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Chronic graft-versus-host disease triples risk for morbidity, frailty among transplant survivors
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ATLANTA — Long-term survivors of allogeneic bone marrow transplant who develop chronic graft-versus-host disease are three times more likely to develop multiple chronic health conditions, according to study results presented at the ASH Annual Meeting and Exposition.
These conditions include oral/ocular, gastrointestinal and neurological complications, as well as pulmonary compromise.
Transplant survivors with chronic GVHD also appeared nearly three times as likely to be frail, results showed.
“The overall burden of morbidity — and the potential for frailty — really is striking,” Mukta Arora, MD, MS, associate professor of medicine in the division of hematology, oncology and transplantation at University of Minnesota, told HemOnc Today. “We can use this evidence to design strategies to screen for these complications or even prevent them from happening. These strategies can be built into transplant treatment and survivorship guidelines.”
Chronic GVHD increases risk for morbidity and compromised quality of life; however, long-term risks for specific morbidities in this patient population have not been firmly established.
In addition, no prior studies evaluated whether transplant survivors with chronic GVHD are more likely to be frail, further compromising their functional status.
Arora and colleagues analyzed data from 581 adults (55% male; 77% non-Hispanic white) from the Blood or Marrow Transplant Survivor Study, a retrospective cohort of individuals who underwent bone marrow transplantation at University of Minnesota or City of Hope between 1974 and 1988 for severe aplastic anemia (9%) or hematologic malignancy. Primary diagnoses included chronic myeloid leukemia (37%), acute myelogenous leukemia (28%) and acute lymphocytic leukemia (14%).
Median age at transplant was 30.9 years (range, 0.4-62.9) and median age at study participation was 48 years (range, 18.2-73.7). All members of the cohort survived at least 2 years after transplant.
Study participants completed baseline surveys between 2000 and 2004, and follow-up surveys between 2013 and 2017. Survey respondents self-reported sociodemographic characteristics and physical health conditions.
Researchers used modified Fried criteria to construct the frailty phenotype, and they used medical records to obtain details about chronic GVHD.
Arora and colleagues used multivariable Cox regression analyses to conduct a systematic evaluation of the association between chronic GVHD and several chronic health conditions, including diabetes, hypothyroidism, cardiomyopathy, coronary artery disease, stroke, dry eyes, cataract, glaucoma, pain, subsequent malignancies, cirrhosis and pulmonary complications.
Investigators adjusted their analysis for primary diagnosis, sociodemographics, smoking status, pre-existing comorbidities and receipt of total body irradiation.
Researchers used logistic regression to assess the association between chronic GVHD and frailty, adjusting for the same variables plus chronic health conditions.
Median follow-up was 17.1 years (range, 2-40.5).
More than half of the cohort (52.3%; n = 304) had a history of chronic GVHD. All patients underwent myeloablative conditioning, and 85% underwent total body irradiation.
History of chronic GVHD appeared associated with significantly increased risk for ocular or oral complications, such as difficulty tasting, swallowing or chewing (54% vs. 34%; P < .0001); diabetes (17% vs. 11%; P = .04); osteonecrosis (13% vs. 5%; P = .002); neurological symptoms, such as prolonged pain, tremors or decreased sense (33% vs. 23%; P = .007); pulmonary complications, such as scarring or fibrosis (23% vs. 12%; P = .0005); and gastrointestinal complications, including esophageal strictures or anal/rectal strictures (13% vs. 8%; P = .05).
Multivariable analysis revealed significant associations between chronic GVHD and osteonecrosis (HR = 2.59; 95% CI, 1.4-5), pulmonary complications (HR = 2.04; 95% CI, 1.3-3.2), ocular/oral complications (HR = 1.91; 95% CI, 1.4-2.5), gastrointestinal complications (HR = 1.87; 95% CI, 1.1-3.3), diabetes (HR = 1.58; 95% CI, 0.96-2.6) and neurological complications (HR = 1.52; 95% CI, 1.1-2.2).
Transplant recipients with chronic GVHD appeared nearly twice as likely as those without chronic GVHD to have two or more chronic health conditions (45% vs. 25%; P < .0001).
Results showed frailty frequency was nearly three times as high among transplant recipients with chronic GVHD (17.1% vs. 6.1%; P < .0001). Multivariable analysis adjusted for chronic health conditions, demographics and clinical variables showed odds for frailty were 2.66 (95% CI, 1.4-5.1) times higher among transplant recipients with chronic GVHD than those without chronic GVHD. – by Mark Leiser
For more information:
Arora M, et al. Abstract 336. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Arora reports a consultant role with Takeda Oncology. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Navneeet Majhail, MD
Despite tremendous advances in the field, chronic GVHD continues to be the scourge of allogeneic hematopoietic cell transplantation. The negative impact of chronic GVHD on overall morbidity, mortality and quality of life for transplant survivors has been well described. Transplant clinicians know from their experience that survivors with chronic GVHD are prone to specific late complications, either due to the underlying effect of the GVHD itself or as a result of exposure to its treatments.
Arora and colleagues provide empirical evidence on the risks of specific comorbidities and show that patients with this syndrome are at higher risk for frailty than those who do not develop chronic GVHD. A major limitation of their analysis is that the practice of transplantation today does not reflect the population included in the study, which comprised patients who underwent hematopoietic cell transplantation between 1974 and 1998. On the other hand, chronic GVHD continues to occur at similar rates, and we now transplant older patients and patients with a greater number of comorbidities. Hence, the results of this study are very relevant in the contemporary era.
Although the findings from this study are not necessarily novel, they do substantiate and quantify the risks for specific comorbidities and overall frailty among patients who develop chronic GVHD. This will be of great importance as we focus on improving surveillance recommendations for preventing late complications among survivors of allogeneic hematopoietic cell transplantation.
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