Top

Published in:

Open Access 01-09-2023 | Cryotherapy | Research

Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning

Authors: Saori Oku, Toshiko Futatsuki, Yoshiko Imamura, Haruna Hikita, Akemi Inada, Shinsuke Mizutani, Yasuo Mori, Haruhiko Kashiwazaki

Published in: Supportive Care in Cancer | Issue 9/2023

Abstract

Purpose

Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens.

Methods

Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis.

Results

Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085–13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41–23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (β = 0.515; 95% CI, 9.712–21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use.

Conclusion

Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

Jenq RR, van den Brink MR (2010) Allogeneic hematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat Rev Cancer 10:213–221. https://doi.org/10.1038/nrc2804CrossRefPubMed

Copelan EA, Chojecki A, Lazarus HM, Avalos BR (2019) Allogeneic hematopoietic cell transplantation; the current renaissance. Blood Rev 34:34–44. https://doi.org/10.1016/j.blre.2018.11.001CrossRefPubMed

Bollero P, Passarelli PC, D'Addona A, Pasquantonio G, Mancini M, Condò R, Cerroni L (2018) Oral management of adult patients undergoing hematopoietic stem cell transplantation. Eur Rev Med Pharmacol Sci 22:876–887. https://doi.org/10.26355/eurrev_201802_14365

Chaudhy HM, Bruce AJ, Wolf RC, Litzow MR, Hogan WJ, Patnaik MS, Kremers WK, Phillips GL, Hashmi SK (2016) The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: a systematic review. Biol Blood Marrow Transplant 22:605–616. https://doi.org/10.1016/j.bbmt.2015.09.014CrossRef

Shouval R, Kouniavski E, Fein J, Danylesko I, Shem-Tov N, Geva M, Yerushalmi R, Shimoni A, Nagler A (2019) Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation. Eur J Haematol 103:402–409. https://doi.org/10.1111/ejh.13299CrossRefPubMed

Valeh M, Kargar M, Mansouri A, Kamranzadeh H, Gholami K, Heidari K, Hajibabaei M (2018) Factors affecting the incidence and severity of oral mucositis following hematopoietic stem cell transplantation. Int J Hematol Oncol Stem Cell Res 12:142–152PubMedPubMedCentral

Patel P, Robinson PD, Baggott C, Gibson P, Ljungman G, Massey N, Ottaviani G, Phillips R, Revon-Rivière G, Treister N, White M, Cabral S, Dupuis L, Sung L (2021) Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update. Eur J Cancer 154:92–101. https://doi.org/10.1016/j.ejca.2021.05.013CrossRefPubMed

Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB (2003) The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98:1531–1539. https://doi.org/10.1002/cncr.11671CrossRefPubMed

Robien K, Schubert MM, Bruemmer B, Lloid ME, Potter JD, Ulrich CM (2004) Predictors of oral mucositis in patients receiving hematopoietic cell transplants for chronic myelogenous leukemia. J Clin Oncol 22:1268–1275. https://doi.org/10.1200/JCO.2004.05.147CrossRefPubMed

10.

Valer JB, Curra M, Gabriel AF, Schmidt TR, Ferreira MBC, Roesler R, Evangelista JMC, Martins MAT, Gregianin L, Martins MD (2021) Oral mucositis in childhood cancer patients receiving high-dose methotrexate: prevalence, relationship with other toxicities and methotrexate elimination. Int J Paediatr Dent 31:238–246. https://doi.org/10.1111/ipd.12718CrossRefPubMed

11.

Oosterom N, de Jonge R, Smith DEC, Pieters R, Tissing WJ E, Fiocco M, van Zelst BD, van den Heuvel-Eibrink MM, Heil SG. (2019) Changes in intracellular folate metabolism during high-dose methotrexate and leucovorin rescue therapy in children with acute lymphoblastic leukemia. PLoS One 14: e0221591. https://doi.org/10.1371/journal.pone.0221591

12.

AlJohani NI (2021) Role of folinic acid in methotrexate-based prophylaxis of graft-versus-host disease following hematopoietic stem cell transplantation. Hematology 26:620–627. https://doi.org/10.1080/16078454.2021.1966222CrossRefPubMed

13.

Sugita J, Matushita T, Kashiwazaki H, Kosugi M, Takahashi S, Wakasa K, Shiratori S, Ibata M, Shono Y, Shigematsu A, Obara M, Fujimoto K, Endo T, Nishino M, Kondo T, Hashino S, Tanaka J, Asaka M, Imamura M (2012) Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD. Bone Marrow Transplant 47:258–264. https://doi.org/10.1038/bmt.2011.53CrossRefPubMed

14.

Brennan MT, Hasséus B, Hovan AJ, Raber-Durlacher JE, Blijlevens NM, Huysmans MC, Garming Legert K, Johansson JE, Moore CG, von Bültzingslöwen I (2018) Impact of oral side effects from conditioning therapy before hematopoietic stem cell transplantation: protocol for a multicenter study. JMIR Res Protoc 7:e103. https://doi.org/10.2196/resprot.8982

15.

Blijlevens N, Sonis S (2006) Palifermin (recombinant keratinocyte growth factor-1):a pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis. Ann Oncol 18:817–826. https://doi.org/10.1093/annonc/mdl332CrossRefPubMed

16.

Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, Shea T, Yanovich S, Hansen K, Noga S, McCarty J, LeMaistre CF, Sung EC, Blazar BR, Elhardt D, Chen MG, Emmanouilides C (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–2598. https://doi.org/10.1056/NEJMoa040125CrossRefPubMed

17.

Zadik Y, Arany PR, Fregnani ER, Bossi P, Antunes HS, Bensadoun RJ, Gueiros LA, Majorana A, Nair RG, Ranna V, Tissing WJE, Vaddi A, Lubart R, Migliorati CA, Lalla RV, Cheng KKF, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) (2019) Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer 27:3969-3983. https://doi.org/10.1007/s00520-019-04890-2

18.

Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V, Bossi P; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) (2020) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 126:4423-4431.https://doi.org/10.1002/cncr.33100

19.

Lilleby K, Garcia P, Gooley T, McDonnnell P, Taber R, Holmberg L, Maloney DG, Press OW, Bensinger W (2006) A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 37:1031–1035. https://doi.org/10.1038/sj.bmt.1705384CrossRefPubMed

20.

Lu Y, Zhu X, Ma Q, Wang J, Jiang P, Teng S, Zhou L, Wu D, Wang H (2020) Oral cryotherapy for oral mucositis management in patients receiving allogeneic hematopoietic stem cell transplantation: a prospective randomized study. Support Care Cancer 28:1747–1754. https://doi.org/10.1007/s00520-019-04966-zCrossRefPubMed

21.

Peterson DE, Ohrn K, Bowen J, Fliedner M, Lees J, Loprinzi C, Mori T, Osaguona A, Weikel DS, Elad S, Lalla RV; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) (2013) Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy. Support Care Cancer 21:327-332.https://doi.org/10.1007/s00520-012-1562-0

22.

Wang L, Gu Z, Zhai R, Zhao S, Luo L, Li D, Zhao X, Wei H, Pang Z, Wang L, Liu D, Wang Q, Gao C (2015) Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. PLoS One 10: e0128763. https://doi.org/10.1371/journal.pone.0128763. eCollection 2015

23.

Marchesi F, Tendas A, Giannarelli D, Viggiani C, Gumenyuk S, Renzi D, Franceschini L, Caffarella G, Rizzo M, Palombi F, Pisani F, Romano A, Spadea A, Papa E, Canfora M, Pignatelli A, Cantonetti M, Arcese W, Mengarelli A (2017) Cryotherapy reduces oral mucositis and febrile episodes in myeloma patients treated with high-dose melphalan and autologous stem cell transplant: a prospective, randomized study. Bone Marrow Transplant 52:154–156. https://doi.org/10.1038/bmt.2016.207CrossRefPubMed

24.

Askarifar M, Lakdizaji S, Ramzi M, Rahmani A, Jabbarzadeh F (2016) The effects of oral cryotherapy on chemotherapy-induced oral mucositis in patients undergoing autologous transplantation of blood stem cells: a clinical trial. Iran Red Crescent Med J 18:e24775. https://doi.org/10.5812/ircmj.24775. eCollection 2016 Apr

25.

Salvador P, Azusano C, Wang L, Howell D (2012) A pilot randomized controlled trial of an oral care intervention to reduce mucositis severity in stem cell transplant patients. J Pain Symptom Manage 44:64–73. https://doi.org/10.1016/j.jpainsymman.2011.08.012CrossRefPubMed

26.

Svanberg A, Ohrn K, Birgegård G (2010) Oral cryotherapy reduces mucositis and improves nutrition-a randomized controlled trial. J Clin Nurs 19:2146–2151. https://doi.org/10.1111/j.1365-2702.2010.03255.xCrossRefPubMed

27.

Vokurka S, Svoboda T, Jungova A, Karas M, Koza V (2012) Oral cryotherapy can significantly reduce oral mucositis but not acute GVHD incidence in Flu/Mel conditioning allo-SCT. Bone Marrow Transplant 47:739–741. https://doi.org/10.1038/bmt.2011.156CrossRefPubMed

28.

Aisa Y, Mori T, Kudo M, Yashima T, Kondo S, Yokoyama A, Ikeda Y, Okamoto S (2005) Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer 13:266–269. https://doi.org/10.1007/s00520-004-0726-yCrossRefPubMed

29.

Mori T, Yamazaki R, Aisa Y, Nakazato T, Kudo M, Yashima T, Kondo S, Ikeda Y, Okamoto S (2006) Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer 14:392–395. https://doi.org/10.1007/s00520-005-0016-3CrossRefPubMed

30.

Quinn B, Potting CM, Stone R, Blijlevens NM, Fliedner M, Margulies A, Sharp L (2008) Guidelines for the assessment of oral mucositis in adult chemotherapy, radiotherapy and hematopoietic stem cell transplant patients. Eur J Cancer 44:61–72. https://doi.org/10.1016/j.ejca.2007.09.014CrossRefPubMed

31.

Baysal E, Sari D (2019) Effects of cryotherapy in preventing oral mucositis in hematopoietic stem cell transplantation patients: literature review. Complement Ther Clin Pract 35:342–347. https://doi.org/10.1016/j.ctcp.2019.03.017CrossRefPubMed

32.

Zhang X, Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J (2015) The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 21:895–905. https://doi.org/10.1038/nm.3914CrossRefPubMed

33.

Zhou B, Xia X, Wang P, Chen S, Yu C, Huang R, Zhang R, Wang Y, Lu L, Yuan F, Tian Y, Fan Y, Zhang X, Shu Y, Zhang S, Bai D, Wu L, Xu H, Yang L (2018) Induction and amelioration of methotrexate-induced gastrointestinal toxicity are related to immune response and gut microbiota. EBioMedicine 33:122–133. https://doi.org/10.1016/j.ebiom.2018.06.029CrossRefPubMedPubMedCentral

34.

Van der Beek JN, Oosterom N, Pieters R, de Jonge R, van den Heuvel-Eibrink MM, Heil SG (2019) The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: a systematic review. Crit Rev Oncol Hematol 142:1–8. https://doi.org/10.1016/j.critrevonc.2019.07.003CrossRefPubMed

35.

Shea B, Swinden MV, Ghogomu ET, Ortiz Z, Katchamart W, Rader T, Bombardier C, Wells GA, Tugwell P (2014) Folic and acid folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol 41:1049–1060. https://doi.org/10.3899/jrheum.130738CrossRefPubMed

36.

Cutler C, Li S, Kim HT, Laglenne P, Szeto KC, Hoffmeister L, Harrison MJ, Ho V, Alyea E, Lee SJ, Soiffer R, Sonis S, Antin JH (2005) Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. Biol Blood Marrow Transplant 11:383–388. https://doi.org/10.1016/j.bbmt.2005.02.006CrossRefPubMed

37.

Gori E, Arpinati M, Bonifazi F, Errico A, Mega A, Alberani F, Sabbi V, Costazza G, Leanza S, Borrelli C, Berni M, Feraut C, Polato E, Altieri MC, Pirola E, Loddo MC, Banfi M, Barzetti L, Calza S, Brignoli C, Bandini G, De Vivo A, Bosi A, Baccarani M (2007) Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group. Bone Marrow Transplant 39:347–352. https://doi.org/10.1038/sj.bmt.1705590CrossRefPubMed

38.

de Paula EF, Bezinelli LM, da Graça Lopes RM, Nascimento Sobrinho JJ, Hamerschlak N, Correa L (2015) Efficacy of cryotherapy associated with laser therapy for decreasing severity of melphalan-induced oral mucositis during hematological stem-cell transplantation: a prospective clinical study. Hematol Oncol 33:152–158. https://doi.org/10.1002/hon.2133CrossRef

Title: Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning
Authors: Saori Oku
Toshiko Futatsuki
Yoshiko Imamura
Haruna Hikita
Akemi Inada
Shinsuke Mizutani
Yasuo Mori
Haruhiko Kashiwazaki
Publication date: 01-09-2023
Publisher: Springer Berlin Heidelberg
Keywords: Cryotherapy
Cryotherapy
Methotrexate
Methotrexate
Graft-Versus-Host Disease
Graft-Versus-Host Disease
Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Published in: Supportive Care in Cancer / Issue 9/2023
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-023-07989-9

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2023

Healthcare providers’ perceptions about the unmet needs of their patients with cancer across healthcare systems: results of the International Psycho-Oncology Society survivorship survey

Mepitel film for the prevention and treatment of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials

“Chemobrain” in childhood cancer survivors—the impact on social, academic, and daily living skills: a qualitative systematic review

Prevalence of palliative radiotherapy abstracts presented at the annual scientific meetings of the Canadian Association of Radiation Oncology: 2003–2021

A systematic review of physical function tests as predictors of key clinical outcomes for adults with blood cancers

Could low-intensity blood flow restriction exercise lead to better compliance in people with hematological cancer undergoing chemotherapy?

Keynote webinar | Spotlight on antibody–drug conjugates in cancer