ObjectiveTo investigate the expression of scaffold protein PDLIM5 in multiple sclerosis （MS） patients and the mouse microglial cell line BV2， and to explore its effects on the phagocytosis of microglial cells. MethodsPeripheral blood samples were collected from 24 MS patients and 6 healthy volunteers as controls. The expression levels of PDLIM5 were detected by real-time quantitative PCR. A neuroinflammation cell model was established by treating the mouse microglial cell line BV2 with lipopolysaccharide （LPS， 1 µg/mL）. The expression levels of PDLIM5 were measured by Western Blot. The effect of PDLIM5 expression on phagocytosis was analyzed by transfecting BV2 cells with PDLIM5 shRNA plasmids or PDLIM5 overexpression plasmids. ResultsReal-time quantitative PCR results showed that compared with the healthy control group， the expression level of PDLIM5 from the MS patients was significantly increased in monocytes ［2.78 （0.70-6.86） vs. 0.54 （0.39-1.51）， P=0.036］ and lymphocytes ［1.62 （0.90-2.26） vs. 0.11 （0.05-0.21）， P<0.001］. Western Blot results indicated that PDLIM5 expression was significantly upregulated in BV2 cells following LPS stimulation （P<0.05）. Plasmid transfection experiments demonstrated that knockdown of PDLIM5 inhibited the phagocytic capacity of BV2 cells as measured by trypan blue uptake （P<0.05）， while overexpression of PDLIM5 enhanced the phagocytic ability of BV2 cells （P<0.001）. ConclusionUnder neuroinflammatory conditions， PDLIM5 expression is elevated， and this upregulation promotes the phagocytosis of microglial cell.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

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.

Objective: To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome. Methods: The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen. Results: There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×10⁸/kg in the PNH group and 10.81 (3.96-33.40) ×10⁸/kg in the PNH-AA group (P=0.668) . The median doses of CD34⁺ cells infused were 5.00 (3.14-8.42) ×10⁶/kg and 3.57 (1.97-6.17) ×10⁶/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) . Conclusions allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.

Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph⁺ acute lymphoblastic leukemia (Ph⁺ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph ⁺ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared. Results: Of 76 Ph⁺ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ²=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ²=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ²=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ²=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS. Conclusions There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph⁺ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph⁺ ALL patients.

Objective To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome ( MDS) and erythroid hyperplasia.Methods MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study.The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia ( MDS-E ).The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University.Clinical characteristics , karyotype , and the prognostic significance of erythroid hyperplasia were evaluated.Results A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities.The most frequently involved chromosomes were chromosome 8 (39.5%of all abnormal karyotypes ), chromosome 7 (22.9%), followed by chromosome 5 ( 18.8%) , chromosome 1 ( 16.7%) and chromosome 20 ( 16.7%) .Hemoglobin ( Hb) level affected the prognosis by survival analysis.The overall survival ( OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L ( P<0.001).Allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved the OS compared with best supportive care (P<0.001) and chemotherapy (P<0.001).The extent of erythroid hyperplasia in bone marrow did not impact on prognosis ( P=0.187 ).Conclusions Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia , more common erythroid dyshematopoiesis , more frequent 8 and 1 chromosome abnormalities .The degree of erythroid hyperplasia is not correlated with prognosis.Allogeneic hematopoietic stem cell transplantation improves the prognosis.