Objective: To investigate the characteristics and prognosis of clonal chromosomal abnormalities appearing in Philadelphia negative metaphases (CCA/Ph(-)) cells in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy. Methods: The clinical data of 30 cases with CCA/Ph(-) during TKI treatment in Henan Cancer Hospital from August 2007 to July 2017 were retrospectively analyzed. The univariate factor was analyzed by Kaplan-Meier method. Multiple-factor was analyzed by Cox proportional risk model. Results: Of the 30 cases, 19 (63.3%) were males. At the first detection of CCA/Ph(-) the median age was 44 (rang 14-68) years old and the median treatment of TKI was 13 (rang 2-94) months. The clones proportion of first detected CCA/Ph(-)≥ 50% was found in 18 (60.0%) cases. TKI treatment for 3 months with BCR-ABL(IS) less than 10% was seen in 14 (46.7%) patients. 63.3% (19/30) of CCA/Ph(-) was transient (only one time) and 36.7% (11/30) was repeated (≥2 times) . Trisomy 8 dominant accounted for 60.0% (18/30) , -7/7q- for 13.3% (4/30) , loss of chromosome Y 6.7%. With a median of follow-up 50 months, 76.7% (23/30) cases were in complete cytogenetic response (CCyR) ; 63.3% (19/30) in major molecular response (MMR) , 43.3% (13/30) in undetectable minimal residual disease (UMRD) . The median event-free survival rate of (EFS) were 44 months, and 2-year and 5-year EFS were (82.1±7.3) % and (52.4±12.8) %, respectively. The median overall survival (OS) were 50 months, and 2-year and 5-year OS rates were (92.6±5.0) % and (77.2±14.7) %, respectively. Univariate analysis shows that the 2-year EFS of who in males, more than 2 times CCA/Ph(-), BCR-ABL(IS)>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph(-), and BCR-ABL(IS)≤10% (P<0.05) . The 2-year OS rate in whom the occurrence frequency of CCA/Ph(-) more than twice was significantly lower than those with transient CCA/Ph(-) (P<0.05) . Multivariate analysis showed that CCA/Ph(-) was an independent risk factor (RR=4.741, 95%CI 1.21-18.571, P=0.018) for EFS in CML patients. Conclusion: Trisomy 8, -7/7q-, and -Y were the most common CCA/Ph(-) during TKI treatment, with high clones proportion of ≥50%. CCA/Ph(-) mainly occurred transiently or was permanent occasionally. CCA/Ph(-) recurrence (≥2 times) was an independent risk factor for EFS and OS in CML with TKI.
Adolescent ; Adult ; Aged ; Chromosome Aberrations ; Chromosomes, Human ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Male ; Metaphase ; Middle Aged ; Prognosis ; Protein Kinase Inhibitors ; Retrospective Studies ; Young Adult

Objective: To explore the pregnancy outcome and disease status among patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI) when they stopped TKI treatment during pregnancy. Methods: The clinical characteristics, reproductive outcomes and disease status of the patients who stopped TKI due to pregnancy between November 2004 to November 2017 were retrospectively collected. Results: A total of 14 CML patients in chronic phase (CML-CP), 12 patients were Sokal-low-risk. The median time of TKI treatment was 46.5 (15-123) months before the drug was stopped. The median age at the time of pregnancy was 29 (24-32) years. The median time of TKI exposure was 4 (0-9) weeks in 12 accidental pregnancies. Outcomes were available for 13 pregnancies, 9 cases (69.2%) delivered healthy babies, 1 case (7.7%) delivered polydactylia malformation baby, 3 cases (23.1%) had spontaneous abortion. The last one was still in pregnancy (no organ malformations were observed in color Doppler ultrasound). At the end of the follow up date, 10 children developed normal, the median age was 14 (0.7-65) months. Of the 14 patients who stopped TKI, 7 in complete molecular response (CMR), 3 in MR(4) (BCR-ABL(IS) <0.01%, ABL transcript >10 000), 2 in major molecular response (MMR), 2 in complete cytogenetic response (CCyR). The median time of TKI discontinuation during pregnancy was 33.5 (4-40) weeks. At the end of pregnancy, 4 cases were in CMR, 4 in MR(4), 1 in MMR and 4 in CCyR. No patients lost CCyR and complete hematologic remission. Conclusions: During the treatment of imatinib and Nilotinib, unplanned pregnancy may have a normal infant, but may lead to spontaneous abortion and congenital malformations. Female of CML-CP who had sustained and stable MMR at least 24 months and Sokal-low-risk had higher safety factor discontinued TKI during pregnancy, but still had a risk of increasing tumor load, so monitored the level of BCR-ABL of peripheral blood monthly during pregnancy is necessary.
Adult ; Female ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Pregnancy ; Protein Kinase Inhibitors ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo study the impact of gender factor on the candidate gene study of essential hypertension (EH).

METHODSThe polymerase chain reaction (PCR) was performed to analyze the ACE gene I/D polymorphism of hypertensive patients (50 men and 50 women) and normal controls (50 men and 50 women). The investigation was further focused on possible influence of sex proportion on the conclusion of this kind of research.

RESULTSThe frequency of DD genotype in male hypertensive patients is significantly higher than that in male normal controls (chi(2) = 6.98, P = 0.004). The frequency of D allele in male EH group is significantly higher than that of male normal controls (chi(2) = 6.87, P = 0.009), while no significant difference was observed for II and ID genotype between male EH group and control group (P > 0.05). For female EH group and normal controls, there were no significant differences in frequency of genotype and allele (P > 0.05), the distribution ratio of DD genotype in male EH group is significantly different from that of female EH group (chi(2) = 4.06, P = 0.044). Furthermore, males with DD genotype in EH group had higher SBP and PP than that of males with II and ID genotype (P < 0.05). However, there was no significant difference in DBP in all three genotypes (P > 0.05). At the same time, there was no difference in SBP, DBP and PP (P > 0.05) between II and ID genotype in male EH group. In female hypertensive patients, there was no significant difference in SBP, DBP and PP between all three genotypes (P > 0.05).

CONCLUSIONSThe relationship between DD genotype in male and EH (especially SBP and PP) is closer than any other genotype-EH relationships in both male and female. The gender factor, as a probable confounding factor, can affect many candidate gene studies of essential hypertension including ACE gene I/D polymorphism, and thus biases the conclusion.

Aged ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Sex Factors

Objective To determine the hosts of hantavirus (HV) and its molecular epidemiological characteristics, to provide evidence for prevention and control on hemorrhagic fever with renal syndrome (HFRS). Methods Rodents were captured by a special trap within the residential area. The antigens of HV in lung tissues were detected by direct immuno-fluorescence assay (DFA). Nucleotide sequences of HV were amplified by RT-PCR with HV genotype-specific primer. The amplified genes were then sequenced. Phylogenetic tree were built on nucleotide sequence with Clusta1X 1.83 software. Results 1421 rodents were captured and classified into 8 species of 4 Genera in the epidemic area within 10 counties of Chuxiong prefecture, Yunnan province, between 2005 and 2006. Out of the 1421 rodents, 1056 (74.31%) of them were Rattus norvegicas and 280 (19.70%) belonged to Rattus flavipectus. The antigens of HV were detected by DFA in lung tissues and the total positive rate of HV was 5.15% (53/ 1029). After applying the sequencing nucleotide method to the 53 positive specimens, data showed that 21 specimens were positive and all of them belonged to Seoul type ( 15 samples were from Rattus norvegicus, 4 samples Rattasflavipectas, 2 samples Rattus nitidas). The partial S segments from 12 specimens were sequenced which appeared homologic with R22, L99 and HLD65 from GenBank in relatively high level (87.1%-99.7%). When compared to 76-118 strain of Hantaan type, their homologic degree was only 64.4%-69.1%. Results from Phylogenetic analysis showed that 12 specimens belonged to Seoul type. As for their homology, they were significantly similar to Seoul type and could be tentatively divided into two subtypes S1 and S3. Conclusion It was confirmed that the Seoul type virus, as HFRS' s pathogenetic agent mainly carried by rats, prevailed widely in Chuxiong prefecture. Owing to the local ecological environment, we also noticed the characteristics of different HV subtypes among Seoul type.

Adolescent ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Leukemia ; drug therapy ; mortality ; therapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; therapy ; Male ; Mycophenolic Acid ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Retrospective Studies ; Treatment Outcome

Antineoplastic Agents ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; Hematologic Neoplasms ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mutation ; Protein Kinase Inhibitors

Objective: To observe the pregnancy outcome among patients with chronic myeloid leukemia (CML) treated with Nilotinib (NIL) . Methods: Clinical data of pregnancy delivery in CML patients treated with NIL from March 2015 to January 2019 were retrospectively collected. Results: A total of 11 patients were recruited with median pregnancy age 28 (25-40) years. The median duration of NIL treatment before pregnancy was 34 (3-48) months. There were 12 pregnancies, included 2 planned ones and 10 (83.3%) unplanned. In the 10 unplanned patients, 9 (90.0%) received NIL 600 mg/d. The median exposure time were 4 (4-7) weeks. In eight patients with delivery outcomes, 5 cases had well-developed babies, 2 had spontaneous abortion and 1 case with an baby of syndactyly deformity, whose mother was exposed to NIL 600 mg/d for 7 weeks in the early trimester of pregnancy. Seven infants were 4 boys and 3 girls with the median height at birth 50 (41-54) cm and median weight 3.2 (3.0-4.6) kg. They all grew with a normal pattern and well developed. Now the median age is 19 (4-41) months. The disease status during 12 pregnancies included 3 cases in CMR, 2 cases in MR(4.0), 3 cases in MMR, 4 cases not acquiring MMR. The median time of drug discontinuation was 35 (15-36) weeks during pregnancy. No patient lost CHR during this period. Conclusions: Female CML patients exposed to NIL 600 mg/d for 4 weeks in early pregnancy can give birth to normal babies, but there is still a risk of spontaneous abortion and congenital malformations.
Adult ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Male ; Pregnancy ; Pregnancy Outcome ; Pyrimidines/therapeutic use* ; Retrospective Studies