Long-term morbidity, mortality increased after allogeneic HCT in patients with CML
SAN DIEGO — Patients who received allogeneic hematopoietic cell transplantation to treat chronic myeloid leukemia demonstrated higher long-term morbidity rates than siblings who did not have the disease and higher mortality rates compared with the general population, according to findings presented at the ASH Annual Meeting and Exposition.
However, the study did identify a subgroup of patients where the long-term morbidity was comparable to the sibling cohort.
Jessica Wu, BA, a clinical research assistant at the University of Alabama at Birmingham, and colleagues conducted an analysis of long-term outcomes in 637 patients with CML treated with allogeneic HCT between 1981 and 2010 at either City of Hope Comprehensive Cancer Center or the University of Minnesota.
The researchers sought to assess if a subset of patients with CML treated with allogeneic HCT could demonstrate a relatively lower risk for long-term morbidity.
Patients had to survive 2 years after HCT (median follow-up, 16.7 years) to be included in the study. Eighty-percent of the cohort was aged younger than 45 years at transplant. Sixty-eight percent received transplant during the first chronic phase. Sixty-three percent received a transplant from a matched related donor, 34% had a matched unrelated donor and the remaining 3% received non-myeloablative transplant.
More than half of patients (65.8%) developed chronic graft-versus-host-disease.
Of the 445 patients alive at the time of the analysis, 65% completed the BMTSS health questionnaire used to assess risk for grade 3 or grade 4 adverse events. A sibling comparison group (n = 404) also completed the questionnaire.
OS was 72.1% at 20 years after HCT and 69.6% at 30 years after transplant. The cumulative incidence of relapse-related mortality at 20 years was 3.9% and 18.2% for non-relapse-related mortality.
The most common causes of death at 20 years were infection (7%), chronic GVHD (6%) and subsequent malignant neoplasms (3%).
Patients who received HCT were at a 4.4-fold increased risk for death (P < .0001) than normal populations adjusted for age, race and sex.
Patients who survived 15 years and were transplanted in the first chronic phase demonstrated comparable mortality rates with the general population (Standardized Mortality Ratio = 1.5; 95% CI, 0.9-2.3).
OS was 81.5% at 20 years after HCT in patients (n = 70) who received treatment with the addition of busulfan and cyclophosphamide when they were aged younger than 45 years. This cohort was at a 3.3-fold risk for death when compared with the general population (P < .0001).
The cumulative incidence of severe or life-threating adverse events among HCT survivors at 20 years was 47.2%. Transplant survivors were at a 2.7-fold increased risk for severe or life-threatening conditions when compared with siblings after adjusting for age, sex and race (P < .0001).
Researchers compared the incidence of the most common chronic health conditions reported by patients who achieved long-term survival after HCT with non-diseased siblings and found higher rates of diabetes (11.1% vs 1.5%, P < .001), subsequent malignant neoplasms (10.1% vs. 1.7, P < .001) and coronary artery disease (6.9% vs. 3.2% P < .001).
“While our transplant cohort was at an increased risk of developing severe or life-threatening conditions, we were able to identify a subset of CML patients where the risk of severe or life-threatening conditions was comparable to that of the siblings,” Wu told HemOnc Today.
Patients aged younger than 45 years at transplant treated with the addition of busulfan and cyclophosphamide were not at an increased risk for severe or life-threatening chronic health conditions when compared with siblings (HR = 0.81; 95% CI, 0.26-2.54).
“These results give us preliminary evidence that there is a group of CML patients that does relatively well after transplant,” Smita Bhatia, MD, MPH, a study author and director of the School of Medicine Institute for Cancer Outcomes and Survivorship at the University of Alabama at Birmingham, told HemOnc Today. “With more research, we are hoping to better understand how pre- and post-HCT management of CML contributes to late mortality and long-term morbidity and to describe the lifelong economic burden of transplant.” – by Ryan McDonald
Wu J, et al. Abstract 823. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: Wu and Bhatia report no relevant financial disclosures. Please see the full study for a list of all other relevant financial disclosures.