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DARU Journal of Pharmaceutical Sciences

, Volume 27, Issue 2, pp 709–720 | Cite as

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

  • Kosar Raoufinejad
  • Ahmad Reza Shamshiri
  • Shahrzad Pezeshki
  • Bahram Chahardouli
  • Molouk HadjibabaieEmail author
  • Zahra Jahangard-Rafsanjani
  • Kheirollah Gholami
  • Mehdi Rajabi
  • Mohammad Vaezi
Research article

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.

Graphical abstract

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.

Keywords

Calcitriol Engraftment Immune reconstitution Hematopoietic stem cell transplantation Hodgkin Lymphocyte Lymphoma Mucositis Multiple myeloma Survival Vitamin D 

Notes

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 information

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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kosar Raoufinejad
    • 1
  • Ahmad Reza Shamshiri
    • 2
  • Shahrzad Pezeshki
    • 3
  • Bahram Chahardouli
    • 4
  • Molouk Hadjibabaie
    • 1
    • 5
    Email author
  • Zahra Jahangard-Rafsanjani
    • 1
  • Kheirollah Gholami
    • 1
    • 5
  • Mehdi Rajabi
    • 3
    • 6
  • Mohammad Vaezi
    • 4
  1. 1.Department of Clinical Pharmacy, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  2. 2.Department of Epidemiology and Biostatistics, School of Public HealthTehran University of Medical SciencesTehranIran
  3. 3.Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Islamic Azad University of Tehran Medical SciencesIslamic Azad UniversityTehranIran
  4. 4.Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati HospitalTehran University of Medical SciencesTehranIran
  5. 5.Research Center for Rational Use of DrugsTehran University of Medical SciencesTehranIran
  6. 6.Department of Clinical PharmacyUniversity Hospitals of North MidlandsStoke-on-TrentUK

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