Cytomegalovirus viremia, disease, and impact on relapse in T-cell replete peripheral blood haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide.
Ontology highlight
ABSTRACT:
SUBMITTER: Goldsmith SR
PROVIDER: S-EPMC5394884 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
Publications
Cytomegalovirus viremia, disease, and impact on relapse in T-cell replete peripheral blood haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide.
Goldsmith Scott R SR Slade Michael M DiPersio John F JF Westervelt Peter P Lawrence Steven J SJ Uy Geoffrey L GL Abboud Camille N CN Vij Ravi R Schroeder Mark A MA Fehniger Todd A TA Dubberke Erik R ER Trinkaus Kathryn K Romee Rizwan R
Haematologica 20160721 11
Similar Datasets
Project description:ObjectivesT-cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is at high risk of invasive fungal infections (IFI), and anti-mold-active drug is required for primary antifungal prophylaxis (PAP) according to international guidelines. No data are available on the efficacy of caspofungin as PAP in this setting.MethodsHere, we report our retrospective experience with 103 consecutive patients treated with caspofungin as PAP after Haplo-SCT. Caspofungin was administered only during the pre-engraftment phase.ResultsHundred-day cumulative incidence of proven-probable IFI (PP-IFI) was 8.7% and median day of onset was 19 post-SCT. No patient died of PP-IFI, and overall survival (OS) and non-relapse mortality (NRM) hazard ratio (HR) for patients experiencing IFI were 1.02 (P = 0.9) and 0.7 (P = 0.7), respectively. Three-year overall survival (OS) and 1-year non-relapse mortality (NRM) were 55% and 19%, respectively. By univariate analysis, duration of neutropenic phase and partial remission pre-transplant disease status were associated with increased incidence of IFI, but were not confirmed by multivariate analysis.ConclusionIn summary, PAP with caspofungin is an effective strategy for preventing IFI in the context of Haplo-SCT with PT-Cy. Further efforts are required in order to identify more potent strategies able to avoid the occurrence of breakthrough infections.
| S-EPMC7163667 | biostudies-literature
Project description:ImportancePatient-specific human leukocyte antigen (HLA) genomic loss (HLA loss) is one of the reputed mechanisms of leukemia immune escape and relapse after haploidentical hematopoietic stem cell transplant (HSCT). However, clinical characteristics and prognosis of this distinct relapse type in the setting of haploidentical HSCT based on antithymocyte globulin (ATG) T-cell-replete conditioning are still unknown, especially for patients with lymphoid leukemia.ObjectiveTo identify the incidence of and patient characteristics associated with HLA loss at hematologic cancer relapse after ATG-based haploidentical HSCT and to assess overall survival after HLA loss at relapse.Design, setting, and participantsThis retrospective and multicenter case series study used data from medical records to identify patients who experienced relapse of hematologic cancer after receipt of ATG-based haploidentical HSCT. The study included 788 consecutive patients aged 8 to 70 years with lymphoid or myeloid leukemia who received ATG T-cell-replete haploidentical HSCT at the Zhejiang Cooperative Group for Blood and Marrow Transplantation between May 1, 2012, and May 31, 2021.ExposuresRelapse after ATG-based haploidentical HSCT.Main outcomes and measuresIncidence, risk factors, and postrelapse overall survival among patients with HLA loss at hematologic cancer relapse after receipt of haploidentical HSCT. Logistic regression analysis was used to identify characteristics associated with the likelihood of HLA loss, and Kaplan-Meier and Cox regression analyses were performed to evaluate postrelapse survival.ResultsA total of 788 patients who received haploidentical HSCT for hematologic cancer were identified, 180 of whom experienced relapse after HSCT. Of those, 106 evaluable patients (median age, 30.9 years [range, 8.3-64.6 years]; 54 female [50.9%] and 52 male [49.1%]) were screened for HLA loss, which was detected in 54 patients (50.9%). Patients with HLA loss experienced relapse later than those without HLA loss (lymphoid group: median, 323 days [range, 98-2056 days] vs 151 days [range, 57-2544 days]; P = .01; myeloid group: median, 321 days [range, 55-1574 days] vs 223 days [range, 68-546 days]; P = .03). Among patients with lymphoid leukemia, those with minimal residual disease positivity before hematologic relapse (odds ratio [OR], 28.47; 95% CI, 1.99-407.98; P = .01), those with chronic graft-vs-host disease (OR, 27.68; 95% CI, 1.40-546.88; P = .03), and those with more than 180 days between HSCT and relapse (OR, 6.91; 95% CI, 1.32-36.22; P = .02) were more likely to lose unshared HLA at relapse, whereas male patients (OR, 0.03; 95% CI, 0.003-0.32; P = .04) were more likely to preserve their HLA genome at relapse. Patients with myeloid leukemia had different factors associated with HLA loss, including underweight status (OR, 0.10; 95% CI, 0.02-0.60; P = .01) and acute graft-vs-host disease (OR, 4.84; 95% CI, 1.14-20.53; P = .03). The receipt of preemptive donor lymphocyte infusion among patients with minimal residual disease recurrence did not postpone hematologic cancer relapse in those with HLA loss (median, 322 days [range, 204-1030 days]) compared with no receipt of donor lymphocyte infusion (median, 340 days [range, 215 days to not available]; P > .99).Conclusions and relevanceIn this study, HLA loss at leukemia relapse occurred frequently after receipt of ATG-based haploidentical HSCT. The identification of risk factors associated with HLA loss would help to prompt screening, avoid potentially harmful infusions of donor T cells, and develop alternative therapeutic strategies.
| S-EPMC8987901 | biostudies-literature
Project description:Haploidentical hematopoietic cell transplant (haplo-HCT) with post-transplant cyclophosphamide (PTCY) is utilized for patients with hematological disorders but without conventional donors. The effects of new-onset post-transplant diabetes mellitus (PTDM) following haplo-HCT are unknown. We examined PTDM incidence and outcomes after haplo-HCT with PTCY. Patients without diabetes receiving haplo-HCT (n=64) were analyzed for PTDM diagnosis (defined as blood glucose≥ 200 mg/dL). By day 100, 14 (22%) patients developed PTDM (median, 18 days). Hyperglycemia (blood glucose ≥ 200 mg/dL) preceded corticosteroids in 11 (79%) individuals. PTDM patients had increased death/relapse (p=0.029). PTDM occurs frequently, precedes corticosteroids, and leads to inferior outcomes following haplo-HCT. PTDM prophylaxis/treatment may improve HCT survival.
| S-EPMC7942195 | biostudies-literature
Project description:Aims and objectives: Haploidentical transplants constitute a potential alternative therapy for patients who urgently need transplantation in the absence of human leukocyte antigen-matched donors. We report a single-center experience regarding the initial results of haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) using post-transplant cyclophosphamide (PTCy) at the HCMC Blood Transfusion Hematology (BTH) Hospital. Methods: We conducted a retrospective case series study of 23 patients who underwent haplo-PBSCT using PTCy at the HCMC BTH Hospital between January 2014 and January 2021. The refined disease risk index (DRI) was used to stratify the outcomes. We evaluated the engraftment rate, graft-versus-host disease (GVHD), and complications during haploidentical transplantation. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) were assessed. Results: The majority of the patients in the present study were diagnosed with acute myeloid leukemia. All patients received reduced-intensity conditioning regimens. The engraftment rate was 86.9%. The median times to neutrophil and platelet engraftment were 17 and 31 days, respectively. Two patients (8.7%) reported severe acute GVHD (grade III-IV), while two patients (8.7%) had grade I-II acute GVHD. Three patients experienced limited chronic GVHD of the skin, requiring topical steroids. The most common complication was bloodstream infection (60.9%). Cytomegalovirus reactivation occurred in 19 patients (82.6%) and 17.4% developed hemorrhagic cystitis. The 1-year relapse rate was 32.5%. The cumulative incidence of non-relapse mortality at 1 year was 17.3%. The 1-year OS and DFS rates were 66.3% and 55.7%, respectively. The 1-year GRFS rate was 49.2%. A high/very high DRI score was associated with worse OS after haplo-PBSCT (P=0.038). Conclusion: Haploidentical transplant using PTCy is a feasible therapy for patients without suitably matched donors in Vietnam. Infection after transplantation remains a challenge and requires effective management.
| S-EPMC9847308 | biostudies-literature
Project description:KIR3DL1 alleles are expressed at different levels on the natural killer (NK) cell surface. In particular, the non-expressed KIR3DL1*004 allele appears to be common in Caucasian populations. However, the overall distribution of non-expressed KIR3DL1 alleles and their clinical relevance after T-replete haploidentical hematopoietic stem cell transplantation (hHSCT) with post-transplant cyclophosphamide remain poorly documented in European populations. In a cohort of French blood donors (N = 278), we compared the distribution of expressed and non-expressed KIR3DL1 alleles using next-generation sequencing (NGS) technology combined with multi-color flow cytometry. We confirmed the predominance of the non-expressed KIR3DL1*004 allele. Using allele-specific constructs, the phenotype and function of the uncommon KIR3DL1*019 allotype were characterized using the Jurkat T cell line and NKL transfectants. Although poorly expressed on the NK cell surface, KIR3DL1*019 is retained within NK cells, where it induces missing self-recognition of the Bw4 epitope. Transposing our in vitro observations to a cohort of hHSCT patients (N = 186) led us to observe that non-expressed KIR3DL1 HSC grafts increased the incidence of relapse in patients with myeloid diseases. Non-expressed KIR3DL1 alleles could, therefore, influence the outcome of hHSCT.
| S-EPMC10216127 | biostudies-literature
Project description:In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.
| S-EPMC8504778 | biostudies-literature
Project description:BackgroundRefractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).MethodsIn phase I/II trials, we treated 67 subjects for CMV viremia or disease arising after HCT with adoptive transfer of banked, third-party, CMVpp65-sensitized T cells (CMVpp65-VSTs). All were evaluable for toxicity and 59 for response. Evaluable subjects had CMV disease or persisting viremia that had failed at least 2 weeks of induction therapy with a median of 3 antiviral drugs; 84.7% had more than 3 of 11 high-risk features. CMVpp65-VSTs were specific for 1 to 3 CMVpp65 epitopes, presented by a limited set of HLA class I or II alleles, and were selected based on high-resolution HLA matching at 2 of 10 HLA alleles and matching for subject and subject's HCT donor for 1 or more alleles through which the CMVpp65-VSTs were restricted.ResultsT cell infusions were well tolerated. Of 59 subjects evaluable for response, 38 (64%) achieved complete or durable partial responses.ConclusionsRecipients responding to CMVpp65VSTs experienced an improved overall survival. Of the risk factors evaluated, transplant type, recipient CD4+ and CD8+ T cell levels prior to adoptive therapy, and the HLA restriction of CMVpp65-VSTs infused each significantly affected responses. In addition, CMVpp65-specific T cells of HCT donor or recipient origin contributed to the durability of both complete and partial responses.Trial RegistrationNCT00674648; NCT01646645; NCT02136797 (NIH).FundingNIH (P01 CA23766, R21 CA162002 and P30 CA008748); Aubrey Fund; Claire Tow Foundation; Major Family Foundation; "Rick" Eisemann Pediatric Research Fund; Banbury Foundation; Edith Robertson Foundation; Larry Smead Foundation.
| S-EPMC10178844 | biostudies-literature
Project description:Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.
| S-EPMC10453524 | biostudies-literature
Project description:Leukocyte adhesion deficiency type I (LAD-I) is a rare autosomal recessive inborn error of immunity (IEI) caused by the defects in CD18, encoded by the ITGB2 gene. LAD-I is characterized by defective leukocyte adhesion to the vascular endothelium and impaired migration of leukocytes. Allogeneic hematopoietic cell transplant (HCT) is the only curative treatment for LAD-I. In an absence of ideal donor for HCT, human leukocyte antigen (HLA)-haploidentical HCT is performed. Posttransplant cyclophosphamide (PT-CY) is a relatively new graft-versus-host disease (GVHD) prophylactic measure and has been increasingly used in HLA-haploidentical HCT for malignant and nonmalignant diseases. However, experience in using PT-CY for rare IEIs, such as LAD-I, is very limited. We report a case of LAD-I successfully treated with HLA-haploidentical HCT with PT-CY. Complete chimerism was achieved, and the patient was cured. Her transplant course was complicated by mild GVHD, cytomegalovirus reactivation and veno-occlusive disease/sinusoidal obstruction syndrome, which were successfully treated. HLA-haploidentical HCT with PT-CY is a safe and effective option for patients with LAD-I when HLA-matched donors are unavailable.
| S-EPMC9638093 | biostudies-literature
Project description:Severe infections and their attributable mortality are major complications in recipients of allogeneic hematopoietic stem cell transplantation (alloSCT). We herein report 236 adult patients who received haploSCT with PTCy. The median follow-up for survivors was 37 months. The overall incidence of bloodstream infections by gram-positive and gram-negative bacteria at 37 months was 51% and 46%, respectively. The incidence of cytomegalovirus infection was 69%, while Epstein Barr virus infections occurred in 10% of patients and hemorrhagic cystitis in 35% of cases. Invasive fungal infections occurred in 11% at 17 months. The 3-year incidence of infection-related mortality was 19%. The median interval from transplant to IRM was 3 months (range 1-30), 53% of IRM occurred >100 days post-haploSCT. Risk factors for IRM included age >50 years, lymphoid malignancy, and developing grade III-IV acute GvHD. Bacterial infections were the most common causes of IRM (51%), mainly due to gram-negative bacilli BSI. In conclusion, severe infections are the most common causes of NRM after haploSCT with PTCy, with a reemergence of gram-negative bacilli as the most lethal pathogens. More studies focusing on the severe infections after haploSCT with PTCy and differences with other types of alloSCT in adults are clearly warranted.
| S-EPMC8165955 | biostudies-literature