Volume 1 • Issue 1 • 1000104 J Clin Exp Transplant, an open access journal Research Article Open Access Nagasawa et al., J Clin Exp Transplant 2016, 1:1 Case Report Open Access Journal of Clinical and Experimental Transplantation J o u r n a l o f C l i n i c a l a n d E x p e ri m e n t a l T r a n s p l a n t a t i o n *Corresponding author: Masayuki Nagasawa, Department of Developmental Biology, Post Graduate School, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo 113-8519, Japan, Tel: +81-3-5803-5250; Fax: +81-3-5803-5247; E-mail: mnagasawa.ped@tmd.ac.jp Received April 19, 2016; Accepted June 22, 2016; Published June 28, 2016 Citation: Nagasawa M, Ono T, Aoki Y, Isoda T, Takagi M, et al. (2016) A Pediatric Case of Very Late Onset Non-infectious Pulmonary Complication (LONIPC) after Allogeneic Hematopoietic Stem Cell Transplantation. J Clin Exp Transplant 1: 104. Copyright: © 2016 Nagasawa M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. A Pediatric Case of Very Late Onset Non-infectious Pulmonary Complication (LONIPC) after Allogeneic Hematopoietic Stem Cell Transplantation Masayuki Nagasawa*, Toshiaki Ono, Yuki Aoki, Takeshi Isoda, Masatoshi Takagi, Kohsuke Imai, Michiko Kajiwara and Tomohiro Morio Department of Developmental Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan Abstract 17-months old infant with Wiskott-Aldrich syndrome was transplanted with genetically two-locus mismatched unrelated cord blood cells under the conditioning regimen of busulfan, cyclophosphamide and anti-thymocyte globulin. GVHD prophylaxis was cyclosporine (CSP) plus short-term methotrexate with prednisolone (1 mg/kg). Acute and chronic GVHD were not observed during the course. About six years later, he suffered from severe cough and dyspnea with no fever, and diagnosed as late onset non-infectious pulmonary complications (LONIPC). We have to be careful for LONIPC after SCT even in the absence of chronic GVHD for younger children because the sign of insidious obstructive pulmonary symptoms is diffcult to monitor. To avoid the unexpected LONIPC, introduction of RIC regimen should be considered for younger children, although it has been reported that RIC regimen may increase the risk for GVHD and graft rejection. Keywords: Non-infectious pulmonary complication; Chronic GVHD; Allogeneic hematopoietic stem cell transplantation Introduction Late onset non-infectious pulmonary complications (LONIPC) consist of major causes of morbidity and mortality afer allogeneic hematopoietic stem cell transplantation (allo-HSCT). Tese include bronchiolitis obliterans (BO), bronchiolitis obliterans with organizing pneumonia (BOOP), and idiopathic pneumonia syndrome (IPS), and usually occur three months afer HSCT. According to the literature, the incidence has been reported to be 10-25% [1]. Not well elucidated, it is speculated that allo-immune reactions play a major role in the pathogenesis, because they are closely associated with the presence of chronic GVHD. Concerning to LONIPC among the pediatric patients, few reports are available. Kojima et al have reported as a single institutional experience that the incidence of LONIPC in the pediatric patients was 10.3%, the median onset was 187 days (123-826 days), and it was also related with chronic GVHD as in the cases of adults [2]. Case Report 17-months old infant with Wiskott-Aldrich syndrome was transplanted with genetically two-locus mismatched unrelated cord blood cells. Major clinical symptoms were eczema and thrombocytopenia (<1 × 10 4 /μl) and he had no signifcant infection episodes before SCT. No expression of WASP protein was found in T-lymphocytes, and genetic analysis revealed splicing anomaly due to point mutation in intron2. Conditioning regimen consisted of busulfan (4 mg/kg/day for 4 days), cyclophosphamide (50 mg/kg/ day for 4 days) and horse anti-thymocyte globulin (10 mg/kg/day for 4 days), and GVHD prophylaxis was cyclosporine (CSP) plus short- term methotrexate with prednisolone (1 mg/kg). Dose of oral busulfan was determined by the prior test dose and pharmacokinetic analysis. Methotrexate on day 6 and day 11 was omitted because of elevated serum transaminase. Neutrophil engrafment was on day 19, platelet engrafment on day 71 and complete chimerism was determined on day 21. Because no GVHD was observed, CSP was stopped on day 95, and prednisolone on day 251. He became free of immunoglobulin supplementation one year afer CBT. Tere were no signifcant infection episodes afer CBT. 5 and 1/2 years afer CBT, he began to complain of occasional dry cough, which resolved easily under cough remedy. A couple of months later, he sufered from severe cough and dyspnea with no fever. Auscultation revealed fne crackles on both lungs, and his oxygen saturation was 92% in room air. Chest X-ray presented marked consolidation of bronchioles (Figure 1). Under the suspicion of LONIPC, prednisolone (1 mg/kg/day) was started, which ameliorated his symptoms rapidly. Serum soluble IL-2R was slightly elevated to 937 U/ml (normal value: 145-519), and serum KL-6 was 458 U/ml (normal value: 0-500). Involvement of pathogens including RSV, CMV and fungi was excluded from the later examinations. He has been placed on oral prednisolone with clarithromycin (5 mg/kg/day) and futicasone inhalation (twice daily). Tree years later, he has been placed on home oxygen therapy and lung transplantation has been scheduled. Discussion Between 2001 and 2011, 72 pediatric patients (7m-22y8m; 7y3m ± 6y8m [mean ± SD]) have received 77 allogeneic stem cell transplantations in our institute. 9 patients (13.4%) in 67 patients who survived more than 3 months afer SCT developed LONIPC (Table 1: observation period; 1155-5145 days). Multivariate analysis revealed myeloablative conditioning regimen and chronic GVHD as signifcant risk factors of LONIPC (data not shown). Unexpectedly, two patients developed LONIPC more than fve years afer HSCT and one patient died of respiratpry failure 30 months afer diagnosis of LONIPC. As shown in Table 1, LONIPC was closely related with chronic GVHD also in our experience. Unexpectedly, two patients had no