Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis / 中华内科杂志

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Clinical Significance of Common Gene Mutations in 53 Patients with Acute Myeloid Leukemia Harboring 11q23/MLL Rearrangements / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients.@*METHODS@#53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing.@*RESULTS@#21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy.@*CONCLUSION@#A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.

Efficacy and Safety of the Induction Therapy with Different Doses of Anthracyclines for Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

@#]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups.@*RESULTS@#There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770).@*CONCLUSION@#For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.

Motor skill disorder of children with autism spectrum disorder / 中国实用儿科杂志

Children with autism spectrum disorder(ASD)may suffer from motor skill dysfunction,and perform as motor delay,coordination disorder,fitness decline,visual-motor integration disorder and so on,which disturb their daily life,school-based activities,and other social activities. Due to the obvious core symptoms of children with ASD,the problem of motor skills may be ignored. Children with ASD should be monitored for the motor development at their early stage and be evaluated with proper assessment tools. Children with ASD should be trained with individualized plan according to their features in order to develop motor skills and improve the core symptoms. As evidence of motor intervention for children with ASD is increasing,we should pay more attention to the motor skill dysfunction problem in children with ASD and make them benefit from the motor intervention and sport program.

Risk Factors of Leukemia-free Survival in PhALL Patients with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of BCR-ABL gene transcripts on Leukemia-free survival (LFS) and prognosis of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (PhALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of 107 cases of PhB-ALL patients received allo-HSCT from July 2006 to November 2014 in the First Affiliated Hospital of Soochow University were collected and the relationship between the clinical characteristics and LFS after transplantation was analyzed.</p><p><b>RESULTS</b>Out of 107 PhALL patients (64 males and 43 females) with a median age of 30(7 to 54)years old, 35.5% (38/107) cases relapsed after transplantation within a median time of 6.9 (1.5 to 40.7) months. A total of 39 (36.4%) cases died within a median time of 19.8 (3.6 to 83.7) months after HSCT, of which 51.3% (20/39) due to disease relapse and 25.6% (10/39) due to infection. BCR-ABL gene transcripts of 49 cases turn into negative before transplantation, of which the expected 5-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and overall survival (OS) were 26.5%, 29.5% and 41.6%, respectively. Another 49 cases still had a positive BCR-ABL gene transcripts before transplantation, of which the life expectancy of 5 year CIR, NRM and OS were 64.4%,8.9% and 48.9%, respectively. Compared with BCR-ABL positive patients, BCR-ABL negative patients showed a lower CIR (P<0.001), a higher NRM (P=0.030) and a similar OS (41.6% versus 48.9%, P=0.497). Multivariate analysis showed that BCR-ABL positive (P=0.016) and a disease statusphase ≥CR2 (P<0.001) before HSCT were independent risk factors for LFS, while the age underwent HSCT was the principal element affecting prognosis (P<0.001).</p><p><b>CONCLUSION</b>Both the relapse and infection are the main causes of death in the patients after transplantation. A disease status ≥CR2 and the BCR-ABL positive before transplantation are 2 independent risk factors of LFS in the patients with PhALL after allo-HSCT.</p>

Effect of LPXN Overexpression on the Proliferation, Adhesion and Invasion of THP-1 Cells and Its Mechamisms / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of LPXN overexpression on the proliferation, adhesion and invasion of THP-1 cells and its possible mechanism.</p><p><b>METHODS</b>A THP-1 cell line with stable overexpression of LPXN was constucted by using a lentivirus method, CCK-8 was used to detect the proliferation of cells, adhesion test was used to evaluate adhesion ablity of cells to Fn. Transwell assay was used to detect the change of invasion capability. Western blot was used to detect expression of LPXN, ERK, pERK and integrin α4, α5, β1, the Gelatin zymography was applied to detect activity of MMP2/MMP9 secreted by the THP-1 cells.</p><p><b>RESULTS</b>Successful establishment of THP-1 cells with LPXN overexpression (THP-1 LPXN) was confirmed with Western blot. THP-1 LPXN cells were shown to proliferate faster than the control THP-1 vector cells. Adhesion to Fn and expression of ERK, integrin α4, α5 and β1 in the THP-1 LPXN cells were higher than that in the control cells. Invasion across matrigel and enhanced activity of MMP2 could be detected both in the THP-1 LPXN cells as compared with the control cells.</p><p><b>CONCLUSION</b>Ectopically ovexpression of LPXN may promote proliferation of THP-1 cells through up-regulation of ERK; promote adhesion of THP-1 cells through up-regulating the integrin α4/β1 as well as integrin α5/β1 complex; promote invasion of THP-1 cells through activating MMP2.</p>

IDH1 Gene Mutation and Its Clinical Significance in patients with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis.</p><p><b>METHODS</b>Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed.</p><p><b>RESULTS</b>Among the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>The IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.</p>

Clinical Analysis on Treatment of Chronic Myelomonocytic Leukemia with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze retrospectively the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).</p><p><b>METHODS</b>The engraftment, graft versus host disease (GVHD), infection, relapse, and survival of 13 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.</p><p><b>RESULTS</b>Thirteen (10 males and 3 females) CMML patients with a median age of 38 years old received allo-HSCT including 4 from HLA-matched unrelated donors, 6 from HLA-matched sibling donors and 3 from haploidentical related donors. All 13 patients achieved engraftment, and the median time of neutrophil engraftment and platelet engraftment were 12 (11-18) days and 15 (10-55) days respectively, acute GVHD occurred in 8 patients. After the median follow-up of 13 (6-29) months, the overall survival, disease free survival and relapse were 53.8%, 53.8%, 7.7%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT can improve the survival of patients with CMML, and is a effective method for treatment of CMML.</p>

Application of high resolution HLA typing in unrelated umbilical cord blood transplantation / 中国实验血液学杂志

This study was purposed to investigate the clinical value of HLA matching(low and high resolution) and its effect on outcome of the patients received umbilical cord blood transplantation(UCBT). Sequence-specific oligonucleotide probe (SSOP) , sequence-based typing (SBT) and sequence-specific primers(SSP) were used to perform high resolution HLA matching for HLA-A, -B, -Cw, -DRB1, -DQB1 and low resolution for HLA-A, B, DRB1 among 34 patients with hematologic malignancies who received unrelated UCB transplantation and grafts. The effects of HLA matching (low or high resolution ) on leading engraftment, hematopoietic reconstitution, graft-versus-host disease (GVHD) and infection after UCB transplantation were analyzed by comparison. The results showed that the median of total nucleated cells (TNC) of transplanted cord blood was 6.0×10(7)/kg, The time of neutrophil recovery was significantly shortened when more than 5×10(7)/kg TNC were transplanted (P < 0.05). The HLA-(6-10)/10 group of high resolution HLA matching was better than the HLA (4-5)/10 group in the respect of leading engraftment, the time of platelet recovery and the rate of acute GVHD (P < 0.05). In contrast, HLA-I+II locus, HLA-DRB1 or HLA-DQB1 locus mismatch could prolong the platelet engraftment time (P < 0.05). There was statistical difference in the time of platelet recovery, the rate of acute GVHD between the HLA (5-6)/6 group of low resolution HLA matching and the HLA (3-4)/6 group after UCB transplantation (P < 0.05), but the mismatch locus of HLA with low resolution did not correlate with the time of platelet recovery (P > 0.05). It is concluded that the high resolution HLA matching between patients received unrelated UCB transplantation and grafts may contribute to select the better UCB, that has important clinical value to promote hematopoietic reconstitution and to reduce the complications after UCB transplantation.

Clinical study of unrelated umbilical cord blood transplantation for 25 patients with hematological diseases / 中国实验血液学杂志

This study was purposed to investigate the engraftment, graft-versus-host disease (GVHD), transplantation related mortality (TRM), relapse and survival in hematologic patients received unrelated umbilical cord blood transplantation (UCBT). A total of 25 patients with hematological disease underwent UCBT, including 8 pediatric and 17 young adult patients. Among them 3 cases received single unit of UCBT and 22 cases received double units of UCBT. For donor/recipients human leukocyte antigen (HLA) matching: HLA 6/6 loci matched in 9 cases, HLA 4-5/6 loci matched in 16 cases. There were 19 patients with hematologic malignancies, including 3 cases in the period of disease progression and 6 cases of non-hematologic malignancies. Conditioning regimens were TBI/Cy ± Flu ± ATG or BuCy ± Flu ± ATG for 21 patients and Cy+Flu+ATG for 4 patients. For prophylaxis of acute graft-versus-host disease (aGVHD) the regimen of cyclosporine (CsA) as dominant drug was used. The results showed that among 16 patients (80.0%) achieved engraftment, 20 patients survived for more than 42 d after transplantation. The cumulative neutrophil recovery rate on day 42 after transplant was 64.0%, with a median time of 17.0 d;the cumulative platelet recovery rate on day 100 after transplant was 60.0 %, with a median time of 35.0 d. The cumulative rate of grade II-IV and III-IV aGVHD after transplantation 100 d was 44.0% and 30.7%, respectively. Until the end of the follow-up, the cumulative rate of TRM was 54.3%. For all the patients, overall survival rate was 42.7%. Out of 17 evaluable patients with hematologic malignancies 7 cases (41.2%) survived to date, and only 1 case relapsed, so event-free survival rate was 35.3%. Out of 5 evaluable patients with non-hematologic malignancies, 4 patients survived and 2 patients were in stable engraftment state, 2 cases with autologous hematopoietic recovery. Among 3 cases of hematologic malignancies at advanced stage, only 1 case survived to date. It is concluded that HLA-4-6/6 loci matched UCBT is an effective option to treat hematological diseases. Double cord blood transplantation (dUCBT) can overcome the disadvantage of insufficient cells of single cord blood UCBT to treat overweight children and adult.

Correlation of the level of Reg3α protein in plasma with gastrointestinal acute graft-versus-host disease / 中国实验血液学杂志

This study was purposed to explore the correlation of regenerating Islet-derived 3-alpha(Reg3α) protein level in plasma with the diagnosis and prognosis of the gastrointestinal acute graft-versus-host disease (GI-aGVHD) after all-HSCT, 103 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were observed in our hospital from December 2011 to December 2012. Peripheral blood samples were routinely collected at 9 d before allo-HSCT, 0 d, 14 d, 28 d after allo-HSCT as well as in aGVHD and at the 1 and 4 weeks after aGVHD therapy. The plasma concentrations of Reg3α were measured by using ELISA kit. The results indicated that among the 103 patients, 17 cases never developed aGVHD symptoms (no-aGVHD), 27 cases presented with non-aGVHD associated diarrhea, 10 cases presented with isolated skin aGVHD, 17 cases developed grades I-II GI-aGVHD, 32 cases with grades III-IV GI-aGVHD. The plasma concentrations of Reg3α in group of patients with GI-aGVHD and group of non-aGVHD diarrhea were 111.5 (54.7-180.2) and 23.9 (14.5-89.5) ng/ml respectively with significant difference (P < 0.001). The plasma concentrations of Reg3α in 17 patients of grades III-IV GI-aGVHD who experienced a complete or partial response and 7 patients who had no response to therapy at 4 weeks were 137.2(51.7-205.4) and 679.4(122.3-896.8) ng/ml respectively with the significant difference (P = 0.028). All of the patients who had no response to therapy died of aGVHD associated multiple organ failure. The area under the ROC curve was 0.902 when plasma concentration of Reg3α was set at 87.73 ng/ml. The sensitivity was 81.48% and the specificity was 82.86% when the critical value was used in diagnosis of grades III-IV GI-aGVHD. The probability of grades III-IV GI-aGVHD had statistical difference above and below 87.73 ng/ml after allo-HSCT (P < 0.001). It is concluded that the increase of plasma Reg3α level after transplantation suggests the incidence of grades III-IV GI-aGVHD. The high level of plasma Reg3α protein in patients with grades III-IV GI-aGVHD after the immunosuppressive treatment for four weeks indicates a poor prognosis. The plasma concentrations of Reg3α can be used as a specific biomarker of GI-aGVHD.

Correlation between expression of SIL-TAL1 fusion gene and deletion of 6q in T-cell acute lymphoblastic leukemia / 中国实验血液学杂志

The present study was designed to investigate the prevalence and clinical significance of SIL-TAL1 rearrangements in T-cell acute lymphoblastic leukemia (T-ALL). The incidence of SIL-TAL1 rearrangements was analyzed by nest real-time quantitative polymerase chain reaction (RT-PCR) in 68 patients with T-ALL. Karyotypic analysis was performed by conventional R-banding assay and array-based comparative genomic hybridization (array-CGH). The results showed that SIL-TAL1 rearrangements were identified in 10/26 (38.5%) pediatric and 2/42 (4.8%) adult T-ALL cases, which indicate a pediatric preference for SIL-TAL1 rearrangements in T-ALL. Two different transcripts were detected in 6/12(50%) T-ALL samples. Abnormal karyotypes were detected in 6 out of 11 cases (54.5%) and a deletion of the long arm of chromosome 6 was observed in 4 cases. Array-CGH results of 2 T-ALL cases with SIL-TAL1 rearrangement revealed that this fusion gene was resulted from a cryptic deletion of 1p32, and the overlap region of 6q deletion was 6q14.1-16.3. These cases with SIL-TAL1 fusion had a higher white blood cell (WBC) count and higher serum levels of lactate dehydrogenase (LDH) than cases without SIL-TAL1 fusion. It is concluded that SIL-TAL1 rearrangements are associated with loss of heterozygosity of chromosomal 6q, and SIL-TAL1-positive patients are younger than SIL-TAL1-negative patients. In contrast to the cases without SIL-TAL1 fusion, there are many adverse prognostic factors in the cases with SIL-TAL1 fusion, such as higher WBC count and higher LDH levels.

Clinical significance of common leukemia gene mutations in patients with acute promyelocytic leukemia / 中国实验血液学杂志

This study was aimed to explore whether multiple common gene mutations of leukemia synergistically involved in acute promyelocytic leukemia (APL) pathogenesis, and to investigate their relevance to clinical features, cytogenetics and molecular risk stratification. 84 specimens of admitted de novo APL patients from February 2005 to October 2010 were collected, the gene mutations of bone marrow mononuclear cells and clinical features of mutation-positive patients were analyzed by genomic DNA-PCR. The results indicated that the prevalence of mutations was 60.7% (51/84), in which the mutations with the highest incidence were found as FLT3-ITD, reaching 27.4% (23/84). Next, there were 12 cases WT1 mutation, 9 for FLT3-TKD, 7 for TET2, 5 for N-RAS, 4 for ASXL1, 2 for EZH2 mutation and 1 positive case in MLL-PTD, IDH1 and CBL mutation respectively. No mutation was found in other JAK1, DNMT3, c-Kit, NPM1, IDH2, RUNX1 and JAK2 (V617F) common leukemia-related genes. Combined analysis with clinical data demonstrated that the patients with FLT3-ITD mutation displayed higher white blood cell counts, while the patients with N-RAS mutation showed lower platelet counts. Overall survival of these patients was obviously shorten as compared with patients with wild-type. This difference between mutant and wild-type of all above mentioned cases was statistically significant (P < 0.05). The difference between APL with simple t (15;17) and additional abnormal karyotype was not statistically significant. It is concluded that the FLT3-ITD mutation is recurrent genetic change in APL, and together with N-RAS mutation indicates poor prognosis. Additional abnormal karyotype does not associate with prognosis of APL.

The correlation of cytomegalovirus gB genotype with viral DNA load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of CMV gB genotypes on viral load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Viral load was detected by real-time (RT) quantitative polymerase chain reaction (PCR) (Q-PCR), CMV gB genotypes by PCR restriction fragment length polymorphism (RFLP) (PCR-RFLP) in 115 patients with CMV infection (CMV-DNA positive) after HSCT during July 2004 and May 2010.</p><p><b>RESULTS</b>(1) The distribution of CMV gB genotypes in HSCT recipients were as following: gB1, 42/115 (36.52%); gB2, 3/115 (2.61%); gB3, 43/115 (37.39%); gB4, 2/115 (1.74%). 20 patients (17.39%) had a combination of 2 different CMV genotypes and 5 patients (4.35%) had a CMV variant that lacked an RsaI digestion site, herein named gB5. (2) The median viral load were 2.7×10(3)(1.81×10(3) ∼ 6.03×10(4)) in gB1, 4.0×10(3) (1.32×10(3) ∼ 6.39×10(4)) in gB3 and 1.2×10(4)(2.28×10(3) ∼ 6.50×10(5)) in mixed gB. There was no statistical difference in viral load between gB1 and gB3 (P > 0.050). There was significantly statistical difference in viral load between single-gB (gB1 or gB3) and mixed-gB (P < 0.05). (3) The median treatment time was 17 days in mixed-gB and 14 days in single-gB. There was significantly statistical difference between two groups (P < 0.05). Conclusion gB genotype may have an impact on CMV DNA load and treatment time in HSCT recipients with CMV infection.</p>

Clinical and laboratorial analysis for 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or positive BCR-ABL / 中国实验血液学杂志

The purpose of this study was to summary the clinical and laboratorial features in 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or BCR-ABL fusion gene positive (Ph(+)MPAL), 15 adult patients with Ph(+)MPAL were defined by WHO-2008 classification. The clinical characteristics, results of morphology, immunology, cytogenetics and molecular genetic detections and results of follow-up in 15 adult patients with Ph(+)MPAL were analyzed retrospectively. The results showed that 15 patients among 87 cases of MPAL demonstrated Ph(+)MPAL (17.2%; 15/87) (7 males and 8 females), their median age was 51 (range 16-81) year old and median WBC count at diagnosis was 69 (12.7-921)×10(9)/L. Based on FAB criteria, these patients showed different morphologic types, including AML (13.3%; 2/15), ALL (40.0%; 6/15), HAL (46.7%; 7/15). Immunologic analysis indicated that 15 cases of Ph(-)MPAL were all classified as B-lymphoid +myeloid mixed immunophenotype. Except one patient, all expressed CD34 antigen on the surface of leukemia cells with 64.3% strong positive, only Ph (53.3%; 8/15), Ph with additional chromosomal abnormalities (33.3%; 5/15) and normal karyotype (13.3%; 2/15) were cytogenetically identified. BCR-ABL fusion gene transcript positive were detected by multiplex reverse transcription PCR in all cases, with e1a2 subtype (p190) (40.0%; 6/15) and b2a2 or b3a2 (p210) subtype (60.0%; 9/15). Four out of 7 (57.1%) patients were found to have IKZF1 gene deletion, without other common gene mutations. Seven out of 10 cases (70.0%) achieved complete remission (CR) after one cycle of induction chemotherapy. In the induction stage, CR rate seemed higher when tyrosine kinase inhibitors (TKI) were added to chemotherapy (83.3%:50.0%; P = 0.206). Overall survival (OS) in 4 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was longer than that in 4 patients received chemotherapy alone (P = 0.004). It is concluded that Ph(+)MPAL mainly is expressed as B+My phenotype. The majority of patients is older and has CD34 overexpression. In the aspect of molecular genetics, the Ph(+)MPAL is similar to other acute leukemia with Ph chromosome. Ph(+)MPAL is a subtype of acute leukemia with poor prognosis. WBC count at diagnosis is an independent prognostic factor. The combination of TKI and allo-HSCT can improve their long-term survival, which needs to be confirmed through carrying out a prospective and multicenter clinical trial for newly diagnosed Ph(+)MPAL.

Influence of transplantation and some clinical factors on prognosis of patients with diffuse large B-cell lymphoma / 中国实验血液学杂志

This study was aimed to analyze the survival status of patients with diffuse large B-cell lymphoma (DLBCL) and to investigate the influence of autologous hematopoietic stem cell transplantation (auto-HSCT), different pathological types, International Prognosis Idex (IPI) on prognosis. One hundred and sixteen cases of DLBCL were analyzed retrospectively. The treatment efficacy of R-CHOP alone and R-CHOP combined with auto-HSCT as well as the influence of different immunopathologic types, IPI, hypersensitive C-reactive protein (HSCRP), α-hydroxybutyric acid deaminase (HBDH) on the prognosis of DLBCL patients including overall survival (OS) rate, progression-free survival (PFS) rate were analyzed. The results indicated that the 5-year OS for all patients was 72.4%. in which 30 patients with Ann Arbor staging III-IV received auto-HSCT plus R-CHOP. The prognosis of the 30 patients was better than that of 86 cases received R-CHOP chemotherapy alone (5-year OS was 82.5% vs 69.0%, 5-year PFS was 77.1% vs 68.3%) (P < 0.05). The prognosis of patients in germinal center B-cell-like group (GCB group) was better than that of patients in activated B-cell-like group (ABC group). Some clinical features were associated with poor prognosis including OS and PFS, such as age, B symptoms, IPI scores, the level of LDH, HSCRP and HBDH (P < 0.05) in which the level of LDH, age ≥ 60 years and B symptoms were independent prognostic factors in DLBCL patients (P < 0.05). It is concluded that auto-HSCT combined with R-CHOP can improve the long-term survival of DLBCL patients. The prognosis of patients in GCB group is better than that of patients in the ABC group. The clinical features such as age, B symptoms, IPI scores and LDH are associated with prognosis.

Clinical and cytogenetic study of 6 cases of hematological disorders associated with 20q- and t (20;21) (q11;q11) abnormalities / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical and cytogenetic features of hematological disorders associated with 20q- and t (20;21) (q11;q11) abnormalities.</p><p><b>METHODS</b>Following short-term culture of bone marrow cells, karyotypic analysis was carried out with R-banding. 20q- and t(20;21) (q11;q11) was detected by fluorescence in situ hybridization (FISH) using dual-color 20q11/12 probe, ST 20qter /ST 21qter probes, SE20(D20Z1)/SE 13/21 probes, and WC20/WC21 probes.</p><p><b>RESULTS</b>Six (2.3%) of the 257 patients with 20q- detected by conventional karyotypic analysis were found to have t(20;21) (q11;q11) abnormality. Five cases had myelodysplastic syndrome, 1 had acute lymphoblastic leukemia. Above results were all confirmed by FISH.</p><p><b>CONCLUSION</b>i (20q-), t(20;21) (q11;q11) seems to be a rare but recurrent chromosomal abnormality which is specifically associated with myeloid disease, late occurrence and poor prognosis. The translocation between chromosome 20q11 and 21q11 may form a novel fusion gene which has an important role in the pathogenesis of the disease.</p>

Deletions and rearrangements of PAX5 gene in B-lineage acute lymphoblastic leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the frequency paired-box domain 5 (PAX5) gene alterations in B-lineage acute lymphoblastic leukemia (B-ALL) harboring 9p abnormalities and its implication for clinical prognosis.</p><p><b>METHODS</b>Bacterial artificial chromosomes RP11-344B23 and RP11-652D9 encompassing the PAX5 gene were selected. DNA was extracted with conventional method and labeled with fluorescein by nicking transition. Fluorescence in situ hybridization (FISH) was used to determine the rearrangement or deletion of the PAX5 gene in B-ALL harboring chromosome 9p abnormalities. Clinical and laboratory features of patients were analyzed.</p><p><b>RESULTS</b>Fifty cases were analyzed with FISH. Complete deletion was observed in 23 patients (46%), partial deletion was observed in 2 patients (4%), and rearrangement was detected only in 1 case. The total frequency of abnormalities was 52% (26/50). No significant difference was found in clinical features of patients with or without PAX5 rearrangement or deletion.</p><p><b>CONCLUSION</b>The frequency of PAX5 gene alterations in B-ALL harboring 9p abnormalities was 52%. However, no significant difference was found between patients with and without PAX5 alterations.</p>

Multivariate analysis of imatinib resistance-related factors during the treatment of chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore efficacy of imatinib for patients with chronic myeloid leukemia(CML) and its resistance-related factors during the treatment.</p><p><b>METHODS</b>The clinical data of 214 CML patients received imatinib were analyzed respectively in our hospital from April 2005 to December 2010. The therapy history and efficacy of regular follow-up and factors influencing drug resistance were analyzed. COX regression analysis was used to perform the univariate and multivariate analysis.</p><p><b>RESULTS</b>Until the end of follow up, thirty-one patients (14.5%) occurred drug resistance. One of them was in accelerated phase(AP), and two in blast phase(BP); 69.2% of patients achieved a complete cytogenetic response(CCyR), and 31.3% of patients achieved a major molecular response(MMR). COX analysis was performed in 207 chronic phase(CP) patients. Univariate analysis showed that the course of disease before treatment, the hemoglobin count, the white blood cell count, whether achieved CCyR or not and whether achieved MMR or not were the influencing factors for imatinib resistance. Multivariate analysis showed that whether achieved CCyR or not was the independent factor for drug resistance.</p><p><b>CONCLUSION</b>Whether achieved CCyR or not is an independent factor and also a protective factor for imatinib resistance in patients with CML.</p>