[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies].

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

[Clinical study of mesenchymal stem cells from third-party donors in the treatment of refractory late onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplanation].

Objective: To examine the efficacy and safety of third-party bone marrow-derived mesenchymal stem cells (MSCs) in the treatment of refractory delayed hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Twenty patients with refractory LOHC received conventional therapy combined with MSCs obtained from third-party donors' bone marrow (BM) . MSCs were given intravenously at a dose of 1 × 10(6) cells/kg once weekly until either the symptoms improved or no changes in LOHC were seen after continuous infusion four times. BK viruria (BKV) -DNA, JC viruria (JCV) -DNA, and CMV-DNA were detected by real-time quantitative PCR before and 8 weeks after the MSCs infusion. Results: ① Of the 20 patients with refractory LOHC, 15 were males, and 5 were females, and the median age was 35 (15-56) years. There were 5 cases of acute lymphoblastic leukemia (ALL) , 9 cases of acute myeloid leukemia (AML) , 5 cases of myelodysplastic syndrome (MDS) , and 1 case of maternal plasma cell like dendritic cell tumor (BPDCN) . There were 4 cases of HLA identical transplantation and 16 cases of HLA incomplete transplantation. ②The median number of MSC infusions for each patient was 3 (range: 2-8) . Seventeen patients achieved complete response, and one had a partial response after treatment. The overall response rate was 90%. Over a median follow-up period of 397.5 days (range 39-937 days) post-transplantations, 13 patients survived, and 7 died. The causes of death included aGVHD (1 case) , infections (5 cases) , and TMA (1 case) . ③The copy numbers of BKV-DNA and CMV-DNA in urine in the 8th week after MSCs infusion were significantly lower than those observed before treatment (11342.1×10(8) copies/L vs 5.2×10(8) copies/L, P=0.016; 3170.0×10(4) copies/L vs 0.2×10(4) copies/L, P=0.006, respectively) , while JCV-DNA did not significantly differ when compared to before treatment (P=0.106) . ④ No adverse reactions related to MSC infusion occurred in any of the 20 patients. Conclusion: Third-party bone marrow-derived MSC has significant efficacy and good safety in the treatment of refractory LOHC after allogeneic HSCT.

[Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia].

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

[Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma].

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

[Diagnosis of adult Philadelphia chromosome-like acute lymphoblastic leukemia by fluorescence in situ hybridization].

Objective: To establish a screening system of adult Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) by fluorescence in situ hybridization (FISH) . Method: Based on the genetic characteristics of Ph-like ALL, FISH probes were designed for ABL1, ABL2, JAK2, EPOR, CRLF2, CSF1R, PDGFRB, and P2RY8 gene breakpoints, which were used to screen Ph-like ALL in B-ALL patients without BCR-ABL1, ETV6-RUNX1, MLL, and E2A gene arrangement. Furthermore, it was analyzed in combination with flow immunophenotype, next-generation sequencing for targeted gene mutations, and RNA sequencing (RNA-seq) . Results: A total of 189 adult B-ALL patients diagnosed in Nanfang Hospital from January 2016 to April 2019 were enrolled in this study. Using FISH and/or PCR, BCR-ABL1, ETV6-RUNX1, MLL, or E2A arrangement was detected in 83 of them, and Ph-like ALL was detected by FISH in the other 106, resulting in the presence of typical gene arrangements of Ph-like ALL in 12 patients (11.3% , 12/106) . Validated by RNA-seq, the sensitivity and specificity of FISH for Ph-like ALL were 71.4% and 95.8% , respectively. After further analysis with immunophenotype, targeted gene mutations, and RNA-seq, 14 (13.2% , 14/106) were diagnosed with Ph-like ALL. Conclusion: This data shows high specificity of FISH for identification of Ph-like ALL and combining immunophenotype and sequencing technology can improve the diagnostic system.

[Sorafenib combined with chemotherapy and donor lymphocyte infusion as salvage therapy in patients with FLT3-positive acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation].

To explore the efficacy of sorafenib combined with chemotherapy and donor lymphocyte infusion (DLI) in patients with FLT3-positive acute myeloid leukemia (AML) relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of the 14 patients relapsed after allo-HSCT, 9 achieved complete remission after salvage therapy of sorafenib combined with chemotherapy and DLI, 6 with complete molecular remission, 2 with partial remission, and 3 with no response. With a median follow up of 220 (range, 30-1 782) days after post-transplantation relapse, 7 patients were still alive and 7 died. Salvage therapy of sorafenib combined with chemotherapy and DLI shows a decent therapeutic effect for FLT3-positive AML relapsed after allo-HSCT.

Donor and recipient age, gender and ABO incompatibility regardless of donor source: validated criteria for donor selection for haematopoietic transplants.

Prior data indicate similar outcomes after transplants from human leukocyte antigen (HLA)-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors. We used our prospective data set to answer a clinically important question: who is the best donor for a person with acute leukaemia transplanted in first complete remission. Patients were randomly divided into training (n=611) and validation (n=588) sets. A total of 1199 consecutive subjects received a transplant from an HLA-haplotype-matched relative using granulocyte colony-stimulating factor and anti-thymocyte globulin (n=685) or an HLA-identical sibling (n=514); 3-year leukaemia-free survivals (LFSs) were 75 and 74% (P=0.95), respectively. The multivariate model identified three major risk factors for transplant-related mortality (TRM): older donor/recipient age, female-to-male transplants and donor-recipient ABO major-mismatch transplants. A risk score was developed based on these three features. TRMs were 8%, 15% and 31% for subjects with scores of 0-1, 2 and 3, respectively, (P<0.001). Three-year LFSs were 78%, 74% and 58%, respectively, (P=0.003). The risk score was validated in an independent cohort. In conclusion, our data confirm donor source is not significantly correlated with transplant outcomes. Selection of the best donor needs to consider donor-recipient age, matching for gender and ABO incompatibility among persons with acute leukaemia receiving related transplants under our transplant modality.

[Value of two left atrium and pulmonary vein stereoscopic imaging reconstruction methods on guiding radiofrequency ablation for atrial fibrillation].

Objective: To compare the value of two 3D imaging reconstruction methods for left atria and pulmonary vein on guiding the catheter ablation for atrial fibrillation (AF). Methods: From January 2014 to January 2017, a total of 100 drug refractory paroxysmal AF patients were divided into left atria direct angiography group (n=50), and indirect angiography group (n=50). 3D CARTO system was applied for mapping and guiding the ablation procedure. Patients assigned to direct angiography group were treated as follows: intraoperative puncture of atrial septum, inject contrast agent directly into the left atrium, conduct left atrial and pulmonary venous rotation angiography, reconstruct three-dimensional image, integrate the image into real-time X-ray system to facilitate circumferential pulmonary vein isolation. Patients assigned into the indirect angiography group were treated as follows: inject contrast agent through the right ventricle, conduct delayed rotation angiography of the left atria and pulmonary vein to guide circumferential pulmonary vein fixation and ablation. The left atrial and pulmonary venous image acquisition, the operation and X-ray exposure time, the success rate and the incidence of complication of the two groups were compared. The patients were followed up for 3-6 months. Results: General clinical characteristics of the two groups were similar(all P>0.05). Ablation was successful in all 100 patients. The operation time[(112.0±21.4)min vs. (134.0±24.3)min]and X-ray exposure time((10.7±4.7)min vs. (15.8±5.2)min)were significantly lower in direct angiography group than in indirect angiography group (both P<0.01). There was no significant difference between the two groups in the immediate (86%(43/50) vs. 82%(41/50), P=0.59) and short-term (76%(38/50) vs. 72%(36/50), P=0.65) success rate and complication rate (1 aneurysm in the direct angiography group, 1 pericardial tamponade in the indirect angiography group). In-hospital mortality was zero percent. Conclusion: It is safe and effective method to guide the radiofrequency catheter ablation of paroxysmal atrial fibrillation by reconstruction 3D image of left atrium and pulmonary vein. Compared with indirect angiography group, direct angiography group can improve the imaging quality of left atrium and pulmonary vein, decrease the X-ray exposure time of the ablation procedure.

A review of hematopoietic cell transplantation in China: data and trends during 2008-2016.

Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and 5253 autologous (24%)) were reported by 76 centers in China between 1 January 2008 and 30 June 2016. HCT trends included continued growth in transplant activity, a continued rapid increase in haploidentical donors (HID), and slower growth for unrelated donors, matched-related donors (MRD) and cord blood transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7% (1157/2237) in the first half of 2016. During this time frame, the proportion of MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0% (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have been increasing continuously for all indications except chronic myelogenous leukemia. Severe aplastic anemia is a common HCT indication among non-malignant diseases in China. The number of cases of allogeneic HCT for this disorder has increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334 (14.9%) in the first half year in 2016. This survey clearly shows recent trends for HCTs in China.