Need for hemodialysis in patients undergoing hematopoietic stem cell transplantation: risk factors and survival in a retrospective cohort

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.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation / 中华血液学杂志

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Effects of FAC combined with Bu conditioning for SAA patients undergoing allogeneic stem cell transplantation / 西安交通大学学报(医学版)

【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.

Clinical outcomes and early immune reconstitution in patients with acute lymphoblastic leukemia underwent allogeneic hematopoietic stem cell transplantation / 中国输血杂志

【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.

Advances in conditioning regimens for allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia / 中华器官移植杂志

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.

Risk factors of hemorrhagic cystitis after allo-HSCT and therapeutic effects of early transfusion of umbilical cord mesenchymal stem cells / 中华器官移植杂志

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.

Research advance of mesenchymal stem cell-derived exosomes in graft-versus-host disease / 中华器官移植杂志

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.

Allogeneic hematopoietic stem cell transplantation for children with aggressive natural killer cell leukemia: one case report with a literature review / 中华器官移植杂志

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.

Clinical characteristics of patients with human adenovirus infection undergoing allogeneic hematopoietic stem cell transplantation / 中华内科杂志

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.

Pathogenic characteristics of bloodstream infections in patients with hematological diseases and the impact of stem cell transplantation on them / 中国热带医学

@#Abstract: Objective To investigate the epidemiological characteristics of pathogens causing bloodstream infection in hematology patients during treatment and to compare the effects of allogeneic hematopoietic stem cell transplantation (HSCT) on them, so as to provide evidence for the diagnosis and treatment of bloodstream infection. Methods A total of 292 cases with bloodstream infection in hematology wards of the PLA General Hospital were collected from 2017 to 2021, which were divided into HSCT group and N-HSCT group according to whether performed HSCT or not. The epidemiological characteristics and influence of pathogenic bacteria in blood stream infection were analyzed and compared between the two groups. Results A total of 362 strains of pathogenic bacteria were collected from 292 cases, including 106 strains in HSCT group (84 cases) and 256 strains in N-HSCT group (208 cases). Bloodstream infections were more common in acute myeloid leukemia (130/392, 44.52%), followed by non-Hodgkin's lymphoma (74/292, 25.34%). The rate of once bloodstream infection in HSCT group was higher than that in N-HSCT Group, but the rate of twice bloodstream infections in N-HSCT group was higher. Gram-negative Bacilli were the most common pathogens (56.08%), with Escherichia coli being absolutely dominant (109/362, 30.11%), followed by Klebsiella pneumoniae (39/362, 10.77%). Coagulase-negative staphylococci (CoNS) (107/362, 29.56%) were the most common Gram-positive cocci. The detection rate of fungi in HSCT group (10/106, 9.43%) was significantly higher than that in N-HSCT Group (3.52%). The drug resistance rate of the common pathogenic bacteria was at a high level, and there was a certain proportion of multi-drug resistant strains (except for Pseudomonas aeruginosa). The resistance rates of CoNS to penicillin, gentamicin, moxifloxacin, clindamycin and rifampicin in HSCT group were higher than those in N-HSCT Group. The resistance rate of Escherichia coli to piperacillin/tazobactam, cephalosporins and etapenem in HSCT group was significantly higher than that in N-HSCT group. Conclusions The pathogens of blood stream infection in hematology patients are complicated and various. It is difficult for clinical diagnosis and treatment to detect multiple infections and multiple pathogens. HSCT patients have a higher risk of fungal bloodstream infection and more multi-drug resistant strains detected. Therefore, the identification of bloodstream infection and multi-drug resistant strains associated with HSCT patients should prompt surveillance.

Analysis of interleukin-36 expression in tears of allogeneic hematopoietic stem cell transplantation patients and its correlation with the ocular surface microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the expression of interleukin(IL)-36(α, β, γ)in tears of patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT), investigate its correlation with ocular surface microenvironment, and further analyze the relationship between its expression and ocular graft-versus-host disease(oGVHD).METHODS: Prospective study. A total of 35 patients(70 eyes)underwent allo-HSCT in the hematology department of our hospital in January 2020 were selected, and 35 healthy volunteers(70 eyes)with appropriate age and gender were selected as normal control group. The patients in the allo-HSCT group were followed up 3 times after operation once every 3mo. The subjects with postoperative ocular symptoms were divided into oGVHD and Non-oGVHD group.Ocular surface disease index(OSDI)questionnaire, Schirmer test, tear break-up time(TBUT), corneal fluorescein staining(FL), and conjunctival impression cytology(CIC)was conducted in three groups. Furthermore, the expression levels of IL-36(α,β,γ)in tears were detected by ELISA.RESULTS: In the normal control group, IL-36(α, β, γ)expression levels were 74.32±5.27, 70.02±8.43, 97.41±8.66 pg/mL, respectively; in the allo-HSCT group, IL-36(α, β, γ)baseline expression levels were 77.27±7.03, 74.53±7.53, 100.77±9.74 pg/mL, with no statistically significant differences between the two groups(t=1.648, 1.954, 1.262, all P&#x003E;0.05). There were no significant differences in IL-36α, IL-36β and IL-36γ in Non-oGVHD group at different time points(P&#x003E;0.05), while there were significant differences in IL-36α, IL-36β and IL-36γ in oGVHD group at different time points(P&#x003C;0.05). Compared with Non-oGVHD group, the levels of IL-36α and IL-36β at different time points were significantly increased in oGVHD group(all P&#x003C;0.05).IL-36(α, β, γ)of oGVHD group was positively correlated with OSDI score, FL and CIC, while it was negatively correlated with TBUT and Schirmer test(all P&#x003C;0.05).CONCLUSION: Evaluation of levels of tear IL-36(α, β, γ)can be of significance in diagnosing oGVHD after allo-HSCT. IL-36(α, β, γ)is highly expressed in the tears of oGVHD patients before the onset of ocular symptoms, and it is correlated with the ocular surface parameters.

Treatment of severe aplastic anemia and hematopoietic stem cell transplantation / 器官移植

Severe aplastic anemia (SAA) is a severe bone marrow failure syndrome caused by multiple causes, which is clinically manifested with severe anemia, infection and bleeding. The complex pathogenesis of SAA has not been fully understood. SAA is characterized with acute onset, severe disease condition and rapid progression. At present, with the in-depth study of SAA and the improvement of diagnosis and treatment, the therapeutic strategy for SAA has been evolved from classical immunosuppressive therapy based on antithymocyte globulin and cyclosporine to the application of thrombopoietin receptor agonist and combined treatment based on allogeneic hematopoietic stem cell transplantation, which may promote the reconstruction of hematopoietic function of SAA patients to varying degree and significantly improve survival and clinical prognosis, becoming the research hotspot of SAA treatment. In this article, new advances in the treatment of SAA at home and abroad were reviewed.

Prevention and treatment of high-risk acute myeloid leukemia recurrence after allogeneic hematopoietic stem cell transplantation / 器官移植

Acute myeloid leukemia (AML) is a group of highly-heterogeneous clonal diseases. Chemotherapy and hematopoietic stem cell transplantation are considered as effective treatment for AML. For high-risk AML patients, allogeneic hematopoietic stem cell transplantation is an effective therapeutic option. However, some AML patients may still face the problem of disease recurrence after hematopoietic stem cell transplantation. A majority of recurrent patients cannot be effectively treated by chemotherapy or secondary transplantation, which is the main cause of death after allogeneic hematopoietic stem cell transplantation. Therefore, it is of significance to strengthen follow-up of AML patients after allogeneic hematopoietic stem cell transplantation and implement appropriate measures to prevent postoperative recurrence. In this article, the monitoring, drug prevention and cell therapy of recurrence after allogeneic hematopoietic stem cell transplantation in high-risk AML patients were reviewed, aiming to provide reference for improving clinical prognosis of high-risk AML patients undergoing allogeneic hematopoietic stem cell transplantation.

Prevention and treatment of chronic graft-versus-host disease by mesenchymal stem cells: advances and challenges / 器官移植

Chronic graft-versus-host disease (cGVHD) is the main complication after allogeneic hematopoietic stem cell transplantation, which is also the major cause of non-relapse -related death. Due to its complex pathophysiological process, the response rate of conventional glucocorticoids combined with immunosuppressants is less than 50%. Second-line therapy should be given for patients with glucocorticoid-resistant cGVHD. Nevertheless, no consensus has been reached on current second-line therapy and the therapeutic effect is relatively poor. Mesenchymal stem cell (MSC) is one of the most common adult stem cells. Due to multi-dimensional and multi-target immune regulating function, MSC has been widely applied in the prevention and treatment of cGVHD. In addition, accumulated studies have confirmed the safety and efficacy of MSC in the treatment of cGVHD, which is expected to become a novel strategy for the prevention and management of cGVHD. In this article, research progress, mechanism and existing problems of prevention and treatment of cGVHD by MSC were reviewed, aiming to provide novel ideas for optimizing therapeutic regimens of MSC and enhancing the prevention and treatment effect of cGVHD in subsequent research.

Progress on methotrexate gene polymorphisms in allogeneic hematopoietic stem cell transplantation / 国际儿科学杂志

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.

Maintenance therapy following allogeneic hematopoietic stem cell transplantation in myeloid neoplasms / 白血病·淋巴瘤

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.