Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS).

HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.

[1]  M. Hudson,et al.  Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. , 2011, Blood.

[2]  Michael Boeckh,et al.  Reduced mortality after allogeneic hematopoietic-cell transplantation. , 2010, The New England journal of medicine.

[3]  L. Robison,et al.  Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. , 2010, Blood.

[4]  D. Mulrooney,et al.  Corticosteroid dose as a risk factor for avascular necrosis of the bone after hematopoietic cell transplantation. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[5]  S. Bhatia,et al.  Predictors of late cardiovascular complications in survivors of hematopoietic cell transplantation. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[6]  K. Baker,et al.  The burden of cure: long-term side effects following hematopoietic stem cell transplantation (HSCT) in children. , 2010, Pediatric clinics of North America.

[7]  D. Mulrooney,et al.  Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort , 2009, BMJ : British Medical Journal.

[8]  J. Passweg,et al.  Late complications after hematopoietic stem cell transplantation , 2009, Expert review of hematology.

[9]  R. Porcher,et al.  Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. , 2009, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[10]  S. Bhatia,et al.  Predictors of avascular necrosis of bone in long‐term survivors of hematopoietic cell transplantation , 2009, Cancer.

[11]  D. Green,et al.  Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  John D Boice,et al.  The Childhood Cancer Survivor Study: a National Cancer Institute-supported resource for outcome and intervention research. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  R. Miralbell,et al.  Quality of life and social integration after allogeneic hematopoietic SCT , 2008, Bone Marrow Transplantation.

[14]  Jon Sharp,et al.  Late congestive heart failure after hematopoietic cell transplantation. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  S. Bhatia,et al.  Incidence and predictors of delayed chronic kidney disease in long‐term survivors of hematopoietic cell transplantation , 2008, Cancer.

[16]  L. Robison,et al.  Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. , 2008, Blood.

[17]  G. Dini,et al.  Endocrinological late complications after hematopoietic SCT in children , 2008, Bone Marrow Transplantation.

[18]  G. Dini,et al.  Non-endocrine late complications in children after allogeneic haematopoietic SCT , 2008, Bone Marrow Transplantation.

[19]  K. Baker,et al.  Quality of life and recovery after graft-versus-host disease. , 2008, Best practice & research. Clinical haematology.

[20]  K. Ness,et al.  Twenty years of follow‐up among survivors of childhood and young adult acute myeloid leukemia , 2008, Cancer.

[21]  C. Sklar,et al.  Endocrine complications of hematopoietic stem cell transplantation. , 2007, Endocrinology and metabolism clinics of North America.

[22]  K. Ness,et al.  Late effects in survivors of Hodgkin and non-Hodgkin lymphoma treated with autologous hematopoietic cell transplantation: a report from the bone marrow transplant survivor study. , 2007, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[23]  M. Hudson,et al.  Pediatric hodgkin lymphoma: maximizing efficacy and minimizing toxicity. , 2007, Seminars in radiation oncology.

[24]  A. Baruchel,et al.  Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies , 2007, Bone Marrow Transplantation.

[25]  F. Tana,et al.  Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Workin , 2007, Bone Marrow Transplantation.

[26]  U. Forinder,et al.  Risk factors for lower health‐related QoL after allogeneic stem cell transplantation in children , 2007, Pediatric transplantation.

[27]  Kevin C Oeffinger,et al.  Chronic health conditions in adult survivors of childhood cancer. , 2006, The New England journal of medicine.

[28]  Edward A Copelan,et al.  Hematopoietic stem-cell transplantation. , 2006, The New England journal of medicine.

[29]  K. Ness,et al.  Visual, auditory, sensory, and motor impairments in long‐term survivors of hematopoietic stem cell transplantation performed in childhood , 2006, Cancer.

[30]  J. Wingard,et al.  Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[31]  J. Steinberger,et al.  Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. , 2005, Blood.

[32]  K. Ness,et al.  Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. , 2005, Blood.

[33]  G. Kaspers,et al.  Treatment of childhood acute myeloid leukemia , 2005, Expert review of anticancer therapy.

[34]  B. Storer,et al.  Late effects of hematopoietic cell transplantation among 10-year adult survivors compared with case-matched controls. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  M. Ranke,et al.  Late effects after stem cell transplantation (SCT) in children – growth and hormones , 2005, Bone Marrow Transplantation.

[36]  J. Beaumont,et al.  Long-term health-related quality of life, growth, and spiritual well-being after hematopoietic stem-cell transplantation. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  Kevin C Oeffinger,et al.  Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. , 2003, JAMA.

[38]  A. Tichelli,et al.  Nonmalignant late effects after allogeneic stem cell transplantation. , 2003, Blood.

[39]  G. Dini,et al.  Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission. , 2003, Blood.

[40]  M. Schrappe,et al.  New treatment strategies in childhood acute lymphoblastic leukaemia. , 2002, Best practice & research. Clinical haematology.

[41]  John D Potter,et al.  Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project. , 2002, Medical and pediatric oncology.

[42]  L. Robison,et al.  Validation of self-reported complications by bone marrow transplantation survivors , 2000, Bone Marrow Transplantation.

[43]  S. Davies,et al.  Unrelated donor bone marrow transplantation: influence of HLA A and B incompatibility on outcome. , 1995, Blood.

[44]  H. Heslop,et al.  Pediatric Blood and Marrow Transplantation: State of the Science , 2008, Bone Marrow Transplantation.

[45]  R. Arceci.  Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Long-term Follow-up Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline , 2006 .