Abnormal Glucose Tolerance in Allogeneic Hematopoietic Stem Cell Transplantation

A Study of the Impact of Abnormal Glucose Tolerance in Allogeneic Hematopoietic Stem Cell Transplantation Donors on Recipients' Post-Transplant Survival Outcomes: A Multicenter Retrospective Cohort Study Based on HIS Data

To investigate the impact of abnormal glucose tolerance in hematopoietic stem cell transplantation donors on patients' post-transplant survival outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; Impaired Fasting Glucose

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important means of treating a variety of hematologic disorders. With the progress of HSCT technology, especially the research on haploidentical transplantation (HID-HSCT), the range of donor choices for hematological patients has been expanded, and theoretically, the era of "everyone has a donor" has been reached, which has increased the chances for hematological patients to receive allo-HSCT . The efficacy of allo-HSCT has improved dramatically over the past decades, but post-transplant complications such as graft-versus-host disease (GvHD), infections, and disease recurrence may still lead to treatment failure. In order to improve the efficacy of allo-HSCT, in addition to the improvement of pretreatment regimen and post-transplant management, the selection of the best donor among the many alternatives (including sibling donors, parents, children, and collateral hematologic donors, etc.) is still the focus and difficulty of clinical decision-making. The existing studies on donor selection have suggested that the factors to be considered include the number of HLA mismatched sites, donor-recipient consanguinity, donor age and gender, donor-specific antibody (DSA), NK cell isotype reactivity, and clonal hematopoiesis of the donor . However, little is known about whether a donor with metabolic syndrome such as diabetes affects post-transplant survival in allo-HSCT recipients.

It has been shown that diabetes mellitus affects the number and function of hematopoietic and immune cells, and that these effects may be passed on to progeny blood cells through epigenetic mechanisms, with long-term effects on immune cell function in diabetic patients. We therefore hypothesized that the effects of abnormal glucose metabolism in donors on the hematopoietic system may affect hematopoiesis and immune reconstitution in transplant recipients through "metabolic memory". Therefore, the investigator conduct a multicenter retrospective study through multifactorial survival regression. It is expected to provide new theoretical support for optimizing donor selection for allo-HSCT.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Xiaoxia Hu; Phone Number: (86) 13795437259; Email: hu_xiaoxia@126.com

Study Locations

• China
  • Tianjin, China
    • Hospital of Hematology of the Chinese Academy of Medical Sciences
    • Contact: Yawei Zheng; Email: zhengyawei@ihcams.ac.cn
  • Henan
    • Zhengzhou, Henan, China
      • The first affiliated hospital of Zhengzhou university
      • Contact: Weijie Cao; Email: caoweijie2003@126.com
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital of Huazhong University of Science and Technology, Wuhan
      • Contact: Yang Cao; Email: yangcao@tjh.tjmu.edu.cn
  • Shanghai
    • Shanghai, Shanghai, China
      • Li Quan Hospital
      • Contact: Chun Wang; Email: wangchun2@medmail.com.cn
    • Shanghai, Shanghai, China
      • Ruijin Hospital of Shanghai Jiaotong University
      • Contact: Xiaoxia Hu, Doctor; Phone Number: (86) 021-64370045; Email: hxx12276@rjh.com.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Hospital of Zhejiang University School of Medicine
      • Contact: Yanmin Zhao; Email: yanminzhao@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who were diagnosed with hematological disorders and underwent allo-HSCT

Description

Inclusion Criteria:

• Patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) between March 2019 and March 2024;
• Donor had fasting blood glucose and/or HbA1c records
• Eastern Cooperative Oncology Group (ECOG) physical fitness score of 0-2
• Survived at least 12 weeks after HSCT
• Voluntarily signed the Informed Consent Form
• Had appropriate organ function;

• Laboratory results within 7 days prior to HSCT met the following criteria:

  1. Aspartate aminotransferase (AST) ≤ 3-fold (upper limit of norma, ULN);
  2. Alanine aminotransferase (ALT) ≤ 3x ULN;
  3. Total serum bilirubin ≤ 1.5 times the upper limit of normal ULN unless the patient has documented Gilbert syndrome; patients with Gilbert-Meulengracht syndrome with bilirubin ≤ 3.0 times the upper limit of normal and direct bilirubin ≤ 1.5 times the upper limit of normal may be included;
  4. Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min;
  5. Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN, Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN;

Exclusion Criteria:

• Active autoimmune diseases such as SLE, rheumatoid arthritis, etc.
• Active cardiovascular disease such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, any Grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) Functional Class, or a history of myocardial infarction in the 6 months prior to screening;
• Other serious medical conditions that may limit the patient's participation in this trial (e.g., progressive infection, uncontrolled diabetes);
• HIV infection, or chronic infection with hepatitis B virus (HBsAg-positive) or hepatitis C virus (anti-HCV-positive) that cannot be controlled by medications;
• Patients with other uncured tumors
• Patients with neurological or psychiatric disorders
• Patients who were unable to understand or comply with the research protocol or are unable to sign the Informed Consent Form

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case Group; patients who underwent allogeneic hematopoietic stem cell transplantation from March 2019 to March 2024; donor fasting blood glucose and/or HbA1c data available; fasting blood glucose ≥6.1 mmol/L or HbA1c ≥5.7%
Control Group; patients who underwent allogeneic hematopoietic stem cell transplantation from March 2019 to March 2024; donor fasting blood glucose and/or HbA1c data available; fasting blood glucose <6.1 mmol/L; HbA1c <5.7% (if available)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Patient's overall survival time since hematopoietic stem cell transplantation	One year-overall survival since hematopoietic stem cell transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-relapse Mortality (NRM)	NRM after hematopoietic stem cell transplantation	One year since hematopoietic stem cell transplantation
Relapse-free Survival (RFS)	RFS after hematopoietic stem cell transplantation	One year since hematopoietic stem cell transplantation
Event-free Survival (EFS)	EFS after hematopoietic stem cell transplantation	One year since hematopoietic stem cell transplantation
Graft versus Host Disease (GvHD) incidence	GvHD incidence after hematopoietic stem cell transplantation	One year since hematopoietic stem cell transplantation
GvHD and Relapse-free Survival (GRFS)	GRFS incidence after hematopoietic stem cell transplantation	One year since hematopoietic stem cell transplantation
Cumulative Incidence Rate (CIR)	CIR after hematopoietic stem cell transplantation	One year since hematopoietic stem cell transplantation
Graft Time of Different Cell Subpopulation	Graft Time of Platelet, Neutrophil	One year since hematopoietic stem cell transplantation

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Jingtao Huang, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: November 13, 2024
• First Submitted That Met QC Criteria: November 24, 2024
• First Posted (Estimated): November 26, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 24, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: RJBMT-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No