Acute leukemia with NUP98-DDX10 fusion gene-positive: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of acute leukemia (AL) with NUP98-DDX10 fusion gene-positive.Methods:The clinical data of 2 AL patients with NUP98-DDX10 fusion gene-positive who admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences in April 2020 and February 2021, respectively were retrospectively analyzed. Transcriptome gene sequencing was used to detect fusion gene, and the fusion gene fragment was amplified by using reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing was used to clarify sequences. The clinical and experimental indicators characteristics were analyzed and the relevant literatures were reviewed.Results:According to the clinical diagnosis, 1 patient was diagnosed as acute myeloid leukemia M 5 (AML-M 5) and 1 patient was diagnosed as acute leukemia of ambiguous lineage, not otherwise specified (ALAL-NOS). The AML-M 5 patient presented with severe coagulation abnormalities, and fulfilled the diagnostic criteria for diffuse intravascular coagulation (DIC) at the initial visit. Transcriptome sequencing of 2 patients showed NUP98-DDX10 fusion gene- positive. RT-PCR confirmed that sequencing results identified 2 different splice fusion modes: one was NUP98 exon 14 fused with DDX10 exon 7(usually called "type Ⅱ"), the other was NUP98 exon 14 fused with DDX10 exon 13, which was never reported and named as "type Ⅳ". From 1997 to 2018, a total of 16 cases with NUP98-DDX10 related hematologic neoplasms were reported in the literature. A summary analysis of 16 cases added with 2 patients in our center included 13 males and 5 females with median age 31.5 years (0.08-61 years). The median overall survival was 12 months (1-46 months). Conclusions:A novel fusion gene NUP98-DDX10 transcriptome is identified in ALAL-NOS patient. Hematological malignancies with NUP98-DDX10 are very rare. They respond poorly to conventional treatment and require allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve the prognosis.

Therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia: a report of four cases and literature review / 中华血液学杂志

Objective@#To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) .@*Methods@#Clinical data of 4 patients, diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019, were collected retrospectively. T-MNs related literature was reviewed.@*Results@#The 4 cases were all females, with the median age 42 (range 40-53) years old at the diagnosis of APL. Regarding the induction and consolidation regimens, 3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine. One patient only received ATRA and other auxiliary drugs. Alkylating agents were not administrated. The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL, including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML) . The PML-RARα fusion genes were all negative when t-MNs developed. The three patients with t-AML were treated with 3 to 4 re-induction regimens, one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR) . One patient with t-MDS received hypomethylating agents. After a median follow-up of 54.5 (48-62) months, 2 patients with t-AML died, the median overall survival after t-MN was 12 (5-18) months. From 1989 to 2018, a total of 63 t-MN cases were reported in the literature. Therefore, 67 cases were analyzed when four patients in our center were added, including 27 males and 40 females with median age 52.5 (15-76) years. The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months.@*Conclusions@#Although rare, t-MNs may occur after successful control of APL. There are no existing guidelines for prevention and treatment of t-MNs, which have very poor prognosis. If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL, t-MNs should be considered as a differential diagnosis.

Myeloid/lymphoid neoplasms with eosinophilia and FGFR1 rearrangement: 5 cases report and literatures review / 中华血液学杂志

Objective@#To investigate the clinic-pathological features, diagnosis and treatment of 8p11 myeloproliferative syndrome (EMS) .@*Methods@#Five patients diagnosed as EMS from Jan 2014 to May 2018 at Blood Disease Hospital, Chinese Academy of Medical Sciences were enrolled. The clinical manifestations, laboratory characteristics, treatment and outcome of these patients were summarized.@*Results@#The peripheral blood leukocyte count of 5 patients with EMS increased significantly, accompanied with an elevated absolute eosinophils value (the average as 18.89×109/L) . The hypercellularity of myeloid cells was common in bone marrow, always with the elevated proportion of eosinophils (the average as 17.24%) , but less than 5% of blast cells. The chromosome karyotype of the 5 cases differed from each other, but presenting with the same rearrangement of FGFR1 gene by fluorescence in situ hybridization technology. The average interval between onset and diagnosis was 4.8 months with a median survival of only 14 months.@*Conclusion@#EMS was a rare hematologic malignancy with poor prognosis and short survival. It was commonly to be misdiagnosed. Analysis of cytogenetics and molecular biology were helpful for early diagnosis.

A single-center, randomized controlled trial of PEG-rhG-CSF and common rhG-CSF to promote neutrophil recovery after induction chemotherapy in newly diagnosed acute myeloid leukemia / 中华血液学杂志

Objective@#To compare the time of the recovery of neutrophils or leukocytes by pegylated recombinant human granulocyte stimulating factor (PEG-rhG-CSF) or common recombinant human granulocyte stimulating factor (rhG-CSF) in the myelosuppressive phase after induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients. At the same time, the incidences of infection and hospitalization were compared.@*Methods@#A prospective randomized controlled trial was conducted in patients with newly diagnosed AML who met the enrollment criteria from August 2014 to December 2017. The patients were randomly divided into two groups according to a 1:1 ratio: PEG-rhG-CSF group and rhG-CSF group. The time of neutrophil or leukocyte recovery, infection rate and hospitalization interval were compared between the two groups.@*Results@#60 patients with newly diagnosed AML were enrolled: 30 patients in the PEG-rhG-CSF group and 30 patients in the rhG-CSF group. There were no significant differences in age, chemotherapy regimen, pre-chemotherapy ANC, WBC, and induction efficacy between the two groups (P>0.05) . The median time (range) of ANC or WBC recovery in patients with PEG-rhG-CSF and rhG-CSF were 19 (14-35) d and 19 (15-26) d, respectively, with no statistical difference (P=0.566) . The incidences of infection in the PEG-rhG-CSF group and the rhG-CSF group were 90.0%and 93.3%, respectively, and there was no statistical difference (P=1.000) . The median days of hospitalization (range) was 20.5 (17-49) days and 21 (19-43) days, respectively, with no statistical difference (P=0.530) .@*Conclusions@#In AML patients after induction therapy, there was no significant difference between the application of PEG-rhG-CSF and daily rhG-CSF in ANC or WBC recovery time, infection incidence and hospitalization time.

Application of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia / 中华血液学杂志

Objective@#To investigate the application values of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia (APL) .@*Methods@#The retrospective analyses of flow cytometric (FCM) immunophenotypic anyalysis, chromosome karyotype and chromosome fluorescence in situ hybridization (FISH) of 798 outpatient or hospitalization APL patients referred to our hospital between May 2012 and December 2017 were performed to further study the application values of FCM and molecular genetics in the diagnosis of APL.@*Results@#The sensitivity and specificity of FCM were 91.9% and 98.7% respectively. The typical characteristic immunophenotype for APL was as of follows: a high SSC, absence of expression of cluster differntiation (CD) CD34 and HLA-DR, and expression or stronger expression of CD33, consistent expression of CD13, CD9, CD123, expression of CD56, CD7, CD2 (sometimes) . The rest 10% of the cases harbored atypical APL phenotypes, generally accompanied by CD34 and/or HLA-DR expression, decreased SSC and often accompanied by CD2 expression, it was difficult to definitively diagnose APL by this FCM phenotype, and their diagnoses depended on the results of genetics or molecular biology tests. Compared with normal individuals, complex karyotypes APL with t (15;17) translocation, other variant translocations and variant t (11;17) , t (5;17) had no significant differences in terms of their FCM phenotypes.@*Conclusions@#FCM could rapidly and effectively diagnose APL. Despite the fact that complex karyotypes with various additional chromosomal abnormalities were detected in approximately one third of APL cases in addition to the pathognomonic t (15;17) (q22;q21) , they had no observable impact on the overall immunophenotype. Molecular and genetic criteria were the golden criteria for the diagnosis of APL. About 10% of immunophenotyping cases relied on molecular genetics for diagnosis.

Clinical significance of minimal residual disease in patients with Ph-negative precursor B-acute lymphoblastic leukemia / 中华血液学杂志

Objective@#To explore the predictive value of minimal residual disease (MRD) level in Ph-negative precursor B-acute lymphoblastic leukemia (ALL) patients.@*Methods@#De novo 193 Ph-negative B-ALL patients from Sep 2010 to Nov 2017 were involved in the study. The patients' MRD evaluation which can be performed by multiparametric flow cytometry (MFC) after 1 month, 3-month, 6-month treatment. Relapse free survival (RFS) and overall survival (OS) were compared in patients with different MRD level.@*Results@#The median follow-up was 22 months. All patients was evaluated at 497 MRD level. Patients who reach the good MRD level at 1 month (<0.1% or ≥0.1%), 3-month (negative or positive), 6-month (negative or positive) had a significantly higher probability of estimated RFS (74.5% vs 29.9%; 75.6% vs 29.7%; 74.6% vs 11.6%) and of estimated OS (67.5% vs 30.3%; 71.6% vs 27.8%; 74.0% vs 15.7%). Patients who reach the MRD negative at all 3 times had a significantly higher probability of estimated RFS (80.5% vs 30.5%) and better estimated OS (77.1% vs 29.4%) compared to patients with at least MRD failure in one time (P<0.001). Multivariable analysis showed MRD level at 3-month was an independent prognostic factor for DFS and OS.@*Conclusion@#MRD is an important prognosis factor for Ph-negative B- ALL patients.

Characteristics and prognosis in adult patients with early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective@#To analyze the clinical, laboratory characteristics and prognosis of adult early T-cell precursor acute lymphoblastic leukemia (ETP-ALL).@*Methods@#The clinical data of 13 adult ETP-ALL patients from January 2009 to March 2017 were retrospectively analyzed and compared with non-ETP ALL patients.@*Results@#13 ETP-ALL patients (17.3%) were identified in 75 adult T-ALL patients, the median age of the patients was 35 years old (15 to 49 years) and 10 patients were male (76.9%). ETP-ALL patients had lower WBC count, LDH level, blasts in peripheral blood, lower incidence of thymic mass and higher PLT count compared to non-ETP ALL patients. The CR rate after one course induction chemotherapy for ETP-ALL and non-ETP ALL patients was 33.3% and 90.1%, respectively (χ2=26.521, P<0.001). The median overall survival(OS) was 11.33 (95%CI 0-28.46) and 25.69 (95%CI 11.98-39.41) months, respectively. The 3-year OS was 41.7% and 40.7%, respectively (P=0.699). The median event free survival (EFS) was 1.51 (95%CI 1.23-1.79) and 21.36 (95%CI 4.67-38.04) months, respectively. The 3-year EFS was 16.7% and 39.5%, respectively (P=0.002). The 3-year relapse free survival (RFS) was 53.0% and 52.0%, respectively (P=0.797). Multivariate analysis revealed that CNSL and allo-HSCT were independent risk factors affecting OS of T-ALL and ETP-ALL didn’t affect the prognosis of T-ALL.@*Conclusion@#To our knowledge, this study is the first report on characteristics and prognosis of adult ETP-ALL patients in China. At total of 13 T-ALL patients (17.3%) were classified as having ETP-ALL. These patients had a lower leukemia burden and lower CR rate after one course induction compared to non-ETP ALL patients. Allo-HSCT can improve the prognosis of ETP-ALL.

Impact of duration of antibiotic therapy on the prognosis of patients with acute myeloid leukemia who had Gram-negative bloodstream infection in consolidation chemotherapy / 中华血液学杂志

Objectives@#To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. @*Methods@#Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. @*Results@#A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×109/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. @*Conclusion@#Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.

Spectrum of somatic mutations and their prognostic significance in adult patients with B cell acute lymphoblastic leukemia / 中华血液学杂志

Objective@#To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis.@*Methods@#DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods.@*Results@#Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph+ B-ALL and Ph- B-ALL patients. Ph- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph+ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047).@*Conclusion@#Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Characteristics and prognosis in adult acute myeloid leukemia patients with MLL gene rearrangements / 中华血液学杂志

Objective@#To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements.@*Methods@#The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed.@*Results@#92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M3) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×109/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients’ partner genes weren’t identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS.@*Conclusions@#AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.

Acute myeloid leukemia with NPM-MLF1 fusion gene: report of one case and review of literature / 白血病·淋巴瘤

Objective To investigate the characteristics of NPM-MLF1 fusion gene in acute myeloid leukemia (AML). Methods The data of one AML patient with NPM-MLF1 fusion gene was analyzed,and literatures were reviewed. Results A female patient was diagnosed as AML M6. In the course of the disease, 2 hematologic relapsed, and 2 recurrences were associated with NPM-MLF1 fusion gene positive. After inductive treatment, hematologic complete remission was achieved, and NPM-MLF1 fusion genes were all negative. Survival time surpassed 6 years when the chemotherapy was performed alone. Conclusion The incidence of NPM-MLF1 fusion gene in AML is low. It is necessary to collect more clinical data to judge whether an independent disease type or not.

Screening of adult Ph-like acute lymphoblastic leukemia by multiplex real-time quantitative PCR / 中华血液学杂志

Objective@#To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos.@*Method@#A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients.@*Result@#Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph+ patients, MLL+ patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) .@*Conclusion@#Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

Prognostic significance of flow cytometric minimal residual disease in acute myeloid leukemia during aplasia / 中华血液学杂志

Objective@#To investigate the impact of minimal residual disease (MRD) by multiparameter flow cytometry (MPFC) during aplasia on efficacy and prognosis of de novo acute myeloid leukemia (AML) (non M3) patients.@*Methods@#The MRD data by 8-color MPFC during aplasia (day 14-15 of induction therapy) in 85 de novo AML (non M3) patients and the MRD impact on efficacy and prognosis were retrospectively analyzed.@*Results@#Data of 85 patients, including 42 males (49.4%) and 43 females (50.6%) , were collected, with a median age of 35 (15-54) years. The median MRD by MPFC during aplasia was 0.58% (0-81.11%) , and 70 (82.4%) patients achieved complete remission (CR) after first induction chemotherapy. The cutoff of MRD by receiver operating characteristic (ROC) analysis was 2.305% (Se= 0.867, Sp=0.800) . The CR rate after one course was significantly higher in patients with MRD<2.305% [96.6% (56/58) ]than in patients with MRD≥2.305%[51.9% (14/27) ] (χ2=22.348, P<0.001) ; no significant difference with respect to relapse-free survival rate (χ2=1.08, P=0.299) or overall survival rate (χ2=0.42, P=0.516) could be demonstrated for the comparison of the two groups. Multivariates analysis showed MRD divided by 2.305% was the only independent prognostic factor for CR after one course (OR= 21.560, 95% CI 4.129-112.579, P<0.001) .@*Conclusion@#Flow cytometric MRD divided by 2.305% during aplasia could be a predictor of efficacy after first induction therapy in AML patients.

Prediction of outcome in acute myeloid leukemia by measurement of WT1 expression as a basic marker of minimal residual disease / 中华血液学杂志

Objective@#To probe the potential utility of Wilms tumor 1 (WT1) as a marker of minimal residual disease (MRD) in acute myeloid leukemia (AML) to estimate the relapse-predicting cut-off value.@*Methods@#Quantitative assessment of bone marrow WT1 mRNA level was preformed using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) assay. The expression levels of WT1 dynamically measured with RQ-RT-PCR were retrospectively analyzed in 121 AML cases (not including acute promyelocytic leukemia) achieving complete remission (CR) after induction therapy followed by consolidation therapy. By comparing WT1 levels of patients with different post-therapy outcomes, the investigators used the receiver operating characteristic (ROC) curve to determine WT1 threshold so as to predict their clinical relapses. Then prognoses and the significance of intervention were analyzed between WT1 positive and negative patients according to the cut-off value of WT1.@*Results@#According to ROC curve, WT1 level higher than 2.98% predicted the possibility of relapse. For simplicity and clinical application, 3.00% was used as the cut-off value of WT1 level for relapse. WT1 levels in 41 patients at diagnosis were detected, meanwhile 3 patients whose WT1 levels at diagnosis below 3.00% were excluded, then the median WT1 level of the rest 38 patients at diagnosis was 44.09% (range 7.19%-188.06%) . The median WT1 level in remission was 0.48% (352 samples, range 0-8.41%) . The median WT1 level at diagnosis was higher than that in remission. Excluding the 3 patients with WT1 level at diagnosis under 3.00%, the relapse rate of WT1 positive group (>3.00% during consolidation phase and follow-up) and WT1 negative group (≤3.00%) was 70.0% (14/20) and 12.2% (12/98) respectively (P<0.001) . The median time from WT1 positivity to clinical relapse was 58 days.@*Conclusions@#WT1 expression level above 3.00% was associated with markedly high risk of relapse, which could be as a useful marker for monitoring MRD following consolidation therapy.

Primary antifungal prophylaxis with posaconazole plays a pivotal role during chemotherapy of acute myeloid leukemia / 中华血液学杂志

Objective@#To evaluate the incidence of invasive fungal infections (IFI) and usage of intravenous antifungal drugs during remission induction chemotherapy in patients with acute myeloid leukemia (AML) under primary antifungal prophylaxis with posaconazole.@*Methods@#Clinical records from newly diagnosed AML patients above 15 years old in one single center from February 2014 to January 2016 were retrospectively reviewed and analyzed, excluding acute promyelocytic leukemia. The incidence of IFI and usage of intravenous antifungal drugs were investigated between control group (not receiving any broad spectrum antifungal prophylaxis) and treatment group (receiving posaconazole as primary prophylaxis).@*Results@#A total of 147 newly diagnosed AML patients were enrolled. Of them, 81 received prophylaxis with posaconazole, and 66 did not receive broad-spectrum antifungal treatment. 7 IFI occurred in posaconazole group, and all were possible cases; 19 IFI occurred in control group (3 proven, 4 probable, 12 possible). The incidence of IFI was significantly lower in treatment group than that in control group (8.6% vs 28.8%, χ2=10.138, P=0.001). Usage of intravenous antifungal drugs was significantly decreased in posaconazole group (18.5% vs 50.0%, χ2=16.390, P<0.001).@*Conclusion@#Prophylaxis with posaconazole coulf prevent IFI and reduce usage of intravenous antifungal drugs significantly during remission induction chemotherapy in AML patients.

Clinical features and prognosis in CD10- pre-B acute lymphoblastic leukemia / 中华血液学杂志

Objective@#To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10-pre-B (CD10- pre B-ALL) .@*Methods@#6 adult cases with CD10- pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients’ clinical features and prognosis.@*Results@#CD10- pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33.5 years old, the median white blood cells was 101.78×109/L, MLL-AF4 fusion transcripts were evident in all cases. Complete remission (CR) was achieved in 5 patients after first induction chemotherapy, 1 patient failed to respond to induction therapy, and got CR after 3 courses of chemotherapy. 2 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, 1 patient relapsed in the short term and underwent allo-HSCT in CR2. 1 patient was still waiting for allo-HSCT. Of the 2 patients who didn’t receive transplantation, 1 died following a relapse, the other remained to be in CR.@*Conclusions@#CD10- pre B-ALL was a rare but distinct subtype in adult ALL characterized by male dominance, high onset white blood cells and MLL rearrangement rate. Conventional chemotherapy produced a high response rate but more likely relapse, allo-HSCT may have the potential to improve the prognosis of these patients.

Analysis on the laboratory examination characteristics in 22 patients with acute megakaryoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the ultra microstructures and the expression of platelet peroxidase (PPO) of megakaryocytes from bone marrow, their clinical manifestations and laboratory characteristics in patients with acute megakaryoblastic leukemia (AMKL).</p><p><b>METHODS</b>Karyocytes from bone marrow of 22 AMKL patients were divided into two parts by lymphocyte separation liquid, one part was used to prepare the ordinary transmission electron microscope specimens to observe the morphological structures of megakaryocytes, the other was used to prepare the histochemical specimens of platelet peroxidase to analyze the positive reaction of PPO in AMKL, which were coupled with the patients' data of with bone marrow morphology, cell chemistry, and chromosome karyotype examination.</p><p><b>RESULTS</b>Megakaryocytes from 17 of 22 patients were in the first stage, less than 20 µm in diameter, the nucleis were round, the cytoplasm contained microtubules, membranous vesicles and minute dense granules, no demarcation membrane system and surface-connected canalicular system, less dense granules and α-granules; Megakaryocytes in 5 cases were mainly in the first stage, while containing second and third stage megakaryocytes; the positive rate of PPO in megakaryocytes of 22 patients was 0-80%. The primitive and naive megakaryocytes were found in bone marrow smears of 22 cases, CD41 staining of the megakaryocytes was detected in the primitive and naive megakaryocytes, and more complex chromosome karyotype anomalies were observed.</p><p><b>CONCLUSION</b>The majority of megakaryocytes in AMKL patients were the first stage ones, the rest were second and third stage ones, and the positive PPO reaction was significantly different. CD41 staining of the megakaryocytes was specific with complex chromosome karyotypeswere.</p>

Autologous hematopoietic stem cell transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: a single center experience from the BDHALL2000/02 protocol / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the results of autologous hematopoietic stem cell transplantation (auto-HSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL).</p><p><b>METHODS</b>From January 2000 to December 2007, the clinical data of auto-HSCT in adults Ph-ALL with complete remession (CR) 1 according to BDHALL2000/02 protocol were analyzed.</p><p><b>RESULTS</b>A total of 56 patients were enrolled and the probabilities of standard risk, intermediated risk and high-risk group were 41.1%, 33.9%, and 25.0%, respectively. After a median follow-up of 75 months (range 7-177 months), the 5-year overall survival (OS), events free survival (EFS) and relapse free survival (RFS) were (51.8 ± 6.7)%, (51.8 ± 6.7)%, and (60.5 ± 6.9)%, respectively. And the 5-year accumulative relapse rate was (39.1 ± 6.9)%. The 5-year OS of standard risk, intermediate risk, high-risk group were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 2.8)%, respectively. The 5-year RFS among three groups were (68.3 ± 9.9)%, (62.5 ± 12.1)%, and (44.9 ± 14.1)%, respectively. The 5-year EFS among three groups were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 12.8)%, respectively. The 5-year accumulative relapse rate among three groups were (31.7 ± 9.9)%, (37.5 ± 12.1)%, and (55.1 ± 14.1)%, respectively. There was no statistical significance of any survival rates between standard and intermediate risk groups, just as intermediate and high-risk groups. The OS and EFS in standard risk group were superior to those in high-risk group (P=0.040 and P=0.029, respectively), while there was no statistical significance of RFS and accumulative relapse rate between the two groups. The clinical factors listed below did not influenced the prognosis in the univariate analysis (P>0.05), including more than 5 weeks reaching to CR, WBC count at diagnosis, different immunophenotype (T or B cells), myeloid antigen expression, hyperdiploid chromosome karyotype, complex chromosome abnormality, conditioning regimen with or without TBI, duration between transplantation and diagnosis.</p><p><b>CONCLUSION</b>Ph-ALL adults could achieve a satisfactory CR and better survial according to BDHALL2000/02 protocol followed by auto-HSCT, especially for the standard or intermediate risk group, and no-donors high-risk patients.</p>

Expression of cMPO in 502 cases of acute myeloid leukemia (AML) and its diagnosis significance in AML subtypes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the myeloperoxidase (cMPO) expression pattern by flow cytometry (FCM) in patients with acute myeloid leukemia (AML) and its role in classifying AML.</p><p><b>METHODS</b>Eight- color multiparametric FCM with CD45/SSC gating was used to determine the cMPO expression in 502 AML patients.</p><p><b>RESULTS</b>The positive rate of cMPO in all patients was 58.0%, in which the proportion of normal positivity, dim positivity and partial positivity was 21.5%, 34.1% and 2.4%, respectively. The remaining case (42.0%) were all negative. In AML with t (15;17）(q22;q12)/PMLRARα, the positive rate was the highest (100%) and the intensity was similar to that of the normal granular leukocytes, followed by AML with t (8;21（q22;q22/RUNX1-RUNX1T1, the positive rate was 91.4% and the intensity was mostly dim. AML with minimal differentiation and acute megakaryoblastic leukemia were all cMPO negative. The positive rates of cMPO in the remaining subtypes were between 22.7% and 76.2%.</p><p><b>CONCLUSION</b>The positive rate and intensity of cMPO were significantly different among different subtypes of AML.</p>

Reversible pulmonary arterial hypertension related to dasatinib in the treatment for chronic myelogenous leukemia: a case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical features and prognosis of pulmonary arterial hypertension associated with dasatinib.</p><p><b>METHODS</b>To present a case of pulmonary arterial hypertension (PAH) associated with long-term exposure to dasatinib and review the related literatures.</p><p><b>RESULTS</b>A 23-year-old female with chronic myelogenous leukemia was treated with dasatinib at a dosage of 140 mg/d after failure of imatinib treatment and achieved complete cytogenetic response. The patient was presented with exertional dyspnea after 35 months of administration with dasatinib. The electrocardiogram showed right ventricular hypertrophy and right axis deviation; transthoracic Doppler echocardiography documented a reduction in diameters of left heart chambers with normal systolic left ventricular function, right heart chambers and pulmonary trunk dilatation, an estimated pulmonary arterial pressure of 114 mmHg; Computed tomography showed thickened pulmonary artery. PAH related to dasatinib was diagnosed and dasatinib was permanently discontinued. The symptom of dyspnea disappeared quickly after withdrawal of dasatinib. The heart structure and pulmonary arterial pressure completely recovered after 7 months of dasatinib discontinuation.</p><p><b>CONCLUSION</b>PAH is a rare adverse effect of dasatinib treatment. Echocardiograhpy, as a non-invasive screening test for PAH, should be performed before starting dasatinib treatment and repeated during the administration with dasatinib. Dasatinib should be withdrawn permanently in patients with PAH.</p>