Objective:This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD + R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods:The clinical data of 26 patients with FLT3-ITD + R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results:A total of 26 patients with FLT3-ITD + R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment ( P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion:The Gilt-based combination therapy is highly effective in treating FLT3-ITD + R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Objective:To explore the effects of tyrosine kinase inhibitors (TKI) on SARS-CoV-2 infection, the related symptoms, and recovery in patients with chronic myeloid leukemia (CML) during the SARS-CoV-2 epidemic.Methods:A retrospective case series study was conducted. The information including general data and SARS-CoV-2 infection of 319 CML patients treated in the First Affiliated Hospital of Soochow University from January 2021 to December 2021 and 547 co-residents during the SARS-CoV-2 epidemic was collected by telephone follow-up from December 2022 to January 2023. The differences in clinical characteristics, infection rate, symptom severity, and recovery time of the SARS-CoV-2 between CML patients and their co-residents, between patients whether getting vaccine for SARS-CoV-2, between patients whether receiving TKI and among CML patients receiving different types of TKI were compared. The multivariate logistic regression analysis was used to analyze the factors influencing the infection rate, symptom severity, and recovery time of SARS-CoV-2.Results:The median age [ M ( Q1, Q3)] of CML patients was 46 years (36 years, 57 years) and all 319 CML patients included 188 (59.0%) males and 131 (41.0%) females; the median age of co-residents of CML patients was 41 years (22 years, 55 years), and all 547 co-residents included 266 (48.6%) males and 281 (51.4%) females. There were statistically significant differences in age, gender, vaccination against SARS-CoV-2 or not, infection rate [83.7% (267/319) vs. 90.5% (495/547)], distribution of symptomatic patients at different severity levels (mild, moderate, severe, and fatal), and recovery time [7 d (5 d, 14 d) vs. 6 d (2 d, 8 d)] between CML patients and co-residents (all P < 0.05). There were statistically significant differences in age, gender, SARS-CoV-2 infection rate, distribution of symptomatic patients at different severity levels and recovery time between CML patients (143 cases) and their co-residents (517 cases) who received the SARS-CoV-2 vaccine (all P < 0.05); there were no statistically significant differences in age, gender, infection rate, distribution of symptomatic patients at different severity levels and recovery time between vaccinated and unvaccinated CML patients with SARS-CoV-2 vaccine (all P > 0.05). There were 297 (93.1%) CML patients who took TKI and 22 patients who did not take TKI. There were no statistically significant differences in age and gender distribution between patients taking TKI and those not taking TKI (all P > 0.05). The infection rate of SARS-CoV-2 in patients taking TKI was lower than that of patients not taking TKI [82.5% (245/297) vs. 100.0% (22/22)], and the difference was statistically significant ( P = 0.032); however, there were no significant differences in distribution of symptomatic patients at different severity levels and recovery time between patients taking TKI and those not taking TKI (all P > 0.05). The results of multivariate logistic regression analysis showed that TKI therapy was an independent protective factor for SARS-CoV-2 infection in CML patients (taking TKI vs. not taking TKI: OR = 1.970, 95% CI: 1.093-3.554, P = 0.024), and was an independent risk factor for severe symptoms of SARS-CoV-2 infection (assigning mild, moderate, severe and fatal levels the value of 0, 1, 2, 3; OR = 0.042, 95% CI: 0.004-0.421, P = 0.007) and recovery time exceeding 7 d (> 7 d vs. ≤ 7 d, OR = 0.649, 95% CI: 0.426-0.988, P = 0.044). The third TKI therapy was given in 1 patient, and there were no statistically significant differences in SARS-CoV-2 infection rate, the symptoms at different severity levels and recovery time > 7 d between CML patients receiving first generation TKI (63 cases) and those receiving second generation TKI (77 cases) who were vaccinated against SARS-CoV-2 (all P > 0.05). Conclusions:TKI can reduce the infection rate of SARS-CoV-2 in CML patients, but will aggravate the severity of symptoms and prolong the recovery time. TKI types may have no impact on whether infected with SARS-CoV-2, the severity level of symptoms after infection and recovery time.

This review described the clinical data of 6 recipients with Legionella pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) through metagenomic next generation sequencing (mNGS) from September 2019 to July 2023 at First Affiliated Hospital of Soochow University. The clinical characteristics and treatment outcomes were retrospectively examined. Legionella infection is a rare opportunistic infection after allo-HSCT. A definite diagnosis is rather difficult and an earlier diagnosis yields a better prognosis. As an early and accurate diagnostic tool for clinical practice, mNGS detection is worthy of wider applications.

Objective:To explore the clinical application value of rapid next-generation sequencing (NGS) strategy based on targeted amplicon sequencing in the diagnosis of myeloid neoplasms.Methods:In this observational study, both rapid NGS and conventional NGS on the bone marrow or peripheral blood samples of 682 patients were prospectively performed from February 2021 to August 2022 in First Affiliated Hospital of Soochow University. The sequencing results were analyzed using the local Ion Reporter software and our lab′s self-built bioinformatics platform, respectively. The timeliness of the two sequencing platforms was compared, and the Kappa consistency test was used to evaluate the consistency between the two sequencing platforms. Patients aged between 18 and 59 years with newly diagnosed acute myeloid leukemia (AML) underwent screening by rapid NGS combining multiplex RT-PCR and in situ fluorescence hybridization technique within 72 hours, from whom high-risk patients according to European LeukemiaNet (ELN) 2017 were screened for individualized induction therapy.Results:In terms of timeliness, the median time from sample receipt to report issuance were 3 (2, 4) days and 13 (11, 15) days under rapid NGS and conventional NGS testing, respectively, with a statistically significant difference ( Z=?22.636, P<0.001). Among 682 specimens with a total of 1 507 variants, rapid NGS detected a total of 1 499 variants, with a detection rate of 99.5% and 674 cases were accurate, with an accuracy rate of 98.8%; the conventional NGS detected 1 506 variants, with a detection rate of 99.9% and 681 cases were accurate, with an accuracy rate of 99.9%. In 682 specimens, there were 181 negative and 501 positive, in which 8 cases were missed under rapid NGS, and 1 case was missed under conventional NGS. The kappa value was 0.967 by Kappa consistency test, and P<0.001, suggesting good consistency and consistency between the two NGS platforms. From February 2021 to July 2022, 286 patients who were rapidly diagnosed of AML contained 78 patients screened as the ELN 2017 adverse-risk category, including 42 patients enrolled, with age 39 (33, 52) years old. After one cycle of venetoclax combined with decitabine induction therapy, 78.6%(38/42) of the patients achieved composite complete remission. Among the rest 104 additional myeloid neoplasms, rapid NGS detected mutations in 80 patients, with a detection rate of 76.9%, among which 89.0%(215/242) of the variants could serve as the basis for the diagnostic classification, prognostic evaluation, and target therapy of myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Conclusion:The rapid NGS based on targeted amplicon sequencing is in good consistency with conventional NGS, and shorters the diagnostic time, whose sensitivity and detection range meets the need for diagnostic classification, prognostic stratification, and target therapy of myeloid neoplasms.

Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma (BCL) due to their reliable efficacy, manageable safety, high accessibility, and convenience for use. Still, no guidelines or consensus focusing on oral drug therapies for BCL is available. To provide a reference of oral agent-based treatment for mature BCL, a panel of experts from the Lymphocyte Disease Group, Chinese Society of Hematology, Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China, combined with the latest authoritative guidelines in the world and current research reports. This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients. With the deepening of research and the development of standardized clinical applications, oral medications will bring better treatment to BCL patients, enabling more patients to benefit from them.
Humans ; Consensus ; Lymphoma, B-Cell/drug therapy* ; China

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Objective:To summarize the clinical characteristics of an early death in patients with de novo acute promyelocytic leukemia (APL) , analyze the risk factors and direct causes of early death, and perform survival analysis.Methods:The clinical data of 368 patients with de novo APL in three centers (First Affiliated Hospital of Soochow University, Soochow Guangci Hospital, and Soochow Hopes Hospital of Hematology) during January 2011-December 2017 were retrospectively analyzed. The clinical characteristics of patients who suffered hemorrhagic early death and non-hemorrhagic early death were compared. The risk factors for early death, survival, and prognosis of patients with APL were analyzed.Results:Among the 368 de novo APL patients, 31 died early with an early mortality rate of 8.4%. The median time from diagnosis to death was 7 (0-29) d. On comparison of the clinical characteristics of patients with early death and non-early death and subsequent multivariate analysis using a logistic regression model, it was observed that age ≥50 years and WBC ≥10×10 9/L were independent risk factors for early death ( P<0.01) . A total of 27 (87.1%) of the 31 early deaths was directly attributed to hemorrhage as the immediate cause of early death. Hemorrhage was the only cause of death in patients <50 years old and the major cause of death in patients ≥50 years old. A comparison of the clinical characteristics of patients with hemorrhagic early death and patients with non-hemorrhagic early death suggested that the median age and indirect bilirubin concentration of patients with hemorrhagic early death were lower than those with non-hemorrhagic early death ( P<0.05) . The median follow-up time for all patients was 41.0 (0.3-101.4) months. The 2-year overall survival (OS) rate was (93.5±1.3) %, and the 5-year OS rate was (91.0±1.5) %. The 2-year disease-free survival (DFS) rate was (98.8±0.6) %, and the 5-year DFS rate was (97.1±0.9) %. The 2-year OS rate of patients ≥50 years old and patients <50 years old was 79.3% vs 94.2%, P=0.000; the 2-year DFS rate was 92.3% vs 98.1%, P=0.023. The respective 2-year OS rates of high-risk and non-high-risk patients were 77.3% and 96.7% ( P=0.000) and the respective 2-year DFS rates were 94.0% and 98.4% ( P=0.139) . Conclusion:Age and WBC are independent prognostic factors for early death. We observed a difference in early mortality between high-risk and low-risk APL, but no difference in DFS rate.

Objective To investigate the monitoring significance of WT1 gene level in the prognosis of acute myeloid leukemia (AML) patients with normal karyotype after hematopoietic stem cell transplantation (HSCT). Methods The clinical data of 115 AML patients with normal karyotype who were treated with HSCT from July 2009 to March 2017 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. The dynamic detection of bone marrow WT1 gene was carried out by using reverse transcription_polymerase chain reaction (RT_PCR). According to the relative expression level median of WT1 gene before transplantation, the whole patients were divided into the two groups (

Objective: To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) . Methods: The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups. Results: There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34⁺ cells infused were 10.74 (4.80-22.86) ×10⁸/kg and 12.19 (5.14-17.25) ×10⁸/kg (P=0.866) , 3.57 (0.68-7.80) ×10⁶/kg and 4.00 (3.02-8.42) ×10⁶/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups. Conclusion The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.