Background The prognosis of multiple myeloma (MM),has been improved by the emergence of novel agents such as immunomodulatory drugs and proteasome inhibitors, which have become the cornerstone of MM treatment. The persistent nature of MM and the relatively long survival of MM patients have raised concerns over the safety and efficacy of continuous long-term therapy. The all-oral regimen consisting of ixazomib(I), lenalidomide(R), and dexamethasone(D)(IRD) has been widely used in the treatment of myeloma, which greatly improves patient adherence and facilitates medication application; however, there is a lack of real-world clinical data as to whether IRD maintenance therapy improves patient's outcome. This study reports long-term real-world data from 59 myeloma patients who were switched to IRD maintenance therapy. Methods The median age of 59 patients with multiple myeloma was 66 years with 35 (59%)patients≥65 years. International Myeloma Working Group (IMWG) risk stratification was highrisk in 45 (76%)patients, and Intermediate risk in 14 (24%)patients. The amplification of 1q21 (1q21 amp) was found in 18 (31%) patients. Patients included in the observation group had received at least two courses of different induction therapies with treatment outcomes of stable disease(SD) or better were converted to an IRD all-oral regimen with weekly ixazomib 4mg or 3mg for 3 weeks, lenalidomide 25mg qd for 21d consecutively, and weekly dexamethasone 20mg orally for 3 weeks. The patients were evaluated for the remission rate (patients reached partial response[PR], very good partial response[VGPR], and complete response[CR]), duration of remission, and adverse events (AEs) after IRD treatment. The cutoff time was July 1, 2024. Results Fifty-nine patients were treated with the IRD regimen for a median of 25 months(12-55), with a maximum duration of 55 months. Twenty-two (37.3%) patients received oral therapy at the cutoff for follow-up. After six courses of treatment, 79.7% of patients reached (15 vs 47)VGPR, with 6 of 9 (66.7%)SD patients achieving VGPR or higher after switching to oral therapy and 15 of 24 (62.5%)PR patients achieving VGPR. Subgroup analyses showed that patients with 1q21 amp, either in the IMWG high-risk or Intermediate-risk group, could benefit from a treatment switch, with the VGPR rate increasing from 50% to 78% after switching to I-base oral regimens and increasing to 73% and 100% in high-risk and Intermediate-risk patients, respectively. In patients ≥65 years of age after switching to an oral I-base regimen, VGPR rates increased from 28.5% to 80% with a mean DOT of 8.2 months when evaluated over 6-12 courses. The ixazomib-based oral maintenance regimen was generally well-tolerated by patients. The major adverse effect of the bortezomib-based induction regimen was peripheral neuropathy (PN), which reached grade 3 or more in 7 patients. No TAEs above grade 3 occurred after switching treatments. The major adverse effect of the ixazomib-based oral maintenance regimen was diarrhea, which mostly disappeared after the intervention, with only one patient seeing a worsening of PN that led to termination of treatment. Discuss Clinical studies have shown that continuous maintenance therapy after induction therapy for MM improves treatment outcomes and prognosis, especially to patients at high cytogenetic risk. Real-world data from our center showed that maintenance therapy with IRD improved the depth of remission and reduced the risk of disease progression in high-risk patients. Although the induction therapy regimen before the study was different, 80% of the patients improved the depth of remission after long-term sustained IRD maintenance therapy, which provides an option for follow-up treatment of high-risk myeloma patients. Despite the limited cases in this study, we still noticed that the IRD regimen achieved significant therapeutic responses in elderly patients with comorbidities, regardless of age, gender, ISS stage, renal insufficiency, comorbidities status, first-line therapeutic exposures, or 1q21+status, which is similar to literature. The main adverse effect of the maintenance regimen was diarrhea. The longest maintenance treatment duration reached 55 months in this study, with no significant hematologic toxicity, PN exacerbation, or herpes zoster infection during treatment. Patient compliance and quality of life were improved.

OBJECTIVE:Ruxolitinib was recently approved to treat corticosteroid-resistant acute graft-versus-host disease (GvHD). However, it is unknown as to whether starting ruxolitinib at a lower versus higher acute GvHD grade or earlier versus later affected outcomes. This study identified the impact of starting acute GvHD grade and start time after declaring corticosteroid resistance and the effect on complete and overall response rates to ruxolitinib therapy.METHODS:Retrospective, observational multi-center study. We divided cohorts into starting ruxolitinib ≤ 7 days (N = 45) versus at > 7 days after declaring corticosteroid resistance (N = 24).RESULTS:In ≤ 7 days cohort complete response (CR) rates at day 28 were 69% (54, 81%) versus 25% (11, 47%; p = .001) in > 7 days cohort, and overall response (OR) rates were 91% (78, 96%) versus 80% (48, 92%; p = .25).CONCLUSIONS:Our data suggest that starting ruxolitinib in ≤ 7 days of declaring corticosteroid failure regardless of G vHD grade improves complete response rate but not OR rates. Starting ruxolitinib at grade I and within 7 days may get a more significant response.

Aims/Background Pre-frailty is common in patients undergoing maintenance hemodialysis (MHD). Without proper management, it can quickly worsen and progress into frailty, leading to various adverse clinical outcomes. Therefore, timely interventions for pre-frail MHD patients are crucial. However, the response of pre-frail MHD patients to such interventions is currently unclear. This study evaluated the effect of a multicomponent intervention on changes in pre-frailty status, risk factors for frailty, quality of life, and clinical outcomes in pre-frail patients undergoing MHD. Methods Sixty MHD patients were randomly assigned to intervention (received a 12-week multicomponent intervention) and control (received standard care) groups, with 30 participants per group, between February and May 2018. Data were collected at baseline and at 3 and 9 months thereafter. Analyzed outcomes included changes in pre-frailty status, frailty risk factors (such as albumin level, pain, and anxiety), quality of life, and clinical outcomes during the follow-up period. Results Data from a total of 58 MHD patients were collected at three time points. At week 12, frailty scores were 0.9 points lower in the intervention group compared to the control group (p = 0.007). The intervention group showed a 26.2% higher proportion of patients who improved from pre-frailty to non-frailty compared to the control group (p = 0.029), and a 25.9% lower proportion of patients who progressed from pre-frailty to frailty (p = 0.021). Additionally, improvements in albumin levels, pain, anxiety, and quality of life were more significant in the intervention group (all p < 0.05). Although there were fewer incidents of falls and rehospitalizations in the intervention group during follow-up, these differences did not reach statistical significance (all p > 0.05). Conclusion This study validates the effectiveness and practicality of a multicomponent intervention in improving pre-frailty status, frailty risk factors, and quality of life in patients undergoing MHD. Clinical Trial Registration Chinese Clinical Trial Registry (ChiCTR-IOR-17012176).

Background Although the multi-drug chemotherapy regimen known as VDCLP can induce hematological remission in 70-90% of adults with acute lymphoblastic leukemia, many patients, particularly young women, remain concerned about chemotherapy-related complications such as alopecia, infection, and bleeding risk. Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, has notably enhanced the remission rates for relapsed and refractory adult ALL when combined with chemotherapy. Additionally, the combination of blinatumomab and TKI has demonstrated significant efficacy in treating ph+ adult ALL. However, there is currently no clinical evidence indicating whether blinatumomab, as a first-line therapy, can achieve higher remission rates and reduce toxic and side effects in newly diagnosed adult ALL patients. In this report, we present the findings from our center where we have used the blinatumomab regimen as the primary treatment for adult ALL. Method A total of 12 newly diagnosed adult ALL patients were enrolled in this study. These patients consisted of 3 males and 9 females, with ages ranging from 23 to 72 years. All patients underwent bone marrow aspiration and were diagnosed according to morphology, immunophenotyping, cytogenetics, and molecular biology（MICM）. They were categorized into 7 cases of Ph+ ALL and 5 cases of Ph- ALL(Table1). All patients received a combination regimen consisting of vincristine (1.4mg/m2 on D1 and D8), prednisone (1mg/kg orally from D1-14,decrease gradually after D15), and blinatumomab. Blinatumomab was initiated on D3 and administered in an escalating dose manner for 15-28 days (9 μg/day from D1-7, 28 μg/day from D8) . Result Seven patients completed the 15-day treatment course, and five patients completed the full 28-day treatment course. Bone marrow morphology and MRD assessments were conducted on days 15 and 28 post-treatment. On day 15, the hematological remission rate (HCR) of bone marrow reached 100% (12 out of 12 patients), while the MRD negativity rate was 16.7% (2 out of 12 patients tested). five patients completed the full 28-day treatment course, and upon re-examination on day 28, maintained a 100% HCR. Among these, the MRD negativity rate improved to 80% (4 out of 5 patients). No significant difference in HCR was observed between ph+ ALL and ph- ALL groups. Five patients underwent allogeneic stem cell transplantation, and four of these patients were thriving, while one patient died of COVID-19 infection 3 months after transplantation. Of the seven patients without a transplant, two elderly patients received non-chemotherapy maintenance treatment but unfortunately passed away due to disease recurrence within 12 months. Four patients with ph+all received alternating chemotherapy and oral TKI treatment and are currently in good health and alive. One patient with ph-all received CAR-T therapy and still alive with MRD negative. (Figure1) Discuss Our center's findings further corroborate that for adults with new diagnosis Ph+/- ALL, initial treatment involving blinatumomab combined with low-dose chemotherapy can attain a 100% HCR rate, absent of pronounced toxicity or side effects, thereby offering a viable option for patients intolerant or averse to chemotherapy. Currently, there is insufficient evidence to determine the ideal duration for blinatumomab treatment in adult ALL patients. However, for refractory and relapsed ALL cases, a continuous 28-day course of blinatumomab therapy may be required. Initial findings from our center indicate that after 15 days of VP+blinatumomab therapy, all patients achieved hematological remission. This outcome is particularly advantageous for patients in developing nations and regions. Switching to chemotherapy or oral TKI promptly after 15 days of blinatumomab treatment can considerably decrease treatment expenses and minimize complications associated with combined chemotherapy. Nevertheless, the sample size in this study is limited, necessitating further clinical evidence to validate this perspective.

Background ： The 5-year overall survival rate (OS) for children with thalassemia major who undergo allogeneic stem cell transplantation is 90% and the event-free survival (EFS) rate is 86%. Due to the limited availability of matched sibling donors, the proportion of transplantations from alternative donors is increasing, particularly from haplo-identical donors. Post-transplant infections and graft-versus-host disease (GVHD) remain the major causes of mortality, especially in those who receive transplantation from alternative donors. Post-transplant cyclophosphamide (PTCY) has shown outstanding results of GVHD prophylaxis in haploidentical matched related donors transplantation with hematological malignancies. However, there is insufficient clinical evidence for its application in pediatric patients who received transplantation from haplo-identical donors with non-malignant hematological disease. Here, we retrospectively analyzed the results of 40 cases that underwent allogeneic stem cell transplantation from haploidentical matched related donors (Haplo-RD) and unrelated donors (UD) to evaluate the safety and efficacy of the novel regimen in GVHD prophylaxis. Method A total of 40 patients with β-thalassemia major received stem cell transplantation, 10 haploid donors (Group Haplo-RD), and 30 unrelated donors (Group UD). Among Group UD, 15 donors were 1 or 2 HLA locus mismatched, remaining 15 were identically matched. The median age of the patients was 5.5 years, ranging from 2 to 12. The Conditioning regimen mainly consisted of fludarabine, busulfan, cyclophosphamide, and thiotepa. GVHD prophylaxis included ATG 1.5mg/kg×3d, cyclophosphamide (CTX) 25mg/kg×2d, cyclosporin A (CsA), and mycophenolate mofetil (MMF). We analyzed the engraftment rate, GVHD incidence, survival rate, and virus reactivation rate for each group. Results Engraftment rate was 100%, with a median time of 11 (10-15) days for neutrophil implantation and 12 (6-31) days for platelet implantation. All patients achieved complete chimerism on day 30 after transplantation. Three cases (7.5%) suffered from Ⅲ-Ⅳ aGVHD, with one being in the Group Haplo-RD group and two in the Group UD. Four cases (10.0%) of cGVHD were recorded. The overall survival (OS) rate and thalassemia-free survival rate were both 92.5%. In Group Haplo-RD, both the OS and thalassemia-free survival rates were 100%. Eight cases reported cytomegaloviremia but no one developed to CMV disease. The total activation rate for CMV was 20%. Nine cases suffered from BK virus urinary tract infection, resulting in a total activation rate of 22.5%. Detailed results are shown in Table 1 and Figure 1. Discussion Due to the high risk of GVHD and infection, stem cell transplantation from haploidentical and unrelated donors cannot be routine therapy for children with thalassemia major. Standard-dose PTCY regimen significantly increases the risk of CMV and BK infection after transplantation and is not suitable for non-malignant disease. The results have been reported that low-dose PTCY/ ATG can reduce the risk of GVHD as compared with standard-dose ATG in haploidentical donor stem cell transplantation. In our study, the novel GVHD prophylaxis regimen, semi-dose PTCY (25mg/kg×2d) combined with low-dose ATG (1.5mg/kg×3d), was used for stem cell transplantation from haploidentical and unrelated mismatched donors. The incidence of III-IV aGVHD was 7.5% and cGVHD was 10.0%, and there was no rejection of the transplant. The activation rate of CMV and BKV was significantly lower than reported in the literature, and the non-relapse mortality (NRM) after transplantation was significantly reduced. There was no statistical difference in the rate of OS, EFS, aGVHD, and cGVHD between Group Haplo-RD and Group UD. The results provide an effective approach for preventing GVHD and infectious diseases in thalassemia patients who underwent allo-HSCT with high-risk GVHD.

BACKGROUND:Immunogenic cell death (ICD)is a kind of regulatory cell death, which causes a series of antigen-specific adaptive immune responses by generating and emitting some danger signals or damage-associated molecular patterns (DAMPs). At present, little is known about the prognostic value of ICD and its related processes in acute myeloid leukemia (AML). The aim of the study was to explore the relationship between ICD and tumor immune microenvironment changes in AML.RESEARCH DESIGN & METHODS:In the study, AML samples were divided into two groups by consensus clustering analysis, and then gene enrichment analysis and GSEA analysis were performed on the ICD high expression group. Furthermore, CIBERSORT was used to analyze the tumor microenvironment and immune characteristics of AML. Finally, a prognostic model related to ICD was constructed by using univariate and multivariate regression analysis.RESULTS:ICD was divided into two groups according to the level of ICD gene expression. The ICD high expression group was associated with good clinical results and high levels of immune cell infiltration.CONCLUSIONS:The study constructed and verified the prognostic characteristics of AML related to ICD, which has important value in predicting the overall survival time of AML patients.

目的 分析输血依赖型地中海贫血儿童非亲缘造血干细胞移植后BK病毒(BKV)相关出血性膀胱炎的发生率、临床特征和影响因素.方法 回顾性分析2018 年2 月至2021 年2 月厦门大学附属中山医院62 例输血依赖型地中海贫血儿童接受非亲缘造血干细胞移植后的临床资料,包括患儿年龄、人类白细胞抗原(HLA)相合程度、急性移植物抗宿主病(aGVHD)和慢性移植物抗宿主病(cGVHD)的发生以及与BKV感染的关联性.结果 14 例(22.58%,14/62)发生出血性膀胱炎,尿液中均检出BKV感染,BKV copies最高达107/ml,出血性膀胱炎与BKV感染符合率为100.00%.在预处理方案相同情况下,非亲缘全相合、移植物抗宿主病(GVHD)是发生BKV相关出血性膀胱炎的影响因素.结论 BKV感染是输血依赖型地中海贫血儿童非亲缘造血干细胞移植后发生出血性膀胱炎的主要原因,非亲缘全相合、GVHD是发生BKV相关出血性膀胱炎的影响因素.

HLA-DPB1*1352:01 differs from HLA-DPB1*02:01:02:01 by one nucleotide in exon 4.

BackgroundTo evaluate the effect of addition of ruxolitinib in Graft-versus-Host Disease (GVHD) prophylaxis on pediatric patients with beta-thalassemia major after allogeneic hematopoietic stem cell transplantation(HSCT). MethodsThis retrospective study reviewed 49 consecutive beta-thalassemia major pediatric patients who underwent HSCT from unrelated or haploidentical donors from February 2018 to October 2022. All transplantation recipients received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate (MTX) as GVHD prophylaxis; while 27 of them in the ruxolitinib group had added ruxolitinib oral to GVHD prophylaxis regimen at 2.5 mg twice daily once successful engraftment after January 2020. ResultsThe outcome showed that the ruxolitinib group had a lower cumulative incidence than the control group regardless of acute GVHD (22.2% vs.40.9%; p = .153) or chronic GVHD (18.5% vs.40.9%; p = .072); especially, the incidence of grade III-IV acute GVHD was reported significantly less frequently in ruxolitinib group than that of the control group (0 vs. 27.3%, p = .005). No significant difference was detected between the two groups in EBV (Epstein-Barr virus)/CMV (cytomegalovirus) reactivation and BKV (BK virus) infection (p = .703, 1.000, and .436, respectively). Twenty-six patients (96.3%) in the ruxolitinib group were alive, while two patients (9.1%) in the control group died of intestinal acute GVHD. The 2-year overall survival (OS) and thalassemia-free survival (TFS) were both 96.296% in the ruxolitinib group, while both 90.909% in the control group. ConclusionThis study reveals that ruxolitinib prophylaxis is a promising option to decrease the incidence of grade III-IV acute GVHD in pediatric patients with beta-thalassemia major.

Abstract Purpose:: Multiple myeloma(MM) is a common malignant tumor in the blood system. Despite recent advances in its treatment, its symptomatic remission rate and survival rate are still not optimistic. In the future, it is necessary to continue to search for different treatment targets and new treatment methods in order to improve the quality of life and survival time of patients with MM. The study aims to explore the potential immune related pivotal genes and immune infiltration patterns in MM. Methods: The study included peripheral blood samples from patients with MM who our hospital from October 2020 to April 2022. Obtain a gene chip for research from a comprehensive gene expression database, perform differential expression analysis on the processed gene dataset, and then perform functional enrichment analysis, weighted gene co expression network analysis, GSEA immune infiltration analysis, and LASSO regression analysis on the obtained differential expression genes to obtain the hub genes. Finally, the hub gene TNFSF14 (LIGHT) was validated by qRT-PCR. Results: In the study, three immune-related hub genes (ADAM8, CR2, and TNFSF14) and three main types of peripheral immune cells (activated CD8 T cells, macrophages, and plasma cell like dendritic cells) were obtained, which are closely related to the pathogenesis of MM. Then, by collecting peripheral blood samples from some patients in our hospital and conducting real-time fluorescence quantitative polymerase chain reaction, it was confirmed that the hub gene TNFSF14 (LIGHT) mined in this study was highly expressed in peripheral blood samples from patients with MM, which may indicate that it plays a pathogenic role in MM. Conclusion: The study found that immune-related hub genes (ADAM8, CR2, and TNFSF14) are closely related to the pathogenesis of MM, and should be further researched.

目的:提高对异基因造血干细胞移植（allo-HSCT）后发生肺部移植后淋巴组织增殖性疾病（PTLD）的认识。方法:回顾性分析厦门大学附属中山医院2例allo-HSCT后肺部PTLD患者的临床资料，并复习相关文献。结果:2例患者均在移植后1年内诊断为肺部PTLD，伴EB病毒（EBV）血症。例1接受利妥昔单抗联合减停免疫制剂治疗，例2单纯减停免疫抑制剂治疗，2例患者均缓解，EBV-DNA均转阴性。结论:PTLD是HSCT后一种罕见的严重并发症，大多与EBV感染有关，累及肺部者罕见。对可疑PTLD患者需尽早行病灶穿刺活组织检查。

OBJECTIVE:To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients.METHODS:The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed.RESULTS:Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively.CONCLUSION:The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

目的 探讨融合抑制(SUFU)基因多态性与地中海贫血(TM)患儿接受异基因造血干细胞移植(allo-HSCT)后发生移植物抗宿主病(GVHD)之间的关系.方法 选择2018年10月1日至2020年12月31日厦门大学附属中山医院接收的44例接受allo-HSCT的TM患儿作为研究对象,经SUFU rs17114808位点基因多态性检测,比较不同基因型患儿的临床资料,记录GVHD的发生率和严重程度,并分析SUFU基因型与移植后发生GVHD的关系.结果 44例TM移植患儿中,SUFU基因位点(rs17114808)CC、CT、TT的基因型发生率分别为29.55％、52.27％、18.18％.CC型组和CT/TT型组性别、移植年龄、供受者关系、人类白细胞抗原匹配程度、末次随访存活率比较,差异无统计学意义(P>0.05).移植后CC型组急性GVHD(aGVHD)和慢性GVHD(cGVHD)的发生率均高于CT/TT型组,但差异无统计学意义(P>0.05).多因素logistic回归分析显示,携带CC基因型对Ⅱ～Ⅳ度aGVHD的发生有影响(OR=6.601,P<0.05).两组基因型cGVHD累及器官范围及受累器官类型比较,差异无统计学意义(P>0.05).结论 SUFU基因CC型可能与TM患儿移植后发生严重aGVHD有关,可作为预测发生Ⅱ～Ⅳ度aGVHD的指标.

Six children with steroid resistant graft versus host disease (GVHD) after hematopoietic stem cell transplantation admitted in the hospital, including 4 cases of acute GVHD and 2 cases of chronic GVHD. Among the 4 acute GVHD cases, the main manifestations were large area rash and fever in 2 cases, and abdominal pain and diarrhea in 2 cases. In 2 chronic GVHD cases, one presented lichenoid dermatosis, and the other showed repeated oral ulcers with difficult mouth opening. Patients received tocilizumab (8 mg/kg per dose every 3 weeks) and ruxolitinib (5-10 mg/d, 28 d), at least 2 courses were completed. All patients had complete responses (100%), and 5 patients responded after completion of two treatment courses, with the median time of remission was 26.7 d. The median follow-up period was 11 (7-25) months, and no severe treatment-related adverse reactions were observed.

HLA‐DPB1*1352:01 differs from HLA‐DPB1*02:01:02:01 by one nucleotide in exon 4.

OBJECTIVE:To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation.METHODS:The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups.RESULTS:The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups.CONCLUSION:Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.

目的:探讨持续质量改进对降低造血干细胞移植患儿双腔耐高压经外周静脉置入中心静脉导管(PICC)堵管发生率的影响.方法:将98例在本院行造血干细胞移植而置入双腔耐高压PICC的患儿作为研究对象,按移植时间分为对照组(37例)和干预组(61例).对照组行常规方法置管及维护,干预组在常规护理基础上给予持续质量改进.观察两组患儿PICC堵管发生率,PICC堵管所致非计划性拔管发生率,患儿家属满意度.结果:对照组发生导管阻塞12例,8例因堵管导致非计划性拔管.干预组堵管8例,2例因堵管导致非计划性拔管.两组患儿堵管发生率及堵管所致的非计划性拔管发生率比较差异均有统计学意义(P<0.05),干预组患儿家属满意度显著高于对照组(P<0.05).结论:持续质量改进可有效降低造血干细胞移植患儿双腔耐高压PICC堵管发生率以及堵管所致的非计划性拔管发生率,并提高患儿家属满意度.

Objective:To explore the efficacy and safety of unrelated mismatched hematopoietic stem cell transplantation(HSCT)for thalassemia major.Methods:For this retrospective cohort study, 15 patients with β-thalassemia major underwent unrelated mismatched HSCT between January 2018 and April 2022. There were 8 males and 7 females with a median age of 7(3-12)years and a median ferritin level of 3 417.3(223-14 485)μg/L. The conditioning regimens on the basis of fludarabine(Flu), busulfan(Bu)and cyclophosphamide(CTX)and GVHD prophylaxis on the basis of cyclosporine(CsA), mycophenolate mofetil(MMF), anti-human thymocyte immunoglobulin(ATG)plus low-dose post-cyclophosphamide(PTCy)and mesenchymal stem cells were offered.Results:Up until April 1, 2022, 15 children were successfully implanted during a median follow-up period of 24.1(11-49)months and all of them achieved stable donor chimerism. The median time to neutrophil and platelet engraftment were 12(11-22)and 14(8-38)days respectively. Except for 2 deaths, 13 cases survived. The estimated 2-year probability of overall survival(OS)and thalassemia-free survival(TFS)were both 86.67%. There were 5 cases of acute graft versus host disease (aGVHD) below grade Ⅱ, 2 cases of grade Ⅲ to Ⅳ aGVHD, and 3 cases of localized chronic graft versus host disease (cGVHD) after transplantation. No gengralized cGVHD occurred. Both cytomegalovirus and Epstein-Barr virus were activated in five recipients.Conclusions:Unrelated mismatched donor HSCT is both safe and feasible for thalassemia major.

Objective:To explore the safety and advantages of non-cryopreserved sibling umbilical cord blood hematopoietic stem cell transplantation for major thalassaemia in children.Methods:From October 2016 to June 2021, 9 patients with major beta thalassaemia received non-cryopreserved hematopoietic stem cell transplantation of sibling umbilical cord blood at Zhongshan Hospital of Xiamen University. The pretreatment scheme, the process of stem cell implantation and follow-up were analyzed and summarized.Results:Among the 9 cases, there were 5 males and 4 females with a median age of 4(2~11)years. Median level of ferritin was 2 997(1 936~5 512)μg/L. At gestational weeks 12~16, each patient's mother underwent villi testing to confirm that the donor without thalassaemia major was complete HLA-matched with the patient. All of them received an intensive conditioning regimen made up of cyclophosphamide(CTX), fludarabine and busulfan(Bu). Graft-versus-host disease(GVHD) was prevented by cyclosporine A(CSA)and mycophenolate mofetil(MMF)with or without methotrexate(MTX). Except for one failed implant, 8 cases were successfully engrafted. Median time of neutrophil implantation was 19.5(15~26)days, median time of platelet implantation 32(22~34)days and median time of erythrocyte implantation 30.5(18~37)days. Up until September 1, 2021, the median follow-up period was 27(3~59)months and the rate of successful engraftment 88.89%. There was no transplant-related mortality. Overall survival was 100% and thalassaemia-free survival 88.89%. Two patients developed grades Ⅱ skin acute GVHD(22.2%). No grade Ⅲ-Ⅳ GVHD or chronic GVHD occurred. Epstein-Barr virus infection occurred in 1 case.No infection of cytomegalovirus occurred.Conclusions:For major thalassaemia in children, stem cell transplantation of non-cryopreserved sibling cord blood is both safe and feasible with a high implantation rate and a low incidence of GVHD.

BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system (CNS) leukemia. CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration. It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement. CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis, with no involvement in peripheral blood or bone marrow. Identification of abnormal phenotypes of blast cells, and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia. The patient received a combination of intrathecal therapy and high-dose chemotherapy. But the benefits of the treatments were short-lived and she experienced recurrence. CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy. New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.