Application value of a new lesion positioning stickers in breast lesion surface localization / 中南大学学报(医学版)

OBJECTIVES@#Accurate breast lesion surface localization can guarantee accurate biopsy and local treatment. But there is no guideline to regular equipment and methods for the localization of breast lesions. The conventional non-invasive localization method is marker-based localization. The advantages of this method are simple and efficient. The disadvantages are that markers disappear easily under coupling agents; the positioning length of markers cannot last long on skin; and healthcare associated infection due to many patients using the same marker pen is potentially unavoidable. Breast lesion sticker (called sticker for short) is a new-type localization medical instrument in 2020. Our study aims to explore the clinical value of a new lesion stickers in breast lesion surface localization via comparison of the sticker and marker pen localization methods.@*METHODS@#This was a prospective cohort study. It was conducted in 67 patients who needed breast lesion surface localization before biopsy. The patients were randomly assigned into 2 groups. One group of patients used marker pen to mark breast lesion surface location by ultrasonography. The other group of patients used stickers. Patients labeled with markers on skin were swabbed agents before marking. Then the markers were checked by ultrasound scan. If the surface positions of breast lesion were not correct, the above procedure was repeated. In the sticker group, the stickers were released synchronously after the lesions were detected by ultrasound scan. Then locations were checked via scanning hole. If the surface positions of breast lesion were not correct, the above procedure was repeated. The accuracy of positioning, the length of positioning time and satisfaction of patients between the 2 groups were compared. The length of positioning time was calculated from the time when ultrasound detected the lesion to the time when the surface position of breast lesion was confirmed. The total score of patients' satisfaction was 5 points according to Service Quality Evaluation of SERVQUAL Scale, including sonographers' service attitude and their technical proficiency, other medical staffs' service attitude and their technical proficiency, hospital service procedures, positioning comfort, and positioning effects.@*RESULTS@#All 67 patients were females, aged 18-66 (39.73±13.10). There were 35 patients in the marker pen group and 32 patients in the sticker group. The time length of group used marker pen to localization was 22-88 (52.20±2.90) s, and the sticker group was 3-15 (9.22±0.58) s in length. The length of positioning time for the stickers was significantly shorter than that of the marker (P<0.01). Both methods were accurate in the surface localization of lesions before operation. The total scores of patients' satisfaction was 4-5 (4.92±0.02) in the stickers group, and 1-5 (3.35±0.10) in the marker pen group. The patients' satisfaction scores with the sticker were significantly higher than those with the marker pen (P<0.01). The length of positioning time and patients' satisfication scores for sonographer with 20 years' working experience were shorter and higher than those of sonographer with 10 years' working experience, respectively (both P<0.05).@*CONCLUSIONS@#The new breast lesion positioning stickers have more advantages than the marker pen in localization efficiency. It could reduce the workload of medical workers and increase patients' satisfaction to some extent. The stickers can be used not only in the breast lesions surface localization, but also in the skin location of pleural effusion and ascites, the skin location of surface masses, the skin location of thyroid nodule, and many other clinical marker areas, to further expand the scope of clinical application and value of the stickers.

X-linked hyper-IgM syndrome with T-cell large granular lymphocytic leukemia: report of one case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical features, the key point of diagnosis and treatment methods of X-linked hyper-IgM syndrome (XHIGM).Methods:The clinical characteristics and laboratory data of a patient aged 23 years who was diagnosed as XHIGM complicated with T-cell large granular lymphocytic leukemia (TLGLL) in Institute of Hematology & Blood Diseases Hospital in March 2020 were analyzed retrospectively, and the literatures were reviewed.Results:This male patient presented with recurrent infection when he was 17 years old, and was found neutropenia, anemia accompanied by obvious splenomegaly, lower level of IgG and IgA after the visit. The level of IgM was lower than the normal level and the typical XHIGM was manifested with the normal or increased level of IgM, however CD40L homozygous mutation (chromosome: chrX; location: 135730438; variation of amino acid: NM_000074:exon1:c.31C>T:p.R11X; nonsense mutation) was confirmed by next generation sequencing. CD40L heterozygous mutation was detected in his mother, but it was not in his father. The patient was diagnosed as XHIGM. Anemia and neutropenia were alleviated after splenectomy in the patient, who was diagnosed as T-cell large granular lymphocyte elevation and clonal proliferation by flow cytometry, TCR gene rearrangement positive and bone marrow histopathological immunohistochemistry results because of the increasing leukocyte. The patient was eventually diagnosed as XHIGM complicated with T-LGLL.Conclusions:A small number of patients with XHIGM may develop symptoms in adulthood and may present with atypical clinical features of significant reduction in IgG, IgA, and IgM. The confirmed diagnosis of XHIGM is established by identification of CD40L gene mutation. XHIGM gene screening is required in male patients with recurrent infection, IgG level lower than normal and neutropenia. A few XHIGM patients are complicated with T-LGLL.

Mean corpuscular volume ≤100 fl was an independent prognostic factor in patients with myelodysplastic syndrome and bone marrow blast<5 percent / 中华血液学杂志

Objective@#To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) .@*Methods@#321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed.@*Results@#Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) .@*Conclusion@#MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study / 中华血液学杂志

Objective@#To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF).@*Methods@#Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated.@*Results@#Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×109/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT.@*Conclusions@#RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

Objective@#To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees.@*Methods@#Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated.@*Results@#320 subjects (47%) presented severe thrombocytopenia (PLT<50×109/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×109/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×109/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×109/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival.@*Conclusion@#PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

Objective@#To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) .@*Methods@#112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed.@*Results@#Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ2=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model.@*Conclusion@#TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

Analysis of clinical characteristics, treatment response rate and survival of 77 myelodysplastic syndrome patients with del (5q) syndrome / 中华血液学杂志

Objective@#To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria.@*Methods@#A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs.@*Results@#Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) .@*Conclusion@#Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.

Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia / 中华血液学杂志

Objective@#Analysis of the molecular characteristics of eosinophilia. @*Methods@#Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. @*Results@#Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. @*Conclusion@#The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.

Analysis the value of various ultrasound parameters in the diagnosis of placenta accrete / 中华医学超声杂志（电子版）

Objective To investigate the value of various ultrasound parameters in the diagnosis of placenta accreta. Methods To retrospectively analyze the sonographic images of 112 patients with prental diagnosis of placenta previa at Xiangya Hospital of Central South University between April 2016 and July 2017. All patients were confirmed by surgery pathology. Pathology was as golden standard for diagnosis, and the sensitivitity, specificity, positive predictive value and negative predictive value of each ultrasound parameter in the prenatal dianosis of placenata accreta and the predicting postpartum hysterectomy of patients with placenta accreta were calculated. Results Of 112 patients with placenta previa, 71 cases were confirmed with placenta accreta by histology, 41 cases without placenta accrete, accurate prenatal ultrasound diagnosis is 72 cases, the accuracy is 64.1%. Ultrasonic parameters assessed included loss of retroplacental clear zone, smallest myometrial thickness, presence of ″moth-eaten″ lacunar spaces, and sub-placental or the posterior wall of the bladder hypervascularity. The sensitivity (specificity) of diagnosis of placenta accreta was 83.10% (29.27%), 64.79% (73.17%), 43.66% (87.80%), 64.79% (58.54%), respectively, the positive predictive value (negative predictive value) was 67.05% (50.00%), 80.70% (54.55%), 86.11% (47.37%), 73.02% (48.98%), respectively, the loss of retroplacetal clear zone has high sensitivity and low specificity in the prenatal diagnosis of placenata accreta, the presence of ″moth-eaten″ lacunar spaces has the highest specificity. The sensitivity (specificity) of each ultrasound parameter to predict postpartum hysterectomy of patients with placenta accreta was 100% (25.53%), 77.78% (54.26%), 61.11% (73.40%), 83.33% (48.94%), respectively, the positive predictive value (negative predictive value) was 20.45% (100%), 24.54% (92.73%), 30.56% (90.79%), 23.81% (93.88%). The loss of retroplacetal clear zone has high sensitivity and low specificity in predicting the postpartum hysterectomy in patients with placenata accreta, and the presence of″moth-eaten″ lacunar spaces has high sensitivity and specificity. Conclusions Ultrasound is important for the prenatal diagnosis of accreta placentation. The loss of retroplacental clear zone in the prenatal diagnosis of placenta accreta has high sensitivity and low specificity, and the presence of ″moth-eaten″ lacunar spaces has high specificity, and has some correlation with the pregnancy outcomes of patients with palcenta previa. Performing routine detailed placenta ultrasound examination for women with prior caesarean delivery presenting with a low-lying or a placenta previa is essential in improving the detection rate of placenta accreta.

Influence of Peanut Cultivars and Environmental Conditions on the Diversity and Community Composition of Pod Rot Soil Fungi in China

Peanut yield and quality are seriously affected by pod rot pathogens worldwide, especially in China in recent years. The goals of this study are to analyze the structure of fungal communities of peanut pod rot in soil in three peanut cultivars and the correlation of pod rot with environmental variables using 454 pyrosequencing. A total of 46,723 internal transcribed spacer high-quality sequences were obtained and grouped into 1,706 operational taxonomic units at the 97% similarity cut-off level. The coverage, rank abundance, and the Chao 1 and Shannon diversity indices of the operational taxonomic units were analyzed. Members of the phylum Ascomycota were dominant, such as Fusarium, Chaetomium, Alternaria, and Sordariomycetes, followed by Basidiomycota. The results of the heatmap and redundancy analysis revealed significant variation in the composition of the fungal community among the three cultivar samples. The environmental conditions in different peanut cultivars may also influence on the structure of the fungal community. The results of this study suggest that the causal agent of peanut pod rot may be more complex, and cultivars and environmental conditions are both important contributors to the community structure of peanut pod rot fungi.

Gene mutations from 511 myelodysplastic syndromes patients performed by targeted gene sequencing / 中华血液学杂志

Objective@#To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients.@*Methods@#A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed.@*Results@#Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) . 439 subjects (86%) had at least one gene mutation. The mean number of mutations in refractory anemia with unilineage dysplasia (RCUD) was 1.25, refractory anemia with multilineage dysplasia (RCMD) was 1.73, refractory anemia with ring sideroblasts (RARS) was 2.79, refractory anemia with excess blasts-1 (RAEB-1) was 2.22, RAEB-2 was 2.34, MDS with isolated 5q- was 2.67, MDS, unclassified (MDS-U) was 2.00. U2AF1 mutant subjects were more likely to have isolated+8[Q<0.001, OR=4.42 (95% CI 2.23-8.68) ]and less likely to have complex karyotypes[Q=0.005, OR=0.22 (95% CI 0.04-0.72) ]. According to the number of gene mutations, all subjects were categorized into three groups, namely group with 0-1 mutation, with 2 mutations and with three or more mutations. There was a significant difference in overall survival (OS) among three groups (P=0.041) .@*Conclusion@#About 90% patients with MDS have at least one gene mutation. Genes associated with epigenetics and spliceosome are most common mutated genes in MDS. The increased numbers of gene mutations accompany with disease evolution and associate with poor prognosis.

The efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts treated with decitabine alone or CAG/HAG regimen / 中华血液学杂志

Objective@#To observe the clinical efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts (MDS-REAB) treated with decitabine alone or based on low dose cytarabine (Ara-C) regimen CAG/HAG [aclarubrci (ACR) /homoharring-tonine (HHT) +cytarabine+granulocyte colony stimulating factor (G-CSF) ].@*Methods@#Totally 121 patients with MDS-REAB were retrospectively analyzed, including 59 patients treated with decitabine alone (20 mg·m-2·d-1 for 5 days) , the rest 62 ones treated with low-dose Ara-C-based regimen CAG/HAG. Overall response rate (ORR) , overall survival (OS) and adverse events of the two groups were analyzed and compared retrospectively.@*Results@#The ORR of decitabine alone or CAG/HAG were 66.2% and 56.4% respectively, with no statistically significant differences (χ2=1.185, P=0.276) . Initial response rate detected by the end of first cycle of CAG/HAG was higher than that of decitabine alone (94.3% vs 69.2%) , there was statistically significant difference in the overall comparison of two groups (χ2=7.612, P=0.009) . The median OS of decitabine alone was 19.5 (95% CI 10.5-28.4) months, the median OS of CAG/HAG was 20.3 (95% CI 10.7-29.9) months, with no statistically significant differences (χ2=0.004, P=0.947) . Grade 3-4 cytopenia and infection were the most prevalent adverses of two group patients. Grade 3-4 cytopenia rate of CAG/HAG was higher than that of decitabine alone (100.0% vs 64.4%, P<0.001) . The infection rate detected at third cycle of CAG/HAG was higher than that of decitabine alone (52.9% vs 15.2%, P=0.008) .@*Conclusion@#The efficacy of treating MDS-RAEB with decitabine alone or CAG/HAG was equivalent. CAG/HAG treatment came into effect faster, but decitabine alone treatment was safer.

The clinical characteristics, gene mutations and prognosis of chronic neutrophilic leukemia / 中华血液学杂志

Objective@#To investigate the clinical manifestation, cytogenetics, gene mutations and prognostic factors of chronic neutrophilic leukemia (CNL) .@*Methods@#16 CNL cases, according to WHO (2016) -definition, were reviewed retrospectively. Identifications of the CSF3R, ASXL1, SETBP1, CALR and MPL mutations were performed by direct sequencing. JAK2 V617F mutation was detected by AS-PCR.@*Results@#Of the 16 CNL patients, the median age was 64 (43-80) years with a male predominance of 75% (12/16) . The median hemoglobin was 114 (81-154) g/L, with median WBC of 41.20 (26.05-167.70) (109/L and median PLT of 238 (91-394) ×109/L.The median level of marrow fibrosis (MF) was 1 (0-3) degree. There was no other cytogenetic abnormalities except t (1;7) (p32;q11) , +21 and 14ps+ for each. All the 16 CNL patients harbored CSF3R T618I mutation. ASXL1 mutations were identified in 81% (13/16) , while SETBP1 mutations were confirmed in 63% (10/16) . The CALR K385fs*47 mutation was found. There was no mutation in JAK2 V617F or MPL in the above 16 patients. The median overall survival (OS) of patients presented with WBC≥50×109/L at diagnosis (11 months) was significantly shorter than of WBC<50×109/L (39 months, P=0.005) .@*Conclusion@#CSF3R T618I mutation was specific for CNL. The median OS of CNL patients was 24 months, and WBC≥50×109/L at diagnosis was an unfavorable prognostic factor.

Effect of Telbivudine on CD4 + CD25 + CD127low/- Regulatory T cell in Patients with HBeAg-positive ;Chronic Hepatitis B / 实用医学杂志

Objective To study the effect of telbivudine (TBV) on the ratio of CD4+ CD25+CD127low/-regulatory T cell (Treg) of HBeAg-positive chronic hepatitis B (CHB). Methods The ratios of Treg before and after treatment for 12, 24, 36 and 48 weeks with TBV of thirty-five patients with HBeAg-positive CHB were detected. Results Ratios of Treg were (12.55 ± 1.78)%, (10.42 ± 1.04)%, (9.55 ± 0.74)%, (8.78 ± 0.67)%, (8.74 ± 0.71)%respectively before and after treatment of 12, 24, 36 and 48 weeks and all the values were lower than its former one (P < 0.05), except the 48 weeks′. Conclusions The ratio of Treg of HBeAg (+) CHB decreases after treatment with TBV.

The assessment of symptomatic burden among Ph/BCR- ABL negative myeloproliferative neoplasm patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of myeloproliferative neoplasms Symptom Assessment Form total symptom score (MPN-SAF-TSS)in assessing constitutional symptoms among Ph/BCR- ABL negative myeloproliferative neoplasm (MPN)patients.</p><p><b>METHODS</b>A cohort of 628 MPN patients were evaluated by MPN- SAF- TSS.</p><p><b>RESULTS</b>Fatigue was the most common symptom (76.0%, 76.2%vs 89.9%)and the highest average severity of all the symptoms (3.46±2.97, 3.47±2.99vs 4.74±3.04 scores)among polycythemia vera (PV), essential thrombocythemia (ET)and primary myelofibrosis (PMF)patients. Using the MPN- SAF- TSS analysis, PMF patients showed highest burden of symptoms (28.9 ± 19.1), followed by PV patients (19.2 ± 16.8), and finally ET patients (17.1 ± 15.3). Instinct differences were observed between PMF and PV patients (χ(2)=6.371,P=0.021), PMF and ET patients (χ(2)= 14.020,P<0.001). No significant difference was found between PV and ET patients (χ(2)=2.281,P=0.191).</p><p><b>CONCLUSION</b>MPN- SAF- TSS was effective in evaluating the symptomatic burden among Ph/BCRABL negative MPN patients and could be used for serial assessment in this clinical setting.</p>

Long-term outcomes of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.</p><p><b>RESULTS</b>Of 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.</p><p><b>CONCLUSION</b>HAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.</p>

Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical, laboratory characteristics and PIG-A gene mutations in patients of myelodysplastic syndromes (MDS) with PNH clones.</p><p><b>METHODS</b>218 MDS patients diagnosed from August 2013 to August 2015 were analyzed. The PIG-A gene mutations were tested in 13 cases of MDS with PNH clones, 17 cases of AA-PNH and 14 cases of PNH selected contemporaneously by PCR and direct sequencing.</p><p><b>RESULTS</b>13 (5.96%) MDS patients were detected with PNH clones (13/218 cases). 9 patients were treated with cyclosporin A (CsA). Patients showed hematological improvement (HI). There were significant differences between MDS-PNH and PNH patients in terms of granulocyte clone size, red cell clone size and LDH levels [19.2% (1.0%-97.7%) vs 60.2% (3.1%-98.0%), P=0.007; 4.3% (0-67.2%) vs 27.9% (2.5%-83.6%), P=0.026; 246 (89-2014) U/L vs 1137 (195-2239) U/L, P=0.049], while the differences were not statistically significant in patients between MDS-PNH and AA-PNH patients [19.2% (1.0%-97.7%) vs 23.2% (1.5%-96.0%), P=0.843; 4.3% (0-67.2%) vs 14.4% (1.1%-62.8%), P=0.079; 246 (89-2014) U/L vs 406 (192-1148) U/L, P=0.107]. PIG-A gene mutations were detected in 7 MDS-PNH patients, of them, six were missense mutations, one were frameshift mutation and four cases with the same mutation of c.356G>A (R119Q). The PIG-A gene mutations were also detected in 9/11 AA-PNH patients and 11/14 PNH patients, both of them had the mutation of c.356G>A (R119Q). The PIG-A gene mutations of MDS-PNH, AA-PNH, PNH patients were all small mutations, the majority of those (59%) were missense mutation and mainly located in exon 2.</p><p><b>CONCLUSION</b>MDS patients with PNH clones had better response to CsA, smaller PNH clone size. The PIG-A gene mutations of MDS-PNH patients mainly located in exon 2, which could be a mutational hotspot of these patients.</p>

Prognostic evaluation of comorbidities in patients with myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To discuss the impact of comorbidities on the outcomes of patients with MDS.</p><p><b>METHODS</b>The clinical characteristics of 676 MDS patients with detailed comorbidities evaluations was analyzed retrospectively.</p><p><b>RESULTS</b>There were 395/676 cases (58.4%) with comorbidities (group 1), 281/676 cases (41.6%) without (group 2). Significant differences were seen in the distribution of age (≥ 60 y), bone marrow blasts, abnormal karyotype, WHO 2008 subtypes and IPSS-R risk cohorts (P<0.05) between the two groups. While gender, HGB concentrations, WBC levels, platelet levels and serum ferritin were not significantly different (P>0.05). Independent prognostic significance of comorbidities was seen in both uni-variate and multi-variate analyses (P<0.001). According to MDS-specific comorbidity index (MDS-CI), the median survival were 32(1-153) months, 19(2-85) months and 13(1-37) months in the low-risk, intermediate-risk and high-risk cohorts respectively, while 96(1-166) months in cohorts without any comorbidities, of which significant differences were seen (P<0.001). The MDS-CI allowed further stratification in the IPSS-R low-risk, intermediate-risk and high-risk cohorts (P<0.001).</p><p><b>CONCLUSION</b>Comorbidities provides prognostic stratification independently of IPSS-R for MDS patients.</p>

Long- term outcome of thalidomide and cyclosporine in patients with IPSS low/intermediate- 1 myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the long- term outcome of cyclosporin A (CsA) combined with thalidomide regime for Chinese patients with IPSS low/intermediate- 1 myelodysplastic syndromes (MDS) without del（5q）and the predictive variables which could impact the response to the therapy.</p><p><b>METHODS</b>Seventy-six MDS patients who were treated with these drugs at a single institute in China were retrospectively analyzed. The polymorphism of cereblon gene, rs1672753, was detected in patients of this cohort by PCR and direct sequencing.</p><p><b>RESULTS</b>A total of 53% of patients showed hematological improvement（HI）to the therapy. Thirty-one patients（31/73, 43%）achieved erythrocyte response（HI-E）; 15 patients（15/50, 30%）achieved neutrophil response（HI-N); 18 patients（18/58, 31%）achieved platelet response（HI-P). Twenty-seven of the 50 patients（46%）who were dependent on red blood cell transfusion achieved HI- E and became independent of transfusion. The median duration of response among the responders was 22 months (range, 1- 131 + months). Bone marrow blasts ≤2% was the only factor associated with longer response duration in univariate analysis （P=0.010）. There was no significant difference between the two groups of celeblon gene rs1672753 polymorphism either on the response rate or the response duration. The median survival of 67 patients without stem cell transplantation was 82 months. In multivariate analyses, factors significantly correlated with survival were IPSS-R（HR=3.461, 95%CI 1.126-10.639, P=0.030), age ≥ 60 y（HR=4.120, 95%CI 1.070-15.867, P=0.040）and HI-N（HR=7.733, 95%CI 1.007-59.396, P=0.049).</p><p><b>CONCLUSION</b>CsA combined with thalidomide regime could improve the anemia symptom in low/int-1 risk MDS patients without del（5q）. The predictive value of cereblon gene polymorphism, rs1672753, could not be verified in this study.</p>

Comparison of low-dose thalidomide and prednisone combined with or without danazol for the treatment of primary myelofibrosis-associated anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical effects of low-dose thalidomide (THAL) and prednisone (PRED) with or without danazol (DANA) in patients with primary myelofibrosis (PMF) associated anemia.</p><p><b>METHODS</b>A cohort of 58 PMF patients with anemia (Hb<100 g/L) were retrospectively studied. Of them, 28 patients were treated with THAL and PRED (THAL-PRED group), and the rest with THAL, PRED and DANA (THAL-PRED-DANA group). The hematological response was assessed according to the modified criteria of the International Working Group in 2006, and the myelofibrosis degree was evaluated at 3 and 12 month after treatment.</p><p><b>RESULTS</b>The total response rate was 56.9%(33/58) including 1.7% (1/58) partial remission (PR) and 55.2% (32/58) clinical improvement (CI). There was no statistical difference in the response rate between THAL-PRED and THAL-PREDDANA groups (50.0% vs 63.3%, P=0.306). However, the median response duration of clinical improvement, erythroid response (CI-E) and total response prolonged in THAL-PRED-DANA than THALPRED group (61.5w vs 22w, P=0.015; 75w vs 30w, P=0.007, respectively). Myelofibrosis degree at 3 and 12 months after treatment decreased significantly than before treatment (P=0.000 and 0.005, respectively). Side-effects in both groups were only grade 1-2.</p><p><b>CONCLUSION</b>Low-dose THAL together with PRED appeared to be effective in the treatment of PMF-associated anemia, and the response duration would prolong significantly if combined with DANA.</p>