Hematopoietic cell transplantation (HCT) is a lifesaving and often curative procedure for several benign and malignant disorders but carries the risk of several complications, including end organ failure necessitating solid organ transplantation (SOT).1–4 SOT after HCT however comes with higher risk of complications leading to poor graft and patient outcomes. Therefore, SOT decisions should balance these risks with the potential for survival benefit and better quality of life. Given the wide range of conditions for which HCT is indicated, decision-making can be complex. Data to inform decision making is sparse and more are needed.5 In this issue of Transplantation, Dr. Gupta et al report important findings from a retrospective cohort study involving patients with HCT undergoing a subsequent SOT.6 The authors utilized registry data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the Organ Procurement and Transplantation Network (OPTN) to identify a cohort of SOT recipients with a history of HCT. The CIBMTR, comprising 360 centers across multiple countries, voluntarily collects and contributes data on HCT. For this study, the authors integrated CIBMTR data with OPTN data, which captures comprehensive information on organ transplantation in the United States.
Between 2000 and 2017, they identified 80 patients the majority of whom received kidney transplants, followed by lung transplants, with smaller numbers of liver and heart transplants (5 and 2, respectively). The patient cohort was predominantly male, with most having undergone HCT for malignancy. The average age was 45 years, and approximately 40–50% of the transplants were from living donors. The authors analyzed allograft survival and mortality following SOT, along with associations between baseline characteristics and outcomes. Due to the small sample size, their analysis was restricted to univariable methods, and multivariable analysis was not performed. Key findings were that the kidney recipients fared the best whereas liver recipients fared the worst. Among kidney after HCT patients, graft survival at 5 years was close to 80%, which could be considered fair. Univariable analysis suggested that recipient cytomegalovirus (CMV) serostatus and a history of HCT for lymphoma might be potential risk factors for graft failure. Although the recurrence of malignancy is a significant consideration in transplantation decisions, this study suggests that it was not a major direct contributor to mortality following SOT in this cohort.
Clinicians deciding on SOT for patients with previous HCT should consider risk factors beyond the usual donor, recipient and post-transplant variables. Key additional elements to consider are primary hematological disease, duration of remission, CMV serostatus, organ type and the availability of living donors (for those awaiting kidney transplantation). The latter issue is of particular significance if the potential living donor was also the prior donor for HCT as it can eliminate the need for maintenance immunosuppression after SOT and its associated complications. This data was not available for the current analysis and may explain why the survival rates were reasonable after kidney transplantation. Additional important considerations are the likelihood of favorable outcomes following SOT and how these outcomes compare to alternative treatment options. This comparison is particularly relevant for patients with ESKD, where dialysis remains a viable treatment alternative.
Several aspects of this study need consideration. First, the cohort was highly heterogeneous and drawn over a long study period from centers across the United States. Still, the cohort likely represents a highly selective patient population, as characterized by the relatively younger age, good functional status, and a high proportion of living donor transplants. Consequently, the outcomes observed may reflect a “best-case scenario,” whereas patients with poorer baseline characteristics or those receiving marginal organs are likely to have worse outcomes. One of the major limitations of this study is the absence of a comparative group comprising patients with end-organ failure who did not receive an SOT. This lack of comparison makes it challenging to quantify the benefits of SOT relative to alternative treatments, particularly in cases where other options, such as dialysis or ventricular assist devices (VADs), are available. Additionally, while a history of lymphoma and positive CMV serostatus were identified as potential risk factors for graft failure, it remains unclear whether these are true causal risk factors or confounders. The sample size was too small and precluded any formal inferential statistical comparisons. For instance, the risks associated with CMV depend on both donor CMV status and the type of SOT, with donor-positive to recipient-negative transplants posing the highest risk for CMV-related complications.7 The small number of liver transplant recipients (five in total) also limits ability to draw meaningful conclusions and inform clinical practice. While liver recipients fared the worst, it should be noted that the time to liver transplantation post-HCT was the shortest among the organ groups, at an average of 9 months. This may indicate that liver transplant recipients were patients experiencing major complications following HCT that necessitated urgent transplantation. While the authors suggest that lung transplant recipients had better outcomes compared to the general population, this finding should also be interpreted with caution. A notable proportion of the lung transplant recipients had history of allogeneic transplant who had an average age of 31 years. This may have contributed to better outcomes and may not generalize to older recipients. While this study does not provide definitive answers to all the questions surrounding SOT in patients with prior HCT, it provides important data regarding outcomes in this unique patient population where studies are hard to come by.
Future studies should consider developing organ specific (kidney, liver, etc.) longitudinal data collection among HCT recipients so that the benefits of SOT and alternative treatments (i.e., dialysis, VADs, etc.) can be rigorously investigated. This will be invaluable to key stakeholders, including patients, clinicians, and potential living donors. This need is especially pressing given the less-than-robust clinical outcomes observed in this high-risk patient cohort. We should thus continue the efforts towards building SOLID evidence that will more effectively guide these high-stake decisions.
Funding:
National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (K08DK119576).
Abbreviations:
- CMV
Cytomegalovirus
- CIBMTR
Center for International Blood and Marrow Transplant Research
- ESKD
End-Stage Kidney Disease
- GVHD
Graft-versus-Host Disease
- HCT
Hematopoietic Cell Transplantation
- OPTN
Organ Procurement and Transplantation Network
- SOT
Solid Organ Transplant
Footnotes
COI: Replimune (Consulting fees)
References
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