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Lung transplantation for pulmonary graft versus host disease: experience from a referral organ transplantation center

Bone Marrow Transplantation volume 58, pages 1170–1173 (2023)Cite this article

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More than 90 thousand allogeneic hematopoietic cell transplantation (allo-HCT) are carried out annually, and around 1.5 million post allo-HCT survivors exist worldwide [1]. Chronic graft versus host disease (cGvHD) however is increasing with the increased use of alternate donors and peripheral blood as the main stem cell source [2, 3]. Late onset pulmonary complications in allo-HCT recipients are common, the majority are attributed to pulmonary cGvHD, which is a problematic complication with no proven successful therapies, and limited long-term survival [4]. In 1992, the first case of lung transplant (LT) for lung cGvHD was reported [5], and since then a significant number of cases underwent LT with various success rates. The optimal timing for LT is controversial and needs to be made in a multidisciplinary setting. Many aspects have to be accounted for, including the risk of relapse of the underlying malignancy, the risk of other complications post LT, the availability of donors and the comorbidities of the recipient. We retrospectively reviewed our institutional allo-HCT database and identified 10 patients who underwent LT after allo-HCT. Demographics were collected from the charts. Data on allo-HCT and LT including outcomes and transplant related variables were obtained from the institution’s prospective transplantation (allo-HCT and LT) databases. The primary endpoint for our study was the 5 years overall survival (OS) after LT. The secondary endpoints were the long-term complications (chronic lung allograft dysfunction (CLAD) incidence, CLAD-free survival, primary hematologic disease relapse, second cancers and Lung infection during first year post-LT). OS was calculated from the date of LT until death or last follow-up. Table 1 summarizes the recipient’s pre-LT characteristics. At the time of referral for first evaluation for LT, one patient was on triple IS, four on double and five on single IS. At the time of LT, four patients were on single IS, three on double IS and three on no IS. The median time between allo-HCT and bronchiolitis obliterans syndrome (BOS) was 20.5 months (IQR: 12–24). The median time from allo-HCT to LT was 71 months (IQR: 50–137). The median time from first lung transplant evaluation to actual LT was 61 months (IQR: 14–114). The median time from listing for LT to actual LT was 4.8 months (IQR: 2–7.2). The median FEV1 upon referral to LT clinic was 31% (IQR: 23.75–32.6%) and the median FEV1 upon LT was 25% (IQR: 18.5–29.3%) with two patients being on mechanical ventilation, one on high flow oxygen and six dependent on home oxygen. The indication for LT was respiratory failure caused by fibrosis and BOS in all patients. All patients received cadaveric bilateral lung transplants. Five patients had donor specific antibodies against their lung donors. All LTs were ABO compatible except one and none was HLA matched. Lung retrieval and transplant surgery followed standard practice. After a median follow up of 4.5 years (95% CI: 3.9–5.1) post-LT, the estimated 5-years OS after LT was 85.7%. Three patients developed acute lung rejection, however two were grade A1 and did not require any intervention and the third was grade A2 and was managed successfully with pulse steroids. Six patients developed pulmonary infections in the first year post-LT (Acinetobacter, Burkholderia and Staphylococcus, E. coli, Klebsiella and Staphylococcus, Klebsiella and Pseudomonas, Pseudomonas). The cumulative incidence of CLAD was 50% with a median time from LT to CLAD of 47 months (IQR: 20–65). The CLAD-free survival at 5 years was 50%. Two patients died after developing CLAD complicated by frequent infections. Hematologic relapse did not occur in any of the patients nor post-transplant lymphoproliferative disorder. At the time of last follow up, none of the patients is on oxygen and no secondary malignancies have been reported. Table 2 is a summary of the outcomes.

Table 1 summary of the recipient’s pre-LT characteristics.
Full size table
Table 2 summary of the outcomes after LT.
Full size table

Approximately 10% of patients with cGvHD develop pulmonary obstructive syndromes as part of their cGvHD manifestation, with variable rate and extent depending on the severity of cGvHD [6]. The precise causes and risk factors remain unknown with many proclaimed factors (older age, pre allo-HCT lung diseases, autoimmune diseases, alternate donor, conditioning type and intensity, graft source, viral infections post allo-HCT, GvHD, etc.) [7]. The prognosis of these patients is grim and their management is challenging and frustrating with limited survival in advanced case [7]. The management of these patients relies on immunosuppression and other supportive medications in addition to extracorporeal photopheresis (ECP) [8]. Up to six lines of IS agents were tried in this cohort (with a median of four lines) before considering LT, an indication about the suboptimal efficacy of medical interventions for this deleterious condition. The median lines of IS before LT was not reported in the previously published reports to compare to the current report. Many groups reported good outcomes of LT for lung GvHD, however the number of cases reported in the literature still minuscule compared to the scale of the problem [9]. Additionally, it is unknown how many BOS patients need LT but are not eligible or die while on the LT waiting list. Although, the patients we report have a relatively young age, the majority of series reported a younger or similar median age reflecting the inherent selection bias favoring young patients [9]. The majority received a myeloablative and radiation based conditioning along with peripheral blood stem cells as a graft source. All these factors predispose to GvHD and to the development of pulmonary obstructive syndromes [7]. The vast majority of literature reported oxygen dependency and lung function at the time of LT but did not report these upon the referral to consider LT evaluation. The median FEV1 upon referral in our report was 31% (down to 25% at the time of LT with two patients being on mechanical ventilation, one on high flow oxygen and six dependent on oxygen). Reporting these numbers is valuable to establish referral triggers and guidance on when to refer. In our cohort as well as the vast majority of reports, the patients received cadaveric bilateral lung transplants [9]. However, living lobar LT is reported and can be an option for critically ill patients who cannot wait for cadaveric LT [10]. After a median follow up of 4.5 years post-LT, the estimated 5-years OS after LT in our cohort was 85.7%. This compares favorably with most reported literature about LT for cGvHD or other indications [11]. The better survival of LT patients for BOS is probably related to the inherent selection bias as well as the management of these patients in highly specialized centers as compared to lung transplant patients transplanted for other indications. Three out of 10 patients developed acute lung rejection, a rate consistent with rejection rates after lung transplant in general. The cumulative incidence of CLAD was 50% with a median time from LT to CLAD of 47 months, which is also consistent with rates after lung transplant in general [12]. Six patients developed lung infections in the first year post-LT and this does not appear higher than the general population of LT patients [13, 14]. None of our patients developed hematologic disease relapse. Relapse of the underlying disease has been consistently low as reported from different groups and has been linked to time from allo-HCT to LT with higher relapses in patients undergoing LT earlier post allo-HCT [9].

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References

  1. Niederwieser D, Baldomero H, Atsuta Y, Aljurf M, Seber A, Greinix HT, et al. One and half million hematopoietic stem cell transplants (HSCT). Dissemination, trends and potential to improve activity by telemedicine from the Worldwide Network for Blood and Marrow Transplantation (WBMT). Blood. 2019;134:2035.

    Article  Google Scholar 

  2. Chang Y-J, Weng C-L, Sun L-X, Zhao Y-T. Allogeneic bone marrow transplantation compared to peripheral blood stem cell transplantation for the treatment of hematologic malignancies: a meta-analysis based on time-to-event data from randomized controlled trials. Ann Hematol. 2012;91:427–37.

    Article  PubMed  Google Scholar 

  3. El Fakih R, Arat M, Aljurf M. Donor selection and cell dose in haploidentical SCT. Haploidentical Stem Cell Transpl. 2017: 9-16. https://doi.org/10.1007/978-3-319-65319-8_2

  4. Chi AK, Soubani AO, White AC, Miller KB. An update on pulmonary complications of hematopoietic stem cell transplantation. Chest. 2013;144:1913–22.

    Article  PubMed  Google Scholar 

  5. Calhoon JH, Levine S, Anzueto A, Bryan CL, Trinkle JK. Lung transplantation in a patient with a prior bone marrow transplant. Chest. 1992;102:948.

    Article  CAS  PubMed  Google Scholar 

  6. Nakaseko C, Ozawa S, Sakaida E, Sakai M, Kanda Y, Oshima K, et al. Incidence, risk factors and outcomes of bronchiolitis obliterans after allogeneic stem cell transplantation. Int J Hematol. 2011;93:375–82.

    Article  PubMed  Google Scholar 

  7. Dudek AZ, Mahaseth H, DeFor TE, Weisdorf DJ. Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transpl. 2003;9:657–66.

    Article  Google Scholar 

  8. Lucid C, Savani B, Engelhardt B, Shah P, Clifton C, Greenhut S, et al. Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT. Bone Marrow Transpl. 2011;46:426–9.

    Article  CAS  Google Scholar 

  9. Soubani AO, Kingah P, Alshabani K, Muma G, Haq A. Lung transplantation following hematopoietic stem cell transplantation: report of two cases and systematic review of literature. Clin Transpl. 2014;28:776–82.

    Article  Google Scholar 

  10. Yamane M, Sano Y, Toyooka S, Okazaki M, Date H, Oto T. Living-donor lobar lung transplantation for pulmonary complications after hematopoietic stem cell transplantation. Transplantation. 2008;86:1767–70.

    Article  PubMed  Google Scholar 

  11. Yusen RD, Edwards LB, Dipchand AI, Goldfarb SB, Kucheryavaya AY, Levvey BJ, et al. The registry of the International Society for Heart and Lung Transplantation: thirty-third adult lung and heart–lung transplant report—2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transpl. 2016;35:1170–84.

    Article  Google Scholar 

  12. Chambers DC, Cherikh WS, Goldfarb SB, Hayes D Jr, Kucheryavaya AY, Toll AE, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth adult lung and heart-lung transplant report-2018; Focus theme: Multiorgan Transplantation. J Heart Lung Transpl. 2018;37:1169–83. https://doi.org/10.1016/j.healun.2018.07.020.

    Article  Google Scholar 

  13. Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Dobbels F, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report—2012. J Heart Lung Transpl. 2012;31:1073–86.

    Article  Google Scholar 

  14. Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Kirk R, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-eighth adult lung and heart-lung transplant report—2011. J Heart Lung Transpl. 2011;30:1104–22.

    Article  Google Scholar 

  15. Weill D, Benden C, Corris PA, Dark JH, Davis RD, Keshavjee S, et al. A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transpl. 2015;34:1–15.

    Article  Google Scholar 

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Acknowledgements

R.E, M.A, F.A designed and performed the research. R.E wrote the first draft. All the co-authors revised and approved the final manuscript.

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  1. King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia

    Riad El Fakih, Rayid Abdulqawi, Amer Bugnah, Walid Rasheed, Loui Ezzat, Marwan Shaheen, Naeem Chaudhri, Fahad Almohareb, Eid A. Al-Mutairy & Mahmoud Aljurf

  2. College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia

    Riad El Fakih & Tarek Ziad Arabi

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All authors contributed to the concept, design of this report, and contributed to data collection. RE wrote the first draft. All authors reviewed and approved the final version.

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Correspondence to Riad El Fakih.

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El Fakih, R., Abdulqawi, R., Bugnah, A. et al. Lung transplantation for pulmonary graft versus host disease: experience from a referral organ transplantation center. Bone Marrow Transplant 58, 1170–1173 (2023). https://doi.org/10.1038/s41409-023-02074-5

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