|Year : 2019 | Volume
| Issue : 2 | Page : 77-81
Vitamin D supplementation does not affect survival in patients with Hodgkin’s lymphoma
Ahmed M.L Bedewy MD 1, Noha S Kandil2
1 Department of Hematology, Medical Research Institute, Alexandria University, Alexandria, Egypt
2 Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt
|Date of Submission||03-May-2019|
|Date of Acceptance||21-Jun-2019|
|Date of Web Publication||15-Nov-2019|
Ahmed M.L Bedewy
Abraj Al-Shaker, Smouha, Alexandria, 21615
Source of Support: None, Conflict of Interest: None
Background Hodgkin’s lymphoma (HL) is a B-cell lymphoproliferative tumor that has an excellent prognosis in most patients using chemotherapeutic protocols, with or without radiation. Some populations including aged people and adolescents and young adults did not gain similar benefits from treatment advances when compared with pediatric and other adult patients. Vitamin D deficiency was suggested as a risk factor for many malignant tumors, and its supplementation may have a role in management of some cancers.
Aim This study aimed to evaluate vitamin D levels in patients with HL at presentation and after 12 weeks of supplementation in relation to treatment outcome.
Patients and methods A total of 24 treatment-naive patients with pathologically confirmed HL were consecutively recruited. Vitamin D levels were assessed at presentation and after 12 weeks of vitamin D supplementation using automated electrochemiluminescence binding assay. All patients received ABVD protocol as a first-line therapy. The outcome of patients after the six cycles was classified as complete response, partial response, stable disease, or relapsed/progressive disease.
Results Female patients and those with B symptoms had significantly lower vitamin D levels (P=0.032 and 0.045, respectively). Patients who failed to respond to ABVD had significantly lower vitamin D levels compared with that of responders (P=0.022). Vitamin D levels did not affect progression-free survival (log-rank test P=0.69).
Conclusion Lower vitamin D level was associated with nonresponsiveness to ABVD regimen. Vitamin D supplementation in patients with HL did not alter the progression-free survival of the studied patients. However, these findings await more validation through recruiting larger cohorts of patients for longer follow-up periods.
Keywords: Hodgkin’s, lymphoma, supplementation, vitamin D
|How to cite this article:|
Bedewy AM, Kandil NS. Vitamin D supplementation does not affect survival in patients with Hodgkin’s lymphoma. Egypt J Haematol 2019;44:77-81
|How to cite this URL:|
Bedewy AM, Kandil NS. Vitamin D supplementation does not affect survival in patients with Hodgkin’s lymphoma. Egypt J Haematol [serial online] 2019 [cited 2019 Dec 5];44:77-81. Available from: http://www.ehj.eg.net/text.asp?2019/44/2/77/271076
| Introduction|| |
Hodgkin lymphoma (HL) is a B-cell lymphoproliferative tumor that has an excellent prognosis in most patients using chemotherapeutic protocols, with or without radiation . However, high-dose therapy combined with autologous hematopoietic cell transplant may be needed in patients with refractory/relapsed disease . In addition, some populations including aged people  and adolescents and young adults  did not gain similar benefits from treatment advances when compared with pediatric and other adult patients.
Inspired by the continuous need for innovative and alternative treatment approaches , treatment of HL remains under continuous evolvement which includes better identification of significant risk factors, more sensitive diagnostic utilities, and more effective therapeutic approaches .
Vitamin D is a steroid-like hormone that exerts its pleotropic actions via binding to vitamin D receptor. Vitamin D deficiency was suggested as a risk factors for many malignant tumors, including bone , gynecological , cutaneous  and hematological malignancies ,. Evidence derived from clinical , and experimental  studies suggested vitamin D supplementation may have a role in management of some cancers.
In hematological malignancies, it is thought that the role of vitamin D in regulation of immune cell functions and maturation and proliferation of hematopoietic cells makes it a promising candidate for treatment of these malignancies ,.
| Patients and methods|| |
This is a prospective study conducted at the Medical Research Institute, Alexandria University. The study protocol was conducted in accordance with the Helsinki Declaration for medical research involving human participants. The study prospectively recruited a cohort of 24 consecutive treatment-naive patients with pathologically confirmed HL. Patients were excluded if they were on vitamin D supplementation or if they had surgical or medical condition that can interfere with adequate intestinal absorption.
Before treatment, patients were subjected to standard clinical, laboratory, and radiological assessment. Patients were classified according to WHO classification of hematopoietic tumors ,. Tumor was staged according to Cotswold Modification of Ann Arbor Staging System  and performance status was assessed according to Eastern Cooperative Oncology Group Performance Scale . The international prognostic index was used to estimate disease prognosis .
Vitamin D levels were assessed at presentation and after 12 weeks of vitamin D supplementation. The serum level of vitamin D was assayed using automated electrochemiluminescence binding assay for the in-vitro quantitative determination of total 25-hydroxy vitamin D (Cobas E411 analyzer; Roche, Berlin, Germany). Obtained levels were classified as normal (≥30 ng/ml), insufficient (20–29.9 ng/ml), or deficient (<20 ng/ml) . For vitamin D supplementation, we used oral liquid vitamin D3 preparations according to the instructions described by Khan and Fabian .
All patients received ABVD protocol as a first-line therapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) . The response of patients after the six cycles was classified as complete response, partial response, stable disease, or relapsed/progressive disease according to the criteria described by Cheson et al. . Patients who responded to ABVD were followed up for progression-free survival (PFS) (median 20 months, range: 11–35 months).
Statistical analysis was achieved using SPSS 25 (IBM, New York, USA). Numerical variables were expressed as mean±SD whereas categorical data were represented as number and percent. Statistical comparisons were achieved using t-test, paired t-test, or one-way analysis of variance for numerical data and χ2-test for categorical data. The Kaplan–Meier method was used to estimate the probabilities of PFS and the log-rank test was used for univariate comparisons between groups.
| Results|| |
Vitamin D level at presentation ranged from 4.8 to 21.4 IU/ml, with a mean of 11.54±4.23 IU/ml. The relation between baseline vitamin D levels and the clinicolaboratory data of the studied patients is shown in [Table 1]. Female patients and those with B symptoms had significantly lower vitamin D levels (P=0.032 and 0.045, respectively). Moreover, patients with inferior Eastern Cooperative Oncology Group performance status had significantly lower vitamin D levels (P=0.045).
|Table 1 Vitamin D level at presentation in relation to the clinical and laboratory data of the studied patients|
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Vitamin D supplementation resulted in significant improvement of vitamin D levels from 11.5±4.2 to 33.3±8.9 IU/ml (P<0.001) and normalizing the vitamin levels in 11 (45.8%) patients ([Table 2]). Patients who failed to respond to ABVD had significantly lower vitamin D levels compared with that of responders (P=0.022). Vitamin D status after 12 weeks supplementation was not associated with significant difference in PFS (log-rank test P=0.69; [Table 3] and [Figure 1]).
|Table 2 Vitamin D levels in the studied patients at presentation and after 12 weeks of vitamin D supplementation|
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|Table 3 The study treatment outcomes in relation to vitamin D levels after 12 weeks of supplementation|
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|Figure 1 Progression-free survival of 21 patients with ABVD-responsive Hodgkin’s lymphoma (HL) regarding vitamin D status after 12 weeks of supplementation (P=0.69).|
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| Discussion|| |
The relation between vitamin D levels and the biology of various types of cancers remains a matter of continuous debate with many inconsistencies and controversies. The present study sought to contribute to this debate by studying baseline vitamin D levels in patients with HL, a set of patients who were rarely investigated for this association. Moreover, the study used vitamin D supplementation to discover the effect of correction of vitamin D status on treatment outcome.
In this study, all patients with HL had insufficient (4.2%) to deficient (95.8%) vitamin D levels at baseline. This prevalence is fairly higher than prevalence reported by other studies on healthy Egyptian populations ,,,.
Although we should be cautious when interpreting this surprising finding, it raises attention about the association between developing HL and vitamin D deficiency. In this context, the secondary analysis conducted by Ammann et al.  on data from the Women’s Health Initiative calcium/vitamin D trial found that vitamin D supplementation was associated with protective effects against hematological malignancies. In contrast, the meta-analysis conducted by Lu et al.  concluded that high vitamin D levels does not provide protective effects against the development of non-HL. Moreover, a large study with a long-term follow-up period found no significant relation between high-dose vitamin D supplementation and reduction of cancer incidence .
The significantly lower baseline vitamin D levels in female patients is our cohort is a common finding is Egyptian women. It is mainly related to low outdoor activity together with the traditional clothing habits . Patients with B symptoms had significantly lower vitamin D levels. This finding was also reported by the recent study of Hohaus et al.  on patients with aggressive lymphoma and may give a useful clue to understand the etiology of these manifestations in hematological malignancies patients.
Supplementing our patients with vitamin D resulted in normalizing the hormone levels in 11 (45.8%) patients and converting other patients from deficiency to the insufficiency state. These results are comparable to the vitamin D supplementation protocol adopted by Hohaus et al.  which produced normal vitamin D levels in 56.0% of patients.
In this study, vitamin D level was lower in nonresponders compared with ABVD-responsive patients. However, vitamin D status did not affect their PFS. These data are supported by the conclusions of Székely et al.  who studied the effect of season of diagnosis on the patients with diffuse large B-cell lymphoma and HL. They noted that although diffuse large B-cell lymphoma cases diagnosed during summer had better overall survival, this did not apply to patients with HL. Moreover, the study of Shanafelt et al.  failed to document as association between overall survival and vitamin D levels.
In contrast, Drake et al.  found that patients with NHL with lower vitamin D levels had inferior event-free survival and overall survival. Similar conclusions were reported by the studies of Kelly et al.  and Tracy et al.  on patients with follicular lymphoma. Moreover, the recent study of Djurasinović et al.  on patients with lymphoid malignancies including HL found significantly lower progression rate and better event-free survival in patients with higher vitamin D levels. However, results of various tumor types were not revealed in the study.
Conclusively, lower vitamin D level was associated with nonresponsiveness to ABVD regimen. Vitamin D supplementation in patients with HL did not alter the PFS of the studied patients. However, these findings await more validation through recruiting larger cohorts of patients for longer follow-up periods.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]