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Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial

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Abstract

Background

Calcitriol, the active metabolite of vitamin D, is an essential regulator in the hematopoiesis and immunity. However, knowledge revealing its influence on the immune and hematologic reconstitution after hematopoietic stem cell transplantation (HSCT) in clinical trials is very limited.

Objectives

The effects of calcitriol on short-term and long-term hematopoietic recovery, relapse-free survival (RFS) and overall survival (OS) in multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma following autologous peripheral blood HSCT were assessed.

Methods

Eighty patients (age: 18–68 years) in complete remission were allocated 1:1 to two groups by balanced block randomization. Calcitriol 0.25 μg or placebo capsule was administered three times daily from transplantation to day 30. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count (PC) were determined daily from transplantation to day 30. White blood cell count (WBC), PC, and hemoglobin concentration (HC) of days 180 and 365 were extracted from clinic files. A thorough examination for oral mucositis (OM) was completed daily during hospital stay. Adverse drug reactions (ADRs) as well as two-year RFS and OS were evaluated.

Results

Median time to ANC engraftment (≥0.5 × 103/μl: 10.0 vs. 11.0 days; P = 0.98) and PC engraftment (≥20.0 × 103/μl: both 14.0 days; P = 0.58) was similar between groups. However, the median time to ALC recovery was significantly shorter in the calcitriol group (≥0.5 × 103/μl: 13.0 vs. 20.0 days; P < 0.001). Moreover, ALC recovery rates on day 15 (≥0.5 × 103/μl: 82.1% vs. 42.5%; P < 0.001) and on day 30 (≥1.0 × 103/μl: 91.7% vs. 57.5%; P = 0.001) was significantly higher with calcitriol. WBC, PC, and HC on days 180 and 365 were not significantly different between groups. None of the OM indices were modulated by calcitriol. All the ADRs were non-serious and mild, possibly or unlikely related to the intervention. In a median of 29 months follow-up, RFS was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; P = 0.03), albeit the OS was not affected (87.0%, SE = 5.0% vs. 92.0%, SE = 4.0%; P = 0.72).

Conclusion

Calcitriol could improve ALC recovery and RFS as a safe option post-HSCT.

Oral calcitriol 0.25 µg three times daily from transplantation to day 30 improved lymphocytes recovery and two-year relapse-free survival as a safe option in 80 patients of autologous hematopoietic stem cell transplantation in comparison with placebo.

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Acknowledgements

We greatly appreciate the participants without whom this investigational study would not be possible. We thank Ms. Ashraf Sadat Mousavi, Ms. Zahra Shahriari, BMT wards staff of Shariati Hospital, and Dr. Hamid Khoee (drug supply and randomization) for their kind assistances.

Funding

This study was funded through an educational grant to the researchers from the Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, PO Box 14155/6451, 16 Azar Ave., Inqelab Sq., Tehran, Iran

    Kosar Raoufinejad, Molouk Hadjibabaie, Zahra Jahangard-Rafsanjani & Kheirollah Gholami

  2. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Reza Shamshiri

  3. Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Islamic Azad University of Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Shahrzad Pezeshki & Mehdi Rajabi

  4. Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Bahram Chahardouli & Mohammad Vaezi

  5. Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran

    Molouk Hadjibabaie & Kheirollah Gholami

  6. Department of Clinical Pharmacy, University Hospitals of North Midlands, Stoke-on-Trent, Staffordshire, UK

    Mehdi Rajabi

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  1. Kosar Raoufinejad
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Raoufinejad, K., Shamshiri, A.R., Pezeshki, S. et al. Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial. DARU J Pharm Sci 27, 709–720 (2019). https://doi.org/10.1007/s40199-019-00306-y

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