Clinical Characteristics of Early and Late Non-Infectious Pulmonary Complications Following Cord Blood Transplantation.

Objectives: Non-infectious pulmonary complications (NIPC) are fatal disorders following allogeneic SCT. NIPCs include idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), adult respiratory distress syndrome (ARDS), which occur early period (early NIPCs), and late onset NIPCs (LONIPCs) such as bronchiolitis obliterans (BO), cryptogenic organizing pneumonia (COP), and interstitial pneumonia (IP). There has been little information on NIPCs following cord blood transplantation (CBT). We tried to characterize NIPCs after CBT by estimating the incidence, types of NIPC, and prognosis, and to identify risk factors for them.

Methods: We reviewed medical records of 246 patients (291 transplants) with hematological diseases who had received CBT between Jan. 2002 and Dec. 2006 at Toranomon Hospital, Tokyo, Japan. Median age was 55 years (17–79). Most of them had diseases in advanced status (n=255). Median follow-up time was 901 days (111–2470). Most of the pre-transplant conditioning were reduced intensity consisted of fludarabine, melphalan and TBI 4Gy (n=223). Cyclosporine (CSP) (n=102) or tacrolimus (Tac) alone (n=173) and Tac with methotrexate (n=18) or mycophenolate mofetil (n=19) were used as GVHD prophylaxis. HLA disparities were as follows; 6/6 (n=14), 5/6 (n=73), 4/6 (n=198), and 3/6 (n=6). Diagnosis of NIPC was made by Chest X-ray, computed tomography, bronchoscopy, broncho-alveolar lavage (BAL) and pulmonary function test. Infectious complications were excluded by positive result of culture, galactomannan test, and RT-PCR of sputum, pleural effusion and BAL fluid.

Results: The incidence of NIPCs was 33.7% (n=98). Most of NIPCs (95 patients) were developed within 100 days after transplant (median, 17days, range, 2–57). Early NIPCs can be subdivided into 2 on the basis of presence (n=48) or absence (n=47) of pleural effusion (PE). LONIPCs were observed in only 11 cases (4.5%), including 3 cases of COP, 6 of IP, and 2 of BO, and 8 of them occurred within 100 days after transplant. Multivariate analysis revealed 3 risk factors for early NIPCs; GVHD prophylaxis with CSP over Tac (p=0.036, RR 1.65), grade III–IV acute GVHD over grade 0–II (p=0.007, RR 1.84), and 2 and greater HLA mismatch over less than 2 (p=0.046, RR 1.587). The CT finding of IPS with PE revealed ground-glass opacity of lung field, similar to that of COP. IPS with PE responded favorably to low dose corticosteroid therapy as same as COP. In contrast to low 1-year overall survival (OS) of IPS without PE (11.1%, 95%CI: 1.9–20.3), that of IPS without PE was significantly high (53.1%, CI: 38.8–67.4). Among LONIPC patients, those who developed LONIPC later than day 100 post-transplant (n=3), no one required long-term oxygen therapy or died directly from respiratory failure due to the lung diseases.

Discussion: The incidence of IPS was relatively high, whereas that of LONIPCs was low after reduced-intensity CBT using single calcineurin inhibitor as GVHD prophylaxis. Although IPS with PE showed good prognosis similar to COP, further accumulation and more precise investigation of laboratory and clinical data are warranted to clarify the biological mechanism of IPS with PE and without PE or to descriminate IPS from engraftment syndrome or capillary leak syndrome.