Underlying disease-specific pattern of pulmonary comorbidity factors in adults before allogeneic HSCT
Egor A. Kulagin1, Alisa G. Volkova2, Ilya Yu. Nikolaev2, Anna G. Smirnova2, Julia D. Rabik3, Vasiliy I. Trofimov1, Boris V. Afanasyev2
1 M. Chernorutskiy Department of Hospital Therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
2 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
3 Department of Functional Diagnostics №2, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
Contact: Dr. Egor A. Kulagin
Pulmonary comorbidity is one of the key factors determining the risk of complications and non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The unified criteria included in the HSCT-specific index (HCT-CI) do not reflect potential disease-specific pulmonary comorbidity factors. The aim of this study was to characterize the frequency and structure of pulmonary comorbidity factors in adult patients receiving allo-HSCT for various diseases.
Patients and methods
The study included 355 patients (median age 33 years, 18-66) examined before allo-HSCT. Potential pulmonary comorbidity factors have been documented (smoking, broncho-obstructive diseases, infections, pulmonary toxic chemotherapy, mediastinal radiation therapy, etc.). Impairment of the pulmonary function tests (PFT) was documented by the parameters of FEV1 and the diffusing capacity of carbon monoxide (DLco), adjusted for hemoglobin. The analysis was carried out in groups of patients with acute myeloid and lymphoblastic leukemia (n=215), lymphomas (n=59), myelodysplastic syndrome (MDS) and myeloproliferative diseases (MPD) (n=54), acquired aplastic anemia (AA) (n=27).
The factors of lung compromise before allo-HSCT were as follows: smoking (32%), broncho-obstructive diseases (5%), pulmonary infections (45%), pulmonary toxic chemotherapy (79%), immune checkpoint inhibitors (5%), previous autologous HSCT (8%) and radiation therapy (6%). Risk factors associated with prior treatment were most often realized in patients with lymphomas (pulmonary toxic chemotherapy (80%), autologous HSCT (47%), radiation therapy (32%), and immune checkpoint inhibitors (32%). Patients with acute leukemia had a high frequency of cytarabine therapy (94%). Potential drug pulmonary toxicity was not detected in AA. The frequency of infections involving lungs did not statistically significantly differ depending on the diagnosis and amounted to 30%, 47%, 51%, and 37% for AA, acute leukemia, lymphomas and MDS/MPD, respectively (p=0.1637). The proportion of smokers was slightly higher among patients with lymphomas (41%) and MDS/MPD (39%) compared with the group of acute leukemia (30%) and, especially, AA (19%) (p=0.1260). A smoker index of more than 20 packs/year was observed in 48% of smokers diagnosed with MDS and MPD, which was significantly higher than in acute leukemia (22%) and lymphomas (21%) (p=0.0461). Concomitant COPD was detected more often among patients with MDS and MPD (13%) compared with AA (0%), acute leukemia (2%) and lymphomas (5%) (p=0.0038).
A decrease in FEV1 occurred in 90 (25%) patients, including 14%, 9% and 2% of mild, moderate and severe degrees, respectively. DLco disorders were detected in 69% of patients, including 29%, 28%, and 12% of mild, moderate, and severe, respectively. More frequent bronchial obstruction according to the median FEV1/VC parameter was observed in patients with MDS and MPD, while disorders of pulmonary diffusing capacity according to the median adjusted DLco were more pronounced in patients with lymphomas.
The revealed patterns are partially explained by differences in the age of patients and the duration of the disease at the time of allo-HSCT. The median age of patients with AA, acute leukemia, lymphomas, and MDS/MPD was 28, 32, 37, and 45 years, respectively (p <0.0001). Accordingly, the median of disease duration before allo-HSCT was 1.9, 1.1, 3.6 and 1.4 years (p <0.0001).
Adult recipients of allogeneic HSCs have a wide range of potential causes and a high frequency of pulmonary comorbidity, which is confirmed by the PFT data. Pulmonary comorbidity factors and the PFT disorders have underlying disease-specific features.
Allogeneic hematopoietic stem cell transplantation, adults, underlying disease, pulmonary comorbidity, pulmonary functional tests.