710	L. Samy et al.

on a previously discussed randomized trial [43]. Once there has been improvement or stabilization of the disease, the dose can be slowly decreased to a maintenance dose of 400 mcg of budesonide twice per day. Lung transplantation should be considered in some cases in which the severity of airfow obstruction is debilitating and treatment refractory. For instance, a pan-European series of lung transplant recipients­ following HSCT showed comparable outcomes to patients with other end-stage diseases [53–55].

Post-HSCT Organizing Pneumonia

Organizing pneumonia (OP) is characterized by intra-­ alveolar connective tissue plugs of granulation tissue consisting of intermixed myo broblasts and connective tissue that ll the lumen of the distal airways and extend into the alveolar ducts in association with chronic interstitial infammation [56] (Fig. 40.2b). OP can be idiopathic (cryptogenic organizing pneumonia) or secondary to various diseases, including postinfection diseases related to connective tissue disease, drugor radiation-induced diseases, hematological malignancies, lung transplantation or allogeneic HSCT. OP is a well-recognized entity following HSCT. In fact, a strong association has been described between the occurrence of OP and previous signs of acute or chronic GVHD [57]. In 2003, Freudenberger et al. identi ed a median time of 108 days post-HSCT of OP onset [57]. However, there seemed to be two peaks of OP onset: one within the rst 100 days post-HSCT and another 2–3 years afterwards. In the earlier form, constituting 22% of cases, the respiratory symptoms followed immunosuppressive treatment tapering [57]. The clinical presentation is similar to COP, mimicking nonresolving pneumonia with fever, cough, and dyspnea. Radiologically, OP can present in a similar way to COP with

a

dense alveolar in ltrates. However, when related to HSCT, OP tends to present with an interstitial bronchovascular pattern that does not wax and wane, like COP typically does [57–60] (Fig. 40.2a). On PFT, a restrictive pattern can be found in 43% of patients, but an obstructive defect is seldom observed. The treatment of OP includes early initiation of high-dose corticosteroids, with a generally good response with resolution or stabilization. However, steroids should be tapered very slowly to decrease relapse risk [57, 61, 62].

Other Late-Onset NonInfectious Pulmonary Complications (LONIPCs)

As mentioned earlier, the approach to ILD should be the same as for a non-HSCT recipient. Indeed, all idiopathic interstitial pneumonia (IIP) patterns described in the international multidisciplinary classi cation have been observed following HSCT apart from usual interstitial pneumonia [28, 61]. These ILDs can be drug induced but can also occur solely from HSCT itself or present in the setting of an autoimmune disorder [7]. Recently, a retrospective study from a single center reported 15 cases of pleuroparenchymal broelastosis, of which 7 had histological con rmation [63]. The heterogeneity and rarity of ILD in the setting of HSCT explain the paucity of evidence. In a retrospective study combining all cases of ILD (including organizing pneumonia), diagnosis occurred at a median time of 11.3 months following allogeneic HSCT [61]. Symptoms are nonspeci c, including cough, dyspnea, and fever. A thorough examination should be performed seeking signs of connective tissue disease. Bronchoalveolar lavage is warranted to exclude an infectious process. Alveolar lymphocytosis (≥15%) has been observed in 67% of cases but could be missing. Pulmonary function tests are more often restrictive, but concomitant

b

Fig. 40.2  Lung computed tomography (CT) scan (a) and lung biopsy (b) from a patient who was diagnosed with organizing pneumonia 8 months after an allogeneic hematopoietic stem cell transplantation.

The CT scan shows an alveolar condensation (a). On lung biopsy, all the alveolar spaces are lled by broblast plugs (HES ×100) (b)