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Pulmonary function after hematopoietic stem cell transplantation is significantly better in pediatric recipients following reduced toxicity compared with myeloablative conditioning

Bone Marrow Transplantation volume 51, pages 1530–1532 (2016)Cite this article

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Myeloablative conditioning (MAC) (full-intensity conditioning) followed by hematopoietic stem cell transplant (HSCT) provides curative therapy for malignant and non-malignant conditions.1 Reduced toxicity conditioning (RTC) followed by HSCT is efficacious and can reduce the risk of transplant-related morbidity and mortality.2, 3 Deterioration in long-term pulmonary function in HSCT survivors is often observed.4, 5, 6 Risk factors include underlying diagnosis, prior treatment, TBI, GvHD and infection.4, 5, 6 Whether RTC can reduce the risk of deterioration of pulmonary function in pediatric HSCT recipients is unclear. We compared the effects of RTC versus MAC on pulmonary function tests (PFT) in pediatric HSCT recipients.

We analyzed data from 40 patients with a median age of 13 years (range 5–21) who underwent pre-HSCT and ~1 year post-HSCT PFTs. Patients included in the study were consecutive pediatric patients who underwent HSCT at Columbia University Medical Center over a period of 10 years who could comply with pulmonary function testing and survived more than a year to undergo a follow-up study. Transplant conditioning involved RTC (n=26, 65%) and MAC (n=14, 35%) and the decision to use either conditioning regimen was protocol-driven and disease-specific.7 All RTC regimens were fludarabine-based (150–180 mg/m2). Busulfan-containing conditioning regimens were targeted to achieve 600–900 ng/mL Busulfan steady-state concentration. Acute GvHD (aGvHD) prophylaxis in the allogeneic recipients comprised tacrolimus and mycophenolate mofetil. All patients received growth factor support and prophylaxis against HSV, Pneumocystis jiroveci and fungus. Patients at risk of acquiring CMV infection (CMV-positive donor and/or recipient) who achieved an ANC>750/mm3 had prophylaxis with foscarnet alternating with ganciclovir. Pulmonary function testing was performed only on patients aged 5 years and older. Diffusion capacity for carbon monoxide (DLCO) and lung volume measurement by whole body plethysmography were only performed on those who could cooperate with these procedures. At least three maximal expiratory maneuvers were performed and forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were calculated. Lung volumes were measured using a constant volume body plethysmograph. Functional residual capacity (FRC) was calculated as the mean end-expiratory thoracic gas volume. Other lung volume measurements (total lung capacity (TLC) and residual volume) were calculated using vital capacity obtained right after measuring FRC. DLCO was measured as a single-breath test. Percent-predicted values for spirometry were based on the NHANES III reference formulas specific for black, white and Hispanic patients.8 Lung volume percent-predicted values were calculated based on the Polgar equations9 and diffusion capacity was calculated based on the Knudson reference values.10 Pre- and 1 year post-HSCT spirometry, lung volume and DLCO values were compared using paired t-tests. Differences in pre- and 1 year post-HSCT PFTs between risk factor groups (malignant versus non-malignant, RTC versus MAC, related or autologous donor versus allogeneic donor, Busulfan versus none, TBI versus none, mediastinal radiation versus none, aGvHD versus none and chronic GvHD (cGvHD) versus none) were examined using unpaired two-sided t-tests.

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Acknowledgements

This study was supported in part from grants from the Pediatric Cancer Research Foundation (PCRF), Children’s Cancer Fund and the Marisa Fund.

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Author notes

  1. R Majzner and C Sandoval: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Columbia University, New York, NY, USA

    R Majzner & R Dalal

  2. Department of Pediatrics, New York Medical College, Valhalla, NY, USA

    C Sandoval, A J Dozor, C van de Ven, E Morris, L Harrison, K Wolownik, S Fabricatore & M S Cairo

  3. Department of Biostatistics, Columbia University, New York, NY, USA

    Z Jin

  4. Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    L A Baxter-Lowe

  5. Department of Medicine, New York Medical College, Valhalla, NY, USA

    M S Cairo

  6. Department of Pathology, New York Medical College, Valhalla, NY, USA

    M S Cairo

  7. Department of Microbiology & Immunology, New York Medical College, Valhalla, NY, USA

    M S Cairo

  8. Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA

    M S Cairo

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  1. R Majzner
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  6. R Dalal
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  7. E Morris
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  8. L Harrison
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Correspondence to M S Cairo.

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Majzner, R., Sandoval, C., Dozor, A. et al. Pulmonary function after hematopoietic stem cell transplantation is significantly better in pediatric recipients following reduced toxicity compared with myeloablative conditioning. Bone Marrow Transplant 51, 1530–1532 (2016). https://doi.org/10.1038/bmt.2016.172

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