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Comparative Study
. 2025 Mar 11;23(1):24.
doi: 10.1186/s12969-025-01080-9.

Cyclophosphamide treatment with a comparison in both pediatric rheumatology and pediatric nephrology practices

Deniz Gezgin Yildirim  1 , Emine Yılmaz Orulluoglu  2 , Cisem Yildiz  3 , Ceyhun Acari  4 , Hatice Adiguzel Dundar  5 , Okan Akaci  6 , Nurver Akinci  7 , Emil Aliyev  8 , Bedriye Nuray Alpman  9 , Ozge Altug Gucenmez  10 , Elif Arslanoglu Aydin  11 , Bahriye Atmis  12 , Pinar Ozge Avar Aydin  13 , Fatma Aydin  14 , Ozge Baba  15 , Esra Baglan  11 , Ilknur Bagrul  11 , Kenan Barut  16 , Ozge Basaran  8 , Umut Selda Bayrakci  17 , Nuran Belder  3 , Burcu Bozkaya Yucel  18 , Bahar Buyukkaragoz  19 , Sengul Caglayan  20 , Mustafa Cakan  21 , Elif Celikel  22 , Ferhat Demir  23 , Selcan Demir  24 , Yasemin Demir Yigit  25 , Fatma Gul Demirkan  26 , Nida Dincel  27 , Seyda Dogantan  28 , Zahide Ekici Tekin  22 , Esra Genc  29 , Fatih Haslak  16 , Rana Isguder  5 , Aslihan Kara  29 , Muserref Kasap Cuceoglu  8 , Ummusen Kaya Akca  30 , Hakan Kisaoglu  31 , Rabia Miray Kisla Ekinci  32 , Zehra Kızıldag  5 , Tuba Kurt  33 , Batuhan Kucukali  3 , Emre Leventoglu  34 , Hulya Nalcacioglu  35 , Gulcin Otar Yener  36 , Semanur Ozdel  11 , Yesim Ozdemir Atikel  37 , Sumeyra Ozdemir Cicek  38 , Sule Pektas Leblebiciler  39 , Erkin Serdaroglu  27 , Hafize Emine Sonmez  40 , Emine Nur Sunar Yayla  11 , Serra Surmeli Doven  41 , Sezgin Sahin  16 , Seher Sener  8 , Ayse Tanatar  42 , Merve Tanidir  3 , Sema Nur Taskin  36 , Betul Tiryaki  43 , Serife Tuncez  11 , Serkan Turkucar  44 , Bahriye Uzun Kenan  45 , Nurdan Yildiz  46 , Kenan Yilmaz  47 , Yilmaz Tabel  48 , Ismail Dursun  49 , Nur Canpolat  50 , Sevgi Mir  51 , Harun Peru  52 , Rezan Topaloglu  53 , Metin Kaya Gurgoze  29 , Ayse Balat  43 , Yelda Bilginer  8 , Banu Celikel Acar  22 , Betul Sozeri  54 , Erbil Unsal  5 , Ozgür Kasapcopur  16 , Sevcan A Bakkaloglu  19
Affiliations
Comparative Study

Cyclophosphamide treatment with a comparison in both pediatric rheumatology and pediatric nephrology practices

Deniz Gezgin Yildirim et al. Pediatr Rheumatol Online J. .

Abstract

Background: Cyclophosphamide (CYC) is an inactive alkylating agent that transforms the alkyl radicals into other molecules and is used in combination with systemic corticosteroids in the treatment of many childhood rheumatic diseases, such as systemic lupus erythematosus (SLE), and ANCA-associated vasculitis (AAV). In recent years, rituximab (RTX), a B-cell-targeting anti-CD20 monoclonal antibody, has emerged as a new alternative treatment modality over CYC for induction therapy of childhood-onset rheumatic diseases. Clinicians adopt different practices for using CYC particularly in relation to indications, posology, pre-treatment laboratory work-up, post-treatment follow-up, and screening pre- and post-treatment vaccination status. This study aimed to evaluate the principles and approaches of administering CYC therapy in pediatric rheumatology and pediatric nephrology practices and to compare the clinician preferences for CYC and RTX in induction therapy of childhood-onset rheumatic diseases.

Methods: This study includes a web-based questionnaire executed on 87 participants (56 pediatric rheumatologists (PRs) and 31 pediatric nephrologists (PNs)). Both pediatric subspecialties evaluated and compared the most common indications for CYC treatment, pre-treatment consent protocols, pre-and post-treatment laboratory tests, dosing strategies, and side effects.

Results: Childhood-onset SLE (95%) and AAV (69%) were the most common diseases for which CYC treatment is used. All clinicians, except 2 PNs prescribed CYC via intravenous route. 61% of the PRs and 71% of PNs reported using a monthly dose of 500 mg/m² CYC for 6 months in accordance with the National Institutes of Health (NIH) protocol. All clinicians conducted pre-CYC treatment assessments of complete blood count and kidney function tests. Hepatitis B (82%), chickenpox (76%), and mumps-measles-rubella (72%) were the most frequently assessed vaccines. Adverse effects associated with CYC include cytopenia (86%), nausea (52%), liver toxicity (20%), hair loss (31%), hemorrhagic cystitis (37%), allergic reactions (16%), dyspnea (5%), and infertility (2%). 9 clinicians stated that they performed gonad-sparing interventions before CYC, which clarifies why CYC was more commonly preferred in the induction therapy of SLE and AAV over RTX by both PRs and PNs.

Conclusions: Clinicians still tend to choose CYC over RTX in induction therapy of SLE and AAV and mostly prefer the high-dose CYC treatment regimen suggested by the NIH.

Keywords: Cyclophosphamide; Pediatric nephrology; Pediatric rheumatology; Rituximab; Side effects; Vaccination.

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Conflict of interest statement

Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. The present study was approved by the Ethics Committee of the Gazi University (2024, approval number: 1362). Consent for publication: Not applicable. Consent to participate: All participants consented to participate in the survey study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Cyclophosphamide vs. rituximab CYC: cyclophosphamide; RTX: Rituximab; SLE: systemic lupus erythematosus; AAV: anti-neutrophilic cytoplasmic antibody-associated vasculitis Fig. 1 shows clinicians’ responses when asked about their approximate preference for CYC or RTX as the first choice of SLE and/or AAV induction treatment
See this image and copyright information in PMC

References

    1. Chabner B, Allegra C, Curt G, et al. Antineoplastic agents. In: Hardman J, editor. Goodman and Gilman’s the Pharmacological basis of therapeutics. New York: McGraw-Hill; 1996. pp. 1233–87.
    1. Austin HA 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986;314:614–9. - PubMed
    1. Bernatsky S, Ramsey-Goldman R, Joseph L, Boivin JF, Costenbader KH, Urowitz MB, et al. Lymphoma risk in systemic lupus: effects of disease activity versus treatment. Ann Rheum Dis. 2014;73:138–42. - PMC - PubMed
    1. Hsu CY, Lin MS, Su YJ, Cheng TT, Lin YS, Chen YC, et al. Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case-control study. Rheumatology (Oxford). 2017;56:620–8. - PubMed
    1. Silva CA, Deen ME, Febrônio MV, Oliveira SK, Terreri MT, Sacchetti SB, et al. Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea. Rheumatol Int. 2011;31:1037–43. - PubMed

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