FROM JCO

Patients with myeloid malignancies who have vitamin D deficiency prior to an allogeneic stem cell transplant (alloSCT) are significantly more likely to experience a relapse and have worse overall survival after transplant than patients with adequate vitamin D levels at baseline, investigators have found.

Among 492 patients with lymphoid or myeloid malignancies who had an alloSCT at a single center, those with vitamin D deficiency had a risk of post-transplant relapse that was nearly double the risk of patients with sufficient vitamin D levels. Also, this relapse risk contributed to significantly worse overall survival for the vitamin D–deficient patients, reported Thomas Luft, MD, PhD, and his colleagues from the University of Heidelberg, Germany.

In multivariate analysis, the risk for relapse was limited to patients with myeloid rather than lymphatic disease, they reported in the Journal of Clinical Oncology.

“[O]ur study suggests that VitD deficiency might affect disease control after alloSCT, in particular, in patients allografted for myeloid malignancies. However, the question of whether improving VitD status before alloSCT has an impact on outcome can only be answered by clinical trial,” they wrote.­­

To see whether pre-transplant vitamin D deficiency – serum levels of 25-hydroxyvitamin D3 less than 20 ng/mL – might have prognostic significance, the investigators looked at a training cohort of 492 patients who underwent alloSCT at their center from 2002 through 2013, and a validation cohort consisting of 398 additional patients with myeloid malignancies treated at the University of Essen, Germany.

Overall survival for the 396 patients (80%) in the training cohort with vitamin D deficiency was significantly worse than for patients with adequate levels (hazard ratio, 1.78; P = .007) in a multivariate analysis adjusted for type of malignancy, disease stage, conditioning intensity, patient age, donor type, and recipient/donor sex match.

Analysis also showed that the excess hazard was accounted for by higher risk of relapse than nonrelapse mortality (HR, 1.96; P = .006).

When the investigators looked at relapse risk by disease type, they found a significantly higher risk among vitamin D–deficient patients with myeloid malignancies (HR, 2.55; P = .014) but not with lymphoid malignancies.

The risk for relapse among patients with myeloid malignancies in the validation cohort was similarly high (HR, 2.60; P = .017).

“The growth inhibitory, pro-differentiation, and pro-apoptotic effects of VitD in vitro are well recognized, and low VitD levels have been shown to enhance clonal proliferation of leukemic cells. Therefore, with regard to treatment before alloSCT but also to conditioning, one might speculate that VitD deficiency facilitates resistance to chemotherapy,” the researchers wrote.

Low vitamin D levels have been associated in other studies with shorter relapse-free and overall survival in patients with acute myeloid leukemia apart from alloSCT.

The researchers recommend clinical trials to explore the possibility that vitamin D supplementation pre-transplant could improve post-transplant outcomes.

The study was supported by a grant from the BLUT Foundation and the European Union’s Seventh Framework Program. Dr. Luft disclosed consulting with Alexion and Jazz Pharmaceuticals, and institutional research funding and travel support from Medac, Neovii, and Jazz.

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