Child's Nervous System

, Volume 33, Issue 5, pp 793–800 | Cite as

Effect of Nigella sativa seed administration on prevention of febrile neutropenia during chemotherapy among children with brain tumors

  • HebatAlla Fathi Mohamed MousaEmail author
  • Nesrin Kamal Abd-El-Fatah
  • Olfat Abdel-Hamid Darwish
  • Shehata Farag Shehata
  • Shady Hassan Fadel
Original Paper



Seeds of Nigella sativa (NS) are used to combat various disease conditions through their antibacterial effects. To evaluate the seeds’ potential, we studied their effect on the prevention of febrile neutropenia (FN) in children with brain tumors.


A randomized pretest-post-test control group study including 80 children (2–18 years) with brain tumors undergoing chemotherapy were equally allocated into two groups. Intervention group received 5 g of NS seeds daily throughout treatment while controls received nothing. CBC with differentials, incidence of FN, and LOS were noted on each follow-up.


The majority of children 38/40 (95%), of the intervention group, took the seeds for 3–9 consecutive months. Eight out of 372 (2.2%) FN episodes were experienced by children of intervention group compared to controls 63/327 (19.3%) (p = 0.001) and a shorter LOS (median = 2.5 days) vs 5 days in the control group (p = 0.006). Children in both groups belonged to almost same geographical area with similar socio-economic background. Weights of children were almost equal at diagnosis.


NS seeds showed a decrease in incidence of FN in children with brain tumors with shortening of subsequent LOS which may improve their outcome and thereby quality of life. Larger scale studies are needed to further evaluate the seeds’ potential.


Nigella sativa Febrile neutropenia Pediatric oncology Pediatric brain tumors Black seed Nutrition 



Acute lymphoblastic leukemia


Atypical teratoid rhabdoid tumors


Body mass index


Central nervous tumors


Common toxicity criteria for adverse events


Relative dose intensity


Febrile neutropenia


Fisher’s exact probability


Granulocyte colony-stimulating factor


Granulocyte macrophage colony-stimulating factor




Length of hospital stay






Monte-Carlo exact probability





We would like to show our gratitude to all children who were involved in this study and their parents for their patience and cooperation during the course of this research.

Compliance with ethical standards

Ethical approval was obtained from ethics committees of High Institute of Public Health and Faculty of Medicine, Alexandria University.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

381_2017_3372_MOESM1_ESM.docx (55 kb)
ESM 1 (DOCX 54 kb)


  1. 1.
    Packer RJ (1999) Brain tumors in children. Arch Neurol 56:421–425CrossRefPubMedGoogle Scholar
  2. 2.
    Ostrom QT, de Blank PM, Kruchko C, Peterson CM, Liao P, Finlay JL, Stearns DS, Wolff JE, Wolinsky Y, Letterio JJ, Barnholtz-Sloan JS (2015) CBTRUS statistical report: Alex's lemonade stand foundation infant and childhood primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro-Oncology 16(10):x1–x36CrossRefPubMedGoogle Scholar
  3. 3.
    El-Mahallawy H, El-Wakil M, Moneer MM, Shalaby L (2011) Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer. Pediatr Blood Cancer 57:283–288CrossRefPubMedGoogle Scholar
  4. 4.
    Castagnola E, Fontana V, Caviglia I (2007) A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin Infect Dis 45(10):1296–1304CrossRefPubMedGoogle Scholar
  5. 5.
    Fortner BV, Houts AC, Schwartzberg LS (2006) A prospective investigation of chemotherapy-induced neutropenia and quality of life. J Support Oncol 4:472–478PubMedGoogle Scholar
  6. 6.
    Miguel SC, Calleja-Hernández MÁ, Menjón-Beltrán S, Vallejo-Rodríguez I (2015) Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia. Support Care Cancer 23(2):547–559CrossRefGoogle Scholar
  7. 7.
    Hossain S, Sikes-Thurston E, Leppla SH, Wein AN (2012) Thymoquinone as a novel antibiotic and chemotherapeutic agent: a natural therapeutic approach on Staphylococcus aureus, Bacillus anthracis, and four NCI-60 cancer cell lines. JESS 2(1):19–22Google Scholar
  8. 8.
    Alp S, Akova M (2013) Management of febrile neutropenia in the era of bacterial resistance. Ther Adv Infect Dis 1(1):37–43CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Packer RJ, Gajjar A, Vezina G, Adams LR, Burger PC, Robertson PL et al (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24:4202–4208CrossRefPubMedGoogle Scholar
  10. 10.
    Gnekow A, De Salvo GL, Von Hornstein S, Perilongo G, Stokland T, Sandstrøm PE et al (2008) SIOP-LGG 2004: comprehensive treatment strategy for low-grade glioma in children and adolescents, including a randomized chemotherapy trial and a radiotherapy trial. Neuro-Oncology 10:452–453Google Scholar
  11. 11.
    Wolff JE, Sajedi M, Brant R, Coppes MJ, Egeler RM (2002) Choroid plexus tumors. Br J Cancer 87(10):1086–1091CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA et al (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27(3):385–389CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bueren AO, Hoff K, Pietsch T, Gerber NU, Metz MW, Deinlein F et al (2011) Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. Neuro-Oncology 13(6):669–679CrossRefGoogle Scholar
  14. 14.
    Calaminus G, Kortmann R, Worch J, Nicholson JC, Alapetite C, Garrè ML (2013) SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro-Oncology 15(6):788–796CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Abdulrhman MA, Hamed AA, Mohamed SA, Hassanen NA (2016) Effect of honey on febrile neutropenia in children with acute lymphoblastic leukemia: a randomized crossover open-labeled study. Complement Ther Med 25:98–103CrossRefPubMedGoogle Scholar
  16. 16.
    Castagnola E, Boni L, Giacchino M, Cesaro S, De Sio L, Garaventa A, Zanazzo G, Biddau P, Rossi MR, Schettini F, Bruzzi P, Viscoli C (2003) A multicenter, randomized, double blind placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer. Pediatr Infect Dis J 22(4):359–365PubMedGoogle Scholar
  17. 17.
    Wittman B, Horan J, Lyman GH (2006) Prophylactic colony-stimulating factors in children receiving myelosuppressive chemotherapy: a meta-analysis of randomized controlled trials. Cancer Treat Rev 32(4):289–303CrossRefPubMedGoogle Scholar
  18. 18.
    Mitchell PL, Morland B, Stevens MC, Dick G, Easlea D, Meyer LC, Pinkerton CR (1997) Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients. J Clin Oncol 15(3):1163–1170CrossRefPubMedGoogle Scholar
  19. 19.
    Riikonen P, Saarinen UM, Mäkipernaa A, Hovi L, Komulainen A, Pihkala J, Jalanko H (1994) Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children. Pediatr Infect Dis J 13(3):197–202CrossRefPubMedGoogle Scholar
  20. 20.
    Basu K, Fernandez ID, Fisher SG, Asselin BL, Lyman GH (2005) Length of stay and mortality associated with febrile neutropenia among children with cancer. J Clin Oncol 23(31):7958–7966CrossRefPubMedGoogle Scholar
  21. 21.
    Al Omar S, Nazer L, Alkayed K (2013) A prospective study of febrile neutropenia in pediatric cancer patients in Jordan. J Pediatr Hematol Oncol 35(8):614–617CrossRefPubMedGoogle Scholar
  22. 22.
    Barakat EM, El Wakeel LM, Hagag RS (2013) Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol 19(16):2529–2536CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Alenzi FQ, El-Bolkiny Y-S, Salem ML (2010) Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide. Br J Biomed Sci 67(1):20–28CrossRefPubMedGoogle Scholar
  24. 24.
    Haggag AA, Abd Elaal AM, Elsheik A, Elzamarany EA (2013) Protective effect of Nigella sativa oil against methotrexate induced hepatotoxicity in children with acute lymphoblastic leukemia. J Leuk 1(4):123–130Google Scholar
  25. 25.
    El-Abhar HS, Abdallah DM, Saleh S (2003) Gastroprotective activityof Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. J Ethnopharmacol 84(2–3):251–258CrossRefPubMedGoogle Scholar
  26. 26.
    Khaled AAS (2009) Gastroprotective effects of Nigella sativa oil on the formation of stress gastritis in hypothyroidal rats. Int J Physiol Pathophysiol Pharmacol 1:143–149Google Scholar
  27. 27.
    Tayman C, Cekmez F, Kafa IM, Canpolat FE, Cetinkaya M, Uysal S, Tunc T, Sarici SU (2012) Beneficial effects of Nigella sativa oil on intestinal damage in necrotizing enterocolitis. J Investig Surg 25(5):286–294CrossRefGoogle Scholar
  28. 28.
    Beghetto MG, Luft VC, Mello ED, Polanczyk CA (2009) Accuracy of nutritional assessment tools for predicting adverse hospital outcomes. Nutr Hosp 24:56–62PubMedGoogle Scholar
  29. 29.
    de Luis DA, Izaola O, Cuellar L, Terroba MC, Cabezas G, Rojo S, Aller R, Sagrado MG (2006) Nutritional assessment: predictive variables at hospital admission related with length of stay. Ann Nutr Metab 50:394–398CrossRefPubMedGoogle Scholar
  30. 30.
    Diaz-Montes TP, Zahurak ML, Bristow RE (2007) Predictors of extended intensive care unit resource utilization following surgery for ovarian cancer. Gynecol Oncol 107:464–468CrossRefPubMedGoogle Scholar
  31. 31.
    Gupta D, Vashi PG, Lammersfeld CA, Braun DP (2011) Role of nutritional status in predicting the length of stay in cancer: a systematic review of the epidemiological literature. Ann Nutr Metab 59:96–106CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • HebatAlla Fathi Mohamed Mousa
    • 1
    • 2
    Email author
  • Nesrin Kamal Abd-El-Fatah
    • 1
  • Olfat Abdel-Hamid Darwish
    • 1
  • Shehata Farag Shehata
    • 4
  • Shady Hassan Fadel
    • 3
  1. 1.Department of Nutrition, High Institution of Public HealthAlexandria UniversityAlexandriaEgypt
  2. 2.BuraidahSaudi Arabia
  3. 3.Department of Pediatric oncology, Faculty of MedicineAlexandria UniversityAlexandriaEgypt
  4. 4.Department of Biostatistics, High Institute of Public HealthAlexandria UniversityAlexandriaEgypt

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