Overview Leukemia and Vitamin D

See also Vitamin D Life

• 229 Genes related to vitamin D - Aug 2010 CLL 8.3X more likely when a VDR gene is defective
• All items in category Vitamin D Receptor 512 items
• Chemo reduced leukemia patients vitamin D levels – Jan 2013
• Role of Vitamin D in human Diseases and Disorders – An Overview – DBP, VDR June 2014
• Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014
• Vitamin D Receptor can be modulated with a new compound – Feb 2014
• Overview Cancer and vitamin D

All Vitamin D Life items in category Leukemia

100,000 IU Vitamin D helped bones after Leukemia Chemo Treatments - RCT 2017

A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia.
Leuk Lymphoma. 2017 Oct;58(10):2370-2378. doi: 10.1080/10428194.2017.1289526. Epub 2017 Feb 20.
Orgel E1,2, Mueske NM3, Sposto R1,2, Gilsanz V2,4, Wren TAL2,3, Freyer DR1,2, Butturini AM1,2, Mittelman SD2,5.

 Download the PDF from Vitamin D Life

Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.

Low 25(OH) vitamin D3 levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia

Cancer. 25 OCT 2013, DOI: 10.1002/cncr.28368
Hun Ju Lee MD1,†, Josephia R. Muindi MD, PhD2, Wei Tan MA3, Qiang Hu PhD3, Dan Wang MA3, Song Liu PhD3, Gregory E. Wilding PhD3,
Laurie A. Ford BS1, Sheila N. J. Sait PhD4, Annemarie W. Block PhD4, Araba A. Adjei PhD2, Maurice Barcos MD, PhD5, Elizabeth A. Griffiths MD1,
James E Thompson MD1, Eunice S. Wang MD1, Candace S. Johnson PhD2, Donald L Trump MD6, Meir Wetzler MD1,*
1 Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
2 Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York
3 Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, New York
4 Clinical Cytogenetics Laboratory, Roswell Park Cancer Institute, Buffalo, New York
5 Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York
6 Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas
*Corresponding author: Meir Wetzler, MD, Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263; Fax: (716) 845-2343; meir.wetzler at roswellpark.org

BACKGROUND: Several studies have suggested that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in patients with acute myeloid leukemia (AML).

METHODS: Vitamin D levels were evaluated in 97 consecutive, newly diagnosed, intensively treated patients with AML. MicroRNA expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome.

RESULTS: Thirty-four patients

• (35%) had normal 25(OH) vitamin D3 levels (32-100 ng/mL), 34 patients
• (35%) had insufficient levels (20-31.9 ng/mL), and 29 patients
• (30%) had deficient levels (<20 ng/mL).

Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared with normal vitamin D3 levels.
In multivariate analyses,

• deficient 25(OH) vitamin D3,
• smoking,
• European Leukemia Network genetic group, and
• white blood cell count

retained their statistical significance for RFS. Several microRNAs and SNPs were associated with 25(OH) vitamin D3 levels, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with

• a lower complete remission rate (P = .0442) and with

(shorter RFS (P = .0058) and

• overall survival (P = .0011).

CONCLUSIONS: It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve outcomes for patients with AML. Cancer 2013. © 2013 American Cancer Society.

Chronic lymphocytic leukemia strongly associated with seasonal low vitamin D levels - Sept 2013

Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition.
Am J Clin Nutr. 2013 Sep;98(3):827-38. doi: 10.3945/ajcn.112.054676. Epub 2013 Jul 24.
Łuczyńska A, Kaaks R, Rohrmann S, Becker S, Linseisen J, Buijsse B, Overvad K, Trichopoulou A, Valanou E, Barmpitsioti A, Masala G, Agnoli C, Tumino R, Panico S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Peeters PH, Vermeulen R, Weiderpass E, Brustad M, Skeie G, González CA, Jakszyn P, Quirós JR, Sánchez MJ, Huerta JM, Ardanaz E, Melin B, Johansson AS, Almquist M, Malm J, Khaw KT, Wareham N, Travis RC, Fedirko V, Romieu I, Jenab M, Gallo V, Riboli E, Vineis P, Nieters A.
Centre of Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, Freiburg, Germany.

BACKGROUND: The relation between vitamin D status and lymphoma risk is inconclusive.

OBJECTIVE: We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk.

DESIGN: We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs.

RESULTS: No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with ≥2 y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006).

CONCLUSIONS: Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall.
However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.

PMID: 23885049

Leukemia should be helped by vitamin D – Review July 2012

Vitamin D insufficiency predicts time to first treatment (TFT) in early chronic lymphocytic leukemia (CLL).

Leuk Res. 2012 Apr;36(4):443-7. doi: 10.1016/j.leukres.2011.10.004. Epub 2011 Nov 1.
Molica S, Digiesi G, Antenucci A, Levato L, Mirabelli R, Molica M, Gentile M, Giannarelli D, Sperduti I, Morabito F, Conti L.
Dipartimento di Emato-oncologia, Azienda Ospedaliera di Catanzaro, Catanzaro, Italy. smolica at libero.it

Although vitamin D insufficiency is related to inferior prognosis in some cancers, limited data exist in hematologic malignancies. We evaluated the relationship between 25(OH)D serum levels and time to first treatment (TFT), a disease-specific end point, in 130 previously untreated Binet stage A chronic lymphocytic leukemia (CLL) patients. Measurement of 25(OH)D was performed by means of a direct, competitive chemiluminescence immunoassay using the DiaSorin LIAISON 25(OH)D TOTAL assay (DiaSorin, Inc., Stillwater, Minnesota). Overall, 41 patients (31.5%) had severe vitamin D insufficiency (<10 ng/mL), 66 (50.7%) had mild to moderate insufficiency (10-24 ng/mL), and 23 (17.6%) had 25(OH)D levels within the optimal range (25-80 ng/mL), with no relationship with between the season of sample collection and 25(OH)D level (P=0.188). A patient stratification according to these 3 groups led to significant difference in terms of TFT, with vitamin D insufficient patients having the shortest TFT (P=0.02). With respect to continuous 25(OH)D levels and clinical outcome, TFT was shorter as 25(OH)D decreased until a value of 13.5 ng/mL at which point the association of 25(OH)D and TFT remained constant. As a matter of fact, the 25(OH)D value of 13.5 ng/mL identified two patients subsets with different TFT risk (HR=1.91; 95% CI=1.06-3.44; P=0.03). In multivariate analysis the variable entering the model at a significant level were mutational status of IgVH (P<0.0001), serum thymidine kinase (P=0.02) and absolute lymphocyte count (P=0.03). Thus confirming the Mayo clinic experience, our data provide further evidence that 25(OH)D levels may be an important host factor influencing TFT of Binet stage A patients. Whether normalizing vitamin D levels may delay disease-progression of patients with early disease will require testing in future trials.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID: 22047708

Chronic lymphocytic leukaemia responsive to vitamin D administration.

Br J Haematol. 2012 Jan;156(1):148-9. doi: 10.1111/j.1365-2141.2011.08828.x. Epub 2011 Aug 25.
Arlet JB, Callens C, Hermine O, Darnige L, Macintyre E, Pouchot J, Capron L.

PMID: 21883139
No abstract – PDF is attached at the bottom of this page

Significant 25-hydroxyvitamin D deficiency in child and adolescent survivors of acute lymphoblastic leukemia: treatment with chemotherapy compared with allogeneic stem cell transplant.

Pediatr Blood Cancer. 2011 Jul 1;56(7):1114-9. doi: 10.1002/pbc.22949. Epub 2010 Dec 22.
Simmons JH, Chow EJ, Koehler E, Esbenshade A, Smith LA, Sanders J, Friedman D.
Department of Pediatrics, Division of Endocrinology and Diabetes, Vanderbilt Children's Hospital, Nashville, Tennessee, USA. jill.h.simmons at vanderbilt.edu

BACKGROUND: 25-hydroxyvitamin D insufficiency is common in healthy children and adolescents. There have been limited studies of the 25-hydroxyvitamin D status of survivors of pediatric and adolescent acute lymphoblastic leukemia (ALL).

PROCEDURE: In a cohort of 78 ALL survivors (52 chemotherapy-treated and 26 HCT-treated), we determined the prevalence of, and host, treatment and environmental risk factors for 25-hydroxyvitamin D insufficiency and deficiency.

RESULTS: There were no differences in serum 25-hydroxyvitamin D levels between ALL survivors treated with conventional chemotherapy and those treated with HCT (median 26.0 vs 25.5 ng/ml). Fifty-three percent of pediatric ALL survivors were 25-hydroxyvitamin D insufficient (15-29 ng/dl), and 12% were deficient (<15 ng/dl). Younger age, higher reported dietary vitamin D intake, use of vitamin D supplementation, and increased ambient ultraviolet light were associated with higher serum 25-hydroxyvitamin D levels. There was not enough evidence to suggest treatment type, gender, race, years since diagnosis or BMI were associated with serum 25-hydroxyvitamin D levels. Only 27% of conventional chemotherapy-treated ALL survivors and 8% of HCT-treated ALL survivors met RDA for dietary vitamin D intake.

CONCLUSIONS: The prevalence of vitamin D deficiency and insufficiency in ALL survivors is similar to that of the general pediatric population in the United States, and there is no difference in serum 25-hydroxyvitamin D status between chemotherapy-treated and HCT-treated ALL survivors. ALL survivors rarely meet the RDA requirements for vitamin D. Further studies are needed to determine whether dietary and behavioral interventions can improve the vitamin D status of ALL survivors.

Copyright © 2010 Wiley-Liss, Inc.

PMID: 21488156
PDF is attached at the bottom of this page

Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia.

Blood. 2011 Feb 3;117(5):1492-8. doi: 10.1182/blood-2010-07-295683. Epub 2010 Nov 3.
Shanafelt TD, Drake MT, Maurer MJ, Allmer C, Rabe KG, Slager SL, Weiner GJ, Call TG, Link BK, Zent CS, Kay NE, Hanson CA, Witzig TE, Cerhan JR.
Division of Hematology, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated the relationship of 25(OH)D serum levels with time-to-treatment (TTT) and overall survival (OS) in newly diagnosed CLL patients participating in a prospective cohort study (discovery cohort) and a separate cohort of previously untreated patients participating in an observational study (confirmation cohort). Of 390 CLL patients in the discovery cohort, 119 (30.5%) were 25(OH)D insufficient. After a median follow-up of 3 years, TTT (hazard ratioHR = 1.66; P = .005) and OS (HR = 2.39; P = .01) were shorter for 25(OH)D-insufficient patients. In the validation cohort, 61 of 153 patients (39.9%) were 25(OH)D insufficient. After a median follow-up of 9.9 years, TTT (HR = 1.59; P = .05) and OS (HR 1.63; P = .06) were again shorter for 25(OH)D-insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, Rai stage, CD38 status, ZAP-70 status, immunoglobulin heavy chain variable (IGHV) gene mutation status, CD49d status, and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing, 25(OH)D insufficiency remained an independent predictor of TTT (HR = 1.47; P = .008), although the association with OS was not significant (HR = 1.47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing.
Comment in CLL: a supplementary question? [Blood. 2011]
PDF is attached at the bottom of this page

CLL: a supplementary question?

Blood. 2011 Feb 3;117(5):1439-40. doi: 10.1182/blood-2010-11-318451.
Pepper C, Fegan C. Cardiff University.

In this issue of Blood, Shanafelt and colleagues provide the first evidence that vitamin D deficiency is a risk factor for disease progression in chronic lymphocytic leukemia (CLL).
Their findings imply that dietary vitamin D supplementation could potentially modify the natural history of this incurable disease.
Comment on: Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia. [Blood. 2011]

PMID: 21292782
PDF is attached at the bottom of this page

See also web

• For Drugs That Save Lives, a Steep Cost New York Times, april 2014
  Gleevec, needed to treat Leukemia, now costs about $90,000/year and is needed for entire life (vs 1000X less cost for Vitamin D)
• Leukemia Vitamin D Council, written by Dr. Grant 2011
• Chronic lymphocytic leukaemia (CLL) incidence statistics UK

FDA Approval of Tisagenlecleucel - Promise and Complexities of a $475 000 ALL Cancer Drug - Nov 2017

JAMA
25% of people getALL recurrence, and need a second injection
Vitamin D Life suspects that Vitamin D treats acute lymphoblastic leukemia (ALL) better than this new drug, at 10,000 X lower cost
To see first page of PDF click on the following thumnail