Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders.

This study aimed to assess the feasibility of diagnosing secondary pulmonary fungal infections (PFIs) in patients with hematological malignancies (HM) using computerized tomography (CT) imaging and a support vector machine (SVM) algorithm. A total of 100 patients with HM complicated by secondary PFI underwent CT scans, and they were included in the training group. Concurrently, 80 patients with the same underlying disease who were treated at our institution were included in the test group. The types of pathogens among different PFI patients and the CT imaging features were compared. Radiomic features were extracted from the CT imaging data of patients, and a diagnostic SVM model was constructed by integrating these features with clinical characteristics. Aspergillus was the most common pathogen responsible for PFIs, followed by Candida, Pneumocystis jirovecii, Mucor, and Cryptococcus, in descending order of occurrence. Patients typically exhibited bilateral diffuse lung lesions. Within the SVM algorithm model, six radiomic features, namely the square root of the inverse covariance of the gray-level co-occurrence matrix (square root IV), the square root of the inverse covariance of the gray-level co-occurrence matrix, and small dependency low gray-level emphasis, significantly influenced the diagnosis of secondary PFIs in patients with HM. The area under the curve values for the training and test sets were 0.902 and 0.891, respectively. Therefore, CT images based on the SVM algorithm demonstrated robust predictive capability in diagnosing secondary PFIs in conjunction with HM.

The novel HLA-C*12:368 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*12:368 differs from HLA-C*12:03:01:01 by one nucleotide in exon 4.

[Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia].

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION: TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

Fludarabine and antithymocyte globulin-based conditioning regimen combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia and myelodysplastic syndrome.

INTRODUCTION: Relapse and graft-versus-host disease (GVHD) are the important complications influencing mortality for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in haploidentical HSCT (haplo-HSCT). OBJECTIVE: We developed a modified intensified conditioning regimen including fludarabine (Flu) and investigated the effect of ATG-PTCy combination on transplant outcomes in high-risk AML and MDS compared with those patients who received only ATG as GVHD prophylaxis. METHODS: A total of 80 patients with high-risk AML and MDS were divided into two groups and assigned to one-to-one pairing. RESULTS: The modified ATG-PTCy group had more infused mononuclear cells, CD34-positive cells and CD3-positive cells than those in the ATG group (P < 0.05). The amount of platelet transfusion was higher in the ATG group than the modified ATG-PTCy group [2 (range, 1-6) U vs 2 (range, 1-5) U, P = 0.005]. The median of platelet recovery was better in the modified ATG-PTCy group than in the ATG group (12 days vs 13 days,P = 0.041). The infection rates of bacteria, fungi and virus at 100 days after transplantation were similar in both groups. Compared with the ATG group, individuals who received the modified ATG-PTCy regimen had higher 2-year GVHD- and relapse-free survival(GRFS) [60.0% (95%CI, 44.9-75.1%) vs 34.8% (95%CI, 19.9-49.7%), P = 0.028]; lower 180-day incidence of II-IV acute GVHD (aGVHD) [15.0% (95%CI, 4.0-26.0%) vs 39.8% (95%CI, 23.9-55.7%), P = 0.029]; lower 1-year incidence of moderate to severe chronic GVHD (cGVHD) [2.9% (95%CI, 2.0-3.8%) vs 19.6% (95%CI, 5.3-33.9%), P = 0.039]; and without an increase in the 2-year cumulative incidence of relapse (CIR) [19.5% (95%CI, 6.6-32.4%) vs 30.4% (95%CI, 15.3-45.5%), P = 0.291]. CONCLUSIONS: High-dose stem cells can promote blood cell implantation. The modified ATG-PTCy combination was associated with decreased risk of aGVHD and cGVHD, no increased risk of recurrence, and improved GRFS. It represents an effective strategy for high risk AML and MDS.

Lenalidomide, bortezomib and dexamethasone followed by tandem- autologous stem cell transplantation is an effective treatment modality for multi-hit multiple myeloma.

In order to investigate the efficacy of lenalidomide, bortezomib and dexamethasone (VRD) induction chemotherapy regimen combined with tandem autologous stem cell transplantation (ASCT) in treating multi-hit multiple myeloma (MM), we analyzed 252 cases of newly diagnosed MM treated with the bortezomib-containing induction chemotherapy from June 2016 to June 2019. According to the fluorescence in situ hybridization (FISH) results on diagnosis, the patients were divided into multi-hit MM group (47 cases), single-hit MM group (81 cases), and standard-risk group (124 cases). Our analysis showed that R-ISS stageⅢ in transplantation group and R-ISS stageⅢ, multi-hit and VGPR or above was not achieved at the fourth cycle of chemotherapy in non-transplantation group were independent factors for poor prognosis by univariate and multivariate analyses. Moreover, the overall response rate (ORR) of VRD induction chemotherapy group was significantly higher than that of the non-VRD group in the single-hit and multi-hit groups (P = 0.021, P = 0.032); In terms of ASCT, tandem-ASCT can significantly improve the 2-year PFS (77.8 ± 3.9 %) and OS (83.3 ± 5.6 %) of multi-hit MM (P = 0.024, P = 0.037), while single-ASCT only has a limited effect on PFS (61.5 ± 3.0 %) and OS (71.9 ± 4.5 %) (P = 0.115, P = 0.155).

Successful haploidentical transplantation using plasma exchange and post-transplantation cyclophosphamide for severe aplastic anemia patients with anti-human leukocyte antigen donor-specific antibodies.

Haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) has emerged as a novel strategy to treat patients suffering from severe aplastic anemia (SAA) who lack matched donors due to the availability and easy access to sources of donors. Anti-human leukocyte antigen donor-specific antibodies (DSAs) have been found to influence the outcome of Haplo-HSCT. Between March 2016 and March 2020, 7 SAA patients with DSAs underwent Haplo-HSCT in our center. We employed a modified protocol of post-transplantation cyclophosphamide and plasma exchange aiming to decrease the levels of DSAs. All 7 patients successfully achieved hematopoietic reconstruction. The median follow-up is 31 (range, 8 to 45) months. They survived and were transfusion-independent in the absence of clonality. No occurrence of primary or secondary graft failure has been noted among any of the patients. There was no severe acute and chronic GVHD occurred. This protocol is effective for Haplo-HSCT in SAA patients with DSAs, which provides an option for the SAA patients without other alternative donor.

High expression of COMMD7 is an adverse prognostic factor in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a frequent malignancy in adults worldwide; identifying preferable biomarkers has become one of the current challenges. Given that COMMD7 has been reported associated with tumor progression in various human solid cancers but rarely reported in AML, herein, RNA sequencing data from TCGA and GTEx were obtained for analysis of COMMD7 expression and differentially expressed gene (DEG). Furthermore, functional enrichment analysis of COMMD7-related DEGs was performed by GO/KEGG, GSEA, immune cell infiltration analysis, and protein-protein interaction (PPI) network. In addition, the clinical significance of COMMD7 in AML was figured out by Kaplan-Meier Cox regression and prognostic nomogram model. R package was used to analyze incorporated studies. As a result, COMMD7 was highly expressed in various malignancies, including AML, compared with normal samples. Moreover, high expression of COMMD7 was associated with poor prognosis in 151 AML samples, as well as subgroups with age >60, NPM1 mutation-positive, FLT3 mutation-negative, and DNMT3A mutation-negative, et al. (P < 0.05). High COMMD7 was an independent prognostic factor in Cox regression analysis; Age and cytogenetics risk were included in the nomogram prognostic model. Furthermore, a total of 529 DEGs were identified between the high- and the low- expression group, of which 92 genes were up-regulated and 437 genes were down-regulated. Collectively, high expression of COMMD7 is a potential biomarker for adverse outcomes in AML. The DEGs and pathways recognized in the study provide a preliminary grasp of the underlying molecular mechanisms of AML carcinogenesis and progression.

Ruxolitinib combined with etanercept induce a rapid response to corticosteroid-refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi-center prospective study.

About half of patients with severe acute graft vs host disease (aGVHD) show resistance to treatment with first-line steroids. We enrolled 64 patients with grades III-IV SR-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT), to assess the efficacy and safety of the combination therapy of ruxolitinib and etanercept. The overall response rate was 87.5% (95% CI, 79.7%-95.3%) at day 28 of the combination treatment, from which 73.4% reached complete response (CR). A marked reduction ≥75% in daily corticosteroid dosing was documented in 75.4% of patients at day 28. Delayed time from aGVHD to ruxolitinib (OR = 4.88, 95% CI, 0.98-23.56), stages 3-4 liver aGVHD (OR = 8.57, 95% CI, 0.96-46.59) and gut Enterobacteriaceae colonization (OR = 12.39, 95% CI, 1.71-59.77) were related to incomplete response. Grades 3/4 anemia, leukopenia, or thrombocytopenia and CMV-reactivation were found in 29.7%, 26.6%, 39.1%, and 50.0% of patients, respectively. So, 25 (39.1%) experienced complications of severe infection ≥3 grade, in which pulmonary infections were most frequent (15/64, 23.4%). The 2-year overall survival (OS) after the combination therapy was 61.2%. The 2-year incidence of non-relapse mortality and relapse of the underlying malignancy was 26.7% and 15.7%, respectively. Combined treatment with ruxolitinib and etanercept was very effective and relatively safe for severe aGVHD patients, while the various infection complications deserve more attention. This study was registered at the Chinese Clinical Trial Registry (ChiCTR1900024408).

Comprehensive characterization of driver genes in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy and is one of the most frequent non-Hodgkin lymphomas. Large-scale genomic studies have defined genetic drivers of DLBCL and their association with functional and clinical outcomes. However, the lymphomagenesis of DLBCL is yet to be fully understood. In the present study, four computational tools OncodriveFM, OncodriveCLUST, integrated Cancer Genome Score and Driver Genes and Pathways were used to detect driver genes and driver pathways involved in DLBCL. The aforementioned tools were also used to perform an integrative investigation of driver genes, including co-expression network, protein-protein interaction, copy number variation and survival analyses. The present study identified 208 driver genes and 31 driver pathways in DLBCL. IGLL5, MLL2, BTG2, B2M, PIM1, CARD11 were the top five frequently mutated genes in DLBCL. NOTCH3, LAMC1, COL4A1, PDGFRB and KDR were the 5 hub genes in the blue module that were associated with patient age. TP53, MYC, EGFR, PTEN, IL6, STAT3, MAPK8, TNF and CDH1 were at the core of the protein-protein interaction network. PRDM1, CDKN2A, CDKN2B, TNFAIP3, RSPO3 were the top five frequently deleted driver genes in DLBCL, while ACTB, BTG2, PLET1, CARD11, DIXDC1 were the top five frequently amplified driver genes in DLBCL. High EIF3B, MLH1, PPP1CA and RECQL4 expression was associated with decreased overall survival rate of patients with DLBCL. High XPO1 and LYN expression were associated with increased overall survival rate of patients with DLBCL. The present study improves the understanding of the biological processes and pathways involved in lymphomagenesis. The driver genes, EIF3B, MLH1, PPP1CA, RECQL4, XPO1 and LYN, pave the way for developing prognostic biomarkers and new therapeutic strategies for DLBCL.

[Cytomegalovirus infection monitoring in patients with long-term survival after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To analyze the cytomegalovirus (CMV) infection status and the risk factors in patients with long-term survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: 159 long-term survivors receive allo-HSCT from January 2008 through December 2011 in the Bone Marrow Transplantation Center of Zhejiang University were included, CMV-pp65 antigen in peripheral blood leukocytes was detected by immunofluorescence assay at regular intervals, to retrospectively analyzed the clinical data. Ganciclovir or foscarnet was used for prevent and curative therapy. RESULTS: A total of 159 patients with long-term survival at 18-66 months after allo-HSCT were investigated. And 8 047 specimens were detected, including 2 553 positive samples. All patients were at least one time positive for CMV-pp65 antigen after allo-HSCT. The CMV antigen positive rate increased gradually from 100 days after transplantation to within 100 days until 1 year while the positive rate decreased, after 1 year. The difference was statistically significant (all P < 0.01). The CMV antigen positive rate in patients after non-myeloablative allo-HSCT (NST) and those after myeloablative allo-HSCT were 167/608(27.5%) and 2 386/7 439 (32.1%) respectively. The difference was statistically significant (P = 0.019). No statistically significant difference existed between those with acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) (both P > 0.05). The CMV antigen positive rate in patients with I-IIgrade aGVHD and those with III-IV grade aGVHD were 1 017/3 284(31.0%) and 227/641(35.4%) respectively. And it had statistically significant difference (P = 0.027). The CMV antigen positive rate in patients none-used of ATG and those used of ATG were 1 255/3 755 (33.4%) and 1 298/4 292 (30.2%) respectively. And it had statistically significant difference (P = 0.002). By Logistic multivariate analysis, the none-use of ATG and III-IV grade aGVHD were the risk factors for CMV antigen positive after allo-HSCT (OR = 1.174, 95%CI:1.068-1.290, P = 0.001;OR = 1.174, 95%CI:0.681-0.958, P = 0.014). CONCLUSIONS: Regular monitoring of CMV-pp65 antigen after allo-HSCT is quite necessary for prevent and treat CMV infection in a timely manner. The CMV infection in long-term survival patients may be related to the selection of conditioning regimen, it has no obvious correlation with the incidence of GVHD, but it is associated with the severity of aGVHD.

[Clinical investigation of homoharringtonine in combination with all-transretinoic acid and arsenic trioxide for acute promyelocytic leukemia].

OBJECTIVE: To study the clinical outcome, adverse effect and treatment cost of homoharringtonine (HHT) in combination with all-trans retinoic acid (ATRA) and arsenic trioxide (AS2O3) for newly diagnosed with patients acute promyelocytic leukemia (APL). METHODS: Clinical data of treatment of newly diagnosed patients with APL in experimental group (HHT + ATRA + AS2O3, n = 14) and control group \[Idarubicin (IDA) + ATRA + AS2O3, n = 21\] were analyzed retrospectively. The therapeutic effects, side effects and costs during induction therapy were compared between the two groups. RESULTS: (1) The complete remission (CR) rate were 92.9% (13/14) and 95.2% (20/21) in experimental group and control group, respectively. The time to achieve CR were (28.1 ± 3.8) and (31.7 ± 4.2) days, respectively (P > 0.05). The negative rate of PML-RARα fusion gene at the time of CR were 76.9% (10/13) and 75.0% (15/20), respectively, and that in CR patient at the end of the first cycle treatment were 100.0% (13/13) and 95.0% (19/20), respectively (P > 0.05). (2) 5-year overall survival (OS) rate were (92.6 ± 0.6)% and (89.9 ± 0.5)%, respectively (P > 0.05), 5-year disease free survival (DFS) rate were 100.0% and (86.8 ± 0.6)%, respectively (P > 0.05). (3) During induction therapy, the incidence of infection in experimental and control group were 23.1% (3/13), 60.0% (12/20), respectively (P < 0.05). The amount of platelet transfusion were (54.7 ± 29.6) and (76.5 ± 25.6) units, respectively (P > 0.05), and that of fresh frozen plasma were (1157.1 ± 238.4) and (1423.5 ± 324.6) ml, respectively (P > 0.05). The total medical costs (excluding HHT and IDA) in experimental and control group were (36074.9 ± 1245.6) and (50564.5 ± 3658.4)CNY, respectively (P < 0.05). CONCLUSION: HHT in combination with ATRA and AS2O3 regimen for newly diagnosed APL has a better efficacy, a higher long-term survival rate, and a lower costs, which is one of the reasonable choice.

Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia.

BACKGROUND: Both all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL). METHODS: In this study, 73 newly diagnosed APL subjects were treated with an ATRA and As(2)O(3) combination treatment in remission induction and post remission therapy. Tumor burden was examined with PCR of the PML-RAR fusion transcripts, and side effects were evaluated by means of clinical examination. RESULTS: The results showed that ATRA/As(2)O(3) combination therapy yielded a CR rate of 94.5% (69/73) with a shorter time to enter CR (median: 27 days; range: 21-43 days). Four cases failed to enter CR; three of these died of cerebral hemorrhage and disseminated intravascular coagulation (DIC) within 72 hours of starting induction therapy, one older patient died of severe pulmonary infection. The early death rate was 5.5% (4/73). All 69 cases that obtained CR remained in good clinical remission after a follow-up of 35-74 months (median: 52 months).The drug toxicity profile with the use of As(2)O(3) showed mainly hepatotoxicity. Liver dysfunction was slight in most cases. There were no severe side effects in long term follow-up. CONCLUSION: We conclude that APL patients may benefit from the use of the combination of ATRA and As(2)O(3) in either remission induction or consolidation/maintenance.