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      Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation

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          Abstract

          Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (e.g. umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, periand post-transplant exposures and risk-factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplant experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.

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          Long-term survival and late deaths after allogeneic hematopoietic cell transplantation.

          Allogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied. Records of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed. Median follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time. The prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.
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            Late cardiotoxicity after treatment for Hodgkin lymphoma.

            We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.
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              Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study.

              We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE = 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio = 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapse-related mortality was increased among patients older than 18 years at HCT (18-45 years: relative risk [RR] = 1.7; 46+ years: RR = 3.7) and among those with cGVHD (RR = 2.7), and was lower among patients who received methotrexate for GVHD prophylaxis (RR = 0.5). HCT survivors were more likely to report difficulty in holding jobs (odds ratio [OR] = 13.9), and in obtaining health (OR = 7.1) or life (OR = 9.9) insurance compared with siblings. This study demonstrates that mortality rates remain twice as high as that of the general population among 15-year survivors of HCT, and that the survivors face challenges affecting their health and well-being.
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                Author and article information

                Journal
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Revista Brasileira de Hematologia e Hemoterapia
                Associação Brasileira de Hematologia e Hemoterapia
                1516-8484
                1806-0870
                2012
                : 34
                : 2
                : 109-133
                Affiliations
                [1 ] National Marrow Donor Program, Minneapolis, MN, USA
                [2 ] Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA
                [3 ] Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA
                [4 ] Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [5 ] King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
                [6 ] Nagoya University Graduate School of Medicine, Nagoya, Japan
                [7 ] Universidade Federal do Paraná, Curitiba, PR, Brazil
                [8 ] University of Minnesota, Minneapolis, MN, USA
                [9 ] Cincinnati Children's Hospital, Cincinnati, OH, USA
                [10 ] Keio University School of Medicine, Tokyo, Japan
                [11 ] Instituto de Oncologia Pediátrica GRAACC Unifesp, São Paulo, Brazil
                [12 ] Hôpital Saint-Louis, Paris, France
                [13 ] Royal Melbourne Hospital, Parkville, Victoria, Australia
                [14 ] San Martino Hospital, Genoa, Italy
                [15 ] University of Florida College of Medicine, Gainesville, FL, USA
                [16 ] University Hospital Basel, Basel, Switzerland
                Author notes
                Corresponding author: Navneet S Majhail Medical Director National Marrow Donor Program 3001 Broadway Street NE, Suite 100 55413-1753 Minneapolis, MN Phone: 612 884 8676 nmajhail@ 123456nmdp.org>
                Article
                10.5581/1516-8484.20120032
                3459383
                23049402
                5f392c44-96e9-4386-8302-f7080b44196f

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 January 2012
                : 27 January 2012
                Categories
                Special Article

                Hematology
                autologous,prevention,late complications,hematopoietic cell transplantation,allogeneic,screening

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