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Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein-Barr virus infection
Luo, Y., Wei, A., Wang, B., Zhu, G., Zhang, R., Jia, C., Yan, Y., Zhou, X., Yang, J., Qin, M., et al
Pediatric investigation. 2022;6(4):250-259
Abstract
IMPORTANCE Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the only effective treatment for chronic active Epstein-Barr virus infection (CAEBV). The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear. OBJECTIVE To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning (MAC) regimen for children with CAEBV and also the factors affecting the outcomes. METHODS We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children's Hospital, Capital Medical University from October 2016 to June 2021. Data related to the clinical manifestations, engraftment, and outcome were extracted from the medical records. RESULTS The cohort comprised 41 patients (24 males, 17 females) with a median transplantation age of 92.6 (60.4, 120.7) months and a median follow-up time of 28.2 (15.3, 40.2) months. Four patients (9.8%) died, among which three died from primary disease relapse, and one died from grade IV acute graft-versus-host diseases (aGVHD) after stopping treatment. The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates were 88.8% ± 5.4% and 85.0% ± 5.7%, respectively. The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis (HLH) and the patient without HLH (87.7% ± 6.8% vs. 91.7% ± 8.0%, P = 0.790; 85.0% ± 6.9% vs. 84.6% ± 10.0%, P = 0.921), or among the patients with complete remission, partial remission, and activity disease before HSCT (all P > 0.05). Multivariate analysis showed that grade III-IV aGVHD was a risk factor for mortality (Hazards ratio: 11.65, 95% confidence interval: 1.00, 136.06; P = 0.050). INTERPRETATION Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV. This treatment benefits patients with HLH or active disease. Patients with Grade III-IV aGVHD may be associated with worse outcomes.
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Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1
Ustun, C., Kim, S., Chen, M., Beitinjaneh, A. M., Brown, V. I., Dahi, P. B., Daly, A., Diaz, M. A., Freytes, C. O., Ganguly, S., et al
Blood advances. 2019;3(17):2525-2536
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Abstract
Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT-comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, <1-99 days]; RIC/NMA, 21 days [range, <1-100 days]; P < .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P < .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P < .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.
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Invasive Fungal Disease in Patients Undergoing Umbilical Cord Blood Transplantation after Myeloablative Conditioning Regimen
Montoro, J., Sanz, J., Lorenzo, J. I., Montesinos, P., Rodriguez-Veiga, R., Salavert, M., Gonzalez, E., Guerreiro, M., Carretero, C., Balaguer, A., et al
European journal of haematology. 2018
Abstract
OBJECTIVE Characteristics and risk factors (RFs) of invasive fungal disease (IFD) have been little studied in the setting of umbilical cord blood transplantation (UCBT). METHOD We retrospectively included 205 single-unit myeloablative UCBT recipients with a median follow-up of 64 months. RESULTS Fifty-six episodes of IFD were observed in 48 patients (23%) at a median time of 123 days after stem cell infusion. Invasive mold disease (IMD) occurred in 42 cases, 38 of them (90%) caused by invasive aspergillosis whereas invasive yeast disease (IYD) occurred in 14 cases, most of them due to candidemia (n= 12, 86%). The 5-year cumulative incidence of IFD, IMDs and IYDs was 24% 19% and 7%, respectively. In multivariate analysis, 3 RFs for IMDs were identified: age > 30 years (HR 3.5, p=0.017), acute grade II-IV graft-versus-host disease (HR 2.3, p=0.011) and 1 previous transplant (HR 3.1, p=0.012). The probability of IMDs was 2.5%, 14% and 33% for recipients with none, 1, or 2 to 3 RFs, respectively (p< 0.001). Among IFD, IMDs had a negative effect on non-relapse mortality in multivariate analysis (HR 1.6, p=0.039). IMDs showed a negative impact on overall survival (HR 1.59, p=0.018). CONCLUSION IMDs were very common and serious complication after UCBT. This article is protected by copyright. All rights reserved.
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Pre-engraftment bloodstream infections in acute leukemia patients undergoing unrelated cord blood transplantation following intensified myeloablative conditioning without ATG
Zheng, C., Tang, B., Zhu, X., Zhang, X., Zhang, L., Geng, L., Liu, H., Sun, Z.
Annals of Hematology. 2017;96(1):115-124
Abstract
The aim of this study is to investigate the impact of pre-engraftment bloodstream infections (BSIs) on the outcomes in acute leukemia patients undergoing myeloablative cord blood transplantation (CBT). A total of 226 acute leukemia patients who received unrelated CBT were enrolled in this study, and all these patients received an intensified myeloablative conditioning without ATG. Pre-engraftment BSIs occurred in 72 patients (31.9 %), and the median time of onset was 4.5 days after cord blood infusion, BSIs of gram-negative bacilli, and gram-positive cocci comprised of 63.8 and 36.2 %, respectively. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic graft versus host disease (GVHD) were comparable among the non-BSI, gram-negative bacilli BSI, and gram-positive cocci BSI groups. The cumulative incidence of transplant-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) was similar between the non-BSI and the BSI groups. For subgroups analysis, TRM was lower in gram-positive cocci BSI patients compared with that of gram-negative bacilli BSI patients (8.3 vs 39.3 %) (p=0.01) (HR=0.39, p=0.034), and the 5-year OS was higher in gram-positive cocci BSI cohort (79.1 vs 44.2 %) (p=0.01) (HR=0.36, p=0.046). Our study demonstrated that, for acute leukemia patients who received CBT after myeloablative conditioning that omitted ATG, pre-engraftment BSI had no impact on engraftment, GVHD, TRM, relapse, and long-term survival. Due to the fact that gram-negative bacilli BSI was associated with poor outcomes compared with gram-positive cocci BSI, appropriate early empirical antimicrobial management strategies and better supportive care are required to decrease the gram-negative bacilli BSI-related mortality.