[Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients. METHODS: The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed. RESULTS: Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 109/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048). CONCLUSION: Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 109/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.

Long-term outcomes of imatinib in patients with FIP1L1/ PDGFRA associated chronic eosinophilic leukemia: experience of a single center in China.

BACKGROUND: The FIP1L1/PDGFRA (F/P) fusion gene is the most common clonal genetic abnormality of chronic eosinophilic leukemia (CEL). Tyrosine kinase inhibitors (TKI), such as imatinib, have been demonstrated to be effective therapies for F/P mutated disease. The aim of this study was to analyze the treatment response and long term prognosis in patients with F/P mutated CEL. METHODS: The clinical features and treatment responses of 33 consecutive patients with F/P mutated CEL between August 2006 and October 2014 were analyzed. The 33 cases received imatinib therapy at an initial dose of 100 mg/day (30 patients) or 200 mg/day (3 patients); the maintenance dose depended on the response condition and patient willingness. Through the follow up, the molecular responses were regularly monitored. RESULTS: With a median follow up of 64 months, 94% of the 33 patients with F/P mutated CEL achieved a complete hematologic remission (CHR), and 97% achieved a complete molecular remission (CMR) after a median of 3 (1.5-12) months. Twenty-four cases received maintenance therapy, with a median CMR duration of 43 (5-88) months. Imatinib therapy was discontinued in 8 cases, including 4 cases who experienced relapse, and 4 patients who maintained CHR or CMR after discontinuing therapy with a median time of 47 (2-74) months. One case exhibited primary resistance with a PDGFRA T674I mutation. CONCLUSIONS: F/P mutated CEL has an excellent long-term prognosis following imatinib therapy. A 100 mg daily dose of imatinib is sufficient to induce remission, and a single 100 mg weekly dose maintains a durable remission. A subgroup of patients may maintain a durable remission after discontinuing therapy with a CMR.

[Epidemiological investigation on fascioliasis and its risk factors in population of Binchuan County, Yunnan Province].

OBJECTIVE: To understand the infection status of Fasciola and related risk factors in population of Binchuan County, Yunnan Province. METHODS: In February and March, 2014, 6 natural villages from 2 administrative villages in Zhoucheng Town were selected as investigated sites, and the permanent residents aged ≥ 5 years were examined by ELISA for the serum antibody detection, and then the positive ones were examined by Kato-Katz technique and the hatching method for Fasciola egg detection. Meanwhile, the fascioliasis cases that checked out by the above methods were further surveyed, and the residents who with the same gender, similar age and negative results in the blood examination were selected as the controls, then the risk factors were explored through a case control study. RESULTS: Totally 1 207 people were included in the blood examination, and 36 positives were found with a positive rate of 2.98%. Though the differences between the positive rates of the serum antibody in people with different genders and age were not statistically significant (χ2 = 1.686, 7.106, both P > 0.05) , those between the rates of people in different administrative villages and natural villages were statistically significant (χ2 = 4.103, 13.181, both P < 0.05). Two cases were determined as positives in fecal examinations with a positive rate of 6.45% (2/31), among which, 1 case was newly discovered. The case control study showed that OR values of eating out- purchased cold dish (4.30), raw mint (1.22) , raw leek (4.30) and drinking unboiled-water (3.75) were relatively higher, but all of them were not statistically significant (χ2 = 0.524, 0.046, 0.524, 1.571, all P > 0.05). CONCLUSIONS: There is still sporadic Fasciola infection in Binchuan County. Eating raw vegetables and drinking unboiled water which are contaminated by Fasciola metacercariae may be the infection routes of local people, and to find out the exact entrance way is the key points for the infection control.

[Relationship between polymorphisms of tumor necrosis factor alpha gene and primary myelodysplastic syndromes].

OBJECTIVE: To investigate the association of single nucleus polymorphisms(SNP)of tumor necrosis factor alpha (TNF-α) gene (-308 G>A and -238 G>A genotypes) with susceptibility to primary myelodysplastic syndromes (MDS). METHODS: Two SNPs (TNF-α-308 G>A,TNF-α-238 G>A) of TNF-α gene were detected by Taqman probes in 341 MDS patients and 365 unrelated-healthy controls. RESULTS: Compared to healthy controls, the frequency of TNF-α-308 AA+AG genotype and A allele increased (18% vs 10%, P=0.015, 9% vs 5%, P=0.021, respectively) in refractory cytopenia with multilineage dysplasia (RCMD) patients. There was no correlation of TNF-α-308 G>A genotype and allele frequency between MDS and controls. No difference in the genotype and allele frequency of TNF-α-238 G>A were found between controls and MDS or the subtypes of MDS (P>0.05). We did not find any linkage between plasma level of TNF-α and TNF-α-308 G>A or TNF-α-238 G>A genotype. Statistic differences were observed between platelet count[58(1-611)×109/L vs 90(7-352)×109/L]and bone marrow blasts in MDS patients carrying TNF-α-308 G>A GG and AA+AG genotype (P=0.024, 0.019, respectively). CONCLUSION: TNF-α-308 G>A polymorphism was correlated with susceptibility to MDS-RCMD.

[Analysis of clinical features and prognosis of primary myelodysplastic syndromes with myelofibrosis patients].

OBJECTIVE: To analyze the clinical features and prognosis of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients and to improve the cognition of MDS-MF. METHODS: Four hundred and sixty-six primary MDS patients with bone marrow (BM) biopsy were divided into two groups according to whether BM associated with fibrosis, the clinical features and prognosis of the two groups were analyzed retrospectively. RESULTS: 167 (35.8%) MDS cases revealed myelofibrosis, of which MF-1 123 cases (26.4%), MF-2 40 cases (8.6%), MF-3 4 cases (0.9%). The proportion of hepatosplenomegaly in MDS-MF group was significantly higher than in MDS without MF group, the difference had statistical significance (P = 0.031). The proliferation of BM biopsy in MDS-MF group was significantly more active than in MDS without MF group. The number of blasts, megakaryocytes and abnormal megakaryocytes in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P < 0.05). Among the 345 patients who had available results of cytogenetic analysis, 121 cases were MDS-MF patients, the proportion of middle and high-risk prognostic group according to IPSS karyotype prognosis groups in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P = 0.047). The median survival was 17 (1 - 60) months in MDS-MF group, and was 32 (1 - 62) months in MDS without MF group. The difference had statistical significance (P = 0.001). Myelofibrosis had independent prognostic significance by multi-variable analysis (P = 0.019). CONCLUSION: The myelofibrosis in MDS is main the proliferation of reticular fiber. The proliferation of reticular fiber is closely related with the number of blast cells, the proliferation and developmental abnormalities of megakaryocytes and the karyotype. The prognosis of MDS-MF patients is poor.

[Clinical study on combination of homoharringtonine, Ara-C and idarubicin induction for treatment of newly diagnosed acute myeloid leukemia patients].

The purpose of this study was to assess the efficacy and toxicity of HAI regimen [(homoharringtonine 2.5 mg/(m(2)×d), days 1 - 7; cytarabine 150 mg/(m(2)×d), days 1 - 7; idarubicin 9 mg/(m(2)×d), days 1 - 7)] for induction treatment of newly diagnosed acute myeloid leukemia (AML) (except acute promyelocytic leukemia). 31 patients with newly diagnosed AML, aged 39 (14 - 58) years, were enrolled in this clinical study. The complete remission (CR) rate, especially after one course, the overall survival (OS) rate and relapse free survival (RFS) rate were estimated. The outcomes were compared between different prognostic groups according to World Health Organization (WHO) classification, genetics and initial WBC count. Safety was evaluated using standard WHO criteria. The results showed that 26 patients (84%) achieved CR after 1 course of induction. The CR rate for the patients with favorable, intermediate and unfavorable cytogenetics was 90%, 88% and 60% respectively. All 7 patients with a high initial WBC count (≥ 100×10(9)/L) obtained CR, while 19 out of 24 without a high initial WBC count obtained CR. With a median follow-up of 15(range 2-56) months, the estimated 3-year OS rate for all patients and the patients with CR was 44% and 52% respectively. The 3-year RFS rate was 51%. The patients receiving induction chemotherapy died of the chemotherapy. Profound myelosuppression was seen in all patients after the HAI induction with the median duration of neutropenia (ANC < 0.2×10(9)/L) of 16 (6 - 24) days. As the most common toxicity, severe infections (grade III-IV) involved in all the patients and the duration of febris was 6 (1 - 36) days. The incidence of septemia and invasive fungus infection were 19.4% and 45.2% respectively. The incidence of non-infection fever, increased glutamic-pyruvic transaminase (GPT), diarrhea, increased bilirubin and oral cavity mucositis were 6.5%, 6.5%, 3.2%, 3.2%, 3.2% respectively, as the more frequent severe non-hematological toxicities. It is concluded that HAI regimen is a high efficient induction schedule for the newly diagnosed AML, and archive the higher CR rate after one course than DNR/Ara-C standard induction regimen. Side effects are acceptable, except severe infection.

[Substance P and its receptors are involved in the effect of histamine H3 receptor agonist, IMETIT on nasal allergic symptoms in guinea pigs].

OBJECTIVE: To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R) mRNA in AR model in guinea pigs. METHODS: Guinea pigs were divided randomly into 4 groups: AR group (group A), IMETIT group (group B), Loratadine group (group C) and IMETIT+Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13.0 software. RESULTS: In Group B, the mean (x ± s) number of sneeze [(15.0 ± 1.3) times], scratching nose [(16.5 ± 2.3) times] and respiratory frequency [(76.3 ± 4.1) times/min] were significantly improved than those in group A [(23.5 ± 2.6) times, (26.1 ± 4.1) times and (66.5 ± 5.8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP-positive cells [(11.6 ± 3.6)/HP] and SP-R mRNA expression (0.64 ± 0.04) in group B were reduced significantly compared to group A [(27.1 ± 9.7)/HP, (0.83 ± 0.03), P value were 0.000, 0.000, respectively]. Sneeze [(10.0 ± 2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [(90.0 ± 5.0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0.002 and 0.000, respectively). SP-positive cells [(2.0 ± 1.7)/HP] and SP-R mRNA expression (0.52 ± 0.06) in Group D compared with group B were also significantly reduced (P value were 0.012 and 0.000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11.59, 8.28, 5.61, 5.48, 6.50, respectively, P value were 0.002, 0.008, 0.025, 0.027, 0.017). CONCLUSIONS: IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-R mRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.

SRWD: a novel WD40 protein subfamily regulated by salt stress in rice (OryzasativaL.).

By analysis with microarray data, we found that a gene encoding a novel protein containing five WD40 repeats, was regulated by salt stress in rice and named as SRWD1 (Salt responsive WD40 protein 1). By database searching, additional four SRWD1-like genes (SRWD2-SRWD5) were found in rice genome, and these five SRWD genes formed a novel WD40 subfamily. Phylogenetic analysis showed that plant SRWD proteins divided into four groups. The significant functional divergences during SRWD evolution were found. The tissue-specific and salt responsive expression profiling for SRWD genes was investigated based on microarray data. It was found that all five SRWD genes in rice were regulated by salt stress. Further, we found that SRWD1 was regulated with different patterns by salt stress in two rice cultivars responding differently to salt stress. Our study correlates WD40 proteins with salt stress in plants and provides fundamental information for the further investigation of plant SRWD proteins.

Salt induces expression of RH3.2A, encoding an H3.2-type histone H3 protein in rice (Oryza sativa L.).

Histone H3 is one of the four histones, along with H2A, H2B, and H4, which form the eukaryotic nucleosome octamer core. In this study, a new gene RH3.2A encoding an H3.2-type histone H3 protein from rice (Oryza sativa L.) was reported. RH3.2A was cloned through RT-PCR from salt-treated rice seedlings. This gene encoded a protein of 136 amino acid residues that were similar to some plant histone H3 proteins reported previously. However, the cDNA sequence of RH3.2A and other rice H3 genes were different. Alignment of RH3.2A encoding protein with other plant histone H3 proteins revealed that three amino acid residues (32, 88, and 91) were markedly different between H3.1-type and H3.2-type proteins. The mRNA expression analysis of RH3.2A revealed that RH3.2A gene was upregulated by salt stress in rice roots and ABA treatment in seedlings. The potential role of RH3.2A during salt stress was discussed.