Mortality Risk Factors in Allogeneic Transplant Recipients

Mortality Risk Factors in Allogeneic Transplant Recipients

Allogeneic blood or bone marrow transplantation (BMT) has expanded over the last 4 decades, reaching almost 30,000 cases across Europe and North America in 2019. Compared with 40 years ago, more patients are now receiving BMT at an older age, use of non–human leukocyte antigen-matched sibling donors has increased, and use of peripheral blood stem cells (PBSCs) is on the rise. As transplantation practices have evolved, there has been a decrease in relative mortality. However, patients who receive BMT still carry a substantial burden of late-onset morbidity and increased mortality rates due to recurrence of primary disease and a high burden of nonrecurrence-related morbidity (NRM).

The cumulative effects of morbidity and premature mortality after allogeneic BMT and the impact of modifications in transplant practice were explored by Dr Smita Bhatia et al in a large, multi-institutional cohort study. Their analysis included 4,741 patients from the Blood or Marrow Transplant Survivor Study who have lived 2 years or more after BMT between 1974 and 2014. Patients were divided into 3 subgroups (ie, transplant received 1974–1989, 1990–2004, 2005–2014). Over 40 years, the median age at BMT increased from 19.5 to 43 years and the proportion of patients receiving unrelated donor BMT rose from 4.8% to 55.7%. BMT for high-risk disease increased from 17.9% to 33.6%.

Across the full cohort, there was an 8.8-fold higher risk for all-cause mortality compared with the general population. Thirty-year overall survival was 57.8% for the entire cohort. Mortality rates increased with age, and patients in the study experienced a 20.8% decrease in life expectancy, with 8.7 years of life lost. Leading causes of death were disease recurrence, infections, subsequent malignant neoplasms (SMNs), cardiovascular disease (CVD), and pulmonary disease. Recurrence-related mortality plateaued at 10 years and was 12.2% 30 years post-BMT, while NRM incidence continued to increase, nearly doubling to over 20% by 30 years post-BMT. Infections, SMNs, CVD, and pulmonary disease were leading causes of NRM.

Risk factors for 10-year, all-cause late mortality were older age at BMT, male gender, high-risk disease, use of PBSCs as the stem cell source, and a history of chronic graft-versus-host-disease. Therefore, despite overall improvements in younger patients, the authors concluded that there remains a need to address the causes of late mortality among older BMT recipients and those who receive PBSCs, to improve outcomes.

High level
This study highlighted the progress that has been made, and also uncovered some gaps in the care of patients receiving allogeneic transplants. In a linked editorial, Dr Lohith Gowda and Dr Stuart Seropian suggested several areas of focus for future research, including looking at novel agents and immune manipulation strategies in high-risk patients, studies of pre-emptive maintenance drugs, management of patients with posttransplant relapse, the association of PBSC use with NRM risk, and efforts to mitigate the negative effects of PBSC grafts. It was also suggested that the burden of NRM needs to be addressed, particularly infection (standardized mortality ratio [SMR] 52.0), pulmonary disease (SRM 13.9), subsequent malignant neoplasms (SMR 4.8), and CVD (SMR 4.1). Additionally, since most patients receive long-term care with primary care clinicians, it is vital that education regarding long-term risk factors be provided to the broader medical community. The development of evidence-based guidelines with localized implementation may help to improve long-term outcomes.

Ground level
This study illustrates the need for long-term stewardship of medical care among the transplant community. Focus on early morbidity and mortality is typically highest in the first 2 years following BMT, as that is the time of greatest risk. However, the challenges of survivorship in the years or decades that follow must also be considered in caring for patients post-BMT. Survivorship care should proactively address the risk of late cardiopulmonary events and encompass a multidisciplinary format that includes screenings and monitoring of both physical and mental health. Given the aging population, the ideal care team would include primary clinicians and specialists who have expertise in geriatrics and transplantation.