Low Vitamin D Ups Relapse Risk after Stem Cell Transplant – MedPage Today
Pre-existing vitamin D deficiency doubled the odds of recurrence of myeloid malignancies after allogeneic stem cell transplant (alloSCT), a retrospective analysis involving 900 patients showed.
Analysis of two separate cohorts yielded hazard ratios for recurrence of 1.98 and 2.60 for patients with pretransplant vitamin D deficiency versus those with pretransplant 25-hydroxyvitamin-D3 (25[OH]D) levels ≥20 ng/mL. Pre-SCT 25(OH)D deficiency also was associated with worse survival, which was driven primarily by relapse as opposed to nonrelapse mortality.
Additional analyses showed that the adverse impact of 25(OH)D deficiency was limited to patients with myeloid disease, and not those with lymphatic disease, reported Thomas Luft, MD, PhD, of University Hospital Heidelberg in Germany, and colleagues in the Journal of Clinical Oncology.
The results suggested a fairly simple solution to a common problem, but the authors noted the sketchy history of clinical trials that evaluated vitamin-based interventions for medical conditions.
“Vitamin D status represents an easily modifiable patient risk factor, and our results provide a rationale for the design of interventional studies,” Luft and colleagues wrote. “However, it should be noted that potential effects of other vitamins have not always been shown to be beneficial in clinical trials.”
The results added to an extensive information base about the association of vitamin D insufficiency/deficiency in various diseases and disease processes, including many types of malignancies. A recent meta-analysis involving 17,000 patients with cancer showed that higher circulating 25(OH)D levels at or near cancer diagnosis had an independent association with improved survival. A study of vitamin D deficiency in the general population showed a significant association with all-cause mortality.
The volume of information reflects that widespread nature of “compromised vitamin D status … a common finding all over the world, affecting not only medical inpatients but also the general population,” the authors noted. More relevant to their investigation, several smaller studies suggested an adverse impact of vitamin D insufficiency on alloSCT outcomes. Other small clinical studies demonstrated improvement in symptoms of graft versus host disease with vitamin D treatment.
Few prior studies informed the prognostic impact of pretransplant vitamin D status in patients undergoing alloSCT, providing a rationale for the analyses by Luft’s group.
The authors retrospectively identified 492 patients who underwent alloSCT from 2002 to 2013 and examined serum vitamin D status prior to alloSCT. Disease type of lymphoid in 53% of cases and myeloid in 47%. Using a 25(OH)D cutoff of <20 ng/mL, they found that 80% of the patients had vitamin D deficiency.
By multivariable analysis, pretransplant vitamin D deficiency was associated with a survival hazard of 1.78 compared with patients who had pretransplant 25(OH)D levels ≥20 ng/mL (95% CI 1.16-2.72, P=0.007). Patients with low 25(OH)D levels had a twofold greater risk of relapse (95% CI 1.21-3.18, P=0.006) but no significant increase in nonrelapse mortality (HR 1.72, 95% CI 0.92-3.20, P=0.088).
Evaluation of 25(OH)D status by disease type showed a significant adverse effect of vitamin D deficiency on overall survival (OS) for patients with myeloid versus lymphoid disease (HR 1.43, 95% CI 1.03-1.98, P=0.033). The hazard for relapse and nonrelapse mortality did not differ by disease type.
Analysis of outcomes by disease type showed that vitamin D deficiency increased the hazard for relapse 2.55 among patients with myeloid disease (P=0.014) but not among patients with lymphoid disease (HR 1.60, P=0.147). However, patients with lymphoid diseases had an increased survival hazard associated with vitamin D deficiency (HR 2.06, 95% CI 1.07-3.98, P=0.031), whereas the subgroup with myeloid disease did not. The increased survival hazard was limited to patients with late-stage disease.
Investigators repeated the analyses in a training cohort limited to patients with myeloid diseases. Investigators found that 87% of the 398 patients in the training cohort had vitamin D deficiency. As compared with patients who had 25(OH)D levels ≥20 ng/mL, those with deficiency had a significantly increased likelihood of relapse after alloSCT (HR 2.60, 95% CI 1.19-5.56, P=0.017). OS nonrelapse mortality did not differ significantly pretransplant vitamin D status.
Aside from the retrospective nature of the study and the heterogeneity of patients, the authors acknowledged two limitations of the findings: inability to exclude vitamin D deficiency as a surrogate marker of a generalized deficiency affecting overall health status and lack of evidence for a causal relationship between vitamin D deficiency and posttransplant outcome.
Luft disclosed relevant relationships with Alexion Pharmaceuticals, Jazz Pharmaceuticals, Medac, Neovii, and MedacNeovii, as well as patient/royalty interests.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner