Navneet S. Majhail

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the United States annually. With advances in transplantation technology and supportive care practices, HCT has become safer, and patient survival continues to improve over time. Indications for HCT continue to evolve as research refines the role for HCT in established indications and identifies emerging indications where HCT may be beneficial. The American Society for Blood and Marrow Transplantation (ASBMT) established a multiple-stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on "routine" indications for HCT. This white paper presents the recommendations from the task force. Indications for HCT were categorized as follows: (1) Standard of care, where indication for HCT is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but HCT has been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where HCT has demonstrated effectiveness but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early phase clinical studies show HCT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT. The ASBMT will periodically review these guidelines and will update them as new evidence becomes available.

Quality of life (QOL) after hematopoietic cell transplantation (HCT) is compromised by chronic GVHD. In a prospectively assembled multicenter cohort of adults with chronic GVHD (n = 298), we examined the relationship between chronic GVHD severity defined by National Institutes of Health (NIH) criteria and QOL as measured by the SF-36 and FACT-BMT instruments at time of enrollment. Chronic GVHD severity was independently associated with QOL, adjusting for age. Compared with population normative data, SF-36 scores were more than a SD (10 points) lower on average for the summary physical component score (PCS) and role-physical subscale, and significantly lower (with magnitude 4-10 points) for several other subscales. Patients with moderate and severe cGVHD had PCS scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis, and greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. Moderate to severe cGVHD as defined by NIH criteria is associated with significant compromise in multiple QOL domains, with PCS scores in the range of other systemic autoimmune diseases. Compromised QOL provides a functional assessment of the effects of chronic GVHD, and may be measured in cGVHD clinical studies using either the SF-36 or the FACT-BMT.