Clinical characteristics and prognostic factors in intracranial hemorrhage patients with hematological diseases.

The clinical characteristics and prognosis of intracranial hemorrhage (ICH) in patients with hematological diseases remain controversial. This study aimed to describe the clinical characteristics and explore the prognostic factors in such patients. A total of 238 ICH patients with a hematological disease were recruited from the Institute of Hematology and Blood Diseases Hospital, China, from January 2015 to April 2020. The Cox proportional hazards model was used to identify the prognostic factors for 30-day mortality in ICH patients with a hematological disease. There were 123 cases of acute leukemia (AL), 20 of myelodysplasia/myeloproliferative neoplasm, 35 of aplastic anemia (AA), 29 of immune thrombocytopenia (ITP), 19 of congenital/acquired coagulation factor deficiency, and 12 of other hematological diseases. Furthermore, 121 patients presented with a multi-site hemorrhage (MSH), 58 with a single-site hemorrhage in the brain parenchyma (PCH), 23 with a subarachnoid hemorrhage, 33 with a subdural hemorrhage (SH), and three with an epidural hemorrhage. The Cox proportional hazards model indicated association of SH (vs PCH, hazard ratio [HR]: 0.230; 95% confidence interval [CI]: 0.053-0.996; P = 0.049), low white blood cells (≤ 100 × 109/L vs > 100 × 109/L, HR: 0.56; 95% CI: 0.348-0.910; P = 0.019), AA (vs AL, HR: 0.408; 95% CI: 0.203-0.821; P = 0.012), and ITP (vs AL, HR: 0.197; 95% CI: 0.061-0.640; P = 0.007) with improved 30-day mortality. However, increased age (HR: 1.012; 95% CI: 1.001-1.022; P = 0.034), MSH (vs PCH, HR: 1.891; 95% CI: 1.147-3.117; P = 0.012), and a disturbance of consciousness (HR: 1.989; 95% CI: 1.269-3.117; P = 0.003) were associated with increased risk of 30-day mortality. In conclusion, in this study, we revealed the clinical characteristics of Chinese ICH patients with a hematological disease. Moreover, we identified risk factors (age, white blood cells, AA, ITP, SH, MSH, and a disturbance of consciousness) that may influence 30-day mortality.

Myeloid Neoplasm with PCM1-PDGFRB Transcript Responded to Low-Dose Imatinib: One Case Report with Literature Review.

Through an RNA-seq analysis of an adult patient with unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U), we identified a rare PDGFRB fusion partner gene, PCM1. Conventional chromosome karyotype analysis showed abnormal clones of t(5;8)(q32;p22), and fluorescence in situ hybridization (FISH) confirmed rearrangement of the PDGFRB gene. Reverse transcription PCR (RT-PCR) and Sanger sequencing further confirmed that exon 30 of the PCM1 gene was fused with exon 11 of PDGFRB in frame, and the fusion event was accompanied by a 14 bp deletion of exon 11 of PDGFRB. After low-dose imatinib treatment, the patient achieved complete molecular remission. This study not only broadens the understanding of myeloid/lymphoid neoplasms with PDGFRB rearrangement but also reflects the vital role of RNA-seq in identifying PDGFRB rearrangements.

Histiocytic differentiation in acute monocytic leukemia.

Myeloid histocytes of dendritic cells (DCs), Langerhans cells (LCs), and macrophages in varied tissues, as leukemic blasts in acute monoblastic and monocytic leukemia (AML-M5a and M5b), are derived from monocyte progenitors in bone marrow. Based on DC induction from hematopoietic stem cells, myeloid progenitors, and monocytes, and occasional expressions of histocyte-related antigens (HRAs) in M5, we presume some M5 cases share histiocytic phenotypes originally. To clarify the conception, 93 M5 cases were tested with antibodies for HRAs, CD1a, CD163, S100, fascin, and langerin by immunostaining, and their morphologic characteristics were studied by light and transmission electron microscopy. The study revealed that 23 M5 cases were positive for two or more kinds of HRAs and shared a serial of histocytic immunophenotype and morphologic features, which were closely associated with M5b subtype and expression of CD14 in M5.

Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial.

BACKGROUND: Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukaemia. However, their efficacy has not been tested in a multicentre randomised controlled trial in a large population. We assessed the efficacy and safety of homoharringtonine-based induction treatment for management of newly diagnosed acute myeloid leukaemia. METHODS: This open-label, randomised, controlled, phase 3 study was done in 17 institutions in China between September, 2007, and July, 2011. Untreated patients aged 14-59 years with acute myeloid leukaemia were randomly assigned (by a computer-generated allocation schedule without stratification) to receive one of three induction regimens in a 1:1:1 ratio: homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and aclarubicin 20 mg/day on days 1-7 (HAA); homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and daunorubicin 40 mg/m(2) per day on days 1-3 (HAD); or daunorubicin 40-45 mg/m(2) per day on days 1-3 and cytarabine 100 mg/m(2) per day on days 1-7 (DA). Patients in complete remission were offered two cycles of intermediate-dose cytarabine (2 g/m(2) every 12 h on days 1-3). The primary endpoints were the proportion of patients who achieved complete remission after two cycles of induction treatment and event-free survival in the intention-to-treat population. The trial is registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. FINDINGS: We enrolled 620 patients, of whom 609 were included in the intention-to-treat analysis. 150 of 206 patients (73%) in the HAA group achieved complete remission versus 125 of 205 (61%) in the DA group (p=0.0108); 3-year event-free survival was 35.4% (95% CI 28.6-42.2) versus 23.1% (95% CI 17.4-29.3; p=0.0023). 133 of 198 patients (67%) in the HAD group had complete remission (vs DA, p=0·20) and 3-year event-free survival was 32.7% (95% CI 26.1-39.5; vs DA, p=0.08). Adverse events were much the same in all groups, except that more patients in the HAA (12 of 206 [5.8%]) and HAD (13 of 198 [6.6%]) groups died within 30 days than in the DA group (two of 205 [1%]; p=0.0067 vs HAA; p=0.0030 vs HAD). INTERPRETATION: A regimen of homoharringtonine, cytarabine, and aclarubicin is a treatment option for young, newly diagnosed patients with acute myeloid leukaemia. FUNDING: Chinese National High Tech Programme, Key Special Research Foundation of the Ministry of Science and Technology of China, National Nature Science Foundation of China, National Clinical Key Specialty Construction Project.

Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study.

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

[Application of PROTACs in Hematological Malignancies--Review].

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules by utilizing the ubiquitin proteasome system (UPS) to degrade proteins of interest. PROTACs have exhibited unprecedented efficacy and specificity in degrading various oncogenic proteins because of their unique mechanism of action, ability to target "undruggable" and mutant proteins. A series of PROTACs have been developed to degrade multiple key protein targets for the treatment of hematologic malignancy. Notably, PROTACs that target BCL-XL, IRAK4, STAT3 and BTK have entered clinical trials. The known PROTACs that have the potential to be used to treat various hematological malignancies are systematically summarized in this review.

[Clinical Analysis of SET-NUP214 Fusion Gene Positive Patients with Acute Leukemia].

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION: The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.

A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

[Clinical and laboratory investigation of patients with hematologic malignancies harboring der(1;7)(q10;p10)].

OBJECTIVE: To investigate the clinical and laboratory characteristics of patients with various hematological malignancies harboring der(1;7)(q10;p10). METHODS: Bone marrow samples were collected and undergone short-time unstimulated culture and R-banding, and karyotyped by conventional cytogenetic assay (CCA). Megalokaryocytes were detected by streptavidin-AKP (SAP). Retrospective analyses including the clinical and laboratory data were performed. RESULTS: Nineteen of the 21 patients were male. Most of the patients are of older age. Thirteen cases (61.9%) were der(1;7)(q10;p10) without additional aberrations, 8(38.1%) patients had additional aberrations. Sixteen out of the 18 cases (88.9%) who underwent SAP analysis had diminutive megalokaryocyte, and lymphoid megalokaryocyte was found in 10 cases (55.6%). The der(1;7) patients manifested poor response to treatment. CONCLUSION: The der(1;7) patients demonstrated distinct male predominance, older age at diagnosis, and some clinically distinctive features. These patients showed poor prognosis. The cytogenetic abnormality, i.e., der(1;7)(q10;p10), can be used as a prognostic indicator.

[Clinical and cytogenetic features and their influencing factors of core binding factor acute myeloid leukemia].

OBJECTIVE: To discuss the clinical and cytogenetic features of core binding factor (CBF) acute myeloid leukemia (AML) patients and the main factors that influence the prognosis. METHOD: Totally 130 CBF AML patients were followed up and their clinical features, immunophenotype, chromosome karyotype, treatment regimen, overall survival (OS), and relapse-free survival (RFS) were analyzed. RESULTS: The overall complete remission (CR) rate was 96.1%, among which the CR rate after the first treatment course was 77.2%. The overall median OS was 51.64 (0.26-132.5) months, while the median RFS did not reach 1.18-96.62 months. The 3-year OS was 50% and the 5-year OS was 41%; the 3-year RFS was 59% and the 5-year RFS was 54%. Patients who were over 45 years and those with chromosome karyotype of 9q- tended to have poorer prognosis. During the consolidating chemotherapy, patients who had received two or more courses of intermediate-dose Ara-C therapy had better prognosis and longer survival. AML patients with inv (16) /t (16; 16) had a significantly higher OS than those with t (8; 21) (P = 0.046), while the RFS showed an opposite finding (P = 0.038). CONCLUSIONS: Age, chromosomal karyotype, and consolidating chemotherapy are the main factors that influence the survival and prognosis of CBF AML patients. Two or more courses of intermediate-dose Ara-C during consolidating chemotherapy can obviously prolong the OS and RFS of CBF AML patients. AML patients with a chromosomal karyotype of inv (16) /t (16; 16) have longer OS and better prognosis than those with t (8; 21).

[Efficacy of Arsenic Trioxide Combined with ATRA and Chemotherapy for Relapsed Acute Promyelocytic Leukemia Patients].

OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients. METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed. RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications. CONCLUSION: For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

[The role of BCR/ABL isoforms in the presentations and outcome of Philadelphia-positive acute lymphoblastic leukemia in adult patients].

OBJECTIVE: To investigate the difference of clinical characteristics and outcomes between different isoforms of BCR/ABL in adults with Philadelphia-positive acute lymphoblastic leukemia (ALL). METHODS: The data of 106 adults with Ph+ ALL diagnosed in our hospital from January 1, 1996 to December 31, 2007 were reviewed. The difference of clinical characteristics between different subgroups of BCR/ABL was compared and their relation with outcomes was studied. RESULTS: The median age of the 106 patients was 34 years and the median white blood cell count at baseline was 28.5 x 10(9)/L. Comparative analysis demonstrated that patients in p210 group had an older age, higher blood platelet count (BPC) and more frequent occurrence of splenomegaly. Referring to the outcomes, the complete remission (CR) rate of the two groups were 92.2% and 93.9%, respectively. The median overall survival (OS) and relapse free survival (RFS) in p190 group were 13 months and 10 months, the 1, 3-year estimated OS were (54.7 +/- 6.7)% and (5.5 +/- 5.2)%, and the 1, 3-year estimated RFS were (40.2 +/- 6.8)% and (7.8 +/- 6.7)%, while in p210 group, the median OS and RFS were 15 months and 10 months, respectively, the 1, 3-year estimated OS were (65.8 +/- 8.9)% and (14.5 +/- 7.4)%, and the 1, 3-year estimated RFS were (48.3 +/- 9.4)% and (12.9 +/- 7.7)%. All of the above data had no statistic significance between the two groups. CONCLUSION: Majority of the adults with Ph+ ALL is p190 positive and patients with p210 have older age, higher BPC and more frequent occurrence of splenomegaly, while there is no significant difference between p190 group and p210 group in CR rate, RFS and OS.

[A new prognostic stratification for patients with acute myeloid leukemia].

OBJECTIVE: To evaluate the impact of the percentage of residual blasts in bone marrow at the end of induction chemotherapy (T1) or during myelosuppression phase (T2) on prognosis of de novo acute myeloid leukemia (AML) (non M(3)) in 105 cases. To refine AML risk-stratification by combining the percentage of residual blast cells (T1 or/and T2) with cytogenetic data based the South West Oncology Group (SWOG) criteria. METHODS: The data of 105 de novo AML (non M(3)) patients hospitalized between January 1st 1999 and February 1st 2008 were retrospectively reviewed. Results were analyzed with SPSS15.0 software. RESULTS: (1) Patients were divided into two subgroups by a cutoff of 5% residual bone marrow blasts at T1 or T2 time point. Patients with percentage of residual bone marrow blast cells < 5% had better complete remission (CR) rate, relapse-free survival (RFS) and overall survival (OS) than the patients with percentage > or = 5% at T1 or T2. The percentage of residual bone marrow blast cells at T1 was correlated with that at T2. (2) The prognosis of patients with intermediate karyotypes with percentage < 5% at T1 or T2 was similar to that of the patients with favorable karyotypes. The patients with intermediate karyotypes and percentage of residual bone marrow blasts > or = 5% at T1 or T2 are defined as a subgroup with prognosis similar to that of patients with unfavorable karyotypes. (3) COX regression analysis showed that the percentage of residual bone marrow blasts at T1 or T2 is an independent prognostic factor of AML. The percentage of residual bone marrow blasts at T1 may be more helpful in prognostication than that at T2. CONCLUSION: AML patients with percentage of residual bone marrow blasts < 5% after induction chemotherapy (T1 or T2) have better CR rate, RFS, OS than the patients with percentage > or = 5% at the same time point. Combination of cytogenetics and percentage of residual bone marrow blasts at T1 or T2 is helpful to divide patients with intermediate karyotypes into two subgroups with different prognosis. Thus, a better decision of treatment strategy can be designed.

[FLT3 mutation in patients with acute lymphoblastic leukemia and its clinical significance].

OBJECTIVE: To investigate fms-like tyrosine kinase 3 (FLT3) mutation in patients with acute lymphoblastic leukemia (ALL) and its clinical significance. METHODS: FLT3 mutation-internal tandem duplication (FLT3-ITD) and FLT3 mutation in the tyrosine kinase domain (FLT3-TKD) were detected using polymerase chain reaction (PCR) in the genomic DNA of 61 ALL patients and 7 healthy volunteers (as reference group). The PCR products of these patients who were detected with FLT3-ITD or FLT3-TKD were sent for sequence analysis. RESULTS: In all these 61 ALL patients, FLT3-ITDs were identified in 2 patients and FLT3-TKD were identified in one patient. CONCLUSION: FLT3-ITD and FLT3-TKD exist in a small proportion of ALL patients.

[Clinical Characteristics of Patients with Ph+ Mixed Phenotype Acute Leukemia].

OBJECTIVE: To investigate the clinical biological characteristics and prognosis of the patients with mixed phenotype acute leukemia with t(9;22)(q34;q11.2) and/or BCRABL1 (Ph+ MPAL). METHODS: The morphological, immunological, cytogenetic, and molecular features of 33 in patients with Ph+ MPAL were retrospectively analyzed in our center from June 2002 to June 2016 according to the scoring proposal of European Group for the Classification of Acute Leukemia(EGIL )1998 and WHO 2008 criteria. All the cases were either treated with acute lymphoblastic leukemia (ALL) induction regimen or combined chemotherapy regimens for both acute lymphoblastic and acute myeloid leukemia,part of which also received tyrosine kinase inhibitor(TKI) and 5 cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission. RESULTS: Ph+ MPAL occurred predominantly in male patients (ratio of M/F was 1.75∶1), and a high WBC counts at diagnosis; the WBC count was higher than 30×109/L in 25 patients( 75.8% )， and appeared higher than 100 ×109/L in 13 patients ( 39.4%). Among all the 33 Ph+MPAL patients, 32 (97.0%) had a myeloid / B-lymphoid (M/B) phenotype， and 1 case(3.0%) had a myeloid/ B-lymphoid/ T-lymphoid/ (M/B/T) phenotype. There was no patients displayed myeloid / T-lymphoid (M/T) or B-lymphoid/ T-lymphoid/ (B/T) phenotype. 19 of all cases(57.6%) met the diagnosis criteria of Ph+MPAL based on EGIL 1998 criteria, while the remaining 14 cases can be diagnosed as Ph+ MPAL by WHO 2008 classification,but excluded as Ph+MAPL by EGIL 1998.Karyotype analysis was successfully performed in 31 cases, and out of them 13 (41.9%) had a sole Ph chromosome, 10 (32.3%) had additional chromosome aberration and Ph chromosome was not found in 8 cases (25.8%) .In 31 patients the fusion gene BCR/ABL (P190、P210) was detected,including 17 (54.8%) cases with the p190 BCR/ABL transcript, 8 (25.8%) cases with the p210 BCR/ABL transcript, 4 (12.9%) expressing both transcripts and 2 (6.5%) without any one of these 2 transcripts. 24 out of 33 patients (77.4%) achieved complete remission after induction therapy. The median time achieving CR was 43(26-98)days. The CR rate of patients treated with and without imatinib after the first inducion treatment was 81.3% and 46.7%,respectively (P+0.05). Within the 17 patients treated with imatinib at induction stage，2 of which became BCR/ABLnegative．At consolidation chemotherapy stage, 9 out of 16 patients became BCR/ABL negative, including 3 patients already subjected to HSCT. The median time reached to BCR/ABL negative was 2.87（1.13-9.20）months. CONCLUSION: Ph+ MPAL is more common in male, and inclined to high WBC counts at diagnosis. Myeloid/B lymphoid phenotype is more common, and the prognosis of patients with Ph+MPAL is poor. Imatinib and allogeneic hematopoietic stem cell transplantation may improve survival of patients with Ph+MPAL.

[Clinical Features and Therapeutic Efficacy in Adult Acute Lymphoblastic Leukemia with t (1; 19) (E2A-PBX1)].

OBJECTIVE: To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1). METHODS: The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed. RESULTS: In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188)；RFS (62.5% vs 38.9%) (P=0.166). CONCLUSION: Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.

[Values of Procalcitonin for Predicting Outcome of Infection in Acute Leukemia Patients with Bacterial Bloodstream Infection].

OBJECTIVE: To investigate the effects of serum procalcitonin(PCT) levels for predicting the outcome of bacteria bloodstream infection in acute leukemia patients. METHODS: Clinical data from 236 patients with acute leukemia accompanied by bacterial bloodstream infection during July 2014 to November 2017 were retrospectively analyzed, 236 patients were divided into 5 groups (<0.05 ng/ml, 0.05- <0.5 ng/ml, 0.5- <2.0 ng/ml, 2.0- <10.0 ng/ml and >10.0 ng/ml) according to PCT concentrations. RESULTS: The median age of patients was 40(13-73) years old. The male 123 cases(52.1%) and female 113 cases(47.9%) in 236 patients. The incidence of infection-related dealth in 5 groups was 0%, 1.4%, 13.8%, 25.0% and 33.3%, respectively; the incidence of septic shock and other serious complications in 5 groups was 0%, 2.1%, 13.8%, 25.0%, 33.3% and 6.4%, 7.0%, 24.1%, 41.7%, 50.0%, respectively, showing the concentration dependent manner and statistically significant difference (u=2127, P=0.000; u=2234, P=0.000; u=4102, P=0.000). Further analysis showed that with the increase of PCT concentration, the cumulative incidence of septic shock, infection-related death and other serious complications was gradually increased with statistically significance (HR=2.887, P=0.000, 95%CI:1.960-4.260; HR=3.158, P=0.000, 95%CI: 2.100-4.740; HR=2.158, P=0.000, 95%CI:1.550-3.000) respectively. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death (HR=2.517, P=0.000, 95%CI: 1.520-4.168; HR=2.881, P=0.000, 95%CI: 1.692-4.904)respectively. CONCLUSION: Serum procalcitonin level positively correlates with the incidence of serious bacteria bloodstream infection complications in the patients with acute leukemia. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death, indicating that procalcitonin may be an important prognostic factor for infection outcome in acute leukemia patients with bacteremia.

[Primary Prophylatic Effect of Voriconazole Against Invasive Infection of Pulmonary Aspergillosis during Remission-Induction Chemotherapy for Acute Myeloid Leukemia].

OBJECTIVE: To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML). METHODS: Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups. RESULTS: Among 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group. CONCLUSION: According to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.

Ribosome-lamella complex precursors in acute monocytic leukemia: a study of 6 cases.

The ribosome-lamella complex (RLC) is a cylindrical structure composed of annular lamella associated particles, regarded as ribosomes, around a central core, which is best known in hairy cell leukemia. RLC has been presumed to originate from aggregating rER and ribosomes. Incomplete and maturing RLC structures have been called RLC precursors (pre-RLC). The present paper investigates the various architectural aspects of pre-RLC and the ultrastructural characteristics of the blasts in 6 cases of acute monocytic leukemia (M5) in which these structures occur. Blasts bearing pre-RLC contained irregular nuclei with less heterochromatin and a prominent nucleolus, and many cytoplasmic organelles in an abundant cytoplasm. The findings indicate that pre-RLC might result from an asymmetrical differentiation of organelles in blasts associated with expression of CD117 and CD56 but default of CD14 in M5.

[Clinical and laboratory investigation of hematological malignancy patients carrying 3q21q26 rearrangement].

OBJECTIVE: To investigate the clinical and laboratory characteristics of various hematopoietic malignant patients with t(3;3)(q21;q26) or inv(3) (q21q26). METHODS: Bone marrow samples were collected at presentation, prepared by short-time unstimulated culture and R-binding, and karyotyped by conventional cytogenetical assay (CCA); megalokaryocytes were detected by Streptavidin-AKP (SAP); immunotype of the leukemia cells was tested by flow cytometric anylysis of surface antigens (FACS). RESULTS: All of the 9 hematopoietic malignant patients with t(3;3)(q21;q26) or inv(3) (q21q26) manifested myelodysplasia and poor treatment response. One of them relapsed shortly after allogenic hemotopoietic stem cell transplantation (allo-HSCT). CONCLUSION: Patients with 3q21q26 rearrangement can be found in various hematopoietic malignances and demonstrate an unique entity. These patients show poor treatment response and have extremely poor prognosis.