Publications by authors named "Hongyan Tong"

74 Publications

Whole exome sequencing reveals a novel LRBA mutation and clonal hematopoiesis in a common variable immunodeficiency patient presented with hemophagocytic lymphohistiocytosis.

Exp Hematol Oncol 2021 Jun 13;10(1):38. Epub 2021 Jun 13.

Myelodysplastic Syndromes Diagnosis and Therapy Center, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Common variable immunodeficiency (CVID) was a kind of primary immunodeficiency disorders with heterogeneous phenotype and genotype. Lipopolysaccharide-responsive and beige-like anchor (LRBA) mutation was identified as disease associated in CVID, advanced genetic method will help to detect atypical cases. We report a case of adult patient manifested as hemophagocytic lymphohistiocytosis (HLH), bone marrow examination suggested prosperity to MDS, manifested as increased immature myeloid cells and dysplastic hematopoiesis. Whole exome sequencing (WES) identified a novel heterogeneous c.1876T > C (p.W626R) mutation in LRBA and four somatic mutations: ASXL1 (c.1967dupA); PTPN11 (c.226G > A), U2AF1 (c.101C > T and c.470A > G), among which ASXL1 was a high-risk marker of clonal hematopoiesis. Combined with her recurrent severe infections and immune abnormalities such as hypoimmunoglobulinemia, the patient was diagnosed with CVID. Subsequent hematopoietic stem cell transplantation saved her from severe cytopenia and immune deficiency. This case report highlights the great promise of utilization of WES for diagnosing rare disease with atypical manifestations and guiding further treatment.
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http://dx.doi.org/10.1186/s40164-021-00229-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201866PMC
June 2021

Variables associated with patient-reported outcomes in patients with myeloproliferative neoplasms.

Leuk Lymphoma 2021 Jun 8:1-13. Epub 2021 Jun 8.

Peking University People's Hospital, Beijing, China.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.
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http://dx.doi.org/10.1080/10428194.2021.1933481DOI Listing
June 2021

High expression of COMMD7 is an adverse prognostic factor in acute myeloid leukemia.

Aging (Albany NY) 2021 04 23;13(8):11988-12006. Epub 2021 Apr 23.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Acute myeloid leukemia (AML) is a frequent malignancy in adults worldwide; identifying preferable biomarkers has become one of the current challenges. Given that has been reported associated with tumor progression in various human solid cancers but rarely reported in AML, herein, RNA sequencing data from TCGA and GTEx were obtained for analysis of expression and differentially expressed gene (DEG). Furthermore, functional enrichment analysis of -related DEGs was performed by GO/KEGG, GSEA, immune cell infiltration analysis, and protein-protein interaction (PPI) network. In addition, the clinical significance of in AML was figured out by Kaplan-Meier Cox regression and prognostic nomogram model. R package was used to analyze incorporated studies. As a result, was highly expressed in various malignancies, including AML, compared with normal samples. Moreover, high expression of was associated with poor prognosis in 151 AML samples, as well as subgroups with age >60, mutation-positive, mutation-negative, and DNMT3A mutation-negative, et al. ( < 0.05). High was an independent prognostic factor in Cox regression analysis; Age and cytogenetics risk were included in the nomogram prognostic model. Furthermore, a total of 529 DEGs were identified between the high- and the low- expression group, of which 92 genes were up-regulated and 437 genes were down-regulated. Collectively, high expression of is a potential biomarker for adverse outcomes in AML. The DEGs and pathways recognized in the study provide a preliminary grasp of the underlying molecular mechanisms of AML carcinogenesis and progression.
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http://dx.doi.org/10.18632/aging.202901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109082PMC
April 2021

Lower-dose decitabine improves clinical response compared with best supportive care in lower-risk MDS patients: a prospective, multicenter phase 2 study.

J Cancer 2021 19;12(10):2975-2981. Epub 2021 Mar 19.

MDS Center, Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.

To explore the efficacy and safety of lower-dose decitabine in patients with lower-risk MDS, a prospective multicenter phase II study was conducted to compare decitabine with the best supportive care (BSC). Patients diagnosed with lower-risk MDS from September 2013 to August 2018 were assigned to the decitabine group or the BSC group. Decitabine (12 mg/m/day) was administered over 1 hour/day for 5 consecutive days in a 4-week cycle. BSC, including growth factors, transfusion, thalidomide, lenalidomide, and immunosuppressive agents were given consecutively. The endpoints included the proportion of patients who achieved overall response (OR) in the first 2 or 3 courses, event-free survival (EFS), and overall survival (OS). A total of recruited 82 patients were analyzed. In the decitabine group, 65.9% (27/41) achieved OR after 2 or 3 cycles of treatment, compared with 22.0% (9/41) in the BSC group (p <0.01). Besides, 44.0% (11/25) in the decitabine group became independent of RBC/Platelets transfusion, compared with 27.8% (5/18) in the BSC group. Patients with gene mutation and treated with decitabine achieved a higher OR rate, compared with those without gene mutation [72.0% (18/25) vs 11.5% (3/26), p <0.01]. There was no significant difference in the median EFS between the decitabine and BSC groups (20.6 vs 14.3 months respectively, p = 0.665). In the decitabine group, the most significant adverse events were infections of any grades or neutropenic fever (46.3%, 19/41) and one patient (4.2%) died of acute cerebral infarction within 6 weeks of treatment. Lower-dose decitabine demonstrated promising clinical response with acceptable toxicity profiles in patients with low- and intermediate 1-risk MDS. A higher response rate to decitabine was observed in patients with mutated genes. Therefore, lower-dose decitabine can be advocated for patients with low-risk MDS and mutated genes.
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http://dx.doi.org/10.7150/jca.56207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040893PMC
March 2021

Minimal residual disease level determined by flow cytometry provides reliable risk stratification in adults with T-cell acute lymphoblastic leukaemia.

Br J Haematol 2021 Jun 25;193(6):1096-1104. Epub 2021 Mar 25.

Department of Hematology, School of Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B-cell ALL, reports of adult T-cell ALL (T-ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)-based MRD at the end of induction (EOI-MRD). The present retrospective study included 94 adult patients with T-ALL. MRD was detected by six- to eight-colour FCM. Patients who were EOI-MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse-free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI-MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) at their first remission, EOI-MRD positivity was predictive of post-transplant relapse (2-year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI-MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI-MRD based on FCM was an independent prognostic factor for relapse and survival in adult T-ALL. For patients who underwent HSCT, EOI-MRD could be used to identify patients with a high risk of relapse after allo-HSCT.
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http://dx.doi.org/10.1111/bjh.17424DOI Listing
June 2021

Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes.

Cancer Med 2021 03 20;10(5):1759-1771. Epub 2021 Feb 20.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Purpose: To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS).

Methods: A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS-related mutations sequencing.

Results: 38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and <60 years old (p = 0.046). TP53 mutations were associated with complex karyotype (CK) (p < 0.001). DNMT3A mutations correlated with -Y (p = 0.01) whereas NRAS mutations correlated with 20q- (p = 0.04). The overall survival (OS) was significantly inferior in patients with +8 compared with those with normal karyotype (NK) (p = 0.003). However, the OS of sole +8 and +8 with one additional karyotypic abnormality was not different from NK (p = 0.16), but +8 with two or more abnormalities had a significantly shorter OS than +8 and +8 with one additional karyotypic abnormality (p = 0.02). In multivariable analysis, ≥60 years old, marrow blasts ≥5% and TP53 mutations were independent predictors for poor OS (p < 0.05), whereas SF3B1 mutations indicated better prognosis. Male IDH1 and IDH2 mutations and marrow blasts ≥5% were independent risk factors for worse leukemia free survival (LFS) (p < 0.05).

Conclusion: In this population of Chinese patients, trisomy 8 is the most common karyotypic abnormality. Patients with +8 showed a poorer OS compared with patients with NK. Sole +8 and +8 with one additional karyotypic abnormality had similar OS with NK, whereas +8 with two or more abnormalities had a significantly shorter OS. DNMT3A mutations correlated with -Y and NRAS mutations correlated with 20q-. TP53 mutations were associated with CK and had a poor OS. SF3B1 mutations indicated a favorable OS. IDH1 and IDH2 mutations independently indicated inferior LFS.
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http://dx.doi.org/10.1002/cam4.3786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940222PMC
March 2021

Real-world data of chronic myelomonocytic leukemia: A chinese single-center retrospective study.

Cancer Med 2021 03 8;10(5):1715-1725. Epub 2021 Feb 8.

Myelodysplastic Syndrome Center, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Chronic myelomonocytic leukemia (CMML) is a rare disease of elderly people characterized by the presence of sustained peripheral blood monocytosis, overlapping features of myeloproliferation, and myelodysplasia. We present a large retrospective study of 156 CMML patients in China. Mean age at diagnosis was 68 years old (range 23-91). According to the CMML-specific prognostic scoring system (CPSS), 10 patients (8.3%) were low risk, 27 patients (22.5%) were intermediate-1 risk, 72 patients (60%) were intermediate-2 risk, and 11 patients (9.2%) were high risk. A total of 90 patients (57.7%) received hypomethylating agents (HMAs) treatment, 19 patients (12.2%) received chemotherapy and 47 patients (30.1%) received the best supportive care. Seventeen patients (10.9%) underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) after HMAs treatment or chemotherapy. With a median follow-up of 35.3 months, overall response rate (ORR) was 69.5% in the HMAs ± chemotherapy group, 79.5% in the HMAs monotherapy group, 60.0% in the HMAs + chemotherapy group, and 37.5% in the chemotherapy group. HMAs monotherapy group had prolonged OS compared with the chemotherapy group (23.57 months vs. 11.73 months; p = 0.035). Patients who achieved ORR had prolonged OS (25.83 months vs. 8.00 months; p < 0.001) and LFS (20.53 months vs. 6.80 months; p < 0.001) compared with those not achieved ORR in the HMA ± chemotherapy group. By univariate analysis, only higher hemoglobulin (≥80 g/L) and lower serum LDH levels (<300 U/L) predicted for better OS and LFS. By multivariate analysis, only Hb ≥ 80 g/L predicted for prolonged OS, Hb ≥ 80 g/L, and monocytes < 3 × 109/L predicted for prolonged LFS. In summary, our study highlights the benefit of HMAs therapy in CMML, but we still need to develop novel therapeutics to achieve better outcomes.
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http://dx.doi.org/10.1002/cam4.3774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940209PMC
March 2021

Impact of mutational variant allele frequency on prognosis in myelodysplastic syndromes.

Am J Cancer Res 2020 1;10(12):4476-4487. Epub 2020 Dec 1.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, Zhejiang Province, P. R. China.

The clinical relevance of variant allele frequency (VAF) of recurrent mutations in myelodysplastic syndromes (MDS) has been increasingly reported. However, the prognostic value of mutational VAF across the genetic spectrum of MDS has not been extensively evaluated. In this study, we profiled the mutational spectrum of 382 newly diagnosed MDS patients using targeted next-generation sequencing. Exploratory analysis found that mutational VAF of some genes including , , and had significant associations with patient survival. Specifically, VAF ≥ 32% (HR 1.69, P = 0.025) and VAF ≥ 27% (HR 3.58, P < 0.001) were independently associated with shorter overall survival (OS). In contrast, VAF ≥ 15% had an independent association with better prognosis (HR 0.52, P = 0.048). In addition, high VAF was associated with an increased response to hypomethylating agents relative to low VAF (P = 0.009). Patients with high VAF more often possessed complex karyotypes than those with low VAF (P = 0.034). And patients with high VAF were more frequently classified as MDS with ring sideroblasts (MDS-RS) category than those with low VAF (P = 0.012). Meanwhile, we found that for some other genes like and , once their mutations appeared, it meant poor survival regardless of mutational VAF. These findings suggest that mutational VAF of certain genes should be considered into the routine prognostic prediction and risk stratification of MDS patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783761PMC
December 2020

CAG regimen for refractory or relapsed adult T-cell acute lymphoblastic leukemia: A retrospective, multicenter, cohort study.

Cancer Med 2020 08 3;9(15):5327-5334. Epub 2020 Jun 3.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation.
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http://dx.doi.org/10.1002/cam4.3079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402818PMC
August 2020

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.

Hematol Oncol 2020 Oct 24;38(4):531-540. Epub 2020 Jun 24.

Department of Hematology, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China.

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/m daily, days 1 to 3; idarubicin, 6 mg/m daily, days 4 to 6; cytarabine 25 mg/m 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 × 10 /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.
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http://dx.doi.org/10.1002/hon.2755DOI Listing
October 2020

TP53 mutations are associated with very complex karyotype and suggest poor prognosis in newly diagnosed myelodysplastic syndrome patients with monosomal karyotype.

Asia Pac J Clin Oncol 2020 Jun 7;16(3):172-179. Epub 2020 Feb 7.

Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Aim: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK).

Methods: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy-three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next-generation sequencing. Genetic and biological features and their association with survival were evaluated.

Results: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1-16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9-12.8) than those with non-vCK (16.1 months with 95% CI 11.5-20.8) (P = .02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5-11.5 vs 26.1 months with 95% CI 8.0-44.2, P < .01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild-type TP53 (60% vs 22.2%, P = .03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P = .03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS.

Conclusions: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors.
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http://dx.doi.org/10.1111/ajco.13316DOI Listing
June 2020

Mutation status and burden can improve prognostic prediction of patients with lower-risk myelodysplastic syndromes.

Cancer Sci 2020 Feb 24;111(2):580-591. Epub 2019 Dec 24.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using next-generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129-4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144-8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662-14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848-16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR-MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDS and could help identify those with worse-than-expected prognosis for more aggressive treatment.
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http://dx.doi.org/10.1111/cas.14270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004535PMC
February 2020

Efficacy and safety of early switching to an outpatient therapy model using oral arsenic plus retinoic acid based-regimen in newly diagnosed acute promyelocytic leukemia.

Leuk Res 2019 08 8;83:106168. Epub 2019 Jun 8.

Department of Hematology, Leukemia Centre, First Affiliated Hospital of Zhejiang University, School of Medicine, China; Key Laboratory of Hematology, Diagnose and Treatment, Zhejiang Province, China. Electronic address:

Realgar-Indigo naturalis formula(RIF)is an oral form of arsenic developed for treatment of acute promyelocytic leukemia (APL). We retrospectively evaluated the efficacy and safety of a novel RIF combined with all-trans retinoic acid (ATRA) based chemotherapy-free approach in newly diagnosed APL patients. Patients received oral ATRA (25 mg/m/day in 2 divided doses) plus intravenous arsenic trioxide (0.15 mg/kg/day) or oral RIF (60 mg/kg/day in 3 divided doses) as induction chemotherapy, followed by 2 consolidations with ATRA plus RIF and maintenance therapy with intermittent ATRA and RIF. From January 2015 to December 2017, 40 subjects were enrolled. Eighteen subjects were male. Median age was 42 years (range, 14-77 years) and 10 subjects were ≥ 60 years. All subjects achieved a complete morphologic remission after initial induction. Molecular complete remission achieved 100% after second RIF plus ATRA consolidation. Median follow-up of survivors was 27 months (range, 7-43 months). The 2-year event-free survival (EFS) and overall survival (OS) were both 100%. Adverse events were modest and all patients needed only outpatient care during postremission therapy. Compared to our historical RIF plus ATRA with chemotherapy regimen (the Chinese APL07 trial), the inpatient treatment duration was greatly reduced by the RIF plus ATRA regimen. Our data indicates that early switching to RIF plus ATRA based chemotherapy-free approach has yielded encouraging outcomes and might be considered a practicable option to treat patients with newly diagnosed APL.
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http://dx.doi.org/10.1016/j.leukres.2019.106168DOI Listing
August 2019

Decitabine improves overall survival in myelodysplastic syndromes-RAEB patients aged ≥60 years and has lower toxicities: Comparison with low-dose chemotherapy.

Blood Cells Mol Dis 2019 07 31;77:88-94. Epub 2019 Mar 31.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China. Electronic address:

Decitabine and low-dose chemotherapy are common treatments for intermediate and high risk myelodysplastic syndromes (MDS). In this study, we retrospectively assessed the efficacy and toxicity of the two regimens for MDS-refractory anemia with excess blasts (MDS-RAEB) patients. A total of 112 patients with a diagnosis of MDS-RAEB are included. The overall response (OR) and complete remission (CR) rate was comparable between the two groups (OR: 64.1% vs. 66.7%, p = 0.60; CR: 23.4% vs. 31.3%, p = 0.64). The OR rates of 20 mg/m/day and 15 mg/m/day decitabine regimen were comparable (69.0% vs. 60.0%, p = 0.46). Overall survival (OS) did not differ significantly between the groups (20.7 vs. 13.5 months, p = 0.17). In a subgroup analysis that included only patients at ≥60 years of age, survival benefit of decitabine was apparent (20.6 vs. 10.0 months, p = 0.03). In hematological toxicities, the lowest count of platelet in the decitabine group was higher significantly. And, the incidence of Grade 3-4 infection in the decitabine group was lower significantly. Our results demonstrate that both decitabine and low-dose chemotherapy are effective for MDS-RAEB, but decitabine was safer. Decitabine might be a better choice for patients at ≥60 years of age.
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http://dx.doi.org/10.1016/j.bcmd.2019.03.010DOI Listing
July 2019

Decitabine for myelodysplastic syndromes: dose comparison in a real world clinical setting.

Leuk Lymphoma 2019 07 8;60(7):1731-1739. Epub 2019 Jan 8.

a Department of Hematology, The First Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , Zhejiang , China.

We retrospectively studied 133 myelodysplastic syndrome patients receiving decitabine during January 2009 and September 2017. The dose of 15 mg/m/d ( = 83) and 20 mg/m/d ( = 50) had comparable overall response rates (ORR) (51.8% vs. 52.00%) and complete remission rate (CRR) (15.66% vs. 22.00%). The 15 mg/m/d group had a lower incidence of grade 3/4 neutropenia (60.24% vs. 88.00%,  < .05) and thrombocytopenia (65.06% vs. 88.00%,  < .05). The 15 mg/m/d group had a longer median overall survival (OS) (21.60 months vs. 15.23 months,  = .02). The same results were seen in refractory anemia with excess blasts (RAEB) patients: The 15 mg/m/d group also had comparable ORR, CRR, decreased hematological toxicities and longer OS. Further analysis suggested that survival benefit of 15 mg/m/d group was mainly in those patients with lower risk stratification. In conclusion, 15 mg/m/d decitabine is associated with a lower incidence of hematological toxicities and longer OS and may be more suitable for patients with relatively lower risk.
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http://dx.doi.org/10.1080/10428194.2018.1546853DOI Listing
July 2019

Analysis of clinical and molecular features of MDS patients with complex karyotype in China.

Blood Cells Mol Dis 2019 03 22;75:13-19. Epub 2018 Nov 22.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China. Electronic address:

We retrospectively analyzed 101 primary MDS patients with complex karyotype during January 2010 and April 2017.The median overall survival (OS) time was 13 (95% CI 9.98-16.02) months, and there was no significant difference in OS for different treatment. Chromosome 5/7 involvement was common (78.22%, 79/101) and associated with shorter OS (12 months vs. 28 months, P < 0.01) Monosomal karyotype (MK) is overlapped with CK in 79 patients, but was not statistically associated with shorter OS. While in 59 cases with genes sequenced, 57 (96.61%) patients were found to have at least one mutation of known significance, and TP53 was the most frequent (74.58%, 44/59), the median OS of patients with TP53 mutation was shorter than those without (10 vs. 27 months, P < 0.01). Multivariate analysis demonstrated that only TP53 mutation was the strongest independent prognostic factor for OS. Moreover, high variant allele frequency (VAF) of TP53 mutation (median VAF was 70.00%) was seen and associated with adverse survival (9 months vs. 13 months, p = 0.04). In conclusion, MDS patients with CK implied an unfavorable outcome regardless of any treatment, TP53 mutation occurs at a high frequency and has a higher VAF, both were associated with worse survival.
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http://dx.doi.org/10.1016/j.bcmd.2018.11.006DOI Listing
March 2019

The relation of SF3B1 mutation and intracellular iron in myelodysplastic syndrome with less than 5% bone marrow blasts.

Leuk Lymphoma 2019 05 9;60(5):1179-1186. Epub 2018 Nov 9.

a MDS Center, Department of Hematology, the First Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , China.

According to 2008 WHO classification RARS is regarded as less than 5% blasts and more than 15% ring sideroblasts in the bone marrow. In 2016 WHO classification MDS-RS is revised as more than 15% ring sideroblasts or more than 5% ring sideroblasts in the presence of the SF3B1 mutation. In our study, we classified intracellular iron in bone marrow into four types according to the size and quantity of iron granules. We found that there was a significant difference between SF3B1-mutant and SF3B1-wild-type MDS patients in intracellular iron III, intracellular iron IV and ring sideroblasts. We defined intracellular iron (III + IV + RS)%×100 as 'Iron score'. We suggest that the patients carrying SF3B1 mutation with Iron score ≥10 will extend the subtype of MDS-RS, in addition to the current WHO classification criteria. This study gives us a new insight into the relation of SF3B1 mutation and intracellular iron in lower-risk MDS.
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http://dx.doi.org/10.1080/10428194.2018.1520990DOI Listing
May 2019

Clinical and biological characteristics of acute myeloid leukemia with 20-29% blasts: a retrospective single-center study.

Leuk Lymphoma 2019 05 10;60(5):1136-1145. Epub 2018 Oct 10.

a Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang , China.

It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts should be considered AML or myelodysplastic syndromes (MDS). We retrospectively studied 382 patients, including 108 AML with 20-29% BM blasts (AML20-29), 210 AML with ≥30% BM blasts (AML ≥ 30), and 64 MDS with 10-19% BM blasts (MDS-EB2). We found that AML20-29 were more similar to MDS-EB2 in terms of advanced age, less blood count, the increased presence of poor-risk cytogenetics. The frequency of mutated genes in AML20-29 had both the characters of AML and MDS. Median overall survival of AML20-29 and MDS-EB2 were similar and shorter than those of AML ≥ 30 (p = .045). Multivariate analysis showed inferior survival with increased age, low platelet count and FLT3 mutations. Our findings suggest that AML20-29 have clinical features more similar to MDS than AML.
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http://dx.doi.org/10.1080/10428194.2018.1515938DOI Listing
May 2019

The high NRF2 expression confers chemotherapy resistance partly through up-regulated DUSP1 in myelodysplastic syndromes.

Haematologica 2019 03 27;104(3):485-496. Epub 2018 Sep 27.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

Although cytarabine has been widely considered as one of the chemotherapy drugs for high-risk myelodysplastic syndromes (MDS), the overall response rate is only approximately 20-30%. Nuclear factor erythroid 2-related factor 2 (NRF2, also called NFE2L2) has been shown to play a pivotal role in preventing cancer cells from being affected by chemotherapy. However, it is not yet known whether NRF2 can be used as a prognostic biomarker in MDS, or whether elevated NRF2 levels are associated with cytarabine resistance. Here, we found that NRF2 expression levels in bone marrow from high-risk patients exceeded that of low-risk MDS patients. Importantly, high NRF2 levels are correlated with inferior outcomes in MDS patients (n=137). Downregulation of NRF2 by the inhibitor Luteolin, or lentiviral shRNA knockdown, enhanced the chemotherapeutic efficacy of cytarabine, while MDS cells treated by NRF2 agonist Sulforaphane showed increased resistance to cytarabine. More importantly, pharmacological inhibition of NRF2 could sensitize primary high-risk MDS cells to cytarabine treatment. Mechanistically, downregulation of dual specificity protein phosphatase 1, an NRF2 direct target gene, could abrogate cytarabine resistance in NRF2 elevated MDS cells. Silencing NRF2 or dual specificity protein phosphatase 1 also significantly sensitized cytarabine treatment and inhibited tumors in MDS cells transplanted mouse models Our study suggests that targeting NRF2 in combination with conventional chemotherapy could pave the way for future therapy for high-risk MDS.
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http://dx.doi.org/10.3324/haematol.2018.197749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395322PMC
March 2019

Expression of hypoxia-inducible factor-1a predicts benefit from rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in diffuse large B-cell lymphoma.

Int J Clin Exp Pathol 2018 1;11(9):4472-4482. Epub 2018 Sep 1.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, People's Republic of China.

Hypoxia-inducible factor-1α (HIF-1α) has been identified as an unfavorable prognostic factor in most solid tumors. However, HIF-1α was suggested to predict improved survival in Western patients with diffuse large B-cell lymphoma (DLBCL) under rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment. We studied HIF-1α protein expression by immunohistochemical staining of 155 paraffin-embedded specimens from Chinese patients with DLBCL treated with R-CHOP or CHOP. Results were correlated with patient outcome. HIF-1α expression had no impact on survival for the patients treated with CHOP. In the R-CHOP-treated group, however, HIF-1α expression was significantly correlated with superior OS and EFS (P = 0.048 and 0.040, respectively). Moreover, HIF-1α expression maintained independent prognostic value for OS (RR, 0.41; 95% CI, 0.19-0.92; P = 0.030) and EFS (RR, 0.53; 95% CI, 0.31-0.90; P = 0.020) when it was adjusted by IPI stratification. Therefore, HIF-1α expression benefits from R-CHOP in DLBCL.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962976PMC
September 2018

Usefulness of tocilizumab for treating rheumatoid arthritis with myelodysplastic syndrome: A case report and literature review.

Medicine (Baltimore) 2018 Jun;97(25):e11179

Department of Rheumatology Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Rationale: Dysregulated immune function in rheumatoid arthritis (RA) might lead to the development of myelodysplastic syndrome (MDS). Serum interleukin-6 (IL-6) concentrations are increased in both RA and MDS patients.

Patient Concerns: A 58-year-old woman presented with severe RA. During a recent 8-month period, the patient experienced swelling in multiple joints, dizziness, and severe anemia. The symptoms responded poorly to oral corticosteroids and methotrexate (MTX). Even treatment of the patient's anemia by transfusion of red blood cells was ineffective. Laboratory tests showed high levels of IL-6 (214.24 pg/mL).

Diagnoses: Combining her medical history with clinical and laboratory parameters, especially those obtained by bone marrow aspiration, a diagnosis of RA with MDS was made.

Interventions: MTX was discontinued and the patient was given tocilizumab intravenously at a dose of 8 mg/kg every 4 weeks and oral corticosteroids (15 mg/QD).

Outcomes: The patient's serological, physical, and pathological abnormalities improved significantly.

Lessons: We report a case of RA with MDS successfully treated with tocilizumab. To our knowledge, this is the first case of an RA patient with MDS that was successfully treated with tocilizumab. In addition, our case emphasizes that IL-6 plays a critical role in the pathogenesis of RA with MDS. Tocilizumab might be an effective treatment for RA with MDS, especially in those with high levels of IL-6, elevated C-reactive protein, and severe anemia.
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http://dx.doi.org/10.1097/MD.0000000000011179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023877PMC
June 2018

Improved long-term survival in all Sanz risk patients of newly diagnosed acute promyelocytic leukemia treated with a combination of retinoic acid and arsenic trioxide-based front-line therapy.

Hematol Oncol 2018 Jun 3. Epub 2018 Jun 3.

Department of Hematology, Leukemia center, The First Affiliated Hospital of Zhejiang University, College of Medicine; Key Laboratory of Hematopoietic Malignancies in Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China.

Limited data was available for long-term follow-up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all-trans-retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)-based front-line therapy. The aim of this work was to retrospectively analyze the long-term survival rate and frequency of therapy-related myeloid neoplasia (t-MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9.2% (70/760). Of the remaining 690 patients with complete remission, patients were grouped according to front-line regimens: ATRA plus ATO with or without chemotherapy (ATO group) and ATRA with chemotherapy (non-ATO group). The median duration of follow-up was 7.5 years (1.0-18.3 years). ATO group showed significant superior 10-year estimated relapse-free survival (RFS) up to 90.3% comparing with 65.5% in the non-ATO group (P < 0.0001). In addition, the 10-year estimated overall survival (OS) was 93.9% for patients in the ATO group and 89.1% for those in the non-ATO group (P = 0.03). In the subgroup analysis, the RFS rate was also higher in ATO group comparing with non-ATO group in both low-to-intermediate-risk (94.2% vs 64.6%, P < 0.0001) and high-risk subgroup (89.6% vs 74.7%, P = 0.04). Notably, the 3-year RFS and OS rates in the chemotherapy-free subgroup of the low-to-intermediate-risk patients (n = 88) were 100% and 100%, respectively. In the entire cohort, a total of 10 patients developed secondary malignant neoplasms, including 7 patients with therapy-related myeloid neoplasms (t-MN). The estimated 5-year cumulative incidence risk of t-MN in the ATO and non-ATO groups was 1.0% and 0.4%, respectively (P = 0.34). Thus, our data revealed that the long-term outcome of patients treated with ATRA plus ATO-based regimens was associated with continuing high efficacy in all Sanz risk patients with newly diagnosed APL.
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http://dx.doi.org/10.1002/hon.2519DOI Listing
June 2018

Isocitrate dehydrogenase 2 mutations correlate with leukemic transformation and are predicted by 2-hydroxyglutarate in myelodysplastic syndromes.

J Cancer Res Clin Oncol 2018 Jun 16;144(6):1037-1047. Epub 2018 Mar 16.

Department of Hematology, The First Affiliated Hospital, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.

Purpose: The myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by the presence of somatically mutated hematopoietic stem cells (HSCs) that increase the risk of progression to secondary acute myeloid leukemia (sAML). Mutations in isocitrate dehydrogenase (IDH) are thought to correlate with the increased production of the oncogenic protein 2-hydroxyglutarate (2-HG) in AML. The aim of this study was to examine whether serum 2-HG has utility as a prognostic biomarker, and whether elevated 2-HG levels are predictive of IDH mutations in patients with MDS.

Methods: Genetic profiling was utilized to determine the genetic composition of a large cohort of MDS patients, including the presence or absence of IDH1 or IDH2 mutations (n = 281). Serum 2-HG levels were detected by liquid chromatography-tandem mass spectrometry.

Results: In the current study of MDS patients, elevated serum 2-HG levels were predictive of inferior overall- and leukemia-free survival irrespective of IPSS risk grouping. Higher serum 2-HG levels predicted the presence of IDH mutations. IDH2 patients had a higher risk of leukemic transformation. The co-occurrence of DNMT3A or SRSF2 mutations was found to be increased in IDH2 patients. IDH2 mutations were associated with significantly worse OS and LFS amongst patients with low-risk MDS by IPSS grouping.

Conclusions: The noted predictive value of serum 2-HG levels and IDH2 mutations on OS and LFS support the use of biomarkers and/or underlying cytogenetics in novel prognostic scoring systems for MDS.
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http://dx.doi.org/10.1007/s00432-018-2627-3DOI Listing
June 2018

Publisher Correction: PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation.

Sci Rep 2017 11 7;7(1):15260. Epub 2017 Nov 7.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-017-14858-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677121PMC
November 2017

Effectivity of a modified Sanz risk model for early death prediction in patients with newly diagnosed acute promyelocytic leukemia.

Ann Hematol 2017 Nov 19;96(11):1793-1800. Epub 2017 Aug 19.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, China.

Early death is the main obstacle for the cure of patients with acute promyelocytic leukemia (APL). We have analyzed risk factors of early death from 526 consecutive newly diagnosed APL patients between 2004 and 2016. The overall incidence of early death was 7.2% (38/526). The peak hazard of early death occurred in the first 0-3 days. Multivariate logistic analysis demonstrated white blood cell (WBC) counts [odds ratio (OR) = 1.039; 95% confidence interval (CI): 1.024-1.055; P < 0.001], age (OR = 1.061; 95% CI: 1.025-1.099; P = 0.001) and platelet counts (OR = 0.971; 95% CI: 0.944-0.999; P = 0.038) were independent risk factors for early death. Furthermore, receiver-operator characteristic (ROC) curve analyses revealed a simple WBC/platelet ratio was significantly more accurate in predicting early death [areas under the ROC curve (AUC) = 0.842, 95% CI: 0.807-0.872) than WBC counts (AUC = 0.793; 95% CI: 0.756-0.827) or Sanz score (AUC = 0.746; 95% CI: 0.706-0.783). We stratified APL patients into four risk subgroups: low risk (WBC ≤ 10 × 10/L, platelet >40 × 10/L), intermediate risk (WBC/platelet <0.2 and age ≤ 60, not in low risk), high risk (WBC/platelet ≥0.2 or age > 60, not in low and ultra-high risk) and ultra-high risk (WBC > 50 × 10/L), the early death rates were 0, 0.6, 12.8, and 41.2%, respectively. In conclusion, we proposed a modified Sanz risk model as a useful predictor of early death risk in patients with APL.
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http://dx.doi.org/10.1007/s00277-017-3096-5DOI Listing
November 2017

PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation.

Sci Rep 2017 06 6;7(1):2894. Epub 2017 Jun 6.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.

Patients with secondary acute myeloid leukemia (sAML) arising from myelodysplastic syndromes have a poor prognosis marked by an increased resistance to chemotherapy. An urgent need exists for adjuvant treatments that can enhance or replace current therapeutic options. Here we show the potential of LB100, a small-molecule protein phosphatase 2 A (PP2A) inhibitor, as a monotherapy and chemosensitizing agent for sAML using an in-vitro and in-vivo approach. We demonstrate that LB100 decreases cell viability through caspase activation and G2/M cell-cycle arrest. LB100 enhances daunorubicin (DNR) cytotoxicity resulting in decreased xenograft volumes and improved overall survival. LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3' untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. Our research highlights the therapeutic potential of LB100, and provides new insights into the mechanism of LB100 chemosensitization.
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http://dx.doi.org/10.1038/s41598-017-03058-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460144PMC
June 2017

Prognostic significance of huntingtin interacting protein 1 expression on patients with acute myeloid leukemia.

Sci Rep 2017 04 28;7:45960. Epub 2017 Apr 28.

Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.

Huntingtin interacting protein 1 (HIP1) is an endocytic protein which is overexpressed in a variety of human cancers and involved in cancer-causing translocation in leukemia. However, the prognostic impact of HIP1 expression on AML remains unclear. In this study, quantification of HIP1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As a result, high HIP1 expression was seen more frequently in older patients, M4/M5 morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in favorable karyotype subgroups and CEBPA double allele mutations in our AML patients. We also found high HIP1 expressers showed lower levels of hemoglobin. In addition, overexpression of HIP1 was associated with an inferior overall survival. The prognostic value of HIP1 expression was validated in patients from an independent TCGA cohort. Notably, up-regulation of miR-16, miR-15a, miR-28 and miR-660 were seen in high HIP1 expressers from the two independent cohorts. In vitro, interfereing of HIP1 expression by siRNA suppressed the proliferation of leukemic cells, and downregulation of these miRNAs were seen in THP-1 and Kasumi cell lines after silencing HIP1 expression. In conclusion, the HIP1 gene expression might serve as a reliable predictor for overall survival in AML patients.
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http://dx.doi.org/10.1038/srep45960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408226PMC
April 2017

Salvage therapy with lenalidomide containing regimen for relapsed/refractory Castleman disease: a report of three cases.

Front Med 2017 Jun 3;11(2):287-292. Epub 2017 Apr 3.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Castleman disease (CD) is uncommon non-clonal lymphoproliferative disorder with unknown etiology. No standard therapy is recommended for relapsed/refractory CD patients, thus requiring development of novel experimental approaches. Our cohort of three adult patients with multicentric CD (MCD) were treated with refractory to traditional chemotherapy lenalidomide-containing regimens (10-25 mg lenalidomide perorally administered on days 1-21 in 28-day cycle) as second- to fourth-line treatment. Partial remission was achieved in first plasma-cell CD patient, who relapsed seven months after autologous hematopoietic stem cell transplantation and then failed to respond to four cycles of chemotherapy. Partial remission was obtained in second patient with CD and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Third case showed complete remission with complete disappearance of pleural effusion and ascites and normalization of platelet count. To conclude, encouraging clinical responses were achieved in cohort of three patients with lenalidomide-based regimen, though long-term efficacy remains to be observed.We propose further investigation of therapeutic potential of this drug in treating MCD.
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http://dx.doi.org/10.1007/s11684-017-0510-2DOI Listing
June 2017

Efficacy and prognostic factors of imatinib plus CALLG2008 protocol in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

Front Med 2017 Jun 27;11(2):229-238. Epub 2017 Mar 27.

Institute of Hematology, Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

A CALLG2008 protocol was developed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult acute lymphoblastic leukemia (ALL). We retrospectively analyzed 153 newly diagnosed adult patients with Philadelphia chromosome (Ph)-positive ALL enrolled into imatinib (400 mg/d) plus CALLG2008 regimen between 2009 and 2015. The median age was 40 years (range, 18-68 years), with 81 (52.3%) males. The overall hematologic complete remission (CR) rate was 96.7% after induction. With a median follow-up of 24.2 months, the estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 49.5%(95%confidence interval (CI): 38.5%-59.5%) and 49.2% (95% CI: 38.3%-59.2%), respectively. Fifty-eight (36 with haploidentical donor) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first CR. Among the patients in CR1 after induction, both the 3-year OS and EFS were significantly better in the allo-HSCT group than in the without allo-HSCT group (73.2%, 95% CI: 58.3%-83.5% vs. 22.2%, 95% CI: 8.7%-39.6% and 66.5%, 95% CI: 50.7%-78.2% vs. 16.1%, 95% CI: 5.1%-32.7%, respectively). Multivariate analysis showed that allo-HSCT and achievement of major molecular response were associated with favorable OS or EFS independently. Interestingly, in the allo-HSCT cohort, the donor type (haploidentical versus matched donors) had no significant impact on EFS or OS. All these results suggested that imatinib plus CALLG2008 was an effective protocol for Ph-positive ALL. Haploidentical donors can also be a reasonable alternative expedient donor pool.
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http://dx.doi.org/10.1007/s11684-017-0506-yDOI Listing
June 2017

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone.

J Cancer Res Clin Oncol 2017 May 20;143(5):873-882. Epub 2017 Jan 20.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.

Purpose: The aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes-refractory anemia with excess of blasts (MDS-RAEB).

Methods: The current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens.

Results: A total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2-21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at < 60 years of age, the CR rate in the decitabine priming group was significantly higher than in the chemotherapy group (65.5 vs. 31.0%, p = 0.009). Survival benefit of decitabine priming was apparent in patients at < 60 years of age (22.4 months with 95% CI of 6.7-38.1 vs. 14.7 months with 95% CI of 11.4-18.0 months in the chemotherapy group, p = 0.028), patients with intermediate and unfavorable karyotypes (22.4 months with 95% CI of 15.1-29.7 vs. 11.9 months with 95% CI of 4.0-19.8 months in the chemotherapy group, p = 0.042), and patients with mutated splicing factor genes (35.3 months with 95% CI of 21.4-49.2 vs. 17.8 months with 95% CI of 13.8-21.8 months in the chemotherapy group, p = 0.039). Grade 3-4 hematological and non-hematological toxicities were not significantly different between the two groups.

Conclusions: Decitabine priming prior to low-dose chemotherapy could improve treatment responses in patients with MDS-RAEB.
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http://dx.doi.org/10.1007/s00432-016-2331-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384967PMC
May 2017
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