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ABSTRACT Introduction: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) patients are exposed to acute and chronic nephrotoxic events (drugs, hypotension, infections, and microangiopathy). The need for hemodialysis (HD) may be associated with high mortality rates. However, the risk factors and clinical impact of HD are poorly understood. Aim: To analyze survival and risk factors associated with HD in allo-HSCT Patients and methods: single-center cohort study 185 (34 HD cases versus 151 controls) consecutive adult allo-HSCT patients from 2007-2019. We performed univariate statistical analysis, then logistic regression and competing risk regression were used to multivariate analysis. Survival was analyzed by Kaplan-Meier and Cox proportional-hazards models. Results: The one-year HD cumulative incidence was 17.6%. Univariate analysis revealed that HD was significantly associated with male gender, age (p 0.056), haploidentical donor, grade II-IV acute GVHD, polymyxin B, amikacin, cidofovir, microangiopathy, septic shock (norepinephrine use) and steroid exposure. The median days of glycopeptides exposure (teicoplanin/vancomycin) was 16 (HD) versus 10 (no HD) (p 0.088). In multivariate analysis, we found: norepinephrine (hazard ratio, HR:3.3; 95% confidence interval, 95%CI:1.2-8.9; p 0.024), cidofovir drug (HR:11.0; 95%CI:4.6 - 26.0; p < 0.001), haploidentical HSCT (HR:1.94; 95%CI:0.81-4.65; p 0.14) and Age (HR:1.01; 95%CI: 0.99-1.03; p 0.18). The HD group had higher mortality rate (HR:6.68; 95% CI: 4.1-10.9; p < 0.001). Conclusion: HD was associated with decreased survival in allo-HSCT. Carefully use of nephrotoxic drugs and improving immune reconstitution could reduce severe infections (shock) and patients requiring cidofovir, which taken together may result in lower rates of HD, therefore improving survival.
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a sole viable treatment for acute myeloid leukemia (AML). As the median age of AML is approaching 68 years and the global population is aging, allo-HSCT for is becoming more vital for elderly AML patients (60 years and over). Conditioning regimen is important in determining the clinical outcomes of post-allo-HSCT patients.This review summarized the classic and latest conditioning regimens and evaluated their respective clinical outcomes.Clinicians may appreciate the advantages of each conditioning regimen and formulate optimal options for elderly AML patients.
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Objective:To explore the clinical efficacy and risk factors of umbilical cord mesenchymal stem cells (UCMSCs) infusion at an early stage (i.e.gross hematuria) for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The relevant clinical data were retrospectively reviewed for 300 patients undergoing allo-HSCT from January 2016 to July 2021.According to the presence or absence of HC, they were assigned into two groups of HC (n=89) and non-HC (control, n=211). According to whether or not receiving an infusion of UCMSCs, 51 patients of HC degree Ⅱ-Ⅳ were divided into two groups of UCMSC infusion and non-infusion.The risk factors of HC after allo-HSCT were analyzed by χ2 test.Logistic regression was employed for multivariate analysis of P<0.05.Mann-Whitney U test was utilized for statistically analyzing the duration of gross hematuria and urinary tract irritation symptoms and evaluating the clinical efficacy of UCMSCs infusion for HC. Results:Among them, 89 (29.67%) developed HC post-allo-HSCT.Clinical grades were Ⅰ (n=38, 42.70%), Ⅱ (n=36, 40.45%), Ⅲ (n=13, 14.61%) and Ⅳ (n=2, 2.25%). The median occurrence time was 29 (21.5-35.0) days post-allo-HSCT.In univariate analysis, age ≤30 years, haploid transplantation, antithymocyte globulin (ATG), acute graft-versus-host disease (aGVHD), CMV-DNA positive pretreatment significantly boosted the risk of HC ( P<0.05). In multivariate analysis, aGVHD was an independent risk factor for HC ( OR=10.281, 95% CI: 1.606-65.813, P=0.014). Among 89 HC patients, 38 grade Ⅰ patients were complete remission(CR). Among 51 patients of grade Ⅱ-Ⅳ HC, the outcomes were CR (n=48) and non-remission(NR)(n=3). And 24/51 of them received UCMSCs plus conventional treatment.The duration of gross hematuria was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [12(9-17) vs 17(12.0-26.5) day] and the difference was statistically significant ( P=0.045). And the duration of urinary tract irritation symptoms was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [18(11-30) vs 27(18.0-35.5) days] and the difference was statistically significant ( P=0.048). Conclusions:Indicated for post-ALLO-HSCT HC, infusion of UCMSCs may significantly shorten the course of disease.Age ≤30 years, haploid transplantation and preconditioning with positive ATG, aGVHD and CMV-DNA may boost the risks of HC post-allo-HSCT.And aGVHD is an independent risk factor for HC after allo-HSCT.
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Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewing differentiation, immunoactivity and anti-inflammatory potentials.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the most effective treatment for hematologic malignancies.However, the presence of graft-versus-host disease (GVHD) after transplantation has hindered the development of allo-HSCT.MSC-derived exosomes (MSC-exo) derived from mesenchymal stem cells have been confirmed to have broad therapeutic prospects in allo-HSCT and GVHD.This review focused upon immunomodulatory effects of MSC, biological activities of MSC-exo and research advances of MSC-exo on managing GVHD, aiming to provide new therapeutic rationales for GVHD in the future.
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Objective:To summarize the clinical features, treatments and prognoses of aggressive natural killer cell leukemia (ANKL) in children.Methods:Clinical data and follow-up results were retrospectively reviewed for one hospitalized case of ANKL in June 2019.Through a literature search, the relevant items were retrieved from the databases of China National Knowledge Infrastructure, WanFang and PubMed using the Chinese and English keywords of "aggressive natural killer cell leukemia" and "children" up to December 2021.Results:This 8-year-old girl was diagnosed with ANKL by flow cytometric immunophenotype and immunohistochemical stain.Fever was the initial manifestation accompanied by sallow complexion, fatigue, enlargement of liver, spleen and lymph node and hematopenia of three lines.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed after chemotherapy.As of April 2022, the child stayed in a disease-free survival state after follow-ups for over 2 years.The literature search finally yielded 7 eligible Chinese and 10 English reports with a total of 17 pediatric ANKLs.In this group, there were fever (n=15), rash (n=1), perineal mass (n=1) and diarrhea, vomiting and other digestive tract symptoms (n=1). Six cases were misdiagnosed during an early stage of disease.4 cases received chemotherapy alone, 3 cases received chemotherapy regimen for acute lymphoblastic leukemia, 1 child died and one death occurred after received chemotherapy regimen of "cisplatin + vincristine + doxorubicin + ifosfamide". Allo-HSCT was performed in 5 patients after remission with chemotherapy and one child died from multiple organ failure at 9 months after allo-HSCT.Nine cases gave up treatment.Conclusions:ANKL has a rapid disease progression, diverse clinical manifestations, easy misdiagnosis and poor prognosis.For suspected ANKL cases, clinicians perform multiple bone perforations at multiple sites and immunophenotype by flow cytometry as soon as possible to confirm the diagnosis.Currently allo-HSCT offers a long-term survival of ANKL patients.
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Objective:To investigate the clinical characteristics and prognosis of human adenovirus (HAdV) infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:This is a retrospective case series study. Patients who received allo-HSCT and had symptoms of HAdV infection were tested in the Hematology Department at Perking University People′s Hospital from August 2015 to October 2019. Real-time quantitative PCR was used to detect HAdV DNA from 2 728 patients with potential infection. HAdV DNA-positive patients were defined as having HAdV infection. The clinical features of these patients were analyzed, and a case-pair method was used to select patients without HAdV infection as the control group in a 1∶3 ratio. The clinical results of the two groups were compared using Kaplan-Meier and Log-rank testing.Results:A total of 7 119 samples were tested for HAdV, of which 99 samples from 36 patients were positive. Of these patients, 22 developed HAdV viremia, and 24 patients had concurrent infection with another virus. Nineteen patients had fever (53%), 25 had gastrointestinal symptoms (69%), 11 had respiratory symptoms (31%), nine had reduced liver function (25%), and six had nervous system symptoms (17%). Twenty-three patients developed acute graft-versus-host disease of grade 2 or higher. Of all the patients with HAdV infection, nine were treated with cidofovir, seven of whom became HAdV negative and two had invalid treatment. The median follow-up time was 496 (216, 940) d post-HSCT. The overall survival at 5 years post HSCT was 48.4%±9.2% vs. 91.3%±3.5% ( χ2=65.03, P<0.001) in patients with and without HADV, respectively. The non-relapse mortality at 5 years post-HSCT was 40.8%±8.8% vs. 4.0%±2.0% ( χ2=34.17, P<0.001) in patients with and without HADV, respectively. Conclusions:After allo-HSCT, HAdV-infected patients are dominated by gastrointestinal and respiratory symptoms and have an increased risk of combined acute graft-versus-host disease of >2 degrees. Patients with HAdV infection have poor overall survival and high non-relapse mortality.
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Methotrexate(MTX)is one of the main drugs used to prevent graft-versus-host disease(GVHD)after hematopoietic stem cell transplantation, but it can cause a variety of adverse reactions, including severe mucositis, bone marrow suppression and hepatotoxicity.Studies on MTX gene polymorphisms mainly focused on the efficacy and complications of high-dose MTX therapy for various cancers, with relatively few studies on hematopoietic stem cell transplantation.From the perspective of allogeneic hematopoietic stem cell transplantation(allo-HSCT), this article provided a comprehensive review on the pharmacokinetics, complications, and prognosis with MTX gene polymorphisms in allo-HSCT patients, in order to provide clinical reference.
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The acute myeloid leukemia and myelodysplastic syndromes are common myeloid neoplasms for which allogeneic hematopoietic stem cell transplantation is one of the main curative therapies. In high-risk patients, the relapse rate can be more than 40%, and patients with post-transplantation relapses have a very poor prognosis, so preventing relapse after transplantation is crucial. The maintenance therapy is a group of interventions to prevent relapse when morphological, molecular biological and cytogenetic results are constantly negative after transplantation. Currently, the commonly used maintenance therapy is the application of demethylating drugs, targeted drugs, etc., but their necessity, medicine plan, adverse effects, multi-drug combinations, and other aspects need to be studied urgently. This article will systematically describe the progress of post-transplantation maintenance therapy for high-risk myeloid neoplasms based on drug classification.
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Acute myeloid leukemia (AML) is the most common subtype of acute leukemia in adults with significant heterogeneity. Among hematological malignancies, targeted therapy for AML comes relatively late. Although traditional chemotherapy is still an indispensable part of AML treatment, more and more small molecule targeted drugs have been used in recent years since 2017. This article reviews the progress of small molecule targeted drugs for AML at the 64th American Society of Hematology annual meeting.
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Prolonged thrombocytopenia (PT) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with an incidence of about 5%-37%, which is closely related to the poor prognosis of patients. Previous studies have shown that transplantation type, CD34+ cell number, pretreatment regimen, acute graft-versus-host disease, virus infection, pre-transplantation serum ferritin level and donor specific antibodies can affect platelet implantation after transplantation. Identifying the risk factors of PT is helpful to early identify high-risk patients and take targeted preventive measures according to different risk factors to reduce the incidence of PT, reduce the risk of bleeding and improve the prognosis of patients. This article reviews the latest research progress of risk factors and intervention measures related to PT after allo-HSCT, in order to provide reference for the prevention and treatment of PT after transplantation.
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Humans , Transplantation, Homologous/adverse effects , Thrombocytopenia/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Blood Platelets/metabolism , Risk Factors , Graft vs Host Disease/complications , Retrospective StudiesABSTRACT
OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.
Subject(s)
Male , Humans , Busulfan/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Treatment Outcome , Leukemia, Myeloid, Acute/etiology , Acute Disease , Graft vs Host Disease/prevention & controlABSTRACT
OBJECTIVE@#To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft.@*RESULTS@#There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4+CD25+ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078).@*CONCLUSION@#High number of CD34+ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ cells tend to increase the occurrence of aGVHD, but high number of CD4+CD25+ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.
Subject(s)
Humans , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , CD4-Positive T-Lymphocytes , Leukemia, Myeloid, Acute/complications , Graft vs Host DiseaseABSTRACT
OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.
Subject(s)
Male , Female , Humans , Decitabine , Retrospective Studies , Transplantation, Homologous/adverse effects , Transplantation Conditioning/adverse effects , Myelodysplastic Syndromes/complications , Leukemia, Myeloid, Acute/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Chronic Disease , Graft vs Host Disease/therapy , RecurrenceABSTRACT
OBJECTIVE@#To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival.@*METHODS@#A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed.@*RESULTS@#For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005).@*CONCLUSION@#The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.
Subject(s)
Humans , Viremia/complications , Retrospective Studies , Cytomegalovirus Infections/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Risk Factors , Cytomegalovirus , Graft vs Host Disease/complicationsABSTRACT
OBJECTIVE@#To investigate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of young patients with multiple myeloma (MM).@*METHODS@#The clinical data of 8 young patients (median age：46 years) with MM who underwent allo-HSCT from HLA-indentical sibling donors in the First Affiliated Hospital of Chongqing Medical University from June 2013 to September 2021 were collected, and their survival and prognosis were retrospectively analyzed.@*RESULTS@#All the patients were successfully transplanted, and 7 patients could be evaluated the efficacy after transplantation. The median follow-up time was 35.2 (2.5-84.70) months. The complete response (CR) rate was 2/8 before transplantation and 6/7 after transplantation. Acute GVHD developed in 2 cases and extensive chronic GVHD developed in 1 case. Within 100 days, 1 case died of non-recurrent events, and 1-year and 2-year disease-free survival were 6 and 5 cases, respectively. At the end of follow-up, all the 5 patients who survived for more than 2 years survived, and the longest disease-free survival time has reached 84 months.@*CONCLUSION@#With the development of new drugs, HLA-matched sibling donor allo-HSCT may be a curable treatment for young patients with MM.
Subject(s)
Humans , Middle Aged , Multiple Myeloma , Siblings , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host DiseaseABSTRACT
Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.
Subject(s)
Humans , COVID-19 , SARS-CoV-2 , Hematopoietic Stem Cell Transplantation , Tissue Donors , Graft vs Host DiseaseABSTRACT
Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/μl vs 852 cells/μl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.
Subject(s)
Animals , Rabbits , Humans , Antilymphocyte Serum/therapeutic use , Siblings , Retrospective Studies , Hematopoietic Stem Cell Transplantation , Tissue Donors , Graft vs Host Disease/drug therapy , Transplantation ConditioningABSTRACT
Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.
Subject(s)
Male , Female , Humans , Adult , Treatment Outcome , Anemia, Aplastic/therapy , Retrospective Studies , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hepatitis/etiology , Bronchiolitis Obliterans Syndrome , Transplantation ConditioningABSTRACT
【Objective】 To observe the effects of FAC combined with Bu conditioning for severe aplastic anemia (SAA) patients undergoing allogeneic hematopoietic stem cell transplantation. 【Methods】 The data of 28 SAA patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital from January 2016 to September 2021 were collected and analyzed. The patients were divided into two groups: FAC conditioning group and FAC + Bu conditioning group. We observed the side effects of conditioning regimen, hematopoietic recovery, acute and chronic graft versus host disease (GVHD), viral infection, incidence of venous obstructive disease (VOD), progression free survival (PFS), and overall survival (OS). 【Results】 There was no significant difference between the two groups in age, gender, physical condition, history of disease, gender relationship between donors and recipients, transplantation type, infusion of bone marrow nucleated cells, MNC or CD34 positive cells (P>0.05). Compared with those in FAC group, the side effects of auditory hallucination and visual hallucination in FAC + Bu group increased, the incidence of mixed chimerism decreased, the time of platelet reconstruction shortened, the incidence of grade Ⅲ-Ⅳ aGVHD increased. However, 3-year PFS or OS did not significantly differ between the two groups. 【Conclusion】 FAC combined with Bu conditioning regimen promotes implantation and reduces mixed chimerism. However, it does not improve patients’ overall survival.
ABSTRACT
【Objective】 To investigate the correlation between early immune reconstitution and clinical outcomes in patients with acute lymphoblastic leukemia (ALL) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 The basic information and treatment data of 99 patients with ALL undering allo-HSCT from December 2018 to February 2022 were collected. The proportions of CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD16+CD56+ NK cells were detected before and 30, 60 and 90 days after transplantation using flow cytometry. The correlation between early cellular immune reconstitution and neutrophil engraftment, platelet engraftment, infection, and acute and chronic graft-versus-host disease (GVHD) was analyzed. 【Results】 Among 99 ALL patients, the median time of neutrophil engraftment was day +11 (range, 8-28), and the median time of platelet engraftment was day +14 (range, 10-120). The cumulative incidence of blood stream infection (BSI) was 11.10% and the cumulative incidence of CMV within 100 days of transplantation was 40.40%. The cumulative incidence of EBV within 100 days was 7.10%. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 22.30%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) within 1 year of transplantation was 16.20%. 1 -year cumulative relapse rate was 13.84%. The 1 -year cumulative disease-free survival (DFS) for all patients was 80.60% and the 1-year overall survival (OS) was 90.30%. The CD4+/CD8+ ratio was positively associated with the development of aGVHD at 30 days post-transplant (OR 1.21, 95CI 1.01-1.45, P<0.05). The proportion of CD16+ CD56+ NK cell were higher in the group without BSI than that in the BSI group before and 30 days after transplantation (P < 0.05). The proportion of CD4+ T-cell were lower in the CMV infection group than that in the group without CMV infection at 60 and 90 days post-transplant(P<0.05). The higher level of CD4+ T-cells at 60 days post-transplant was a protective factor for CMV infection within 100 days (HR 0.91, 95CI 0.84-0.99, P<0.05). 【Conclusion】 Early immune reconstitution after allo-HSCT in patients with ALL is associated with aGVHD, CMV and BSI.