Effect of chamomile on chemotherapy-induced neutropenia in pediatric leukemia patients: A randomized triple-blind placebo-controlled clinical trial

Document Type : Original Research Article


1 ​Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Essence of Parsiyan Wisdom Institute, Phytopharmaceutical Technology and Traditional Medicine Incubator, Shiraz University of Medical Sciences, Shiraz, Iran

3 Hematology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

4 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

5 Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.


Objective: Chemotherapy-induced neutropenia is one of the main side effects of acute lymphoblastic leukemia (ALL) treatment. In this trial, we evaluated the efficacy of chamomile in management of neutropenia.  
Materials and Methods: This randomized triple-blind placebo-controlled clinical trial was carried out in 2-18-year-old children with ALL. Participants in each group daily received 2.5 ml of either chamomile syrup or placebo syrup for a period of 30 days. Participants’ white blood cell (WBC), and absolute neutrophil count (ANC), as well as their quality of life were evaluated. 
Results: The study was completed with a total of 40 patients.  An increasing trend of ANC was observed in the treatment group despite the decreasing trend in placebo group, which was statistically significant between the two groups (P Interaction=0.019, 95% confidence intervals=15.076–171.324). No serious side effects were reported.
Conclusion: Using chamomile syrup as a complementary therapy in children with leukemia could improve their immunity (as it increased WBC) by minimizing chemotherapy-induced neutropenia.


Main Subjects

American Botanical Council. 1998. The complete german commission E monographs. Austin: Integrative Medicine Communications. pp. 395-398.
Andavolu MV, Logan LJ. 1999. Leukocytoclastic vasculitis as a complication of granulocyte colony-stimulating factor (G-CSF)–a case study. Ann Hematol, 78:79-81.
Atarzadeh F, Daneshfard B, Dastgheib L, Jaladat AM, Amin G. 2016. Early description of diet-induced blistering skin diseases in medieval Persia: Avicenna's point of view. Skinmed, 14:367-370.
Atarzadeh F, Jaladat AM, Daneshfard B, Dastgheib L, Kamalinejad M, Amin G. 2017. A review on botanicals with wound healing activity for pemphigus vulgaris: perspective of traditional Persian medicine and conventional medicine. Avicenna J Phytomed, 7:486-494.
Barlak A, Kadıköylü G, Bolaman AZ. 2004. Splenomegaly due to the use of granulocyte-colony stimulating factor. Turk J Hematol, 21: 93-96.
Capuzzo A, Occhipinti A, Maffei ME. 2014. Antioxidant and radical scavenging activities of chamazulene. Nat Prod Res, 28:2321-2323.
Choi K-C, Lee B-S, Chung W-T, Choi M-S, Lee J-C. 2010. Protective effects of apigenin and quercetin on aflatoxin B 1-induced immunotoxicity in mice. Food Sci Biotechnol, 19:987-992.
Convention USP. U.S. 2017. Pharmacopeia National Formulary 2018: UPS41-NF36: United States Pharmacopeial Convention Incorporated.
Crawford J, Dale DC, Lyman GH. 2004. Chemotherapy induced neutropenia. Cancer, 100:228-237.
Daneshfard B, Sanaye M, Nimrouzi M. 2019. Prolegomena to a true integrative medical paradigm. Altern Ther Health Med, 25:50-60.
Dinan MA, Hirsch BR, Lyman GH. 2015. Management of chemotherapy-induced neutropenia: measuring quality, cost, and value. J Natl Compr Canc Netw, 13:e1-e7.
Fardell JE, Vetsch J, Trahair T, Mateos MK, Grootenhuis MA, Touyz LM, Marshall GM, Wakefield CE . 2017. Health-related quality of life of children on treatment for acute lymphoblastic leukemia: A systematic review. Pediatr Blood Cancer, 64: e26489.
Farzaneh MR, Shahryari J, Safaei A, Valibeigi B, Davani SK, Tabibi N. 2016. Dicer gene expression as a prognostic factor in acute lymphoblastic leukemia and chronic lymphocytic leukemia in Fars Province. Iran J Med Sci, 41:223-229.
Garcia-Pinto AB, Santos-Filho SD, Carvalho JJ, Pereira MJ, Fonseca AS, Bernardo-Filho M. 2013. In vitro and in vivo studies of an aqueous extract of Matricaria recutita (German chamomile) on the radiolabeling of blood constituents, on the morphology of red blood cells and on the biodistribution of the radiopharmaceutical sodium pertechnetate. Pharmacogn Mag, 9:S49-S56.
Gavioli E, Abrams M. 2017. Prevention of granulocyte-colony stimulating factor (G-CSF) induced bone pain using double histamine blockade. Support Care Cancer, 25: 817-822.
Godwin M, Crellin J, Mathews M, Chowdhury NL, Newhook LA, Pike A, McCrate F, Law R. 2013. Use of natural health products in children Survey of parents in waiting rooms. Can Fam Physician, 59:e364-e371.
Hashempur MH, Ghasemi MS, Daneshfard B, Ghoreishi PS, Lari ZN, Homayouni K, Zargaran A. 2017. Efficacy of topical chamomile oil for mild and moderate carpal tunnel syndrome: A randomized double-blind placebo-controlled clinical trial. Complement Ther Clin Pract, 26:61-67.
Hashempur MH, Heydari M, Mosavat SH, Heydari ST, Shams M. 2015. Complementary and alternative medicine use in Iranian patients with diabetes mellitus. J Integr Med, 13:319-325.
Hosseinpour M, Mobini-Dehkordi M, Teimori H. 2016. Quantitative gene expression of ERG9 in model saccharomyces cerevisiae: Chamomile extract for human cancer treatment. J Clin Diagn Res, 10:FC05-FC08.
Ibn-Sina. 2005. Qanun fi al-Teb (Canon of Medicine) Beirut: Al-Elmi Lel-Matbuat.
Jabbari M, Daneshfard B, Emtiazy M, Khiveh A, Hashempur MH. 2017. Biological effects and clinical applications of dwarf elder (Sambucus ebulus L): A review. J Evid Based Complementary Altern Med, 22:996-1001. 
Jabri MA, Sani M, Rtibi K, Marzouki L, El-Benna J, Sakly M, Sebai H. 2016. Chamomile decoction extract inhibits human neutrophils ROS production and attenuates alcohol-induced haematological parameters changes and erythrocytes oxidative stress in rat. Lipids Health Dis, 15:65.
Kliegman R, Stanton B, Schor NF, Geme JWS, Behrman RE. 2016. Nelson Textbook of Pediatrics. 20’th ed. Philadelphia: Elsevier. Chapter 495. pp. 2437.
Köstler WJ, Hejna M, Wenzel C, Zielinski CC. 2001. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin, 51:290-315.
Lee S-H, Heo Y, Kim Y-C. 2010. Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice. J Vet Sci, 11:35-41.
Marino M, Bersani C, Comi G. 2001. Impedance measurements to study the antimicrobial activity of essential oils from Lamiaceae and Compositae. Int J Food Microbiol, 67:187-195.
Mazokopakis E, Vrentzos G, Papadakis J, Babalis D, Ganotakis E. 2005. Wild chamomile (Matricaria recutita L.) mouthwashes in methotrexate-induced oral mucositis. Phytomedicine, 12:25-27.
McKay DL, Blumberg JB. 2006. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res, 20:519-530.
Miguel MG. 2010. Antioxidant and anti-inflammatory activities of essential oils: a short review. Molecules, 15:9252-9287.
Ogata-Ikeda I, Seo H, Kawanai T, Hashimoto E, Oyama Y. 2011. Cytotoxic action of bisabololoxide A of German chamomile on human leukemia K562 cells in combination with 5-fluorouracil. Phytomedicine, 18:362-365.
Orkin SH, Fisher DE, Ginsburg D, Look AT, Nathan DG, Lux SE. 2015. Nathan and oski's hematology and oncology of infancy and childhood. Philadelphia: Elsevier/Saunders. Chapter 50. pp. 1543.
Ornano L, Venditti A, Ballero M, Sanna C, Quassinti L, Bramucci M, Lupidi G, Papa F, Vittori S, Maggi F, Bianco A. 2013. Chemopreventive and antioxidant activity of the chamazulene‐rich essential oil obtained from Artemisia arborescens L. growing on the Isle of La Maddalena, Sardinia, Italy. Chem Biodivers, 10:1464-1474.
Pourdeghatkar F, Motaghi M, Darbandi B, BagherSalimi A. 2017. The effect of chamomile mouthwash on the prevention of oral mucositis caused by chemotherapy in children with acute lymphoblastic leukemia. Iran J Ped Hematol Oncol, 7:76-81.
Qarshi I. 2008. Al-Shamel Fi Al-Sana't Al-Tebieh. Tehran: Iran University of Medical Sciences.
Rahimi S, Fadakar Soghe R, Tabri R. 2014. Related factors with quality of life among preschool children with cancer. J Holist Nurs Midwifery, 24:30-39.
Rajabli N, Naeimi-Tabeie M, Jahangirrad A, Sedaghat S-M, Semnani S, Roshandel G. 2013. Epidemiology of leukemia and multiple myeloma in Golestan, Iran. Asian Pac J Cancer Prev, 14:2333-2336.
Ruela-de-Sousa R, Fuhler G, Blom N, Ferreira C, Aoyama H, Peppelenbosch M. 2011. Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy. Cell Death Dis, 1:e19.
Safayhi H, Sabieraj J, Sailer E-R, Ammon H. 1994. Chamazulene: an antioxidant-type inhibitor of leukotriene B4 formation. Planta Med, 60:410-413.
Sashidhara K, Verma R, Ram P. 2006. Essential oil composition of Matricaria recutita L. from the lower region of the Himalayas. Flavour Fragr J, 21:274-276.
Sebai H, Jabri M-A, Souli A, Rtibi K, Selmi S, Tebourbi O, El-Benna J, Sakly M. 2014. Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.) decoction extract in rats. J Ethnopharmacol, 152:327-332.
Sharifi H, Minaie MB, Qasemzadeh MJ, Ataei N, Gharehbeglou M, Heydari M. 2017. Topical use of Matricaria recutita L. (Chamomile) oil in the treatment of monosymptomatic enuresis in children: a double-blind randomized controlled trial. J Evid Based Complement Altern Med, 22:12-17.
Shoara R, Hashempur MH, Ashraf A, Salehi A, Dehshahri S, Habibagahi Z. 2015. Efficacy and safety of topical Matricaria chamomilla L. (chamomile) oil for knee osteoarthritis: a randomized controlled clinical trial. Complement Ther Clin Pract, 21:181-187. 
Shukla S, Gupta S. 2010. Apigenin: a promising molecule for cancer prevention. Pharm Res, 27:962-978.
Srivastava JK, Gupta S. 2007. Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells. J Agric Food Chem, 55:9470-9478.
Srivastava JK, Pandey M, Gupta S. 2009. Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity. Life Sci, 85:663-669.
Vetsch J, Wakefield CE, Robertson EG, Trahair TN, Mateos MK, Grootenhuis M, Marshall GM, Cohn RJ, Fardell JE. 2018. Health-related quality of life of survivors of childhood acute lymphoblastic leukemia: a systematic review. Qual Life Res, 27:1431-1443. 
Zolala F, Ayatollahi A, Shahriary M, Ayatollahi M. 2004. Determination of incidence rate of acute lymphoblastic leukemia in children under the age of 15 in Fars province in 2001. Armaghane danesh, 9:59-65.