Results
In the examined period, four patients, all male, aged 16 to 25 years,
underwent surgical procedures for TALS.
All the patients had history of hematological malignancies; two patients
had acute lymphoblastic leukemia (ALL), one had acute myeloid leukemia
(AML) and one had ALK-positive Non-Hodgkin lymphoma (NHL).
All the patients received allogenic HSCT; the two patients affected by
ALL received a second allogenic HSCT for relapsed disease. Two patients
had Bronchiolitis Obliterans (BO) in the early phase (i.e. earlier than
100 days after HSCT).
All the patients developed pulmonary graft-versus-host disease (pGvHD)
as a late complication of allogenic HSCT, i.e. after a mean of 340 days
(range 202 – 582) and presented with clinical symptoms (i.e. exertional
dyspnea and dry cough in the absence of pulmonary infection), evidence
of air trapping, bilateral ground glass lesions and bronchiectasis on
high-resolution chest CT scan (Fig 1) and evidence of restrictive or
mixed restrictive/obstructive pattern at pulmonary function tests.
In three of the four patients, pulmonary function tests were performed
in the 30 days before the diagnosis of TALS; in all these patients
forced vital capacity (FVC), forced expiratory volume (FEV1) and forced
expiratory flow (FEF 25-75%)
were markedly reduced compared to previous tests (see table 2). The
remaining patient did not repeat pulmonary function tests due to poor
compliance.
All these patients had associated comorbidities; three of these patients
had evidence of extra-pulmonary GvHD, three had malnutrition, defined as
age- and sex-adjusted body mass index below 17.012, and two had
cardiac dysfunction.
Clinical characteristics and pulmonary function tests of these patients
are summarized in table 1 and table 2, respectively.
All the patients developed TALS with a mean time lapse of 615 days from
last HSCT (range 327 – 1094) and a mean of 276 days from the diagnosis
of pGvHD (range 42 – 513); these patients experienced on average 4.5
air leak episodes (range 3 – 6). All the patients experienced at least
two episodes before surgery.
Surgery was indicated as an emergency in case of acute deterioration of
respiratory symptoms (i.e., sudden onset of chest pain, tachypnea and
oxygen desaturation) associated with radiological evidence of tension
pneumothorax (Fig 2), or as an elective procedure in case of failure to
improve after initial observation or emergency treatment (Fig 3).
At the first episode of TALS, all patient presented with mild,
progressive worsening of typical symptoms of pGvHD, namely exertional
dyspnea and dry cough; no patient had chest pain or desaturation.
Therefore, the first episode of TALS was treated conservatively in all
the patients.
Patient one had two episodes of TALS that were managed conservatively
and underwent emergency right tube thoracostomy at the third episode for
acute respiratory distress and evidence of tension pneumothorax; this
patient rapidly worsened towards respiratory failure, was admitted to
Intensive Care Unit and passed away 25 days after emergency tube
thoracostomy.
Patient two underwent emergency left tube thoracostomy for respiratory
distress and tension pneumothorax at the second episode of TALS. This
patient had persistent pneumothorax after 24 days of negative pressure
chest drain and underwent left thoracotomy and wedge resection;
pathology demonstrated pleuroparenchymal fibroelastosis. Based on
pathological diagnosis and worsening respiratory function, oral
nintedanib and chronic oxygen supplementation were started. This patient
had ipsilateral relapse three months after surgery, that was managed
conservatively, and contralateral pneumothorax that required emergency
chest drain insertion and, 30 days later, thoracoscopy and pleural
scarification. Pulmonary function progressively worsened with the
development of chronic respiratory failure and hypercapnia. This patient
was referred for pulmonary transplant but was judged non-eligible due to
history of acute myeloid leukemia with a disease-free interval shorter
than 5 years, previous thoracic surgery, ventricular systolic
dysfunction and malnutrition (body mass index 12). Five months after
thoracoscopy, this patient had right tension hydropneumothorax that
required emergency chest drain; the episode of TALS resolved but general
conditions progressively deteriorated and the patient eventually passed
away for respiratory failure five months after the last episode of TALS.
Patient three underwent elective
right thoracoscopy and chemical pleurodesis at the second episode of
TALS after failure of conservative management. This patient underwent
contralateral thoracoscopic bullectomy and chemical pleurodesis one and
half months after initial surgery, followed by thoracotomy and wedge
resection for persistent left pneumothorax after 10 days; pathology
demonstrated pleuroparenchymal fibroelastosis. This patient had left
tension pneumothorax 40 days after thoracotomy that required emergency
chest drain; respiratory function rapidly deteriorated and the patient
died 12 days after the last episode of TALS.
Patient four underwent elective right thoracoscopy and chemical
pleurodesis at the third episode of TALS after failure of conservative
management. This patient had contralateral pneumothorax 14 months after
surgery and two more episodes of TALS, all managed conservatively.
Pulmonary function slowly progressed and the patient started chronic
oxygen therapy 18 months after surgery. This patient was referred for
pulmonary transplant but was judged non-eligible due to history of acute
lymphoblastic leukemia with a disease-free interval shorter than 5
years, previous thoracic surgery, ventricular systolic dysfunction and
malnutrition (body mass index 14.2). The patient ultimately died for
respiratory failure two years after surgery.
Surgical procedures and outcomes are summarized in table3 and table 4,
respectively.