Postremission therapy with repeated courses of high-dose cytarabine,idarubicin, and limited autologous stem cell support achieves a very good long-term outcome in European leukemia net favorable and intermediate-risk acute myeloid leukemia

Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High-dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate-risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long-term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML-01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high-risk AML (adverse cytogenetic, isolated FLT3-internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19–75), were considered standard-risk and received the NILG AML-01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+-PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1-2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment-related mortality was 3/160 (1.8%). After a median follow-up of 66.4 months, overall survival (OS) and relapse-free survival (RFS) at 5-years were 61.4% and 52.4%, respectively. Twenty-eight selected patients aged >65 had similar outcomes. According to European leukemia net-2010 classification, the OS and RFS at 5-years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate-I, 45.2% and 36.5% in Intermediate-II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis.     

FLAG方案治疗难治复发性急性白血病临床疗效

目的探究FLAG方案治疗难治复发性急性白血病的临床疗效。方法择取2017年3月—2018年12月期间医院收治的76例难治复发性急性白血病患者为研究对象,随机分为对照组与观察组,每组38例。对照组患者行MEA方案治疗,观察组患者行FLAG方案治疗,比较两组患者肿瘤控制效果以及不良反应发生率。结果观察组患者肿瘤控制效果73.68%高于对照组50.00%,差异有统计学意义(P<0.05);观察组患者总不良反应发生率31.58%低于对照组55.26%,差异有统计学意义(P<0.05)。结论FLAG方案治疗难治复发性急性白血病效果较为理想,同时具有较高的安全性。     

Vaccine timeliness and prevalence of undervaccination patterns in children ages 0–19 months,U.S., National Immunization Survey-Child 2017

ObjectivesTypically, early childhood vaccination coverage in the U.S. is measured as the proportion of children by age 24 months who completed recommended vaccine series. However, these measures do not reflect whether vaccine doses were received at the ages recommended by the U.S. Advisory Committee on Immunization Practices, or whether children received vaccines concomitantly, per the ACIP recommended schedule. This study’s objective was to quantify vaccine timeliness and prevalence of specific patterns of undervaccination in U.S. children ages 0–19 months.MethodsUsing 2017 National Immunization Survey-Child data, we calculated days undervaccinated for the combined 7-vaccine series and distinguished undervaccination patterns indicative of parental vaccine hesitancy, such as spreading out vaccines across visits (“shot-limiting”) or starting some but not all recommended vaccine series (“selective vaccination”), from other non-hesitancy patterns, such as missing final vaccine doses or receiving all doses, with some or all late. We measured associations between demographic, socioeconomic and other characteristics with undervaccination patterns using multivariable log-linked binomial regression. Analyses accounted for the complex survey design.ResultsAmong n = 15,333 U.S. children, only 41.2% received all recommended vaccine doses on-time by age 19 months. Approximately 20.9% of children had an undervaccination pattern suggestive of parental vaccine hesitancy, and 36.2% had other undervaccination non-hesitancy patterns. Uninsured children and those with lower levels of maternal education were more likely to exhibit undervaccination patterns suggestive of parental hesitancy. Lower levels of maternal education were also associated with other non-hesitancy undervaccination patterns.ConclusionsMore than half of children in the U.S. are undervaccinated at some point by 19 months of age. Ongoing assessment of vaccine timeliness and immunization schedule adherence could facilitate timely and targeted public health interventions in populations with high levels of undervaccination.     

Evaluation of potentially achievable vaccination coverage with simultaneous administration of vaccines among children in the United States

BackgroundRoutine administration of all age-appropriate doses of vaccines during the same visit is recommended for children by the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP).MethodsEvaluate the potentially achievable vaccination coverage for ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (4+DTaP), ≥4 doses of pneumococcal conjugate vaccine (4+PCV), and the full series of Haemophilus influenzae type b vaccine (Hib-FS) with simultaneous administration of all recommended childhood vaccines. Compare the potentially achievable vaccination coverage to the reported vaccination coverage for calendar years 2001 through 2013; by state in the United States and by selected socio-demographic factors in 2013. The potentially achievable vaccination coverage was defined as the coverage possible for the recommended 4+DTaP, 4+PCV, and Hib-FS if missed opportunities for simultaneous administration of all age-appropriate doses of vaccines for children had been eliminated.ResultsCompared to the reported vaccination coverage, the potentially achievable vaccination coverage for 4+DTaP, 4+PCV, and Hib-FS could have increased significantly (P < 0.001), the vaccination coverage would have achieved the 90% target of Healthy People 2020 for the three vaccines beginning in 2005, 2008, and 2011 respectively. In 2013, the potentially achievable vaccination coverage increased significantly across all selected socio-demographic factors, potentially achievable vaccination coverage would have reached the 90% target for more than 51% of the states in the United States.ConclusionsThe findings in this study suggest that fully utilization of all opportunities for simultaneous administration of all age-eligible childhood doses of vaccines during the same vaccination visit is a critical strategy for achieving the vaccination coverage target of Healthy People 2020. Encouraging providers to deliver all recommended vaccines that are due at each visit by implementing client reminder and recall systems might decrease missed opportunities for simultaneous administration of childhood vaccines.     

以高钙血症和骨质改变为首发表现的儿童急性淋巴细胞白血病1 例报告

目的探讨以骨质改变和高钙血症为首发表现的儿童急性淋巴细胞白血病(ALL)的临床特点及诊治。方法回顾分析1例以骨质改变和高钙血症为首发表现的儿童B细胞ALL的临床资料。结果患儿,男性,6岁5个月,以腹痛起病,初期检查发现骨质改变及高钙血症,后确诊ALL。采用CCLG-ALL-2015方案化疗,同时加用伊马替尼口服,目前已获得缓解。结论高钙血症和骨质改变可以是B细胞ALL首发表现。     

A new era of immuno-oncology in acute myeloid leukemia - antibody-based therapies and immune checkpoint inhibition

Acute myeloid leukemia (AML) remains a therapeutically challenging malignancy with high rate of relapse and poor outcomes. There has been increased understanding of the molecular characteristics of AML and the various roles of the immune system in its pathogenesis, the result of which has led to the study and development of multiple immune-based approaches for this disease. In this review, we aim to provide an overview of the recent advancements made in antibody-based approaches to the treatment of AML including monoclonal antibodies, antibody-drug conjugates, and immune checkpoint inhibition. In addition, we provide insight and discuss the promise of these agents, some of which may soon enter the therapeutic armamentarium we currently employ against this lethal disease.     

Changes in long term peripheral nerve biophysical properties in childhood cancer survivors following neurotoxic chemotherapy

ObjectiveIn the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS.MethodsDetailed cross-sectional neurophysiological examination, using median nerve axonal excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment).ResultsCisplatin treated CCS (n = 16) demonstrated multiple sensory axonal excitability changes including increased threshold (P < 0.05), alterations in depolarising and hyperpolarising threshold electrotonus (P < 0.05) and reduction in resting and minimum IV slope (P < 0.01). Vincristine treated CCS (n = 73) were comparable to controls, except for prolonged distal motor latency (P = 0.001). No differences were seen in the non-neurotoxic chemotherapy group (n = 14). Abnormalities were more evident in the cisplatin subgroup with greater clinical neuropathy manifestations.ConclusionPersistent long term changes in axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis.SignificanceThis study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.     

Spindle cell melanoma coexisting with chronic lymphocytic leukemia/small lymphocytic lymphoma: a rare collision tumor in multiple sites

A strong association has been reported between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and malignant melanoma (MM). In rare cases of MM, lymphoid malignancies may be detected incidentally during sentinel lymph node biopsies. In this case, we found a unique collision of MM and CLL infiltration in the skin. An 88-year-old male patient presented with a mass on the nasal root. Histopathological examination of the skin biopsy specimen revealed a deeply infiltrative, atypical spindle cell proliferation in the background of a collagenous stroma. Accompanying this lesion, there were foci of monotonous lymphoid cell populations involving skin appendages. In the immunohistochemical studies, the spindle cells were diffusely positive for S100, and focally positive for Melan-A and HMB45; the lymphoid cells were positive for CD20, CD5, and Bcl-2 and negative for CD3, Bcl-6, CD10, and Cyclin D1. Histopathological and immunohistochemical findings were consistent with diagnoses of spindle cell melanoma and CLL. Interestingly, these two tumors together in their same morphological appearance were confirmed in a subsequent liver biopsy. Active skin surveillance of patients with CLL may be important to detect MM at an early stage that correlates with a better prognosis.