Abnormal Glucose Tolerance in Allogeneic Hematopoietic Stem Cell Transplantation

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.

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:

• Aspartate aminotransferase (AST) ≤ 3-fold (upper limit of norma, ULN);
• Alanine aminotransferase (ALT) ≤ 3x ULN;
• 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;
• Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min;
• 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