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Pretreatment vitamin D deficiency linked to shorter survival in Hodgkin lymphoma
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Vitamin D status appeared to be an independent predictor of clinical outcomes and may affect chemosensitivity among patients with Hodgkin lymphoma, according to results of a prospective case-control study published in Journal of Clinical Oncology.
Based on the results, vitamin D screening and replacement should be incorporated into future randomized trials involving patients with Hodgkin lymphoma, researchers wrote.
“We found increased [Hodgkin lymphoma] mortality and incidence in winter months at higher latitudes,” Sven Borchmann, MD, of the German Hodgkin Study Group and department of internal medicine at University of Cologne in Germany, told HemOnc Today. “Despite a recognized seasonal pattern of incidence and mortality in Hodgkin lymphoma, vitamin D deficiency has not been thoroughly evaluated in Hodgkin lymphoma.”
Borchmann and colleagues evaluated pretreatment vitamin D levels and clinical outcomes of 351 patients with various stages of Hodgkin lymphoma in three German Hodgkin Study Group trials who had been randomly assigned to receive first-line chemotherapy with or without radiotherapy. Researchers matched each case with documented relapse or progressive disease with two nonrelapsed controls.
Describing pretreatment vitamin D status among patients across all stages of disease, comparing baseline vitamin D status between cases and controls, and reporting how baseline vitamin D status impacted PFS and OS served as the study’s primary objectives.
Researchers used 25-hydroxyvitamin D as a marker of vitamin D status.
Half of the patients (n = 175; median age, 32 years; 58% male) exhibited vitamin D deficiency (< 30 nmol/L) before planned chemotherapy, whereas 83 patients (median age, 33 years; 67% male) were vitamin D insufficient ( 30 nmol/L to < 50 nmol/L) and 93 patients (median age, 31 years; 56% male) were vitamin D sufficient ( 50 nmol/L).
Results showed a greater proportion of patients with relapsed or refractory Hodgkin lymphoma had pretreatment vitamin D deficiency than matched relapse-free controls (68% vs. 41%; P < .001; median baseline vitamin D, 21.4 nmol/L vs. 35.5 nmol/L).
Patients with vitamin D deficiency had inferior PFS (10-year difference, 17.6%; HR = 2.13; 95% CI, 1.84-2.48) and OS (10-year difference, 11.1%; HR = 1.82; 95% CI, 1.53 to 2.15) than patients who were not vitamin D deficient. These results remained consistent across trial groups.
In subsequent experiments with cultured Hodgkin lymphoma cell lines, researchers found supplementing physiologic doses of vitamin D (calcitriol) increased antiproliferative effects in combination with chemotherapy. In a Hodgkin lymphoma xenograft mouse model, supplemental vitamin D (cholecalciferol) improved tumor chemosensitivity by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone.
“This is likely not [limited to] Hodgkin lymphoma,” Borchmann said. “There is plenty of evidence for such a link in solid tumors or other hematological malignancies. However, the magnitude of the effect we observed in our study is quite strong and surprised us compared with other studies in other malignancies.” – by John DeRosier
For more information:
Sven Borchmann, MD, can be reached at sven.borchmann@uk-koeln.de.
Disclosures: Borchmann reports honoraria, institutional research funding or travel expenses from Bristol-Myers Squibb and Takeda. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Stephen Ansell, MD, PhD
The role of vitamin D in the outcome of patients with hematological malignancies is complicated. Previous studies have confirmed that in certain hematological malignancies — including diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia — patients who are vitamin D deficient at the time of diagnosis have a poorer overall outcome. As shown in other studies and confirmed in this study, the poor prognosis associated with vitamin D deficiency appears independent of performance status, confirming that this is not simply a measure of patient frailty. Instead, this appears to be associated with the latitude at which the patient lives, as well as the time of the year, suggesting that it is truly due to exposure to sunlight and vitamin D levels. However, it is worth noting that although 50% of patients in this trial were vitamin D deficient, using the same criteria, 25% to 30% of the healthy population in Germany would also be vitamin D deficient. Therefore, this is clearly not simply a case of cause and effect.
The greatest challenge is to determine how to address vitamin D deficiency. It is not clear that simply replacing vitamin D will automatically change the prognosis of patients. It also is not clear whether administering supratherapeutic levels of vitamin D would be of benefit. Studies using other vitamins in lung cancer and head and neck cancer would suggest caution, as this was associated with an inferior outcome in those studies. What is really needed is a randomized trial of vitamin D replacement vs. placebo administration to determine whether vitamin D replacement will improve the poor outcome of those who are vitamin D deficient.
All told, there is clearly an association between vitamin D deficiency and patient outcome in many malignancies. Additional studies are needed to determine the role that vitamin D plays in tumor biology. A more comprehensive understanding of vitamin D biology in malignancies in general may provide a simple intervention to improve the outcome of patients with cancer.
Mayo Clinic
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