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1.
Cells ; 13(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38727291

Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25-57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.


Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Transplantation, Homologous , Humans , Leukemia, Myeloid, Acute/therapy , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Graft vs Host Disease/prevention & control
2.
Medicine (Baltimore) ; 103(19): e38110, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728478

RATIONAL: The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute myeloid leukemia (Ph + AML) is a rare entity with a poor prognosis and a short median survival period. To date, there have been few clinical reports on this disease. And the treatment regimen of this disease has not been uniformly determined. PATIENT CONCERNS: We report a case of a Ph + AML. A 32-year-old male who was admitted to our hospital with weakness for 2 months. DIAGNOSIS: Philadelphia chromosome-positive acute myeloid leukemia. INTERVENTIONS: The patient achieved complete remission by the administration of a tyrosine kinase inhibitor, combined with low-intensity chemotherapy and a B-cell lymphoma 2 inhibitor. Then, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his sister was successfully performed. OUTCOMES: The patient has been in a continuous remission state for 6 months after transplantation. LESSONS: We reported a rare Ph + AML case, successfully treated with allo-HSCT. This case provided strong support for treating Ph + AML with allo-HSCT.


Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Philadelphia Chromosome , Humans , Male , Hematopoietic Stem Cell Transplantation/methods , Adult , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/genetics , Transplantation, Homologous , Remission Induction
3.
Front Immunol ; 15: 1339318, 2024.
Article En | MEDLINE | ID: mdl-38711496

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only curative therapy for many hematologic malignancies, whereby the Graft-versus-Leukemia (GVL) effect plays a pivotal role in controlling relapse. However, the success of GVL is hindered by Graft-versus-Host Disease (GVHD), where donor T cells attack healthy tissues in the recipient. The ability of natural regulatory T cells (Treg) to suppress immune responses has been exploited as a therapeutical option against GVHD. Still, it is crucial to evaluate if the ability of Treg to suppress GVHD does not compromise the benefits of GVL. Initial studies in animal models suggest that Treg can attenuate GVHD while preserving GVL, but results vary according to tumor type. Human trials using Treg as GVHD prophylaxis or treatment show promising results, emphasizing the importance of infusion timing and Treg/Tcon ratios. In this review, we discuss strategies that can be used aiming to enhance GVL post-Treg infusion and the proposed mechanisms for the maintenance of the GVL effect upon the adoptive Treg transfer. In order to optimize the therapeutic outcomes of Treg administration in allo-HSCT, future efforts should focus on refining Treg sources for infusion and evaluating their specificity for antigens mediating GVHD while preserving GVL responses.


Graft vs Host Disease , Graft vs Leukemia Effect , Hematopoietic Stem Cell Transplantation , T-Lymphocytes, Regulatory , T-Lymphocytes, Regulatory/immunology , Humans , Graft vs Leukemia Effect/immunology , Animals , Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Transplantation, Homologous , Adoptive Transfer/methods , Hematologic Neoplasms/therapy , Hematologic Neoplasms/immunology
4.
Virol J ; 21(1): 110, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745209

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.


Hematopoietic Stem Cell Transplantation , Pneumonia, Viral , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Female , Adult , Middle Aged , Prognosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Young Adult , Adolescent , Transplantation, Homologous/adverse effects , Adenoviridae Infections/mortality , Risk Factors , Retrospective Studies , Adenoviridae , Treatment Outcome , Incidence , Adenovirus Infections, Human/mortality , Adenovirus Infections, Human/virology
6.
Klin Onkol ; 38(2): 118-125, 2024.
Article En | MEDLINE | ID: mdl-38697820

BACKGROUNDS: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a substantial therapeutic procedure for the treatment of a wide spectrum of severe diseases. Despite advancements in treatment and supportive care, alloHSCT still carries a considerable mortality risk, primarily caused by graft-versus-host disease (GvHD). Our retrospective analysis aimed to identify the factors influencing overall survival and GvHD development in HLA-identical sibling alloHSCT. We have analyzed patients' and donors' age, AB0 compatibility, recipient-donor gender match, stem cell source, time from the diagnosis to alloHSCT, conditioning regimen type, GvHD prophylaxis, and relapse. PATIENTS AND METHODS: Our study included 96 patients (54 male, 42 female) who underwent HLA-identical sibling alloHSCT. The median follow-up was 64.5 months (range 1-218 months), and the median age of both recipients and donors was 34 years. Malignant hematological diseases were the most common indications for alloHSCT. RESULTS: GvHD and its complications accounted for the highest number of deaths (N = 24; 46.2%), followed by relapse (N = 18; 34.6%). Acute GvHD developed in 30 patients (31.3%), while chronic GvHD occurred in 25 patients (26.0%), resulting in a total of 45 patients (46.9%) experiencing GvHD. Male recipients with female donors had significantly worse overall survival compared to other patients (P = 0.01; HR = 2.33). Overall survival was better in patients transplanted within 1 year from the diagnosis compared to those transplanted after 1 year (P = 0.03; HR = 1.93). No factor reached statistical significance regarding the impact on acute GvHD, chronic GvHD, or overall GvHD. CONCLUSION: We confirmed that sex mismatch, specifically in the case of a female donor and a male recipient, significantly negatively affects overall survival after alloHSCT. Additionally, overall survival is significantly shorter when the interval between the diagnosis and alloHSCT exceeds one year.


Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Humans , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Male , Female , Adult , Retrospective Studies , Young Adult , Middle Aged , Transplantation Conditioning , Adolescent
7.
Front Immunol ; 15: 1381308, 2024.
Article En | MEDLINE | ID: mdl-38745670

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.


Antigens, CD7 , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Receptors, Chimeric Antigen , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Antigens, CD7/immunology , Receptors, Chimeric Antigen/immunology , Male , Tissue Donors , T-Lymphocytes/immunology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Treatment Outcome , Adult
8.
Stem Cell Res Ther ; 15(1): 140, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745184

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .


Crohn Disease , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Rectal Fistula , Humans , Crohn Disease/complications , Crohn Disease/therapy , Male , Adult , Female , Mesenchymal Stem Cell Transplantation/methods , Rectal Fistula/therapy , Rectal Fistula/etiology , Mesenchymal Stem Cells/cytology , Young Adult , Transplantation, Homologous/methods , Adolescent , Middle Aged , Magnetic Resonance Imaging , Treatment Outcome , Quality of Life
9.
Gastroenterol Clin North Am ; 53(2): 221-231, 2024 Jun.
Article En | MEDLINE | ID: mdl-38719374

Intestinal allotransplantation was first described in the 1960s and successfully performed in the 1980s. Since that time, less progress has been made in the preservation of the allograft before transplantation and static cold storage remains the current standard. Normothermic machine perfusion represents an opportunity to simultaneously preserve, assess, and recondition the organ for transplantation and improve the procurement radius for allografts. The substantial progress made in the field during the last 60 years, coupled with the success of the preclinical animal model of machine perfusion-preserved intestinal transplantation, suggest we are approaching the point of clinical application.


Allografts , Intestines , Organ Preservation , Organ Preservation/methods , Humans , Intestines/transplantation , Animals , Perfusion/methods , Transplantation, Homologous , Organ Preservation Solutions
10.
Front Immunol ; 15: 1366101, 2024.
Article En | MEDLINE | ID: mdl-38707905

We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.


Autoimmune Diseases , Glucocorticoids , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Middle Aged , Glucocorticoids/therapeutic use , Autoimmune Diseases/etiology , Autoimmune Diseases/therapy , Rituximab/therapeutic use , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/therapy , Anemia, Hemolytic, Autoimmune/drug therapy , Drug Resistance
11.
JCO Clin Cancer Inform ; 8: e2300205, 2024 May.
Article En | MEDLINE | ID: mdl-38723213

PURPOSE: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of evidence from randomized trials, real-world observational data become beneficial to study the effect of the treatment timing. In this study, a framework to estimate the expected outcome after an intervention in a time-to-event scenario is developed, with the aim of optimizing the timing in a personalized manner. METHODS: Retrospective real-world data are leveraged to emulate a target trial for treatment timing using multistate modeling and microsimulation. This case study focuses on myelodysplastic syndromes, serving as a prototype for rare cancers characterized by a heterogeneous clinical course and complex genomic background. A cohort of 7,118 patients treated according to conventional available treatments/evidence across Europe and United States is analyzed. The primary clinical objective is to determine the ideal timing for HSCT, the only curative option for these patients. RESULTS: This analysis enabled us to identify the most appropriate time frames for HSCT on the basis of each patient's unique profile, defined by a combination relevant patients' characteristics. CONCLUSION: The developed methodology offers a structured framework to address a relevant clinical issue in the field of hematology. It makes several valuable contributions: (1) novel insights into how to develop decision models to identify the most favorable HSCT timing, (2) evidence to inform clinical decisions in a real-world context, and (3) the incorporation of complex information into decision making. This framework can be applied to provide medical insights for clinical issues that cannot be adequately addressed through randomized clinical trials.


Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Precision Medicine , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/methods , Hematologic Neoplasms/therapy , Transplantation, Homologous/methods , Male , Middle Aged , Female , Precision Medicine/methods , Adult , Aged , Retrospective Studies , Myelodysplastic Syndromes/therapy , Young Adult
12.
Am J Reprod Immunol ; 91(5): e13853, 2024 May.
Article En | MEDLINE | ID: mdl-38706383

BACKGROUND: The amniotic membrane (AM) has shown immense potential in repairing wounds due to its great regenerative qualities. Although the role of AM as a biological scaffold in repairing wounds has been studied well, the tissue regenerative potential of AM-derived mesenchymal stem cells (MSCs) and conditioned media (CM) derived from it remains to be discovered as of now. Here, we examined the wound healing abilities of fresh and frozen thawed rabbit AM (rAM) along with the MSCs and their lyophilised CM in rabbits challenged with skin wounds. METHODS: To elucidate the role of rAM-MSCs and its CM in repairing the wound, we isolated it from the freshly derived placenta and characterised their differentiation potential by performing an in vitro tri-lineage differentiation assay besides other standard confirmations. We compared the wound repair capacities of rAM-MSCs and lyophilised CM with the fresh and cryopreserved AM at different timelines by applying them to excision wounds created in rabbits. RESULTS: By monitoring wound contractions and tissue histology of wounded skin at different time points after the application, we observed that rAM-MSCs and rAM-MSC-derived CM significantly promoted wound closure compared to the control group. We also observed that the wound closure capacity of rAM-MSCs and rAM-MSC-derived CM is as efficient as fresh and cryopreserved rAM. CONCLUSION: Our findings suggest that rAM-MSCs and rAM-MSC derived CM can be effectively used to treat skin wounds in animals and correctly delivered to the damaged tissue using AM as a bioscaffold, either fresh or frozen.


Amnion , Mesenchymal Stem Cells , Wound Healing , Animals , Rabbits , Female , Mesenchymal Stem Cells/cytology , Cell Differentiation , Culture Media, Conditioned/pharmacology , Mesenchymal Stem Cell Transplantation/methods , Skin/injuries , Skin/pathology , Pregnancy , Disease Models, Animal , Cells, Cultured , Transplantation, Homologous
14.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 242-248, 2024 Mar 14.
Article Zh | MEDLINE | ID: mdl-38716595

Objective: To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation. Methods: A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University. Results: ① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1ß, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions: Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.


Cytokines , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Tears , Graft vs Host Disease/diagnosis , Graft vs Host Disease/metabolism , Cytokines/metabolism , Cytokines/blood , Humans , Mice , Hematopoietic Stem Cell Transplantation/adverse effects , Animals , Tears/metabolism , Chronic Disease , Biomarkers/metabolism , Disease Models, Animal , Transplantation, Homologous , Female , Interferon-gamma/blood , Interferon-gamma/metabolism , Bronchiolitis Obliterans Syndrome
15.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 249-256, 2024 Mar 14.
Article Zh | MEDLINE | ID: mdl-38716596

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.


Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Transplantation Conditioning , Transplantation, Homologous , Whole-Body Irradiation , Humans , Hematopoietic Stem Cell Transplantation/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning/methods , Prognosis , Adult , Survival Rate , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Cyclophosphamide/administration & dosage , Male , Female , Middle Aged
16.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 308-312, 2024 Mar 14.
Article Zh | MEDLINE | ID: mdl-38716606

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non Hodgkin's lymphoma. The current treatment plan can significantly improve the prognosis of patients, but about 30%-40% of DLBCL patients still experience drug resistance and relapse after treatment. For patients with refractory/relapse DLBCL, clinical treatment remains difficult and their prognosis is poor. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the most important curative methods for refractory/relapse DLBCL patients. This article will review the role and progress of allo-HSCT in the treatment of refractory/relapse DLBCL.


Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Transplantation, Homologous , Humans , Lymphoma, Large B-Cell, Diffuse/therapy , Hematopoietic Stem Cell Transplantation/methods
17.
Blood Cancer J ; 14(1): 76, 2024 May 02.
Article En | MEDLINE | ID: mdl-38697960

Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000-2004) and last (2015-2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5-35%, LFS: 14.5-24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2.


Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Registries , Humans , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/mortality , Middle Aged , Male , Female , Adult , Hematopoietic Stem Cell Transplantation/methods , Aged , Young Adult , Adolescent , Transplantation, Homologous , Recurrence , Transplantation Conditioning/methods , Treatment Outcome , Graft vs Host Disease/etiology , Graft vs Host Disease/epidemiology
18.
BMC Pediatr ; 24(1): 299, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702595

PURPOSE: We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. RESULTS: Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 µg·mL-1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) (p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2, CYP2C19*3, CYP2C19*17, and UGT1A4 (rs2011425) (p > 0.05). CONCLUSION: There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.


Antifungal Agents , Chemical and Drug Induced Liver Injury , Hematopoietic Stem Cell Transplantation , Voriconazole , Humans , Voriconazole/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Child , Male , Female , Prospective Studies , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/genetics , Risk Factors , Antifungal Agents/adverse effects , Child, Preschool , China , Adolescent , Cytochrome P-450 CYP2C19/genetics , Transplantation, Homologous/adverse effects
19.
BMC Med Res Methodol ; 24(1): 112, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734644

Orphan diseases, exemplified by T-cell prolymphocytic leukemia, present inherent challenges due to limited data availability and complexities in effective care. This study delves into harnessing the potential of machine learning to enhance care strategies for orphan diseases, specifically focusing on allogeneic hematopoietic cell transplantation (allo-HCT) in T-cell prolymphocytic leukemia. The investigation evaluates how varying numbers of variables impact model performance, considering the rarity of the disease. Utilizing data from the Center for International Blood and Marrow Transplant Research, the study scrutinizes outcomes following allo-HCT for T-cell prolymphocytic leukemia. Diverse machine learning models were developed to forecast acute graft-versus-host disease (aGvHD) occurrence and its distinct grades post-allo-HCT. Assessment of model performance relied on balanced accuracy, F1 score, and ROC AUC metrics. The findings highlight the Linear Discriminant Analysis (LDA) classifier achieving the highest testing balanced accuracy of 0.58 in predicting aGvHD. However, challenges arose in its performance during multi-class classification tasks. While affirming the potential of machine learning in enhancing care for orphan diseases, the study underscores the impact of limited data and disease rarity on model performance.


Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Prolymphocytic, T-Cell , Machine Learning , Transplantation, Homologous , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Humans , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation, Homologous/methods , Leukemia, Prolymphocytic, T-Cell/therapy , Leukemia, Prolymphocytic, T-Cell/diagnosis , Male , Middle Aged , Female , Adult , Acute Disease
20.
Rev Invest Clin ; 76(2): 91-96, 2024.
Article En | MEDLINE | ID: mdl-38740380

UNASSIGNED: Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6).


Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Mexico , Protein Kinase Inhibitors/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Retrospective Studies , Male , Female , Middle Aged , Adult , Young Adult , Aged , Adolescent , Survival Rate , Transplantation, Homologous
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