05),治疗后期下降(P<0.05);外周白细胞内IL-6活性分别为8.98±8.6U/2×10~5细胞、5.36±4.16U/2×10~5细胞和5.95±3.68U/2×19~5细胞,治疗前似较高(P>0.05),治疗后无明显变化。APL瘤细胞在体外比正常白细胞有更高的IL-6活性(P<0.05)。相关分析表明APL患者外周总白细胞数,骨髓L-CFU及GM-CFU均与IL-6活性变化不相关(P<0.05)。     

Salvage Therapy Outcomes in a Historical Cohort of Patients With Relapsed or Refractory Acute Myeloid Leukemia

BackgroundThe prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is poor, with no universal standard salvage therapy currently available for most patients. Novel therapies with efficacy in patient subsets often have limited activity in alternative subsets, resulting in a majority of patients not gaining benefit from these therapies. This study systematically evaluated patient outcomes in a large cohort of R/R AML patients from a single institution across all salvage therapy lines, up to and including the third line.Patients and MethodsOutcomes of R/R AML patients treated at a single institution (MD Anderson Cancer Center, Houston, TX) between 2002 and 2016 were entered into a central database. Eligible patients received one or more lines of salvage therapy after first occurrence of R/R AML. Patients who received second- or third-line salvage treatment were also included in the first salvage analysis. Eligible patients were ≥ 18 years old at time of initial AML diagnosis, with no central nervous system involvement.ResultsA total of 818 eligible patients received one or more lines of salvage therapy, 809 received second-line salvage therapy, and 397 received third-line salvage therapy. Complete remission rates decreased from 14% after first salvage therapy to 9% after second salvage therapy and 3% after third salvage therapy. Median overall survival was 6.30, 4.07, and 2.98 months after first, second, and third salvage therapies, respectively.ConclusionThese data indicate that the best chance of obtaining long-term remission in AML is with a successful first induction. Strategies that improve initial response and decrease the likelihood of relapse should be pursued.     

Long-Term Studies Assessing Outcomes of Ibrutinib Therapy in Patients With Del(11q) Chronic Lymphocytic Leukemia

BackgroundCertain genomic features, such as del(11q), expression of unmutated immunoglobulin heavy-chain variable region (IGHV) gene, or complex karyotype, predict poorer outcomes to chemotherapy in patients with chronic lymphocytic leukemia (CLL).Patients and MethodsWe examined the pooled long-term follow-up data from PCYC-1115 (RESONATE-2), PCYC-1112 (RESONATE), and CLL3001 (HELIOS), comprising a total of 1238 subjects, to determine the prognostic significance of these markers in patients treated with ibrutinib.ResultsWith a median follow-up of 47 months, ibrutinib-treated patients had longer progression-free survival (PFS) than patients treated in the comparator arm, regardless of genomic risk factors. Among patients treated with ibrutinib, we found that high-risk genomic features were not associated with shorter PFS (63-75% across all subgroups at 42 months) or overall survival (79-83% across all subgroups at 42 months). Surprisingly, we observed that ibrutinib-treated patients with del(11q) actually had a significantly longer PFS than ibrutinib-treated patients without del(11q) (42-month PFS rate 70% vs. 65%, P = .02).ConclusionThese analyses not only demonstrate that genomic risk factors previously associated with poor outcomes lose their adverse prognostic significance but also that del(11q) can be associated with a superior PFS with ibrutinib therapy.     

Lung Metastases Treated With Stereotactic Ablative Radiation Therapy in Oligometastatic Colorectal Cancer Patients: Outcomes and Prognostic Factors After Long-Term Follow-Up

Background

We evaluated a series of oligometastatic colorectal cancer (CRC) patients treated with stereotactic ablative body radiotherapy (SABR) delivered in all active lung metastases.

Outcome of Adolescents and Young Adults Compared With Pediatric Patients With Acute Myeloid and Promyelocytic Leukemia

BackgroundStudies on the outcome of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) are limited.MethodsWe compared the outcome of AYA (19-30 years) patients with AML and PML and pediatric (0-18 years) patients with AML (pAMLs) and APL (pAPLs) utilizing the Surveillance Epidemiology and End Results-18 registry. Early mortality rate (EMR), defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment-related mortality. Survival statistics were computed using the Kaplan-Meier method. Multivariate analysis was done using logistic regression and the Cox proportional hazard regression model.ResultsA total of 6343 patients with AML were identified; 44.7% were AYAs. pAMLs had lower EMR (6.2% vs. 9.2%; P < .01) and higher overall survival (OS) (1-year, 70.3% vs. 62.1%; 5-year, 48.2% vs. 36.4%; P < .01). Nine hundred twenty patients with APL were also identified; 59.5% were AYAs. No statistically significant difference was found between AYAs with APL and pAPLs in EMR (11.4% vs. 14.1%; P = .23) and OS (1-year, 83.8% vs. 81.2%; P = .31 and 5-year, 68.2% vs. 73.1%; P = .11]. Comparing all patients with AML and APL, AYAs with APL and pAPLs had higher EMR (11.4% and 14.1% vs. 6.2% and 9.2%; P ≤ .01) but better OS than AYAs with AML and pAMLs (5-year OS, 68.2% and 73.1% vs. 48.2% and 36.4%; P ≤ .01).ConclusionOur analysis shows AYAs with AML have worse EMR and OS compared with pAMLs. AYAs with APL and pAPLs have similar outcomes. To our knowledge, this is the first study reporting outcomes of AYAs with APL and pAPLs using a large population-based registry and their comparison with same age patients with AML.     

Prognostic Factors in Acute Promyelocytic Leukemia: A Retrospective Study of 67 Cases

In a cohort of 67 adult patients with newly diagnosed untreated acute promyelocytic leukemia (APL), the initial clinical and biological parameters were submitted to multivariate analysis for potential prognostic significance. Median age of the patients was 40 years and the hematologic characteristics of the patients were those regularly seen. Complete remission (CR) was achieved in 43 cases (64%). Fourteen patients died within 4 weeks of diagnosis, due to severe hemorrhage. Factors predictive of hemorrhagic death in the multivariate analysis were hyperuricemia (p = 0.001), splenomegaly (p = 0.009), anemia (p = 0.02), high serum levels of LDH (p = 0.02), increased prothrombin time (p = 0.04), and hypercreatininemia (p = 0.05). Pretreatment patient characteristics for poor prognosis and achieving CR were hyperuricemia (p = 0.0002), splenomegaly (p = 0.01), anemia (p = 0.02), and lymphadenopathy (p = 0.04). The median disease-free survival (DFS) was 15.6 months. Poor prognostic factors for DFS were hyperuricemia (p = 0.007), and splenomegaly (p = 0.03). Maintenance chemotherapy had no statistically significant impact on CR duration. Median survival duration was 10 months. Poor prognostic factors for survival were hyperuricemia (p = 0.0005), and elevated serum LDH levels (p = 0.01).     

Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel

BackgroundPre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy.Materials and MethodsData were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry.ResultsMedian values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001).ConclusionConsistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.     

Prognostic Nomogram for Overall Survival in Early Stage Extranodal Natural Killer/T Cell Lymphoma Treated With High-Dose Radiotherapy

BackgroundThe aim of this study was to develop a prognostic nomogram for early stage extranodal natural killer/T-cell lymphoma, nasal type (ENKL) treated with high-dose radiotherapy (RT).Patients and MethodsA total of 81 patients at 2 cancer centers with stage I to IIE ENKL who received chemotherapy (CT) and high-dose RT were retrospectively analyzed. The development of the nomogram was on the basis of the Cox proportional hazards model. We implemented the concordance index (C-index) and performed a calibration curve to determine its predictive and discriminatory capacity and compared our nomogram with the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI).ResultsThe nomogram included 4 important variables and used a multivariate analysis: lactate dehydrogenase, primary tumor invasion, tumor response, and CT regimen. The 5-year OS rate and progression-free survival were 64.7% and 57.5%, respectively for the entire group. The C-index of the nomogram for overall survival (OS) prediction was 0.87, and it was superior to the predictive power of the IPI and KPI. The calibration curve showed that the nomogram accurately predicted the 5-year OS.ConclusionThe proposed nomogram could provide an individualized risk estimate of the OS for early stage ENKL treated with CT and high-dose RT.     

Impact of Time Between Induction Chemotherapy and Complete Remission on Survival Outcomes in Patients With Acute Myeloid Leukemia

BackgroundThe majority of patients with acute myeloid leukemia (AML) receive intensive induction chemotherapy for obtaining a complete remission (CR). Despite consolidation chemotherapy and advances in allogeneic hematopoietic stem cell transplantation, most of these patients finally relapse and die from AML. The aim of this study is to determine the impact of duration of remission achievement on survival of patients with newly diagnosed AML who achieve CR after induction chemotherapy.Materials and MethodsWe retrospectively analyzed patients with AML who received first induction chemotherapy between 2001 and 2018.ResultsThe 5-year overall survival for patients who had early remission after induction chemotherapy and patients who had delayed remission after induction chemotherapy were 83% (95% confidence interval [CI], 0.79-0.87) and 35% (95% CI, 0.31-0.39), respectively (P < .001). The 5-year disease-free survival for patients who had early remission after induction chemotherapy and patients who had delayed remission after induction chemotherapy were 81% (95% CI, 0.75-0.87) and 28% (95% CI, 0.21-0.35), respectively (P < .001).ConclusionIn conclusion, time to entering CR is a predictor factor of overall survival and disease-free survival for patients with newly diagnosed AML who achieve CR after first induction chemotherapy. Patients achieving CR only after a lengthy time (eg, more than 29 days) should be considered to have high relapse rate and should undergo allogeneic hematopoietic stem cell transplantation.     

Factors Influencing Overall Survival for Patients With Metastatic Clear-Cell Renal-Cell Carcinoma in Daily Practice

Purpose

To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies.

Clinical Features in Patients With Malignant Pleural Mesothelioma With 5-Year Survival and Evaluation of Original Diagnoses

IntroductionMalignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival.Materials and MethodsForty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists.ResultsOur study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time.ConclusionWe confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.