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The letter published in the Blood Cancer Journal discusses the use of luspatercept for treating anemia in patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study involved 16 patients with various hematological diseases, with 81.3% achieving an erythroid response after luspatercept treatment. The treatment was generally well-tolerated, with mild adverse events reported. The study suggests that luspatercept could be an effective option for managing anemia post-allo-HSCT, although further research is needed due to the study's limitations. [Extracted from the article]

Summary: This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small‐dose infusions of granulocyte‐colony‐stimulating factor (G‐CSF)‐mobilized haploidentical lymphocytes as post‐ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease‐free survival (DFS) compared to those without maintenance therapy, with 4‐year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate‐risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small‐dose infusions of G‐CSF‐mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate‐risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long‐term prognosis in this patient population. [ABSTRACT FROM AUTHOR]

Summary: Anti‐thymocyte globulin (ATG) or post‐transplant cyclophosphamide (PTCy)‐based regimens are widely used for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo‐HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo‐PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced‐dose PTCy (40 mg/kg/d on days 3 and 4) combined with low‐dose post‐transplant ATG (2.5 mg/kg on day 8)‐based GVHD prophylaxis (reduced‐dose PTCy/ATG) with fludarabine–busulfan–cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced‐dose PTCy/ATG or a standard‐dose ATG group ('Beijing Protocol', ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II–IV (11.5% vs 39.3%, p = 0.001) and grade III–IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced‐dose PTCy/ATG group. Furthermore, two‐year overall survival, disease‐free survival and GVHD‐free/relapse‐free survival were significantly improved in the reduced‐dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low‐dose ATG to reduced‐dose PTCy with FBA conditioning is a promising strategy in haplo‐PBSCT. [ABSTRACT FROM AUTHOR]

Background: Although sulforaphene has potential anticancer effects, little is known about its effect on oesophageal squamous cell carcinoma (ESCC) invasiveness., Methods: To investigate whether sulforaphene inhibits the growth of oesophageal cancer cells, MTT and anchorage-independent cell growth assays were performed. Global changes in the proteome and phosphoproteome of oesophageal cancer cells after sulforaphene treatment were analysed by mass spectrometry (MS), and the underlying molecular mechanism was further verified by in vivo and in vitro experiments., Results: Sulforaphene treatment markedly affected proteins that regulate several cellular processes in oesophageal cancer cells, and mitogen- and stress-activated kinase 2 (MSK2) was the main genetic target of sulforaphene in reducing the growth of oesophageal cancer cells. Sulforaphene significantly suppressed ESCC cell proliferation in vitro and reduced the tumour size in an oesophageal patient-derived xenograft (PDX) SCID mouse model. Furthermore, the binding of sulforaphane to MSK2 in vitro was verified using a cellular thermal dhift assay, and the effect of MSK2 knockdown on the ESCC phenotype was observed using a shMSK2 model., Conclusion: The results showed that sulforaphene suppresses ESCC growth in both human oesophageal squamous cells and PDX mouse model by inhibiting MSK2 expression, implicating sulforaphene as a promising candidate for ESCC treatment., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Consolidative allogeneic hematopoietic stem cells (allo-HSCs) after chimeric antigen receptor T cells (CAR-T) therapy is an emerging modality in hematologic malignancies. Knowledge about the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T therapy without a conditioning regimen is limited., Case Presentation: We report a patient with relapsed/refractory (R/R) Ph + B-cell acute lymphoblastic leukemia (ALL) who underwent anti-CD19 CAR-T immunotherapy. After 1 month of treatment, bone marrow hyperplasia remained reduced with no hematopoietic improvements. In line with this, allogeneic hematopoietic stem cells (HSCs) were extracted from an HLA-matched sibling donor and administered to the patient on day 33 after CAR-T cell therapy to support hematopoiesis. On day 40, the level of immature bone marrow lymphocytes was at 0% and minimal residual disease-negative, and the fusion gene BCR/ABL 190 was negative. Chimerism analysis showed full donor chimerism. Three months after CAR-T cells infusion, the patient was still in complete remission with full donor chimerism. However, decreased liver function with skin pigmentation and festering, indicative of acute graft versus host disease, was noted. The treatment was halted owing to financial reasons., Conclusion: We report the successful engraftment of allogeneic HSCs using CAR-T cell therapy as a conditioning regimen for R/R B-ALL patients., Competing Interests: Author JSZ is employed by The Shenzhen Pregene Biopharma Company, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Zhao, Yang, Zu, Liu, Zhou, Li, Huang, Zhang, Gao, Song and Zhou.)

Background: The main objective of this study was to explore health-related quality of life (HRQoL) profiles, chronic disease management practices and key factors associated with HRQoL in 540 patients with chronic myeloid leukemia in chronic phase (CML-CP) administered tyrosine kinase inhibitors (TKIs)., Methods: Adult CML-CP patients treated with TKIs in Henan Cancer Hospital from March 2015 to October 2019 were assessed via questionnaires, including demographic characteristics, TKI medications, participation in CML disease management, and HRQoL, in a cross-sectional investigation. Respondents were anonymous. Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used to measure HRQoL. A multivariate linear regression model with stepwise entry was used to investigate variables independently associated with HRQoL domain and total scores., Results: Totally, 540 respondents were included; 302 (55.93%) were male. Mean participant age was 42.90±13.00 years; 169 (31.3%), 178 (32.9%) and 193 (35.7%) individuals had a low, moderate or high disease management level, respectively. Except for insignificant event-free survival information, participants with higher disease management levels also had significantly higher rates of completing re-examination, drug withdrawal, cytogenetic response (CcyR) and/or major molecular response (MMR) (all P<0.01). Moreover, higher disease management level was accompanied by eight significantly higher HRQoL domains (all P<0.01). In multivariate linear regression analysis, variables significantly associated with a higher HRQoL included: (I) high disease management level (B=3.68, P=0.046); (II) transportation convenience (B=6.67, P<0.001); (III) family annual income >10,000 CNY (B=5.97, P<0.001); (IV) completed re-examination (B=4.58, P=0.036); (V) MMR (B=3.75, P=0.021) and CcyR (B=5.15, P=0.035). Female sex (B=-3.53, P=0.010), single status or divorce (B=-1.89 and -2.94, P=0.005 and 0.011), and low education level (B=-1.44, P=0.019) were significantly associated with lower HRQoL., Conclusions: Higher disease management level was significantly associated with higher elevated treatment efficacy and HRQoL in Chinese individuals with CML-CP administered TKIs. These data indicate the importance of chronic disease management on people's HRQoL and clinical outcome.

Objective: To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML)., Methods: The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing., Results: In 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months., Conclusion: T315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.