Abstract
The aim of our study was to assess the cumulative incidence and severity (‘burden’) of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors, at least 2 years after transplantation. The presence and severity of late effects in each survivor was documented according to the Common Terminology Criteria for Adverse Events (version 3.0). The burden of late effects was graded from mild to disabling/life-threatening. Risk factors for a high burden of late effects were assessed by univariate and multivariate logistic regression analyses. Among 162 survivors of HSCT seen in our late effects outpatient clinic, cumulative incidence of late effects was 93.2% after a median follow-up time of 7.2 years (range 2.0–21.0 years) after HSCT. The burden of late effects was mild, moderate, severe and disabling in 28, 41, 24 and 1% of survivors respectively. Risk factors for a severe or disabling burden of late effects were older age at HSCT (P for trend <0.001) and a conditioning regimen including irradiation OR 2.2, 95% CI 1.1–4.7, P=0.03). In conclusion, a high burden of late effects is found in childhood HSCT survivors after a median follow-up of only 7 years.
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References
De Koning J, Van Bekkum DW, Dicke KA, Dooren LJ, van Rood JJ, Rádl J . Transplantation of bone-marrow cells and fetal thymus in an infant with lymphopenic immunological deficiency. Lancet 1969; 1: 1223–1227.
Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 2006; 355: 1572–1582.
Geenen MM, Cardous-Ubbink MC, Kremer LC, van den Bos C, van der Pal HJ, Heinen RC et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA 2007; 297: 2705–2715.
Leiper AD . Non-endocrine late complications of bone marrow transplantation in childhood: part I. Br J Haematol 2002; 118: 3–22.
Leiper AD . Non-endocrine late complications of bone marrow transplantation in childhood: part II. Br J Haematol 2002; 118: 23–43.
Brennan BMD, Shalet SM . Endocrine late effects after bone marrow transplant. Br J Haematol 2002; 118: 58–66.
Leahey AM, Teunissen H, Friedman DL, Moshang T, Lange BF, Meadows AT . Late effects of chemotherapy compared to bone marrow transplantation in the treatment of pediatric acute myeloid leukaemia and myelodysplasia. Med Pediatr Oncol 1999; 32: 163–169.
Faraci M, Barra S, Cohen A, Lanino E, Grisolia F, Miano M et al. Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant. Int J Radiat Oncol Biol Phys 2005; 63: 1568–1575.
Perkins JL, Kunin-Batson AS, Youngren NM, Ness KK, Ulrich KJ, Hansen MJ et al. Long-term follow-up of children who underwent hematopoietic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr Blood Cancer 2007; 49: 958–963.
Ferry C, Gemayael G, Rocha V, Labopin M, Esperou H, Robin M et al. Long-term outcomes after allogeneic stem cell transplantation of children with haematological malignancies. Bone Marrow Transplant 2007; 40: 219–224.
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH . Establishing a standard definition for child overweight and obesity worldwide: international survey. Br Med J 2000; 320: 1240–1243.
Baker KS, DeFor TE, Burns LJ, Ramsay NK, Neglia JP, Robison LL . New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 2003; 21: 1352–1358.
Cohen A, Rovelli A, Merlo DF, van Lint MT, Lanino E, Bresters D et al. Risk for secondary thyroid carcinoma after hematopoietic stem-cell transplantation: an EBMT Late Effects Working Party Study. J Clin Oncol 2007; 25: 2449–2454.
Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997; 336: 897–904.
Friedman DL, Rovo A, Leisenring W, Locasciulli A, Flowers ME, Tichelli A et al. Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party. Blood 2008; 111: 939–944.
Kolb HJ, Socie G, Duell T, van Lint MT, Tichelli A, Apperley JF et al. Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group. Ann Intern Med 1999; 131: 738–744.
Fanfulla F, Locatelli F, Zoia MC, Giorgiani G, Bonetti F, Spagnolatti L et al. Pulmonary complications and respiratory function changes after bone marrow transplantation in children. Eur Respir J 1997; 10: 2301–2306.
Frisk P, Arvidson J, Bratteby LE, Hedenstrom H, Lonnerholm G . Pulmonary function after autologous bone marrow transplantation in children: a long-term prospective study. Bone Marrow Transplant 2004; 33: 645–650.
Marras TK, Szalai JP, Chan CK, Lipton JH, Messner HA, Laupacis A . Pulmonary function abnormalities after allogeneic marrow transplantation: a systematic review and assessment of an existing predictive instrument. Bone Marrow Transplant 2002; 30: 599–607.
Nysom K, Holm K, Hesse B, Ulrik CS, Jacobsen N, Bisgaard H et al. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma. Arch Dis Child 1996; 74: 432–436.
Wieringa J, van Kralingen KW, Sont JK, Bresters D . Pulmonary function impairment in children following hematopoietic stem cell transplantation. Pediatr Blood Cancer 2005; 45: 318–323.
Bakker B, Massa GG, Oostdijk W, Weel-Sipman MH, Vossen JM, Wit JM . Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies. Eur J Pediatr 2000; 159: 31–37.
Bakker B, Oostdijk W, Bresters D, Walenkamp MJ, Vossen JM, Wit JM . Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood. Bone Marrow Transplant 2004; 33: 1049–1056.
Cohen A, Rovelli A, Bakker B, Uderzo C, van Lint MT, Esperou H et al. Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects-EBMT. Blood 1999; 93: 4109–4115.
Couto-Silva AC, Trivin C, Esperou H, Michon J, Baruchel A, Lemaire P et al. Final height and gonad function after total body irradiation during childhood. Bone Marrow Transplant 2006; 38: 427–432.
Sanders JE, Hawley J, Levy W, Gooley T, Buckner CD, Deeg HJ et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood 1996; 87: 3045–3052.
Thibaud E, Rodriguez-Macias K, Trivin C, Esperou H, Michon J, Brauner R . Ovarian function after bone marrow transplantation during childhood. Bone Marrow Transplant 1998; 21: 287–290.
Van der Pas-van Voskuilen IG, Veerkamp JS, Raber-Durlacher JE, Bresters D, van Wijk AJ, Barasch A et al. Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children. Support Care Cancer (e-pub ahead of print 13 January 2009).
Boulad F, Bromley M, Black P, Heller G, Sarafoglou K, Gillio A et al. Thyroid function following bone marrow transplantation using hyperfractionated radiation. Bone Marrow Transplant 1994; 15: 71–76.
Sanders JE, The Seattle BMT Team. The impact of marrow transplant preparative regimens on subsequent growth and development. Sem Hematol 1991; 28: 244–249.
Couto-Silva AC, Trivin C, Thibaud E, Esperou H, Michon J, Brauner R . Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 2001; 28: 67–75.
Larsen EC, Müller J, Schmiegelow K, Rechnitzer C, Andersen AN . Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer. J Clin Endocrinol Metab 2003; 88: 5307–5314.
Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y et al. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab 2006; 91: 1723–1728.
Phipps S, Rai SN, Leung WH, Lensing S, Dunavant M . Cognitive and academic consequences of stem-cell transplantation in children. J Clin Oncol 2008; 26: 2027–2033.
Smedler AC, Winiarski J . Neuropsychological outcome in very young hematopoietic SCT recipients in relation to pretransplant conditioning. Bone Marrow Transplant 2008; 42: 515–522.
Titman P, Pink E, Skucek E, O'Hanlon K, Cole TJ, Gaspar J et al. Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies. Blood 2008; 112: 3907–3913.
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Bresters, D., van Gils, I., Kollen, W. et al. High burden of late effects after haematopoietic stem cell transplantation in childhood: a single-centre study. Bone Marrow Transplant 45, 79–85 (2010). https://doi.org/10.1038/bmt.2009.92
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DOI: https://doi.org/10.1038/bmt.2009.92
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