Risk factors for alloimmune lung syndromes after allogeneic hematopoietic cell transplantation in children

Area of Science:

• Hematology
• Pulmonology
• Transplantation Immunology

Background:

• Idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS) are significant non-infectious pulmonary complications following allogeneic hematopoietic cell transplantation (allo-HCT).
• These conditions contribute substantially to morbidity and mortality in allo-HCT recipients.
• Identifying specific risk factors is crucial for developing targeted preventive strategies.

Purpose of the Study:

• To identify risk factors associated with the development of IPS and BOS in pediatric and young adult allo-HCT recipients.
• To analyze the impact of different conditioning regimens and pre-transplant clinical parameters on these pulmonary complications.

Main Methods:

• Retrospective analysis of baseline characteristics and longitudinal data from 633 pediatric and young adult allo-HCT recipients.
• Statistical analysis including hazard ratios (HR) and confidence intervals (CI) to determine risk factors for IPS and BOS.
• Correlation analysis of pre-transplant biomarkers such as endothelial activation and stress index (EASIX) and immune cell counts with IPS and BOS development.

Main Results:

• Non-malignant diagnosis and adenovirus reactivation were identified as significant risk factors for IPS.
• Busulfan-cyclophosphamide ±melphalan (BuCy ±Mel) conditioning was associated with increased risk for both IPS and BOS compared to other regimens.
• Elevated EASIX, white blood cell, and lymphocyte counts correlated with IPS, while high EASIX and specific CD4+ T-cell populations correlated with BOS.

Conclusions:

• IPS and BOS share some overlapping risk factors but also have distinct predictors.
• Conditioning regimens, viral reactivation, and pre-transplant immune markers are critical factors influencing the development of these pulmonary complications.
• These findings can guide the identification of high-risk patients and the development of targeted preventive interventions to improve allo-HCT outcomes.