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Pulmonary function as a continuum of risk: critical care utilization and survival after allogeneic hematopoietic stem cell transplantation - a multicenter cohort study

Bone Marrow Transplantation (2024)Cite this article

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Abstract

Abnormal pre-transplant pulmonary function tests (PFTs) are associated with reduced survival after allogeneic HCT. Existing scoring systems consider risk dichotomously, attributing risk only to those with abnormal lung function. In a multicenter cohort of 1717 allo-HCT recipients, we examined the association between pre-transplant PFT measures and need for ICU admission (120d), frequency of mechanical ventilation (120d) and overall survival (5 y). Predictive models were developed and validated using Cox proportional hazards, incorporating age, FEV1 (forced expiratory volume in 1-second) and diffusing capacity (DLCO). In univariate analysis, hazard ratios for each outcome (95% CI) were: mechanical ventilation (FEV1: 0.60 [0.52–0.69], DLCO: 0.69 [0.61–0.77], p < 0.001), ICU admission (FEV1: 0.74 [0.67–0.82], DLCO: 0.79 [0.72–0.86], p < 0.001) and overall survival (FEV1: HR 0.87 [0.81–0.94], DLCO: 0.83 [0.77–0.89], p < 0.001). A multivariable Cox model was developed and compared to the HCT-CI Pulmonary score in a validation cohort. This model was better at predicting need for ICU admission and mechanical ventilation, while both models predicted overall survival (p < 0.001). In conclusion, the risk conferred by pre-transplant pulmonary function should be considered in a continuous rather than dichotomous manner. A more granular prognostication system can better inform risk of critical care utilization in the early post-HCT period.

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Fig. 1: Cox proportional hazards modeling of risk of overall survival, mechanical ventilation (within 120 days) and need for intensive care unit admission (within 120 days) for each of the three pulmonary function metrics examined: forced expiratory volume in 1-second, forced vital capacity and diffusing capacity.
Fig. 2: Histogram of hazard ratios for a Cox Model incorporating forced expiratory volume in 1-second, diffusing capacity, and age.
Fig. 3
Fig. 4: Performance of the Revised Pulmonary HCT model in the Test/Validation Cohort.
Fig. 5: Performance of the HCT-CI Pulmonary Score in the Test/Validation Cohort.
Fig. 6: Sensitivity analysis to illustrate the potential additive value of the Revised Pulmonary HCT model.

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Data availability

The data that support the findings of this study are available from the corresponding author, but restrictions apply given stipulations outlined by the Institutional Review Board approval of this study (Mayo Clinic Rochester, Minnesota, number 13-002869). While unrestricted distribution of patient-level information is restricted, the code used to develop the model is freely available at: https://github.com/hemangyadav/AlloHCT/. We have provided the code used so other centers can utilize our work to examine their own data and derive risk equations specific to their patient population and healthcare practice.

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Acknowledgements

This project was supported by Grant Number K23HL151671 (HY) from the National Heart, Lung and Blood Institute of the National Institute of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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NIH/NHLBI Grant Number K23HL151671 (recipient: Hemang Yadav).

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA

    Hemang Yadav, Zhenmei Zhang, Bradley A. White, Alexander S. Niven & Ognjen Gajic

  2. Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA

    Svetlana Herasevich

  3. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Mehrdad Hefazi Torghabeh & William J. Hogan

  4. Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA

    Philip J. Schulte

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Contributions

HY conceived the work leading to the submission, acquired data, interpreted data, analyzed results and drafted the manuscript. SH, ZZ and BW acquired data and revised the manuscript. MHT, WH, AN and OG helped with project design and data interpretation and revised the manuscript. PJS helped with data interpretation and revised the manuscript. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work.

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Correspondence to Hemang Yadav.

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Yadav, H., Herasevich, S., Zhang, Z. et al. Pulmonary function as a continuum of risk: critical care utilization and survival after allogeneic hematopoietic stem cell transplantation - a multicenter cohort study. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02265-8

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