Each month one member of the EBMT Scientific Council will select and comment a recent paper in the field of stem cell transplantation and cellular therapy that was published in high ranked journals.
For this month Newsletter, John Snowden, Chair of the Autoimmune Disease Working Party, comments on the publication entitled "Vitamin D deficiency predicts for poor overall survival in white but not African American patients with multiple myeloma." published in Blood Advances.
Vitamin D deficiency predicts for poor overall survival in white but not African American patients with multiple myeloma.
Yellapragada SV, Fillmore NR, Frolov A, Zhou Y, Dev P, Yameen H, Ifeorah C, Do NV, Brophy MT, Munshi NC.
Blood Adv. 2020 Apr 28;4(8):1643-1646.
My late grandfather was a coal miner from leaving school at the age of 12. When I was a child, he used to swear by the value of daily fish oil capsules that he had taken lifelong. Although we understood that his long days working underground had deprived him of many years of sunlight, we all considered that vitamin supplements had little role in a well-nourished society, so we used to humour him politely about the value of vitamin D on general health. However, unlike most of his generation of coal miners, he did live healthily to the age of 95.
I was much more fortunate in my education, but throughout my medical career the role of Vitamin D repeatedly raised its head not only in relation to its ‘classical’ roles in bone metabolism, but also in association with a range of ‘non-classical’ roles in a wide range of disease processes including immunity, inflammation, auto-reactivity, cancer, and now even in HSCT.1,2,3
Myeloma combines all of these disease processes and HSCT. In this month’s Blood Advances, Yellapragada et al4 have shown that vitamin D deficiency is associated with significantly reduced survival outcomes in patients with symptomatic myeloma. Accessing the Veteran’s Affairs database they identified 1889 patients with myeloma with serum 25-OH vitamin D measurements within 62 months of diagnosis. Using a definition of vitamin D deficiency as <20ng/ml (<50nmol/L), vitamin D deficiency was a significant independent predictor of overall survival in univariate and multivariate analysis in white patients but not in African American patients, despite lower Vitamin D levels and higher rate of deficiency. There was no association between serum vitamin D levels and sex, stage, initial therapy, or HSCT, but in white myeloma patients with vitamin D deficiency there was a stark difference in survival (median, 2.71 years vs 3.87 years, P = 0.005).
Limitations to the study included predominant male veterans population and the possibility that supplementation before vitamin D measurement may have affected findings. However, the investigators reanalyzed the data after excluding these patients, but the results and conclusions remained unchanged.
The study shows potential impact of vitamin D in myeloma and helps justify screening for vitamin D deficiency.5 Vitamin D deficiency may affect mortality in myeloma because of skeletal-related events, bone marrow microenvironment, myeloma cell growth and survival, areas where vitamin D may play a unique role in myeloma compared with other cancers.1,2,3 Although not discussed in the paper, it may be that, like in asthma, vitamin D potentiates the effect of high dose corticosteroids routinely used in myeloma, perhaps enhancing disease control. More studies of vitamin D and its deficiency in myeloma are required to explain these associations. A particular challenge is to disentangle the causes and effects of vitamin D deficiency in myeloma patients, e.g. where limited sunlight exposure or dietary intake may accompany disability and severe disease.
In the meantime, screening for vitamin D deficiency has been recommended in the long-term follow up of patients with myeloma.5 Replacement and maintenance is simple, cheap, and probably harmless in most patients. Although many myeloma patients may be kept vitamin D replete in association with general recommendations that bisphosphonate treatment is routinely accompanied with calcium and vitamin D supplementation, this is usually low dose, and may not always be implemented robustly by clinical teams, or adhered to by patients in the long term. Active monitoring of vitamin D is therefore recommended and higher doses of supplementation may be indicated.
Given its protean effects, further studies of vitamin D biology, its deficiency and supplementation in myeloma and other haematological cancers, as well as HSCT, are warranted.1,2,3
1.Ros-Soto J, Snowden JA, Salooja N, Gilleece M, Parker A, Greenfield DM, Anthias C, Alfred A, Harrington A, Peczynski C, Peggs K, Madrigal A, Basak GW, Schoemans H; Transplant Complications Working Party of the EBMT. Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019 Oct;25(10):2079-2085.
2. Ros-Soto J, Anthias C, Madrigal A, Snowden JA. Vitamin D: is it important in haematopoietic stem cell transplantation? A review. Bone Marrow Transplant. 2019 Jun;54(6):810-820.
3. Ros-Soto J, Anthias C, Madrigal A, Snowden JA. Insights into the role of vitamin D as a biomarker in stem cell transplantation. Front. Immunol. 2020 (in press) doi: 10.3389/fimmu.2020.00966
4. Yellapragada SV, Fillmore NR, Frolov A, Zhou Y, Dev P, Yameen H, Ifeorah C, Do NV, Brophy MT, Munshi NC. Vitamin D deficiency predicts for poor overall survival in white but not African American patients with multiple myeloma. Blood Adv. 2020 Apr 28;4(8):1643-1646.
5. Snowden JA, Greenfield DM, Bird JM, Boland E, Bowcock S, Fisher A, Low E, Morris M, Yong K, Pratt G; UK Myeloma Forum (UKMF) and the British Society for Haematology (BSH). Guidelines for screening and management of late and long-term consequences of myeloma and its treatment. Br J Haematol. 2017 Mar;176(6):888-907.