scholarly journals Analysis of the Short-Term Efficacy of Decitabine Combined with Low-Dose Cytarabine in the Treatment of JMML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-43
Author(s):  
Yuli Cai ◽  
Weiru Liang ◽  
Meihui Yi ◽  
Xiaoyan Zhang ◽  
Fang Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Response Rate ◽  
Risk Group ◽  
Tumor Burden ◽  
High Risk Group ◽  
Juvenile Myelomonocytic Leukemia ◽  
Short Term ◽  
Term Efficacy ◽  
Low Dose Chemotherapy

Objective: Juvenile myelomonocytic leukemia (JMML) has both the disease characteristics of myelodysplastic syndrome and myeloproliferative neoplasm. Currently, hematopoietic stem cell transplantation (HSCT) is the only possible cure. Most of the newly diagnosed pediatric patients with JMML have high tumor burden, rapid disease progression, and may not tolerate HSCT. This study explored the short-term efficacy of decitabine combined with low-dose chemotherapy in the treatment of JMML before transplantation. Methods: A retrospective analysis of the patient files of 9 cases of JMML was performed from January 2019 to May 2020. All patients were given decitabine 20mg/m2× 5 days, supplemented with a small dose of cytarabine (50-100mg/m2×3~5 days), and/or etoposide (50mg/m2×3~5 days) chemotherapy. Each treatment interval is 3~4 weeks, bridging with HSCT after 3~4 treatment courses. Results: The median age of onset of 9 cases of JMML was 2 years old (0.5~4 y), male to female ratio was 8:1, the median size of spleen was 6.4cm (2.9~9.8cm) under the costal arch, and WBC was 28.03×109/L (7.3~127.69×109/L), monocytes were 9.25×109/L (1.66~15.79×109/L) at diagnosis. There were 8 cases in the high-risk group and 1 case in the low-risk group. Second-generation sequencing results show that 7 cases carried PTPN11 somatic mutations. Five in 9 cases had two kinds of classic JMML mutations, and 1 case had only NRAS mutation. Seven patients had normal chromosomal karyotypes, and 3 patients had abnormal 8, 11, and 18 chromosomes, respectively. Median treatment courses with decitabine are 3 courses (1~5 courses), the response rate of one course is 77.8% (7/9), the response rate of three courses is 80% (4/5), one case from high-risk group achieved complete remission after treated with 4 courses of decitabine and low-dose chemotherapy. The five-month progression-free survival rate was 77.8% (7/9). Conclusion: Treating JMML with decitabine combined with low-dose chemotherapy, can reduce patients' tumor burden, improve the general condition, and obtain approximately 80% clinical response rate. Decitabine combined with low-dose chemotherapy can be used as a treatment option for JMML before HSCT. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Safety and effecacy of decitabine applicated in JMML patients have not been confirmed.

What we could know from the semiannually repeated screening with low-dose helical CT in a high-risk cohort over 10 years: Update of Anti-Lung Cancer Association project

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7568-7568
Author(s):  
N. Seki ◽  
K. Eguchi ◽  
M. Kaneko ◽  
H. Ohmatsu ◽  
R. Kakinuma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Cancer Detection ◽  
Detection Rate ◽  
Low Dose ◽  
Risk Group ◽  
Helical Ct ◽  
High Risk Group ◽  
Invasive Adenocarcinoma ◽  
Detection Rates

7568 Background: There have been several randomized trials of low-dose helical CT (LDCT) screening for lung cancer. However, all trials are in progress. Therefore, before they are completed, we summarized what we could know from an update of Anti-Lung Cancer Association project, which was regarded as a longer-term study with LDCT performed at shorter intervals and with a larger number of detected cancers than any other single-armed studies. Methods: Among 2,120 participants, 1,877 (mean age 64 years, 88% male, and 84% smoker) underwent semiannually repeated screening from 1993 to 2004 (median, 3.5 years). We investigated (1) survival of patients with screening detected lung cancers, (2) presence of a stage shift (indicator of a mortality benefit), (3) appropriate duration of repeated screening, (4) identification of high-risk group by age, sex, and smoking, and (5) appropriate screening intervals by high-risk group (6 months or 1 year). Results: (1) The 5- and 10-year survival rates were 84.5% and 84.5%, respectively, in repeated screening group (n = 57) and were 68.7% and 38.1%, respectively, in initial screening group (n = 19) (P = 0.208). (2) Only in invasive adenocarcinoma, both proportion of stage II to IV and tumor size were negatively correlated with duration of repeated screening (r = −0.77, P = 0.007 and r = − 0.60, P = 0.029, respectively). (3) Detection rate of all incidence cancers were positively correlated with duration of repeated screening (r = 0.50, P = 0.020). However, detection rate remained unchanged until 5 years of repeated screening. Moreover, stage shift did not occur until 5 years of repeated screening. (4) Female sex (HR 2.9, P = 0.015) and smoking (HR 2.7, P = 0.046) were demographic risk factors for lung cancer detection at repeated screening. The accumulated 10-year detection rates for female smokers (n = 91), male smokers (n = 1,557), and non-smokers (n = 229) were 15.1%, 6.2%, and 4.3%, respectively (P = 0.002). (5) The estimated relative cancer detection powers of annual screening to semiannual screening were 50% and 57% for female and male smokers with lung cancer, respectively. Conclusions: Semiannually repeated LDCT screening over 5 years might be beneficial to smokers, especially female smokers. No significant financial relationships to disclose.

Preliminary Results of a Phase II Study of Low Dose Decitabine as a Single Agent in Older Patients (age≥60) with Previously Untreated Acute Myeloid Leukemia (AML)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2957-2957 ◽  
Author(s):  
William Blum ◽  
Rebecca Klisovic ◽  
Shujun Liu ◽  
Ramiro Garzon ◽  
Cheryl Kefauver ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
De Novo ◽  
Phase Ii Study ◽  
Risk Group ◽  
Single Agent ◽  
Initial Response ◽  
Clinical Results ◽  
Median Number ◽  
High Risk Group

Abstract The hypomethylating agent decitabine inhibits DNA methyltransferase (DNMT) enzymatic activity and is approved by the FDA for treatment of myelodysplastic syndromes. We previously performed a phase I trial in AML of decitabine (with or without the histone deacetylase inhibitor valproic acid); the trial was designed to establish a biologically effective dose (BED) of decitabine based on drug-induced re-expression of methylated and silenced genes. With the derived BED of 20mg/m2/day given for 10 days, every 4 weeks, clinical activity was observed in previously untreated older AML patients (pts, CR in 4/12); clinical response correlated with gene re-expression (Blum, JCO 2007). The addition of tolerable doses of valproic acid did not appear to improve clinical results or increase gene re-expression compared to decitabine alone. Therefore, we designed a phase II study of single agent decitabine for previously untreated AML pts of age≥60 who were not candidates for intensive chemotherapy (or who refused it). Performance status was ECOG <3. All pts received induction with decitabine at 20mg/m2 IV over 1 hour on days 1–10 of a 28 day cycle. The schedule for subsequent cycles was customized for each patient based on clinical response and/or toxicity (e.g., myelosuppression). Pts with persistent AML at the end of a cycle received a repeat of the 10 day treatment. In contrast, pts with <5% blasts received decitabine as consolidation for only 5 days/cycle (every 4 weeks for 1 year). For CR/CRi patients, the decitabine schedule could be reduced further to 4 or 3 days/cycle for Grade 4 neutropenia lasting more than 2 weeks, if applicable. 33 pts were enrolled; accrual was completed in 13 months. Pts had a median age of 74 years (range, 60–83); 24 pts were age≥70. 18 pts had de novo AML; 15 had secondary or t-AML. Pts had a median presenting white blood cell count of 2,400/uL (range, 400–58,800/uL) with median marrow blasts of 44% (range, 21–92%). 13 pts had complex karyotype (≥3 abnormalities); 12 had normal karyotype; one patient had t(8;21), and the rest had other abnormalities (with one unknown). This was a high risk group by any comorbidity measure. Scoring was as follows on four high-risk factors of age ≥70, antecedent hematologic disorder, unfavorable karyotype, and ECOG 2: 16 pts had 3+ risk factors; 15 had two, and the other 2 pts had one risk factor. Using the transplant comorbidity index for older AML pts (HCT-CI; Giles, BJH 2007), pts had scores of 3+ (N=18), 1–2 (N=10), or 0 (N=5). The median number of cycles received to date is 3 (range, 1–10); 17 pts continue to receive study therapy. 10 pts have received 4+ cycles. Of the first 22 consecutive pts enrolled, 11 achieved CR (50%); 4 more have achieved CRi by IWG criteria for response (Cheson, JCO 2003). 11 pts are <3 months since entry onto the study, with response evaluations ongoing. The response rate was similar between cytogenetic risk subgroups and in both de novo and secondary AML. 4 pts who achieved CR subsequently relapsed, with CR duration of 9, 6, 6, or 2 months, respectively. The other CR pts have maintained ongoing responses for 2–11+ months. 9/11 pts who achieved CR required only 1 cycle of induction therapy (10 day course) before initial response was achieved (CR, N=2; CRi, N=7). For pts who had CRi as initial response, the median number of additional cycles to achievement of full CR was 1 (range, 1–3). In this high risk group, death within 8 weeks of any cause occurred in 4 pts and was related to infection in each case. Though therapy was often administered in the outpatient clinic, febrile neutropenia and infections in the setting of drug and/or disease-related myelosuppression requiring hospitalization during the induction courses were frequent, occurring in nearly all pts. Post-CR therapy, however, was very well tolerated with no hospitalizations for complications during consolidation courses. In conclusion, decitabine in this novel schedule of induction with outcome-adapted modification of consolidation therapy was highly active and well tolerated by most in this poor risk cohort of older AML pts. Clinical results compare favorably to those seen in this population with low dose clofarabine (Erba, ASCO 2008a) or decitabine-5 day schedule (Cashen, ASH 2006a). Correlative studies including re-expression of epigenetically silenced genes, target gene promoter methylation, and global DNA methylation are ongoing.

Predicting Short-Term Risk of Falls in a High-Risk Group With Dementia

2020 ◽  
Author(s):  
Sina Mehdizadeh ◽  
Andrea Sabo ◽  
Kimberley-Dale Ng ◽  
Avril Mansfield ◽  
Alastair J. Flint ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Short Term ◽  
Risk Of Falls

Differential Expression of VEGF and Its Receptors in the Primary Cells of Various Risk Classified Acute Lymphoblastic Leukemia Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4446-4446
Author(s):  
Aibin Liang ◽  
Li Li ◽  
Long-Jun Gu ◽  
Hua Jiang ◽  
Hui Ye
Keyword(s):  
High Risk ◽  
Clinical Data ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Tumor Burden ◽  
High Risk Group ◽  
Cell Counts ◽  
Healthy Donors ◽  
Poor Treatment ◽  
Standard Risk

Abstract Expression of VEGF and its receptors (Flt-1, KDR) were assayed by means of ELISA and RT-PCR on healthy donors (20 cases), patients under remission (20 cases), patients of standard risk (29 cases) and high-risk group cases (12 cases). Meanwhile, the clinical data of all the patients enrolled in this study were collected and then analysed with the detection of VEGF and its receptors. Results showed that expressions of VEGF and its receptors are diversely detected in 4 groups studied. VEGF and its receptors are expressed higher in high risk group than standard risk group, however, compared to remission group and healthy donors standard risk patients expressed higher VEGF and its receptors. Concordantly, the clinical data are in line with the expressions of VEGF and its receptors on all leukemia samples studied. Patients with higher expression of VEGF and its receptors often have higher peripheral white blood cell counts, severe liver infiltration, higher LDH value and poor treatment response. We also found that expression of VEGF and its receptors are not associated with age, sex, sample status and cytogenetic characteristics. This is demonstrated that ALL patients with highly expressed VEGF and its receptors are usually with higher tumor burden, especially in high-risk cases. Detection of VEGF and its receptors might be one of prognostic marker for ALL treatment.

scholarly journals Optimal vaccine strategy to control COVID-19 pandemic in middle-income countries: Modelling case study of Thailand

2021 ◽  
Author(s):  
Nantasit Luangasanatip ◽  
Wirichada Pan-Ngum ◽  
Juthamas Prawjaeng ◽  
Sompob Saralamba ◽  
Lisa White ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Vaccination Strategy ◽  
High Risk Group ◽  
Vaccine Strategy ◽  
Short Term ◽  
Middle Income ◽  
Incidence Group ◽  
High Incidence ◽  
The Right

Abstract Thailand is facing the dilemma of which groups to prioritise for the limited first tranche of vaccinations in 2021. A mathematical modelling analysis was performed to compare the potential short-term impact of allocating the available doses to either the high-risk group (over 65-year-olds) or the high incidence group (aged 20-39). Vaccinating the high incidence group with a vaccine with sufficiently high protection against infection (more than 50%) could provide enough herd effects to delay the expected epidemic peak, resulting in fewer deaths within the 12-month time horizon compared to vaccinating the same number of the high-risk group. After 12 months, if no further vaccination or other interventions were deployed, this strategy would lead to more deaths. With the right vaccine efficacy profile, targeting the high incidence groups could be a viable short-term component of the Thai vaccination strategy. These results and emerging evidence on vaccines and susceptibility suggest prioritisation guidelines should be more nuanced.

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