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.

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.

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.

Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation / 中华血液学杂志

Objective@#To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. @*Method@#The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR2) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR2 rate was analyzed. @*Results@#68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR2. All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR2 compared with non-KIT D816 group (23.1% vs 57.1%, χ2=7.559, P=0.006), and patients with longer CR1 duration achieved significantly higher CR2 than those with CR1 duration less than 12 months (74.1% vs 31.9%, χ2=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR1 duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. @*Conclusion@#KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.

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.

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.

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.

Characteristics and treatment outcomes in 822 adult patients with acute myeloid leukemia:a single center experience / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the characteristics and the short- or long-term treatment outcomes of the adult patients with acute myeloid leukemia (AML) in China.</p><p><b>METHODS</b>From 1999 to 2010, 822 adult cases with AML were enrolled, diagnosed and classified by the FAB and WHO criteria, respectively. The treatment outcomes and prognostic factors were analyzed retrospectively.</p><p><b>RESULTS</b>In all patients with a median age of 38.5(15-83) years, acute monoblastic and monocytic leukemia (M5), AML with t(15;17)/PML-RARα (APL) and AML with t(8;21)/AML1-ETO(M2b) were the most common subtypes, accounting for 29.7%, 20.9% and 14.6% respectively. In APL patients, CR was achieved in 95.2%, with an early death (ED) rate of 4.8%. And the estimated overall survival (OS) and disease-free survival (DFS) at 5 year was 87.5% and 88.8%, respectively. Patients with other AML subtype (Non-APL) revealed a CR rate of 82.0%, ED of 4.3%, and estimated 5-year OS and DFS both of 48.8%. The OS rate of Non-APL patients at 3-year varied significantly (P<0.01) among three prognostic groups by cytogenetic risk stratification:favorable, 69.5%; intermediate, 52.8%; unfavorable, 29.8%. The prognostic factors for OS among Non-APL included age, cytogenetic abnormalities, courses of the median/high-dose cytarabine and allogeneic hematopoietic stem cell transplantation.</p><p><b>CONCLUSION</b>When compared with the previous reports, the AML patients in our study were younger and showed a different subtype distribution. Treatment outcomes of APL and Non-APL were just the same as those in international leukemia centers. Chemotherapy by risk stratification, after diagnosis and classification according to the WHO criteria, is a key point to improve the outcomes in AML.</p>

Optimal treatment of adult Ph negative acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the difference of safety and efficacy between the traditional and the pediatric inspired acute lymphoblastic leukemia (ALL) chemotherapy regimen, and to further observe whether patients in different age group will benefit from the two regimens.</p><p><b>METHODS</b>Adult de novo Ph negative ALL patients in our hospital from Jan 4, 2009 to Sep 4, 2013 were involved in this study and divided into 2 groups according to treatment regimens, the traditional regimen (regimen 1) and modified pediatric regimen (regimen 2) groups, respectively. The safety and the efficacy of all patients and different regimen groups were evaluated statistically.</p><p><b>RESULTS</b>All 144 patients received the induction therapy. The total complete remission (CR) rate was 95.8%, one course CR rate was 92.4%, and 5 year overall survival (OS) and progression free survival (RFS) were 59.0% and 48.6% respectively. The CR rate, 3 year OS and 3 year RFS between the two different regimens were 95.6% vs 96.1% (P = 0.783), 65.3% vs 63.4% (P = 0.885) and 56.0% vs 50.0% (P = 0.931), respectively. Further analysis stratified with age was also performed. For the patients treated with regimen 1, the 3 year OS and RFS between the two different age groups (14-30 years and 31-60 years) was 69.6% vs 54.7% (P = 0.042) and 56.5% vs 57.0% (P = 0.472). For the patients treated with regimen 2, the 3 year OS and RFS between the two different age groups (14-30 years and 31-60 years) was 65.7% vs 60.3% (P = 0.423) and 51.5% vs 46.6% (P = 0.655). No differences were found on the respiratory failure, cardiac dysfunction, fungal infection and intestinal obstruction between the two treatment regimen groups. The incidence of renal dysfunction for regimen 1 was lower than that of regimen 2 (P = 0.011). The incidence of bacteremia for regimen 1 was higher than that of regimen 2 (P = 0.000).</p><p><b>CONCLUSION</b>The two treatment regimens for adult Ph negative ALL patients were well tolerated and showed relative favorable CR rate and long term survival rate. The older patients (31-60 years) tended to benefit from the regiment 2 which was less intensive and consisted of more agents with low suppression to bone marrow.</p>