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

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY DARU Journal of Pharmaceutical Sciences Pub Date : 2019-12-01 Epub Date: 2019-11-11 DOI:10.1007/s40199-019-00306-y
Kosar Raoufinejad, Ahmad Reza Shamshiri, Shahrzad Pezeshki, Bahram Chahardouli, Molouk Hadjibabaie, Zahra Jahangard-Rafsanjani, Kheirollah Gholami, Mehdi Rajabi, Mohammad Vaezi
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引用次数: 11

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.

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口服骨化三醇对自体干细胞移植后造血恢复和存活的影响:一项随机临床试验。
背景:钙三醇是维生素D的活性代谢产物,是造血和免疫的重要调节因子。然而,在临床试验中揭示其对造血干细胞移植(HSCT)后免疫和血液重建影响的知识非常有限。目的:评价骨化三醇对自体外周血造血干细胞移植后多发性骨髓瘤、霍奇金淋巴瘤和非霍奇金淋巴瘤的短期和长期造血恢复、无复发生存率(RFS)和总生存率(OS)的影响。方法:80例完全缓解的患者(年龄:18-68岁)通过平衡分组随机分为两组。Calcitriol 0.25μg或安慰剂胶囊从移植至第30天每天给药三次。从移植到第30天,每天测定中性粒细胞绝对计数(ANC)、淋巴细胞绝对计数(ALC)和血小板计数(PC)。从临床文件中提取第180天和第365天的白细胞计数(WBC)、PC和血红蛋白浓度(HC)。住院期间每天对口腔粘膜炎(OM)进行彻底检查。评估药物不良反应(ADR)以及两年RFS和OS。结果:ANC植入的中位时间(≥0.5 × 103/μl:10.0天对11.0天;P = 0.98)和PC植入(≥20.0 × 103/μl:均为14.0天;P = 0.58)相似。然而,骨化三醇组ALC恢复的中位时间明显更短(≥0.5 × 103/μl:13.0天对20.0天;P 3/μl:82.1%对42.5%;P 3/μl:91.7%对57.5%;P = 0.001)显著高于骨化三醇。第180天和第365天的WBC、PC和HC在各组之间没有显著差异。OM指数均未受到骨化三醇的调节。所有ADR均为非严重和轻度,可能或不太可能与干预有关。在中位29个月的随访中,骨化三醇组的RFS显著改善(77.0%,SE = 7.0%对59.0%,SE = 8.0%;P = 0.03),尽管OS没有受到影响(87.0%,SE = 5.0%对92.0%,SE = 4.0%;P = 结论:Calcitriol可改善ALC的恢复,RFS是HSCT后的安全选择。图形摘要与安慰剂相比,从移植到第30天,每天三次口服0.25µg骨化三醇,作为80名自体造血干细胞移植患者的安全选择,可改善淋巴细胞恢复和两年无复发生存率。
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DARU Journal of Pharmaceutical Sciences
DARU Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
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期刊介绍: DARU Journal of Pharmaceutical Sciences is a peer-reviewed journal published on behalf of Tehran University of Medical Sciences. The journal encompasses all fields of the pharmaceutical sciences and presents timely research on all areas of drug conception, design, manufacture, classification and assessment. The term DARU is derived from the Persian name meaning drug or medicine. This journal is a unique platform to improve the knowledge of researchers and scientists by publishing novel articles including basic and clinical investigations from members of the global scientific community in the forms of original articles, systematic or narrative reviews, meta-analyses, letters, and short communications.
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