Abstract
Late-onset non-infectious pulmonary complications (LONIPCs) that arise beyond 3 months after allogeneic hematopoietic SCT include bronchiolitis obliterans (BO), bronchiolitis obliterans with organizing pneumonia (BOOP) and idiopathic pneumonia syndrome (IPS). We retrospectively analyzed the incidence and outcome of LONIPCs among pediatric hematopoietic SCT recipients. We included 97 patients who survived for more than 3 months among the 114 who underwent allogeneic hematopoietic SCT between April 1997 and May 2007. Of the 97 enrolled patients, 10 (10.3%) developed LONIPCs at a median of 187 days after hematopoietic SCT (range, 123–826 days). Of the 10 patients with LONIPCs, eight had BO and two had IPS. Multivariate analysis showed that the onset of LONIPCs was associated with high-risk underlying disease and extensive chronic GVHD (hazard ratio, 5.42 (95% confidence interval, 1.36–21.7) and hazard ratio, 11.7 (95% confidence interval, 2.40–57.1), respectively). Only two patients responded to therapy with steroids and six of the 10 patients died. The 5-year OS rate was significantly lower among patients with, than without LONIPCs (28.0 vs 87.2%, P=0.000). Considering that we are lacking optimal therapies for LONIPCs, strategies aimed at the prevention of LONIPCs should be attempted.
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References
Michelson PH, Goyal R, Kurland G . Pulmonary complications of haematopoietic cell transplantation in children. Paediatr Respir Rev 2007; 8: 46–61.
Yen KT, Lee AS, Krowka MJ, Burger CD . Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment. Clin Chest Med 2004; 25: 189–201.
Krowka MJ, Rosenow III EC, Hoagland HC . Pulmonary complications of bone marrow transplantation. Chest 1985; 87: 237–246.
Soubani AO, Miller KB, Hassoun PM . Pulmonary complications of bone marrow transplantation. Chest 1996; 109: 1066–1077.
Chan CK, Hyland RH, Hutcheon MA . Pulmonary complications following bone marrow transplantation. Clin Chest Med 1990; 11: 323–332.
Griese M, Rampf U, Hofmann D, Fuhrer M, Reinhardt D, Bender-Gotze C . Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center. Pediatr Pulmonol 2000; 30: 393–401.
Garaventa A, Rondelli R, Castagnola E, Locatelli F, Dallorso S, Porta F et al. Fatal pneumopathy in children after bone marrow transplantation—report from the Italian Registry. Italian Association of Pediatric Hematology–Oncology BMT Group. Bone Marrow Transplant 1995; 16: 669–674.
Palmas A, Tefferi A, Myers JL, Scott JP, Swensen SJ, Chen MG et al. Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation. Br J Haematol 1998; 100: 680–687.
Afessa B, Litzow MR, Tefferi A . Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 28: 425–434.
Sakaida E, Nakaseko C, Harima A, Yokota A, Cho R, Saito Y et al. Late-onset noninfectious pulmonary complications after allogeneic stem cell transplantation are significantly associated with chronic graft-versus-host disease and with the graft-versus-leukemia effect. Blood 2003; 102: 4236–4242.
Patriarca F, Skert C, Bonifazi F, Sperotto A, Fili C, Stanzani M et al. Effect on survival of the development of late-onset non-infectious pulmonary complications after stem cell transplantation. Haematologica 2006; 91: 1268–1272.
Santo Tomas LH, Loberiza Jr FR, Klein JP, Layde PM, Lipchik RJ, Rizzo JD et al. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest 2005; 128: 153–161.
Freudenberger TD, Madtes DK, Curtis JR, Cummings P, Storer BE, Hackman RC . Association between acute and chronic graft-versus-host disease and bronchiolitis obliterans organizing pneumonia in recipients of hematopoietic stem cell transplants. Blood 2003; 102: 3822–3828.
Duncker C, Dohr D, Harsdorf S, Duyster J, Stefanic M, Martini C et al. Non-infectious lung complications are closely associated with chronic graft-versus-host disease: a single center study of incidence, risk factors and outcome. Bone Marrow Transplant 2000; 25: 1263–1268.
Schultz KR, Green GJ, Wensley D, Sargent MA, Magee JF, Spinelli JJ et al. Obstructive lung disease in children after allogeneic bone marrow transplantation. Blood 1994; 84: 3212–3220.
Clark JG, Crawford SW, Madtes DK, Sullivan KM . Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course. Ann Intern Med 1989; 111: 368–376.
Champlin R, Khouri I, Shimoni A, Gajewski J, Kornblau S, Molldrem J et al. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. Br J Haematol 2000; 111: 18–29.
Hoshino Y, Kimura H, Tanaka N, Tsuge I, Kudo K, Horibe K et al. Prospective monitoring of the Epstein–Barr virus DNA by a real-time quantitative polymerase chain reaction after allogenic stem cell transplantation. Br J Haematol 2001; 115: 105–111.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.
Ditschkowski M, Elmaagacli AH, Trenschel R, Peceny R, Koldehoff M, Schulte C et al. T-cell depletion prevents from bronchiolitis obliterans and bronchiolitis obliterans with organizing pneumonia after allogeneic hematopoietic stem cell transplantation with related donors. Haematologica 2007; 92: 558–561.
Duncan CN, Buonanno MR, Barry EV, Myers K, Peritz D, Lehmann L . Bronchiolitis obliterans following pediatric allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41: 971–975.
Yoshihara S, Tateishi U, Ando T, Kunitoh H, Suyama H, Onishi Y et al. Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning. Bone Marrow Transplant 2005; 35: 1195–1200.
Nusair S, Breuer R, Shapira MY, Berkman N, Or R . Low incidence of pulmonary complications following nonmyeloablative stem cell transplantation. Eur Respir J 2004; 23: 440–445.
Majeski EI, Paintlia MK, Lopez AD, Harley RA, London SD, London L . Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes. Am J Pathol 2003; 163: 1467–1479.
Cooke KR, Krenger W, Hill G, Martin TR, Kobzik L, Brewer J et al. Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation. Blood 1998; 92: 2571–2580.
Asavaroengchai W, Wang H, Wang S, Wang L, Bronson R, Sykes M et al. An essential role for IFN-gamma in regulation of alloreactive CD8 T cells following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2007; 13: 46–55.
Wyatt SE, Nunn P, Hows JM, Yin J, Hayes MC, Catovsky D et al. Airways obstruction associated with graft versus host disease after bone marrow transplantation. Thorax 1984; 39: 887–894.
Ostrow D, Buskard N, Hill RS, Vickars L, Churg A . Bronchiolitis obliterans complicating bone marrow transplantation. Chest 1985; 87: 828–830.
Fukuda T, Hackman RC, Guthrie KA, Sandmaier BM, Boeckh M, Maris MB et al. Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. Blood 2003; 102: 2777–2785.
Fullmer JJ, Fan LL, Dishop MK, Rodgers C, Krance R . Successful treatment of bronchiolitis obliterans in a bone marrow transplant patient with tumor necrosis factor-alpha blockade. Pediatrics 2005; 116: 767–770.
Bergeron A, Belle A, Chevret S, Ribaud P, Devergie A, Esperou H et al. Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 39: 547–553.
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Nishio, N., Yagasaki, H., Takahashi, Y. et al. Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone Marrow Transplant 44, 303–308 (2009). https://doi.org/10.1038/bmt.2009.33
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DOI: https://doi.org/10.1038/bmt.2009.33
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