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This study explored the trajectory of teacher concept development during collaborative research practice promoted by a university-school partnership teacher development program. Drawing on Vygotsky’s and Engeström’s notion of concept formation, it examined how a secondary EFL teaching-research officer (TRO) negotiated between scientific and everyday concepts as she co-constructed the research theme “teaching assessment literacy” with mentors and fellow teachers mediated by the program. Multiple sources of data were collected over a span of two years, including six rounds of oral defense and research reporting activities, classroom observations, interviews, journals, and research reports. The analysis showed that the TRO experienced a gradually integrated and transformed path of concept development, and also initiated an expansive learning opportunity for her research participants, triggering collective concept development. While the program played a significant role in providing multi-module facilitating activities, academic-practice joint mentoring and collective scaffolding, more subtle guidance is suggested for the tension-laden process.

Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We conducted this study to compare the superiority of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 176 patients. In the pre-DLI cohort, 42 patients relapsed without chance for pre-DLI while 95 patients remained CR without detectable minimal residual disease (MRD). Thirty-nine patients in the pre-DLI cohort became minimal MRD positive/mixed chimerism and received pre-DLI. Pro-DLI cohort had higher 3-year progression-free-survival (PFS) (63.4%vs.53.0%, P= 0.026) and overall survival (OS) (65.2% vs. 57.0%, P= 0.14) compared to the pre-DLI cohort. The 3-year cumulative incidence of relapse (CIR) was 25.3% in the pro-DLI cohort which was significantly lower than 36.7% in the pre-DLI cohort (P= 0.02). The cumulative incidence of grade III-IV aGVHD, cGVHD and non-relapse mortality were comparable between cohorts. Multivariable analysis demonstrated strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.63, P= 0.04), PFS (HR = 0.54, P= 0.005) and CIR (HR = 0.50, P= 0.005). In high-risk patients with acute leukemia, early scheduled pro-DLI rather than pre-DLI after detectable MRD would reduce post-transplant relapse and improve long-term survival.

Both haploidentical hematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI) exhibit strong graft-versus-leukemia (GVL) effect. However, the role of prophylactic DLI following haploidentical HSCT remains unclear. Here, 34 patients with high-risk acute leukemia who underwent low-dose anti-T-lymphocyte globulin-Fresenius (ATG-F)-based myeloablative haploidentical HSCT and prophylactic modified DLI (pro-DLI) were well-matched with patients without pro-DLI. The 5-year overall survival (OS) (67.8% versus 41.3%, P< 0.01) and leukemia-free survival (LFS) (64.6% versus 33.9%, P< 0.01) of pro-DLI cohort were superior to the control cohort. A slightly higher GVHD-free/relapse-free survival was found in the pro-DLI cohort (32.8% versus 16.3%, P= 0.32). The 5-year cumulative incidence of relapse of the pro-DLI recipients was significantly lower than that of the control cohort (14.7% versus 49.3%, P= 0.01). The cumulative incidence of grades II-IV and III-IV acute GVHD at 100 days after pro-DLI was 17.6% and 9.1%, respectively. There was no difference between the two cohorts in terms of the cumulative incidence of chronic GVHD and non-relapse mortality. Data from the multivariate analysis demonstrated that pro-DLI was an independent protective variable for LFS (P= 0.01, hazard ratio {HR} = 0.35), OS (P= 0.01, HR = 0.32), and relapse (P= 0.02, HR = 0.33). Taken together, we demonstrate that pro-DLI after ATG-F-based HSCT effectively decreases the risk of relapse and improves long-term survival of patients with high-risk acute leukemia without increasing treatment toxicity.

The transplant outcomes of non-first-degree (NFD) related donors in haploidentical haematopoietic stem cell transplantation (haplo-HSCT) remain unclear. This multi-centre analysis compared NFD and first-degree (FD) related donors in haplo-HSCT using a low-dose anti-T-lymphocyte globulin/G-CSF-mobilised peripheral blood stem cell graft-based regimen. Ninety-nine patients (33 NFD; 66 FD) were included. All patients achieved myeloid and platelet engraftment. The 100-day cumulative incidence (CI) of aGVHD, 2-year CIs of relapse, cGVHD, and NRM, and 2-year probabilities of OS and GRFS were comparable between the two cohorts. In multivariate analysis, donor type (NFD vs. FD) had no impact on OS, PFS, GRFS, incidences of relapse, grade II–IV aGVHD or moderate–severe cGVHD. Older donor age was associated with a higher incidence of grade II–IV aGVHD (HR, 1.64, p= 0.03), moderate–severe cGVHD (HR, 1.92, p= 0.01) and worse GRFS (HR, 1.40, p= 0.02). A lower level of donor–recipient HLA matching was associated with a higher incidence of moderate–severe cGVHD (HR, 4.07, p= 0.02), and disease at complete remission was associated with better OS (HR, 0.21, p= 0.01) and PFS (HR, 0.3, p= 0.03). In conclusion, NFD donors may serve as feasible alternatives when FD donors are not available for haplo-HSCT.

Treatment of acute lymphoblastic leukemia (ALL) is still a challenge despite years of researching, especially for those of poor prognosis. Zhang and his team recently proved that FLT3 gene mutation was identified in ~5% of ALL and the mutation spectrum is different from AML. Recently, chimeric antigen receptor T cells (CART) therapy presents great efficacy in treating refractory leukemia. We report a case of a refractory ALL patient with FLT3-ITD mutations and unfavorable karyotypes, who failed to respond to chemotherapy and small molecule tyrosine kinase inhibitors, successfully treated by CART therapy. FLT3-ITD mutations were downregulated dramatically into 14.1% positive 3 days after the infusion and remained negative until now. MRD has stayed to be negative from the 10th day. This case suggests that CART-cell therapy might be effective in treating FLT3-ITD positive refractory ALL, implying the possibility to overcome the traditional prognosis scoring system for leukemia and providing a new chance for other leukemia patients with inferior prognosis factors.

This study outlined the clinical characteristics, outcomes, and risk factors for coronavirus disease 2019 (COVID-19) of 492 patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) during the Omicron wave. The median follow-up of the whole cohort was 62 days. The commonest underlying disease were myeloid malignancies (58.5%) and acute lymphocytic leukemia (30.5%). Of the 492 patients, 415, 67, and 10 had mild, moderate, and severe COVID-19, respectively. The incidence of moderate-to-severe COVID-19 was 15.7% (77/492). The 60-day overall survival and complete resolution rates were 98.1% and 80.6%, respectively. Risk factors for moderate-to-severe COVID-19 were corticosteroid use within 3 months before diagnosis (Odds ratio [OR], 2.115; 95% confidence interval [CI], 1.262-3.546; P=0.004), interval between allo-HSCT and coronavirus disease diagnosis <6 months (OR, 2.234; 95% CI, 1.259-3.969; P=0.006), and anti-thymocyte globulin use for graft-versus-host disease prophylaxis (OR, 3.450; 95% CI, 1.040-11.444; P=0.043). In conclusion, during the Omicron wave, patients with allo-HSCT had a low coronavirus disease-related mortality, and there was a high rate of moderate-to-severe disease and prolonged disease. Prevention in the early post-transplantation period is critical for allo-HSCT recipients receiving corticosteroids.

Background: Though the prognosis of Philadelphia-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has been improved since the introduction of tyrosine kinase inhibitors (TKIs) and combined with allogeneic stem cell transplantation (allo-HSCT), relapse after HSCT remains a concern. Prophylactic TKIs after allo-HSCT seemed a promising strategy to prevent relapse. But the optimal choice of the agent is still obscure.Methods: We retrospectively analyzed the clinical data of Ph-positive ALL patients who underwent allo-HSCT in CR1 from 6 medical centers in China between September 2010 and October 2021. Patients were divided into two cohorts according to different choice of TKI after allo-HSCT, namely Ima cohort with imatinib prophylaxis and Das cohort with dasatinib prophylaxis. Survival and safety outcomes of two cohorts were compared, and prognostic factors were determined by univariate and multivariate analyses.Results: One hundred and forty-one patients, with median age of 37 years (range, 14-61 years), were included, of whom 91 were in Ima cohort and 50 were in Das cohort. After median follow-up of 50.6 months, 5-year cumulative relapse rate (CIR), non-relapse mortality rate (NMR), leukemia-free time (LFS) and overall survival (OS) in Ima and Das cohort were 16.1% and 12.5%; 5.2% and 9.8%; 78.8% and 77.6%; 86.5% and 77.6%, respectively, with no significant difference. Mild cGVHD was higher in Das cohort compared to Ima cohort, while the total, moderate or severe cGVHD were similar. The most common adverse event was neutropenia (66.4%). Das cohort owned higher incidence of gastrointestinal bleeding and gastrointestinal reaction than Ima cohort. The proportion of patients treated on schedule was 30% in Das cohort, lower than that of in Ima cohort (p<0.001). Drug intolerance was the main reason for not completed treatment as intended.Conclusions: For patients with Ph-positive ALL receiving allo-HSCT in CR1, imatinib prophylaxis after transplantation could obtain the same long-term outcome compared to dasatinib, showing better tolerance.

Background:The nucleophosmin 1( NPM1) gene mutations are the most common gene alteration in acute myeloid leukemia (AML) patients, occurring in approximately 30%-35% of adult AML cases. However, molecular and response to therapy heterogeneity are existed in this distinct group. Response to therapy, differing patterns of co-mutation and the prognosis of NPM1-mutated AML patients receving allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment were unknown.

Aims: Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of ATG based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in elderly or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG based haploidentical HSCT.

•We performed a prospective clinical study enrolling 510 patients accepted for blood-derived antithymocyte globulin (ATG)-based haploidentical stem cell transplantation (haplo-SCT).•ABO incompatibility status had no significant impact on overall survival, disease-free survival, nonrelapse mortality, relapse, graft-versus-host disease, engraftment, transfusion requirement, transfusion independence, and incidence of poor graft function after transplantation.•Donor-recipient ABO matching is not a serious factor that requires consideration in ATG-based myeloablative conditioned haplo-SCT using peripheral blood stem cell grafts.

Relapse remains to be the biggest problem for patients with very high risk acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor lymphocyte infusion (DLI) has been widely applied to the prevention and preemptive intervention of relapse post-transplantation. However, the optimal time to implement DLI in patients with a high risk of relapse remains controversial. During August 1, 2014 and August 30, 2020, four hundred and thirty-one consecutive acute leukemia patients with very high-risk features underwent allo-HSCT in our center. Ninety-five patients received prophylactic DLI (pro-DLI) while one hundred and fifty-five patients received preemptive DLI (pre-DLI). Patients were stratified into five risk groups by the disease-risk stratification system (DRSS) which recently introduced by European Society for Blood and Marrow Transplantation: low risk (N=44), intermediate-1 (N=67), intermediate-2 (N=60), high (N=36), and very high (N=43). In the very high group, patients who received pro-DLI achieved higher 3-year overall survival (OS) (50.8% versus 31.8%, P=0.05), leukemia-free survival (LFS) (52.5% versus 31.6%, P=0.03) and graft-versus-host disease (GVHD)-free and relapse-free survival (GRFS) (47.9% versus 31.6%, P=0.04) compared with pre-DLI. Pro-DLI cohort was associated with a trend of lower 3-year cumulative rates of relapse (42.8% versus 57.9%, P=0.12) and non-relapse mortality (NRM) (4.6% versus 10.5%, P=0.43). In the subgroup of intermediate-2 and high (N=96), pro-DLI cohort was associated with superior survival and relapse rate, though without statistical significance. Further analysis was conducted separately between patients with positive minimal residual disease (MRD) and negative MRD pre-transplant in intermediate-2/high subgroup. In the patients with positive MRD before all-HSCT, pro-DLI achieved significant higher 3-year OS (66.7 % versus 26.2%, P=0.028), PFS (68.6 % versus 24.7%, P=0.015) and GRFS (68.6 % versus 14.4%, P=0.007), along with lower cumulative of relapse (31.4 % versus 59.3%, P=0.1) and NRM (0 versus 16%, P=0.1) compared with pre-DLI. However, pro-DLI patients was associated with inferior OS (52.7 % versus 77.8%, P=0.046), PFS(54.8 % versus 75.3%, P=0.247) and NRM (25% versus 3%, P=0.02) in patients with negative MRD. In addition, no difference was found in patients in the group of low and intermediate-1 risk. Taken together, we recommend early pro-DLI in patients of very-high risk group and positive MRD of intermediate-2/high group. Pre-DLI given timely after MRD turning positive achieved better outcome in the remaining patients.

No relevant conflicts of interest to declare.

Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. With the extensive application of CAR-T therapy in clinical settings, CAR-T-associated toxicities have become increasingly apparent. However, information regarding the associated infections is limited. We aimed to evaluate the incidence of infection during CAR-T therapy and identify the potential risk factors. Especially, we evaluated infections and the associated risk factors in 92 patients. The cohort included patients with acute lymphoblastic leukemia (n= 58) and non-Hodgkin lymphoma (n= 34). Fifteen cases of infection (predominantly bacterial) were observed within 28 days of CAR-T therapy, with an infection density of 0.5 infections for every 100 days-at-risk. Neutropenia before CAR-T therapy (P= .005) and prior infection (P= .046) were independent risk factors associated with infection within 28 days after CAR-T therapy; corticosteroid treatment during cytokine release syndrome (P= .013) was an independent risk factor during days 29–180 after CAR-T infusions. Moreover, the 2-year survival duration was significantly shorter in patients with infections than in those without (126 vs 409 days; P= .006). Our results suggested that effective anti-infection therapies may improve prognosis of patients who have a high infection risk. The risk of bacterial infections during the early stages of CAR-T therapy and the subsequent risk of viral infections thereafter should be considered to provide the appropriate treatment and improve patient prognosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. CAR-T therapy has been extensively applied in the clinical setting; however, few systematic studies have evaluated the cost of CAR-T treatment. This study was conducted to evaluate the total cost and cost structure of CAR-T therapy and identify potential risk factors leading to increased costs.Methods: We identified the associated risk factors in 89 patients in a phase 1/2 study. The cohort included patients with acute lymphoblastic leukemia (ALL, n= 55) and non-Hodgkin’s lymphoma (NHL, n= 34).Results: Overall, the treatment of the ALL cohort was costlier than that of the NHL cohort (P< 0.001). Furthermore, in the ALL cohort, it was costlier to treat patients with a high tumor burden (P< 0.001), high cytokine release syndrome (CRS) grade (P< 0.001), and complications of infection after CAR-T cell infusion (CTI) in the whole cohort (P= 0.013) than patients with a low tumor burden, with low CRS grade, and without infection, respectively. CRS grade and length of stay (P≤ 0.005) were independent risk factors associated with the total cost in both the ALL and NHL cohorts during CAR-T therapy. A high tumor burden, duration of fever, and treatment with tocilizumab were independent risk factors associated with the total cost in the ALL cohort (P< 0.05).Conclusions: CAR-T treatment should be extended to patients with a low tumor burden or patients in a state of complete remission, and a corticosteroid approach, as opposed to tocilizumab, may reduce costs.