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 (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) 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.
Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Salvage Therapy

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)×10(9)/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.
Anti-Bacterial Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Bacteremia/drug therapy* ; Consolidation Chemotherapy ; Humans ; Leukemia, Myeloid, Acute ; Prognosis ; Retrospective Studies

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.
Flow Cytometry ; Humans ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

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.
Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Induction Chemotherapy/adverse effects* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Neutrophils ; Prospective Studies ; Recombinant Proteins

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 18.89×10(9)/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.
Chromosomes, Human, Pair 8 ; Eosinophilia/genetics* ; Hematologic Neoplasms/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Lymphatic Diseases/genetics* ; Myeloproliferative Disorders/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/genetics* ; Translocation, Genetic

OBJECTIVETo investigate the clinical and laboratory features of acute myeloid leukemia (AML) with t(11;12)(p15;q13) translocation.

METHODSTwo cases of AML with t(11;12)(p15;q13) translocation were reported and the related literatures were reviewed.

RESULTSThe diagnosis of AML-M3 was supported by morphological, cytochemical staining and electron microscope tests. A rare t(11;12)(p15;q13) translocation, but not classical t(15;17)(q22;q12) translocation and PML- RARα fusion gene, was detected in both cases. Both of the patients were refractory to differentiation induction therapy such as retinoic acid and arsenic trioxide.

CONCLUSIONAML is a group of heterogeneous disease derived from hematopoietic stem cell. Cytogenetic characteristic is important for diagnosis, prognosis stratification and therapy selection. Because of the heterogeneity of clinical and molecular features, it is unsuitable to classify AML with t(11;12)(p15;q13) as AML with recurrent cytogenetic aberration. This group of disease may benefit from allogeneic hematopoietic stem cell transplantation.

Abnormal Karyotype ; Adolescent ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 12 ; Humans ; Leukemia, Myeloid, Acute ; genetics ; therapy ; Male ; Middle Aged ; Prognosis ; Translocation, Genetic

OBJECTIVETo assess complete remission (CR), the overall survival (OS), event-free survival (EFS) and adverse events of newly diagnosed acute promyelocytic leukemia (APL) with homoharringtonine (HHT) plus ATRA, to evaluate the therapeutic effect by comparing HHT plus ATRA with daunorubicin plus ATRA as induction regimen (HA with DA as post-remission regimen).

METHODS115 APL patients (54 in HHT group, 61 in DNR group) after long-term follow-up were enrolled in the analyses of clinical feature, chromosome karyotype, molecular biology, OS and EFS.

RESULTSThe overall CR of 115 patients was 100%, the median interval to achieve hematological CR was 32 (22 - 43) days, the overall median OS was within 0.23 - 77.34 months, median EFS was within 0.23 - 77.34 months. 3-year OS rate was 93%, 5-year OS rate 93%, 3-year EFS rate 85% and 5-year RFS rate 75% respectively. Converting to PML-RARα PCR-negative after the induction therapy in the HHT and DNR group was 31.3% and 15.5% respectively, at the end of 1 consolidation course was 68.6% and 77.6% respectively, while the remaining 4 patients tested PML-RARα PCR-negative at the end of 2 consolidation courses in the DNR group. While both groups obtained the identical molecular biology relapse rate (9.8% and 8.6%, respectively). Survival analysis indicated that no significant difference was found on OS and EFS between the HHT group and the DNR group (P = 0.206 and 0.506). 5-year OS rate was 87% for the HHT group while 98% for the DNR group, 5-years EFS rate was 80% for the HHT group while 71% for the DNR group. And the risk group was not the factor affecting OS and EFS (P = 0.615 and 0.416). Grade 2 fever in the HHT group was less than in the DNR group during induction therapy. And no difference was found in terms of liver dysfunction, renal dysfunction, cardiac dysfunction, and hematologic toxicity between two groups.

CONCLUSIONOur study demonstrated comparable therapeutic effect of HHT or DNR on APL. HHT was also well tolerated and didn't cause serious adverse events.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Harringtonines ; administration & dosage ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Tretinoin ; administration & dosage ; Young Adult

OBJECTIVETo investigate the biologic features of adult acute lymphoblastic leukemia (ALL), and reclassified our ALL patients according to the 2008 WHO classification.

METHODSImmunophenotype and cytogenetic/molecular genetic results were obtained by flow cytometry, R-banding and RT-PCR, respectively.

RESULTS(1) A total of 412 newly diagnosed and previously untreated adult ALL patients, were 239 males and 173 females. Among 410 patients with available immunophenotypic results, 357 were B-ALL and 53 T-ALL. Myeloid antigen (MyAg) was higher expression in B-ALL than in T-ALL, and was correlated with the expression of CD34. (2) 93 Ph + ALL patients, mainly CD10 ALL, was associated with high WBC count and MyAg and CD34 expression. MLL rearrangement was found in 12 cases, mainly pro-B ALL. (3) 299 cases could be analysed, according to the 2008 WHO classification of ALL, including 126 B-ALL with recurrent genetic abnormalities, and 120 B-ALL not otherwise specified. Among the 126 B-ALL with recurrent genetic abnormalities, 92 were Ph + ALL, 10 MLL + ALL, 11 hyperdiploid, 9 hypodiploid, 3 E2A-PBX +, and 1 TEL-AML1 +. Patients with Ph +, MLL +, hypodiploid or E2A-PBX + were associated with older age, higher WBC count, higher HGB, higher peripheral blasts and higher LDH level as compared with other patients.

CONCLUSIONCombination of immunophenotype and cytogenetic-molecular profiles can provide a further detailed classification of B-ALL.

Adolescent ; Adult ; Aged ; Chromosome Banding ; Female ; Humans ; Immunophenotyping ; Karyotyping ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; classification ; genetics ; immunology ; Young Adult

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-M(3)) 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)×10(9)/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.
Adolescent ; Adult ; Aged ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation ; Histone-Lysine N-Methyltransferase ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; Prognosis ; Retrospective Studies ; Young Adult

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 (χ(2)=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.
Adolescent ; Adult ; China ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Precursor Cells, T-Lymphoid ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult