Dataset Information

A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.

ABSTRACT:

Background

Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT.

Methods

Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort.

Results

The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD.

Conclusions

We established a model which could predict the development of severe aGVHD in HID HSCT recipients.

SUBMITTER: Shen MZ

PROVIDER: S-EPMC9067003 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.

Shen Meng-Zhu MZ Hong Shen-Da SD Lou Rui R Chen Rui-Ze RZ Zhang Xiao-Hui XH Xu Lan-Ping LP Wang Yu Y Yan Chen-Hua CH Chen Huan H Chen Yu-Hong YH Han Wei W Wang Feng-Rong FR Wang Jing-Zhi JZ Liu Kai-Yan KY Huang Xiao-Jun XJ Mo Xiao-Dong XD

Experimental hematology & oncology 20220503 1

<h4>Background</h4>Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT.<h4>Methods</h4>Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected a ...[more]

PMID: 35505384

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Project description:Regulatory T cells restore tolerance in preclinical models of immune-mediated diseases and are therefore a promising alternative to conventional immune-suppression for preventing graft-versus-host disease (GvHD) in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Adaptive CD4+ Type 1 regulatory T (Tr1) cells specific for alloantigens are induced in vitro by interleukin-10 (IL-10). Therefore, we evaluated whether infusion of Tr1 cells could promote immune-competence to foreign antigens and long-term alloantigen-specific tolerance. In this phase 1-2 trial, we performed adoptive transfer with IL-10-induced alloantigen-specific Tr1 cells (IL-10-DLI), without immune-suppression, in patients with high-risk hematopoietic malignancies transplanted with CD34+ cells from haploidentical donors. Donor T cells, primed ex vivo with host antigen-presenting-cells and IL-10, are anergic towards host-HLA antigens and contain host-specific Tr1 cells but also memory T cells able to respond to pathogens. Nineteen patients were enrolled in the trial. Twelve received IL-10-DLI. Seven were not evaluable because of early death/relapse, whereas five immune-reconstituted (>100/Âµl CD3+ T cells) at median day 28 after IL-10-DLI. T-cell counts and function progressively normalized in patients who received 105 CD3+ T cells/kg, whereas a higher dose (3x105 CD3+ T cells/kg) caused acute grade III GvHD in one patient. Four patients are alive, in disease remission and immune-suppression-free at a median follow-up of 3.3 years, three of them were analyzed by microarrays; their T-cell receptor repertoire and gene expression profiles are comparable to those of healthy subjects. Cell therapy with IL-10-DLI is feasible, safe, and provides immune-competence. This trial is the first step towards widespread use of Tr1 cells as adjuvant treatment in allogeneic HSCT (IS/11/6172/8309/8391). Keywords: classification of clinical samples Whole blood samples of three healthy donors and three different patients collected at various time points after hematopoietic stem cell transplantation (HSCT) before and after the subsequent administration of IL-10 anergized T cells were analysed on a custom Agilent 8x15K 60mer oligonucleotide microarray encomprising 4610 probes in triplicates. The microarray is dedicated to transplantation research and was designed based on current literature and published and unpublished data provided by the RISET consortium. For the probe selection procedure we specially focused on the detection of multiple transcript variants of a gene, on optimized hybridization properties of the probes, and on the avoidance of crosshybridization. The RISET 1.0 platform (GPL10370) is a precursor of the RISET 2.0 microarray (GPL8136).

Project description:BackgroundCompared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.MethodsThis study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.ResultsA total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P = 0.041), respectively, in the HID and MSD groups.ConclusionHID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registrationClinicalTrials.gov: NCT01883180, NCT02673008.

Dataset Information

A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.

Background

Methods

Results

Conclusions

Publications

A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.

Similar Datasets

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