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Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was KIT mutation (30.6%), followed by NRAS (24.2%) and ASXL1 (14.5%) mutations, which was associated with a higher number of bone marrow blasts (p =.049) and older age (p =.027). The survival analysis showed KIT mutation adversely affected the overall survival (OS) (p =.046). NRAS mutation was associated with inferior OS (p =.016) and RFS (p =.039). Eight patients carried co-mutations of KIT and NRAS and had worse OS (p =.012) and RFS (p =.034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of KIT and NRAS were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of FLT3-ITD mutations on the treatment response and long-term survival of newly-diagnosed patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and arsenic trioxide. Methods: The long-term survival of 90 newly-diagnosed APL patients (age range 12– 75 years) was retrospectively analyzed.The FLT3-ITD mutation rate was assayed by polymerase chain reaction (PCR) amplification and sequencing analysis. Its impact on the treatment response, event-free survival(EFS), or overall survival(OS) was investigated in patients with and without the mutations. Results: The FLT3-ITD mutation rate in newly-diagnosed APL patients was 20% (18/90). The white blood cell (WBC) count at diagnosis in patients with mutations was significantly higher than that in patients without mutations while the FLT3-ITD mutation rate was higher in the high-risk group than in the low/intermediate-risk group. Patients with mutations had a significantly higher early death (ED) rate (16.67% vs 1.39%) for those lacking the mutation (P =0.024). However, the complete remission (CR) and differentiation syndrome (DS) rates in the two groups were similar. Kaplan Meier analysis for EFS and OS at five years showed a significant difference between the patients stratified by FLT3-ITD mutation status (log-rank P =0.010 and P =0.009, respectively). Conclusion: FLT3-ITD mutations can be related to high peripheral WBC counts in APL patients. APL patients with mutations displayed a higher ED rate compared to those without mutations. Patients carrying mutations had reduced five-year EFS and OS rates. Thus, reducing the overall death rate during induction treatment might be an effective way to improve the prognosis of patients with FLT3-ITD mutations. [ABSTRACT FROM AUTHOR]

Immunoglobulin heavy chain variable region (IGHV) mutational status has been an important prognostic factor for chronic lymphocytic leukemia (CLL) for decades. Patients with unmutated IGHV (≥98% identity to the germline sequence) have inferior prognosis and tend to carry unfavorable genetic markers compared to those with mutated IGHV (<98% identity to the germline sequence). However, 98% as the cutoff for IGHV mutational status is a mathematical choice and remains controversial. We have previously reported distinct IGHV repertoire features between Chinese and western CLL populations. Here, we retrospectively studied 595 Chinese CLL patients to determine the best cutoff value for IGHV in Chinese CLL population. Using 1% as the interval for IGHV identity, we divided the studied cohort into seven subgroups from 95% to 100%. Briefer time to first treatment (TTFT) and overall survival (OS) were observed in cases with ≥98% compared to those with <98%, while the differences were obscure within subgroups ≥98% (98%‐98.99%, 99%‐99.99%, and 100%) and <98% (<94.99%, 95%‐95.99%, 96%‐96.99%, and 97%‐97.99%). Multivariate analysis confirmed the independent prognostic value of 98% being the cutoff for IGHV identity in terms of both TTFT and OS. All the prognostic factors, including del(17p13), del(11q22.3), TP53 mutation, MYD88 mutation, NOTCH1 mutation, SF3B1 mutation, CD38, ZAP‐70, Binet staging, gender, and β2‐microglobulin, were significantly different in distribution between group <98% and group ≥98%, but not among subgroups 98%‐98.99%, 99%‐99.99%, and 100%. In conclusion, 98% is the optimal cutoff of IGHV identity for the prognosis evaluation of Chinese CLL patients. [ABSTRACT FROM AUTHOR]

Abstract: The proto‐oncogene NOTCH1 is frequently mutated in around 10% of patients with chronic lymphocytic leukemia (CLL). This study analyzed NOTCH1 mutation status of 317 Chinese patients with CLL by Sanger sequencing. The frequencies of NOTCH1 mutation in the PEST (proline (P), glutamic acid (E), serine (S), threonine (T)‐rich protein sequence) domain and the 3′ untranslated regions (UTR) were 8.2% and 0.9%, with the most frequent mutation being c.7541_7542delCT and c.*371A>G, respectively. Clinical and biological associations were determined including NOTCH1 mutations with advanced stage (Binet stage, P = 0.010), unmutated immunoglobulin heavy‐chain variable region (IGHV) gene (P < 0.001) and trisomy 12 (+12) (P = 0.014). NOTCH1‐mutated patients had lower CD20 expression intensity than NOTCH1‐unmutated patients (P = 0.029). In addition, NOTCH1‐mutated patients had shorter overall survival (OS) (P = 0.002) and treatment‐free survival (TFS) (P = 0.002) than NOTCH1‐unmutated patients, especially for patients with NOTCH1 c.7541_7542delCT and/or c.*371A>G mutations. Patients with both mutated NOTCH1 and unmutated IGHV had shorter OS (P < 0.001) and TFS (P < 0.001) than those with unmutated NOTCH1 or mutated IGHV. These data provide a comprehensive view of the clinical relevance and prognostic impact of NOTCH1 mutations on Chinese patients with CLL. [ABSTRACT FROM AUTHOR]

Abstract: The characteristics of core binding factor (CBF) leukemia appear to differ between Chinese and Caucasian patients. In this study, we analyzed the biological and clinical characteristics of 76 Chinese CBF leukemia patients out of 425 newly diagnosed acute myeloid leukemia (AML) patients. The frequency of CBF AML was 17.9%. Patients harboring t(8;21) were predominant in CBF AML. The incidence of c-kit mutation in CBF AML was 28.9%. The N822K mutation appeared to be more prevalent in Chinese CBF AML patients. Multivariate analysis showed that c-kit mutation and high white blood cell count could negatively impact overall survival (OS) (HR=2.74 and 6.24, P =0.007 and 0.022, respectively) but did not affect relapse-free survival (RFS). Kaplan–Meier analysis showed a significant difference in both OS and RFS between wild-type and mutated c-kit patients. Although we had included recently reported prognostic indicators in our analysis, our results demonstrated that only c-kit mutation and high white blood cell count had prognostic impact on Chinese CBF AML patients. [Copyright &y& Elsevier]

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the Western countries, however, it is infrequent in the Eastern countries. The direct antiglobulin test (DAT) may be positive at some time during the disease course of CLL. The aim of this study was to explore the prognostic impact of positive DAT at diagnosis in Chinese patients with CLL. In 123 Chinese patients with CLL, 34 (27.6%) patients presented with a positive DAT at diagnosis. However only 12 patients (9.8%) with a positive DAT developed autoimmune hemolytic anemia (AHA). According to the correlation analysis, advanced Binet stage (p < 0.001), high level of serum lactate dehydrogenase (LDH) (p = 0.003) and β2-microglobulin (β2-M) (p = 0.011), unmutated immunoglobulin heavy chain variable gene status (p < 0.001), positive ZAP-70 (p = 0.012), and trisomy 12 cytogenetic aberration (p = 0.004) emerged as factors significantly related to the occurrence of DAT-positive. Patients with positive DAT had significantly shorter survival times than patients with negative DAT (p = 0.009). Five-year OS percentages of DAT-positivity and DAT-negative patients were 72.8% and 97.5%, respectively. It was showed that DAT status might be applied for the assessment of prognosis in patients with CLL. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients" published in a previous issue of the periodical.

Abstract: The aim of this study was to explore the clinical and other associated laboratory features of chronic lymphocytic leukemia (CLL) patients with immunoglobulin (Ig) paraproteinemia. Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) were performed to measure serum Ig paraprotein. The correlations between serum Ig paraprotein and other prognostic factors were analyzed. Univariate and multivariate Cox regression analyses were used to assess associations between survival time and potential risk factors. In 133 Chinese CLL patients, 27 (20.3%) patients occurred Ig paraproteinemia at diagnosis. According to the correlation analysis, advanced Binet stage (r =0.314, P <0.001), direct antiglobulin test (DAT)-positive (r =0.366, P <0.001), high level of serum β2-microglobulin (β2-MG) (r =0.296, P =0.001) and thymidine kinase (TK) 1 (r =0.227, P =0.037), unmutated immunoglobulin heavy chain variable gene (IGHV) status (r =0.284, P =0.002), ZAP-70-positive (r =0.305, P =0.001), CD38-positive (r =0.284, P =0.002), and cytogenetic abnormalities of del(17p13) or del(11q22.3) (r =0.208, P =0.032) emerged as factors significantly related to the occurrence of Ig paraproteinemia. Survival analysis showed that the patients with Ig paraproteinemia had significantly shorter survival times than the patients without serum Ig paraprotein (P =0.013). Binet stage (P =0.028), high levels of lactate dehydrogenase (LDH) (P =0.004), IgG paraproteinemia (P =0.048), IgM paraproteinemia (P =0.001), ZAP-70-positive (P =0.003), DAT-positive (P =0.013), unmutated IGHV status (P =0.009), and del(17p13) (P =0.001) were the adverse factors in determining overall survival (OS). Del(17p13) (P =0.006), ZAP-70 (P =0.030), and IgM paraproteinemia (P =0.040) were the variables strongly associated with OS by multivariate Cox regression analysis. It was showed that serum Ig paraprotein might be applied for the assessment of prognosis in patients with CLL. [Copyright &y& Elsevier]

Abstract: B-cell chronic lymphocytic leukemia (CLL) is the most common type of adult leukemias in the Western countries, however, infrequent in the Eastern. A diagnosis of CLL requires a count of B-lymphocytes ≥5.0×109/L. Asymptomatic person with <5.0×109/L B-lymphocytes is defined as monoclonal B-cell lymphocytosis (MBL). To compare the clinical characteristics, prognostic factors, and outcome of Chinese patients with MBL and CLL, we present a study from our single centre of 20 patients with MBL and 136 patients with CLL. The factors included: age at diagnosis, gender, direct antiglobulin test (DAT), immunoglobulin heavy chain variable gene (IgHV) mutational status, ZAP-70 protein, CD38 expression level, and molecular cytogenetic aberrations were analyzed in MBL and CLL subgroups. The Kaplan–Meier method was used to construct survival curves, and results were compared using the log-rank test. Patients in the MBL category were slightly older than in the CLL category. There was no significant difference of these clinical and biological characteristics between patients in MBL subgroup and early stage CLL (Binet A). The incidence of positive DAT was significantly increased in CLL patients at Binet B and C, compared with MBL (P =0.036). IgHV gene mutation in MBL is skewed, with more than 92.3% of subjects harbored mutated IgVH genes (P =0.025). The proportion of MBL patients with a 13q14 deletion or trisomy 12 was similar to that of CLL patients. Moreover, markers associated with poor prognosis (deletion of 11q22 or 17p13) in these MBL populations were less than those in Binet B and C CLL patients (P =0.025). No statistically significant differences in ZAP-70 and CD38 status were observed between the MBL and CLL subgroups. During a median follow-up period of 45.5 months, MBL patients had a low probability of progression, with no patients transformed to aggressive non-Hodgkin''s lymphoma or dying of CLL-related causes. The overall survival of MBL was very similar to Binet A CLL, but longer than that of CLL patients at advanced stages (Binet B and C) (P =0.024). Our study demonstrated that a more indolent clinical course and superior clinical outcome for patients with MBL compared to CLL. [Copyright &y& Elsevier]