Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial.

To reducing chemotherapy-related toxicity, the chemo-free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty-one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow-up of 15.4 months, 2-year disease-free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2-year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2-year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo-free induction and early consolidation regimen was efficacious and well-tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo-free induction.

A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With SF3B1 Mutation.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Thalidomide-induced serious RR interval prolongation (longest interval >5.0 s) in multiple myeloma patient with rectal cancer: A case report.

Primary secondary tumor increased recently with the use of immunomodulatory drugs in patients with multiple myeloma (MM). However, MM with prior diagnosis of primary secondary tumor is relatively rare. In this study, we reported an MM patient with prior diagnosis of rectal cancer. In brief, an 85-year-old man was first diagnosed with rectal cancer. Given the age, heart failure and small-cell hypochromic anemia (hemoglobin level: 54 g/L), rectal cancer resection was not advised and symptomatic treatments were performed (including sufficient iron supplementation). Eight months later, the patient was diagnosed with MM due to worsening anemia. Anemia and heart failure were corrected after three cycles of treatment with thalidomide, dexamethasone and capecitabine. Radical resection of rectal carcinoma (Hartmann) was finally performed due to acute abdominal distension. Meanwhile, RR interval prolongation (longest interval >5.0 s) and atrial fibrillation occurred in the fifth cycle treatment. One month after discontinuation of thalidomide, RR interval returned to normal range, while atrial fibrillation developed into persistent atrial fibrillation.

Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial.

Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m2 daily, days 1 to 3; idarubicin, 6 mg/m2 daily, days 4 to 6; cytarabine 25 mg/m2 every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 µg/kg, from day 4 until neutrophil count increased to 1.0 × 109 /L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2.

Multiple risks analysis for aplastic anemia in Zhejiang, China: A case-control study.

To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (n = 1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3 km of living residence (odds ratio [OR] = 8.73, 95% CI: 1.42-53.74, P = .019), living in a newly decorated house/apartment (OR = 25.37, 95% CI: 4.44-144.81, P < .001), vegetarian diet (OR = 131.60, 95% CI: 3.45-5020.16, P = .009), preference of sugar (OR = 89.38, 95% CI: 7.22-1106.44, P < .001), preference of oily food (OR = 55.68, 95% CI: 5.12-605.26, P = .001), drinking lake water or pond water (OR = 58.05, 95% CI: 3.21-1049.81, P < .001), habit of staying up late (OR = 11.87, 95% CI: 3.43-41.02, P < .001), infection history (OR = 10.08, 95% CI: 2.75-36.93, P < .001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.

Clinical study of pai-neng-da capsule in the treatment of chronic aplastic anemia.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (panaxadiol saponins component, PND), a new Chinese patent medicine, on patients with chronic aplastic anemia (CAA) and to explore the optimal therapeutic regimen for CAA. METHOD: A total of 36 patients with CAA were enrolled and divided into three groups: the AP group (20 cases, andriol 120 mg/day + PND 240 mg/day), the ACP group (13 cases, andriol 120 mg/day + cyclosporine 3-6 mg kd(-1) day(-1) + PND 240 mg/day), and the PND group (3 cases, PND 240 mg/day). All patients were treated and followed up for 6 months. Peripheral blood counts, renal and hepatic function and Chinese medical (CM) symptoms of patients were assessed and all indices were gathered at the beginning and end of the study. RESULT: In the AP group, no significant hematologic difference was observed at the end of 6-month treatment comparing with the beginning. In the ACP group, the blood counts were maintained at the same level after the 6-month treatment. In the PND group, trilineage hematologic improvement was displayed at the end of 6-month treatment comparing with the beginning. No significant difference was showed in renal and hepatic function in all patients. All patients' clinical symptom improved according to CM symptom score. The effective rates were 95%, 73% and 100%, respectively. CONCLUSION: PND improved the efficacy and decreased side effects by cutting down the dosage of andriol, and it could also improve patients' clinical symptom and quality of life. PND were effective and safe in the treatment of CAA, it could be used alone or in combination with pharmacological agents such as andriol and cyclosporine.