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2151 The Effect of Smoking and Pre-Transplant Pulmonary Comorbidity on the Incidence of Lung Graft Versus Host Disease and Post Transplant Outcomes

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster I
Hematology Disease Topics & Pathways:
Therapy sequence, Treatment Considerations, Adverse Events
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Mohammed Kawari, MD1*, Mariana Pinto Pereira, MD1*, Mats Remberger, PhD2*, Ambrose Lau, MD1*, Arjun Law, MD3, Rajat Kumar, MD PhD1, Igor Novitzky-Basso, MD, PhD1, Wilson Lam, MD1, Ivan Pasic, MD1*, Armin Gerbitz, MD, PhD1*, Auro Viswabandya, MD1, Dennis Dong Hwan Kim, MD, PhD4, Jonas Mattsson, MD, PhD1* and Fotios Michelis, MD1*

1Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
2Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
3Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Toronto, Canada
4Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

Introduction:

Allogeneic hematopoietic cell transplantation (Allo-HCT) is the curative treatment for various hematological disorders. Despite advancements in supportive care, graft-versus-host disease (GVHD) continues to be a challenging complication. Smoking is linked with various pulmonary diseases, also elevates the risk of pulmonary complications and overall mortality in Allo-HCT recipients. However, it remains unclear whether smoking adversely affects Allo-HCT outcomes independently of pre-transplant underlying lung conditions.

Methodology:

We conducted a retrospective analysis of 407 patients (pts) who underwent Allo-HCT at Princess Margaret Cancer Centre, Toronto between January 2019 and May 2021. This analysis examined the impact of pre-transplant pulmonary comorbidities, smoking history, and total smoking dose on transplant outcomes. Pre-transplant pulmonary comorbidity was defined according to HCT-specific comorbidity index: DLCO and/or FEV1 less than 80%, or dyspnea on slight activity.

Four groups were formed based on smoking history and pre-transplant pulmonary comorbidity.

Group A: smoker with pre-transplant pulmonary comorbidity, 40 pts (9.8%).

Group B: non-smoker with pre-transplant pulmonary comorbidity, 71 pts (17.4%).

Group C: smoker with no pre-transplant pulmonary comorbidity, 105 pts (25.8%).

Group D: non-smoker with no pre-transplant pulmonary comorbidity, 191 pts (46.9%).

Smokers were categorized into three groups based on their smoking history <10 pack-years (59 pts, 14.5%), 10 to 25 pack-years (50 pts, 12.3%), and >25 pack-years (35 pts, 8.6%).

The primary end point is the incidence of lung GVHD. Secondary end points are the 3 year-overall survivor (OS) and Non-Relapse Mortality (NRM).

Results:

Among the 407 pts, the median age was 58 years (18-76). Of these patients, 94 (23.1%) received grafts from matched related donors, 195 (47.9%) had match unrelated graft, while 79 (19.4%) and 39 (9.6%) had haploidenitcal donor and mismatch unrelated donor, respectively. Two-thirds of the patients, 264 (64.9%), received dual T cell depletion for GVHD prophylaxis, consisting of antithymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). Additionally, 81 pts (19.9%) received only ATG, while 54 pts (13.3%) received only PTCy.

The median number of readmission days in the first year was 45 days for the group A, compared to 36, 31, and 34 days in group B, C and D, respectively (p=0.007). However, there was no difference in the ICU admissions across the four groups (p=0.2).

The 3-year OS for the entire cohort is 65.3% (95% CI: 60.5-69.8), with a NRM of 18.0% (95% CI: 14.4-21.9). The incidence of chronic GVHD is 37.9% (95% CI: 33.0-42.9). The 3-year OS is lowest in Group A at 45.0% (95% CI: 29.3-59.5), compared to 70.4% (95% CI: 58.3-79.6) in Group B, 62.4% (95% CI: 52.3-70.9) in Group C, and 69.4% (95% CI: 62.3-75.5) in Group D (p=0.006). The combination of smoking and pre-transplant pulmonary comorbidities adversely affects NRM, which is 37.5% (95% CI: 22.6-52.3) in this group, while it is 15.5% (95% CI: 8.2-24.9), 18.2% (95% CI: 11.5-26.2), 14.7% (95% CI: 10.1-20.1) in group B, C, and D, respectively (p=0.001).

There were no significant differences among the four groups in the incidence of grade II-IV acute GVHD or chronic GVHD, with p-values of 0.32 and 0.75, respectively. However, Group A had a higher incidence of chronic lung GVHD compared to the other groups (p=0.01).

Patients with >25 pack-years smoking history had the lowest 3-year OS at 45.5% (95% CI: 28.7-60.9), compared to 49.5% (95% CI: 35.0-62.5) for those with 11-25 pack-years and 70.5% (95% CI: 56.8-80.5) for those with <10 pack-years (p=0.02). There were no differences in NRM among the three smoking history groups (p=0.26). Nonetheless, relapse-free survival (RFS) was higher in the group with a lower smoking history of <10 pack-years (p=0.02).

In the multivariate analysis (MVA), a longer smoking history of >10 pack-years is associated with higher mortality and reduced RFS.

Conclusion:

The results exhibit the combination of smoking and pre-transplant pulmonary comorbidities increases the incidence of chronic lung GVHD. This association also correlates with a lower 3-year OS and higher NRM. Moreover, a higher smoking dose is associated with reduced OS. Further research is required to determine the ideal intervention for optimizing outcomes in smokers with pre-transplant pulmonary comorbidities.

Disclosures: Kim: Ascentage: Consultancy; Pfizer: Honoraria, Research Funding; Paladin: Honoraria, Research Funding; Novartis: Honoraria, Other: Advisory board, Research Funding.

*signifies non-member of ASH