Allogeneic hematopoietic stem cell transplantation for treating severe lung involvement in Gaucher disease

Abstract

Objective: To provide strategies for monitoring and treating severe lung involvement in Gaucher disease.

Study design: We reviewed the chart of a 5-year-old boy who developed rapidly progressive, severe infiltrative lung involvement of Gaucher disease (GD) and improved after allogeneic hematopoietic stem cell transplant (HSCT), along with other case studies reported before December 2019. He was diagnosed with GD (homozygous mutation at c.1448 T > C, p.L483P), and started receiving enzyme replacement therapy (ERT) at 17 months old. He developed respiratory distress symptoms after 45 months of ERT; chest imaging reported diffuse interstitial infiltration of the bilateral lungs and consolidations at the right lungs. Allogeneic HSCT using cells from a matched unrelated donor was performed four months upon progressive respiratory symptoms.

Results: His respiratory symptoms subsided in one month; chest imaging improvement, pulmonary function test improvement, and normalized activity of β-glucocerebrosidase were reported in three months.

Conclusion: This is the first report of a patient who received early and regular ERT but developed severe infiltrative lung involvement and recovered after allogeneic HSCT. Based on study results, we suggest regular chest imaging, even for asymptomatic patients. For patients with severe lung involvement, rapid deterioration, and unresponsive to higher ERT dosages, allogeneic HSCT should be considered.

Keywords: CXR, Chest X-ray; ERT, Enzyme replacement therapy; FEF, Forced expiratory flow; FEV, Forced expiratory volume; FVC, Forced vital capacity; GD, Gaucher disease; Glucocerebrosidase; HRCT, High-resolution computed tomography; HSCT, Allogeneic hematopoietic stem cell transplant; Infiltrative lung disease; Lysosomal storage disease; PEF, Peak expiratory flow.

Fig. 1

CXR of patient A. A-1: Two years before the discovery of lung involvement. A-2: Discovery of lung involvement. A-3: Three months after the discovery of lung involvement. A-4: One month after allogeneic HSCT. A-5: Three months after allogeneic HSCT.

Fig. 2

Chest CT of patient A. A-6, A-7: Discovery of infiltrative lung involvement. Diffuse interstitial infiltration at bilateral lungs, with geographic ground glass opacities at bilateral lungs, consolidations mainly at RUL and RLL, and thickening of bronchovascular bundle, interlobar fissure at bilateral lungs. Infiltrative soft tissue lesions at right upper paratrachea, bilateral lower paratrachea, prevascular space, subcarina, AP window, bilateral pulmonary hilum, paraesophageal space, and along the proximal bronchovascular bundle.

Fig. 3

The lung tissue from open biopsy showed accumulation of histiocytes in alveolar spaces as well as in interstitium connective tissue. The histiocytes contain pale to lightly eosinophilic cytoplasm with wrinkled-paper appearance. The histiocytes are immunoreactive for CD68-PGM1 and CD163 and positive with PAS. 1. H&E staining 200×: accumulation of histiocytes in the alveolar spaces and interstitium. 2. H&E staining 400×: accumulation of histiocytes in the alveolar spaces and interstitium. 3. CD163 400×: positive. 4. CD68 400×: positive.

Fig. 4

CXR of patient B. B-1: Lung involvement found on the image with no respiratory symptoms after 30 months of ERT (60 IU/kg/2 weeks). ERT dosage was then increased to 100 IU/kg/2 weeks. Reticular infiltration over bilateral lung fields, with increased perihilar infiltration and suspicious consolidative patchy over bilateral lower lung fields. B-2: 11 months after treatment with higher dose ERT (100 IU/kg/2 weeks). Patient B still presented with no respiratory symptoms and normal pulmonary function tests, radiologic findings were mildly improved. Increased interstitial infiltration noted over the bilateral lung field, with prominent pulmonary vasculature.

Fig. 5

Chest CT of patient B, 1 month after lung involvement was discovered on CXR. B-3, B-4: Peribronchial consolidations and opacities at the posterior segment of RUL. Confluent soft tissue nodules at subcarina, bilateral pulmonary hilum, interlobar space/proximal bronchovascular bundle, and retroperitoneum, mesentery root.