Elevated Cardiovascular Risk Factors at Time of Allotransplant Do Not Impact Survivals in Adult Patients: A Retrospective Study of 194 Cases

Background: Cardiovascular events are complications responsible for morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). However, little is known regarding the impact on outcomes of cardiovascular risk factors at the time of allo-SCT in adult patients.

Patients and Methods: The primary objective of this retrospective study was to examine the impact on overall (OS) and disease-free (DFS) survival of pre-transplant well-recognized cardiovascular risk factors in a large cohort of adult allo-SCT recipients. All adults (>18 years old) allotransplanted in our center between January 2011 and December 2014 (n=194) were eligible for the study. Of the numerous cardiovascular risk factors defined previoulsy (Mahmood SS et al, Lancet 2014), ten were considered here. A point of 1 was attributed to each of them if present, allowing to build various scores for statistical analysis.

Results: The cohort comprised 120 males and 74 females with a median age of 56 years old (range: 21-70). The initial disease was of myeloid lineage for 58% and lymphoid for 42%. Most of the patients were in complete remission (CR) at transplant (CR1 n=78, CR2 or more n=38, Partial remission (PR) 1 n=4, PR2 or more n=30, active disease n=44). Ninety-one patients had received a myeloablative conditioning regimen while 79 and 24 had received a reduced-intensity or a sequential regimen, respectively. Donors were as follows: sibling n=68, haplo-identical n=4, matched unrelated donor n=76, mismatched (9/10) unrelated donor n=19, unrelated cord blood n=27. Peripheral blood stem cells was the main source of graft (n=151) while 16 cases received bone marrow. All patients had a left ventricular ejection fraction >50% at the time of transplant

With a median OS of 66 months (95% CI 34-66), 2-year OS and DFS were 59.3% +/- 3.6 and 51% +/- 3.6, respectively, for the whole group. Overall incidences of grade 2-4 acute and chronic GVHD were 55% and 31% while overall incidences of relapse and NRM were 36% and 16%, respectively.

For each considered cardiovascular risk factor at transplant, the number of patients involved was as follows: male >50 years old (n=75)/female >60 years old (n=24), smoking activity (active or stopped within the last three years, n=86), overweight (BMI>/= 25) and obesity (BMI >/= 30) (n=85), hypertension (n=26), diabetes mellitus (n=7) and previous first-degree familial history of coronary disease (n=4). For factors characterizing dyslipidemia, these numbers were: total cholesterol >2 g/L n=95, total triglycerides >1.5 g/L n=98, HDL cholesterol <0.4g/L n= 67, and LDL-cholesterol >1.6g/L n=29).

In univariate analysis, HDL cholesterol below or above 0.4 g/L and active disease at transplant were the only factors significantly associated with lower 2 year OS (50.6%+/-6.1 vs 65.6%+/-4.5 vs, p=0.02; and 38.3%+/-7.6 vs CR: 68.3%+/-4.4 vs PR: 61%+/-8.5, p=0.001, respectively) and DFS (55.6%+/-4.7 vs 41.5%+/-6, p=0.04; and 28.7%+/-7.1 vs CR 59.1%+/-4.6 vs PR 51%+/-7.1, p=0.0002, respectively). However, in multivariate analysis, only the disease status at the time of transplant retained significance (OS: HR 1.7. 95%CI 1.3-2.24, p=0.0001; and DFS: HR 1.7, 95%CI 1.3-2.17, p=0.0001).

When considering various cardiovascular risk scores for statistical analysis, none were predictive of survivals in patients.

After transplant, the incidence of cardiovascular events was 8.2% (n=16/194) within the first year and 12.5% (n=16/127) for patients alive after one year. None of the patients died of cardiovascular disease.

Conclusion: Elevated cardiovascular risk factors at the time of allo-SCT do not impact survivals in adult patients. Therefore, their presence should not lead to reconsider the procedure and may not make the patients at higher risk for allo-SCT.