---
title: "Immune Reconstitution and Infections with ATG vs Post‑transplant Cyclophosphamide after Nonmyeloab"
id: "frontiers-in-immunology-7-immune-reconstitution-and-infections-with-atg-versus-post-transplant"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-7-immune-reconstitution-and-infections-with-atg-versus-post-transplant"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1739320"
published_at: "2026-08-06T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Immune Reconstitution and Infections with ATG vs Post‑transplant Cyclophosphamide after Nonmyeloab
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-7-immune-reconstitution-and-infections-with-atg-versus-post-transplant
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1739320)
- **Published At:** 2026-08-06T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source page and metadata identify an article comparing **immune reconstitution** and **infections** after use of **ATG** versus **post‑transplant cyclophosphamide (PTCy)** for **GvHD prophylaxis** following **nonmyeloablative matched unrelated donor hematopoietic stem cell transplantation (MUD HSCT)**. - The provided source content contains only the journal website navigation and section listings; the article body, methods, results, and conclusions were not included in the source material supplied. - Because primary article details are missing, specific data on patient cohorts, conditioning regimens, dosing of **ATG** or **PTCy**, timing of immune monitoring, infection rates, pathogen distributions, statistical analyses, and clinical outcomes are not available from the supplied source. - Key clinical terms and study context are present in the title: **GvHD prophylaxis**, **nonmyeloablative conditioning**, **matched unrelated donor (MUD)**, **immune reconstitution**, and **infections**—but no study-specific findings or recommendations are reported in the source. - Any summary of comparative effectiveness, safety signals, or practice-changing implications cannot be generated from the supplied content and would require the full article text or supplementary materials. - Readers should consult the full Frontiers in Immunology article or contact the journal for the complete study text, data, and author conclusions before applying findings to clinical practice.
## Clinical Analysis & Structured Key Points
Frontiers | Immune reconstitution and infections with ATG versus post-transplant cyclophosphamide as GvHD prophylaxis after nonmyeloablative matched unrelated donor hematopoietic stem cell transplantation ORIGINAL RESEARCH article Front. Immunol. , 06 August 2026 Sec. Alloimmunity and Transplantation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1739320 Published in Frontiers in Immunology Alloimmunity and Transplantation 7 impact factor 11.3 citescore Part of a Research Topic PTCY and Allo-HCT: A Deep Dive into Outcomes, Toxicities, and Patient-Centered Care 17k views 8 articles Editor & Reviewers Edited by M Q Maria Queralt Salas Reviewed by M L Maria Laura Fox A T Amin T Turki Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Table 1 Baseline characteristics. View in article Table 2 Engraftment and cumulative incidence of infections. View in article Table 3 Cox regression analysis for infections. View in article Table 4 Causes of readmissions post-transplantation 0.5 x 10 9 /L and platelets >20 x 10 9 /L after the nadir without platelet transfusion. Death before day 30 post-transplantation was considered a competing event. Infections were retrospectively identified from the day of stem cell infusion (day 0) up to 1-year post-transplantation and were categorized as bacterial, fungal, and viral infection (CMV reactivation was registered separately), as described previously ( 19 ). Bacterial and fungal infections were defined based on clinical presentation supported by microbiological findings, and viral infections were defined based on PCR detection with or without clinical symptoms, depending on the pathogen. Only clinically relevant infections requiring medical intervention and/or hospitalization were included. CMV reactivation was defined as a CMV viral load (≥1000 copies/ml) without signs of CMV infection, with the day of sampling being considered as the onset of the reactivation. Epstein–Barr virus (EBV) reactivation was defined as detection of EBV DNA in peripheral blood by quantitative PCR, with the date of first detection considered as the onset of reactivation. Pre-emptive therapy was initiated at an EBV DNA load ≥10³ IU/mL. Pneumonia was accepted as an infection in the presence of both clinical and radiological findings of pneumonia with or without microbiologic confirmation. Fever of undetermined origin (whether during neutropenia or not) was not considered to be an infectious complication. The cumulative incidences of bacterial, fungal, and viral infections as well as CMV reactivation were calculated based on the time-to-first infection, while death without infections was considered a competing risk in the first year. The analysis of infection density - which accounts for multiple infectious events in a patient - was calculated by determining infection frequencies over 1000 patient days at risk. Cumulative incidence and infection density over 2 periods (days 0 to +100 and day +101 to +365) and the whole period (0 to + 365) were compared between the treatment groups. The incidence of CMV disease, EBV reactivation, and EBV-related post-transplantation lymphoproliferative disorder were reported separately. All available data of immune reconstitution (T-cells, NK cells and B-cells) as measured by flow cytometry post-transplantation were analyzed and compared between the groups. Transplantation-related readmissions in the first year were divided into two periods (day 0 to +100 and day +101 to +365) and were summarized per cause of readmission. Hospitalization-free days were defined as days alive, without relapse and out of the hospital in the first-year post-transplantation. The total admission days between the conditioning regimen and engraftment and readmission days post-transplantation were subtracted from 365 days to calculate hospitalization-free days. Patients who died before day +365 were followed from day 0 until the time of death. Statistical analysis Continuous variables were assessed using the non-parametric test (Mann–Whitney U test) and categorical variables were analyzed using the Chi-square test (or Fisher’s exact). The incidences of infections and engraftment between the groups were compared using Gray’s method for competing risk analysis. Covariates associated with infections were explored using the Cox proportional hazards regression model, and the models were tested using Schoenfeld residuals test to explore violations of this assumption. The following covariates were assessed in both univariate and multivariate regression models: ATG versus PTCy, age (≤40 vs. >40 years), diagnosis, occurrence of GvHD and hospital readmissions. Results are expressed as a hazard ratio (HR) with a 95% confidence interval (95% CI). To compare infection densities between time periods and groups, the rate ratio was calculated using the mid-P method. Hospitalization-free days for both groups were calculated using the Wilcoxon signed-rank test. SPSS Statistics 27.0 (IBM Corporation, New York, USA) was used for the baseline characteristics and R 3.5.1 (R Core Team [2020]) for the survival curves ( 20 , 21 ). The data that support the findings of this study are available from the corresponding author upon reasonable request. Results Baseline characteristics and transplantation outcomes Patient and transplantation characteristics are summarized in Table 1 . Between January 2014 and December 2021, 185 adult patients diagnosed with hematological malignancies were transplanted with 10/10 MUD using nonmyeloablative conditioning regimens with either ATG (n = 95) or PTCy (n = 90) as in vivo lymphodepleting method in two transplantation centers in Amsterdam. All patients receiving ATG-based conditioning and 4 patients receiving PTCy-based conditioning were transplanted at location A, the remaining 86 patients receiving PTCy-based transplantations were treated at location B. The ATG-containing conditioning regimen consisted of fludarabine (total dose 90 mg/m 2 ), ATG (total dose 8 mg/kg) and 200 cGy total body irradiation (TBI). The PTCy-based conditioning regimen consisted of cyclophosphamide (total dose 29 mg/kg), fludarabine (total dose 150 mg/m 2 ), 200 cGy TBI and PTCy (50 mg/kg on days +3 and +4) in the majority of patients (96%), while 4 patients (4%) received fludarabine (total dose 150 mg/m 2 ) and TBI 200 cGy with PTCy. Transplantation outcomes have been reported previously ( 18 ). In brief, the 1-year cumulative incidence of grade II–IV acute GvHD was significantly higher in the ATG group compared with the PTCy group (48% vs. 21%, respectively; p < 0.001). Overall survival was higher in the PTCy group, although this did not reach statistical significance (3-year OS: 68% vs. 55% in the ATG group; p = 0.12). Table 1 Characteristic ATG (n = 95) PTCy (n = 90) P-value Age, median (IQR) 60 (52 – 66) 57 (48 – 66) 0.43 Disease risk‡, n (%) 0.29 Non-adverse risk 38 (40) 43 (48) Adverse risk 57 (60) 47 (52) Diagnosis, n (%) 0.58 AML/MDS 62 (65) 54 (60) ALL 6 (6) 11 (12) CLL/HL/NHL 24 (25) 22 (24) CML/CMML 3 (3) 3 (3) Disease response at HSCT, n (%) 0.78 CR1 54 (57) 58 (64) ≥CR2 25 (26) 20 (22) PR 7 (7) 4 (5) SD/Upfront 9 (10) 8 (9) WHO performance score, n (%) 0.11 0-1 93 (98) 83 (92) 2 2 (2) 7 (8) HCT-CI, n (%) 0.11 0-1 41 (43) 50 (56) ≥2 54 (57) 40 (44) CD34+ cell dose, median (IQR) 7.0 (5.7 – 8.9) 7.1 (5.6 – 9.5) 0.53 CD3+ cell dose, median (IQR) 259 (201 – 335) 258 (188 – 329) 0.65 CMV serostatus R/D 0.22 +/+ 43 (45) 35 (39) +/- 8 (9) 17 (19) -/+ 7 (7) 6 (7) -/- 37 (39) 32 (35) Baseline characteristics. ATG, anti-thymocyte globulin; PTCy, post-transplantation cyclophosphamide; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; MDS, myelodysplastic syndrome; CLL, Chronic lymphoblastic leukemia: CML, Chronic myeloid leukemia; CMML, Chronic myelomonocytic leukemia; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; CR; complete remission; PR, partial remission; SD, stable disease; WHO, world health organization; HCT-CI, hematopoietic stem cell transplantation comorbidity index, R/D; recipient/donor, CMV; cytomegalovirus, IQR; interquartile range. ‡ Disease risk is divided in non-adverse (low/intermediate), and adverse (high/very high) risk based on diagnoses, disease status and cytogenetic/molecular abnormalities. Engraftment Graft failure was not observed in any of the participants during the first year post-transplantation. The median time to neutrophil engraftment was 20 days [interquartile range (IQR) 15 – 24] in the ATG group compared to 22 days (IQR 19 – 26) in the PTCy group (p = 0.036). The cumulative incidence of neutropenia (ANC <0.5 x 10 9 /L) prior to engraftment was 60% in the ATG group compared to 96% in the PTCy group (p<0.001). The median time to platelet engraftment was 19 days (IQR 15 – 22) in the ATG group compared to 22 days (IQR 16 – 33) in the PTCy group (p = 0.07). The cumulative incidence of thrombocytopenia (platelet counts <20 x 10 9 /L) was 32% in the ATG group versus 83% in the PTCy group (p<0.001). Death before engraftment occurred in three patients (3.3%) due to infections (n = 2) and cardiogenic shock (n = 1) in the PTCy group and in one patient (1%) due to infectious complications in the ATG group. Infections The cumulative incidence of infections is shown in Table 2 . Patients in the ATG group had a lower incidence of bacterial infections by day +100 compared to those in the PTCy group [17% (95%-confidence interval (CI) 10 – 25) vs. 32% (95%-CI 23 – 42), respectively, p = 0.01]. In contrast, the incidence of bacterial infections after day +100 was higher in the ATG group than in the PTCy group [18% (95%-CI 11 – 27) vs. 1% (95%-CI 1 – 6), p <0.001]. Both acute GvHD (HR 2.30, p = 0.003) and readmissions (HR 2.20, p = 0.005) were significantly associated with bacterial infections ( Table 3 ). The cumulative incidence of fungal infections was comparable between both groups and periods. In multivariate analysis, only readmissions were significantly associated with fungal infections (HR 2.73, p = 0.043). Incidence of viral infections by day +100 was similar in both treatment groups (p = 0.44), while patients in the ATG group developed more viral infections after day +100 [22% (95%-CI 14 – 31) vs. 10% (95%-CI 5 - 17), p = 0.022]. In multivariate analysis, viral infections were more frequent in patients with AML/MDS (HR 1.79, p = 0.02), acute GvHD (HR 1.67, p = 0.042) and readmissions (HR 2.21, p = 0.003). The cumulative incidence of CMV reactivation by day +100 was higher in the ATG group than in the PTCy group [36% (95%-CI 26 – 45) vs. 16% (95%-CI 9 – 24), p<0.001; Figure 1 ]. The cumulative incidence of CMV active disease was 8% (n = 8) in the ATG group and 0% in the PTCy group (p = 0.005). In multivariate analyses, PTCy was associated with a significantly reduced risk of CMV reactivation (HR 0.44, p = 0.012). The cumulative incidence of EBV reactivation was 5 (6%) in the ATG group, and 0% in the PTCy group (p = 0.01). Two of the five patients with EBV reactivation in the ATG group developed EBV-related post-transplantation lymphoproliferative disorder. Densities of infections and CMV reactivations are shown in Figure 2 . Infection density analyses showed higher bacterial infection density (per 1000 person days) by day +100 in the PTCy group than in the ATG group (2.76 in ATG vs. 6.34 in PTCy group respectively, p<0.01) while after day +100 this was higher in the ATG group (1.62 in ATG vs. 0.06 in PTCy group respectively, p<0.01). The overall density (day 0 to +365 post-transplant) for bacterial infections was balanced between the groups. The density of fungal infections was comparable by day +100 (1.43 vs. 0.61, p = 0.10) and after day + 100 (0.36 vs. 0.11, p = 0.13), while the overall density was significantly higher in the ATG group (0.77 vs. 0.28, p = 0.02). Density of viral infections was significantly higher in the ATG group than in the PTCy group in the day +101 to +365 period (1.72 vs. 0.53, p<0.01) and in the overall density analysis in the first year post-transplantation (3.54 vs. 1.89, p<0.01). Density of CMV reactivations was higher in the ATG group from day 0 to +100 (5.34 vs. 1.83, p<0.01) and in the overall density analysis (2.21 vs. 0.68, p<0.01), while it was relatively low in both groups after day+100 (0.29 vs. 0.06, p = 0.09). Infection-related mortality was observed in 13% (n = 13) of patients in the ATG group and 8% (n = 7) of patients in the PTCy group. Tab
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