ABSTRACT
Background: Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously. Objectives: This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. Study Design. The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies. Results: While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide. Conclusion: While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.
ABSTRACT
Crohn's disease is a systemic illness with a plethora of extraintestinal manifestations affecting various organs, of which the lungs are relatively rare. Pulmonary involvement may include airway diseases, lung parenchymal diseases, pleural diseases, or drug-related diseases. Tracheobronchial involvement is the most common respiratory presentation, whereas Crohn's disease-related interstitial lung disease is seen less frequently. A 41-year-old woman with a past medical history of Crohn's disease (status-post subtotal colectomy) presented to the hospital for an enlarging ground-glass opacity in her right middle lobe detected on routine computed tomography of the abdomen six months earlier. The opacity had increased in size from 21 x 18 mm to 28 x 18 mm and another ground-glass opacity in the right lower lobe increased in size from 5 mm to 12.4 mm. A robotic right middle lobectomy with lymph node dissection was done and bronchoscopy showed benign nodular lymphoid hyperplasia and a single perivascular epithelioid granuloma. A year later, her relapsing episodes of cough and shortness of breath were managed with prednisone, 20 mg, for a probable pulmonary manifestation of Crohn's disease. A non-contrast computed tomography of the chest showed interval resolution of the right lower lobe ground-glass opacity. A year after that, she presented to the hospital with increasing cough, shortness of breath, and a new right lower lobe ground-glass opacity (14 x 14 mm) on non-contrast computed tomography of the chest and has been managed with steroids with consideration of immunosuppression. In conclusion, pulmonary manifestations of Crohn's disease present in a myriad of varieties and often present confounding diagnostic problems necessitating an extensive work-up. Thus, Crohn's disease should be kept in the differential list in case of unusual clinical symptoms and radiological signs of idiopathic pulmonary presentations. These infrequent, and sometimes life-threatening, extraintestinal manifestations need to be considered when dealing with Crohn's disease to avoid further impairment of health status and alleviate patient symptoms by prompt recognition and treatment.
