October 10, 2017
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Pretransplant vitamin D deficiency may heighten relapse risk in myeloid malignancies

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A deficiency in vitamin D prior to allogeneic hematopoietic stem cell transplantation increased risk for relapse among patients with myeloid malignancies, according to a retrospective study published in Journal of Clinical Oncology.

Vitamin D deficiency is frequent among patients with cancer and has been associated with poor prognosis of various solid, as well as hematologic, malignancies,” Thomas Luft, MD, PhD, senior physician and associate professor of internal medicine at Heidelberg University Hospital in Germany, and colleagues wrote. “Despite several smaller studies suggesting that insufficient vitamin D levels are likely to harm patients undergoing [allogeneic HSCT], data on the prognostic relevance of the pretransplant vitamin D status and its impact on clinical outcome parameters are sparse.”

Researchers evaluated the impact of pretransplant vitamin D status on OS, relapse mortality and nonrelapse mortality in a training cohort of 492 patients who underwent allogeneic HSCT from 2002 to 2013.

In this cohort, 396 patients (80%; median age, 53 years; 59% men; 43% late-stage disease) had vitamin D deficiency — defined as serum 25-hydroxyvitamin D3 level less than 20 ng/mL (equivalent to less than 50 nM).

Forty-seven percent of patients with vitamin D deficiency had myeloid diseases — which included acute myeloid leukemia and myelodysplastic and myeloproliferative neoplasms — and 53% had lymphoid diseases, or acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma and multiple myeloma.

Patients with vitamin D deficiency demonstrated significantly poorer OS (HR = 1.78; 95% CI, 1.16-2.72), driven by a higher risk for relapse (HR = 1.96; 95% CI, 1.21-3.18) rather than nonrelapse mortality (HR = 1.72; 95% CI, 0.92-3.2).

When analyzed by disease type, vitamin D deficiency increased risk for relapse among patients with myeloid diseases (HR = 2.55; 95% CI, 1.21-5.39), but not among patients with lymphatic diseases (HR = 1.6; 95% CI, 0.85-3.03).

The analysis also included a validation cohort of 398 patients with myeloid malignancies. Of them, 348 (87%; median age, 56 years; 50% men; 47% early-stage disease) had vitamin D deficiency before allogeneic HSCT. These analyses also showed an increased risk for relapse among patients with myeloid diseases and vitamin D deficiency (HR = 2.6; 95% CI, 1.19-5.56).

Researchers acknowledged limitations with their study, including its retrospective nature and patient heterogeneity. They noted that vitamin D deficiency could be a surrogate marker for a more general micronutrient deficiency reflecting overall health status and, thus, their findings do not provide definite evidence of a causal relationship between vitamin D deficiency and posttransplant outcome.

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“Our study suggests that vitamin D deficiency might affect disease control after [allogeneic HSCT], in particular, [among] patients allografted for myeloid malignancies,” Luft and colleagues wrote. “However, the question of whether improving vitamin D status before [allogeneic HSCT] has an impact on outcome can only be answered by clinical trials.” – by Chuck Gormley

Disclosures: Citizens for Leukemia and Tumor Diseases and the European Union’s Seventh Framework Program helped fund this study. Luft reports consultant/advisory roles with Alexion Pharmaceuticals and Jazz Pharmaceuticals, as well as research funding from Medac, Neovii and Jazz Pharmaceuticals. Please see the full study for a list of all other authors’ relevant financial disclosures.