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Variability of high-dose melphalan exposure on oral mucositis in patients undergoing prophylactic low-level laser therapy

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Abstract

The present study outlines the clinical impact and risk factors of oral mucositis in 79 patients with multiple myeloma following high-dose melphalan for autologous transplant. All patients underwent daily prophylactic low-level indium gallium aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm2, 10 s per point) from the beginning of the conditioning regimen up to day +2. Oral mucositis assessments were made daily until hospital discharge. For analysis, oral mucositis was divided into two groups according to severity: group 1, patients with oral mucositis grade <III (n = 71) and group 2, patients with oral mucositis grade ≥III (n = 8). Univariate logistic models were used to determine the risk factors. Patients in group 1 were found to have statistically fewer days of oral pain than those in group 2 (3.94 and 6.25 days, respectively, p = 0.014). Morphine was required in 75% of patients in group 2, versus 42.25% in group 1 (p = 0.06). Risk of severe oral mucositis was associated with higher serum creatinine levels (OR = 6.10; 95% CI 1.25–31.60; p = 0.02) and older age (OR = 1.21; 95% CI 1.05–1.47; p = 0.027). Severe oral mucositis was associated with worse clinical outcomes. Older patients and those with renal dysfunction previous autologous transplant had the greatest risk for severe oral mucositis despite prophylactic laser treatment. Our results highlight the importance of further research to define the dose, application time, and number of prophylactic laser sessions in those patients with the greatest risk for severe oral mucositis.

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References

  1. Harousseau JL, Moreau P (2009) Autologous hematopoietic stem-cell transplantation for multiple myeloma. N Engl J Med 360:2645–2654

    Article  CAS  PubMed  Google Scholar 

  2. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC (2009) Multiple myeloma. Lancet 374:324–339

    Article  PubMed  Google Scholar 

  3. Blijlevens N, Schwenkglenks M, Bacon P, D'Addio A, Einsele H et al (2008) Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy—European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol 26:1519–1525

    Article  CAS  PubMed  Google Scholar 

  4. Grazziutti ML, Dong L, Miceli MH, Krishna SG, Kiwan E et al (2006) Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model. Bone Marrow Transplant 38:501–506

    Article  CAS  PubMed  Google Scholar 

  5. Vera-Llonch M, Oster G, Ford CM, Lu J, Sonis S (2007) Oral mucositis and outcomes of autologous hematopoietic stem-cell transplantation following high-dose melphalan conditioning for multiple myeloma. J Support Oncol 5:231–235

    PubMed  Google Scholar 

  6. Knudsen LM, Nielsen B, Gimsing P, Geisler C (2005) Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure. Eur J Haematol 75:27–33

    Article  PubMed  Google Scholar 

  7. Moreau P, Facon T, Attal M, Hulin C, Michallet M et al (2002) Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 99:731–735

    Article  CAS  PubMed  Google Scholar 

  8. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M et al (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025

    Article  PubMed  Google Scholar 

  9. Jaguar GC, Prado JD, Nishimoto IN, Pinheiro MC, de Castro DO Jr et al (2007) Low-energy laser therapy for prevention of oral mucositis in hematopoietic stem cell transplantation. Oral Dis 13:538–543

    Article  CAS  PubMed  Google Scholar 

  10. McCann S, Schwenkglenks M, Bacon P, Einsele H, D'Addio A et al (2009) The prospective oral mucositis audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT. Bone Marrow Transplant 43:141–147

    Article  CAS  PubMed  Google Scholar 

  11. Epstein JB, Schubert MM (2003) Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and management. Oncology 17:1767–1779

    PubMed  Google Scholar 

  12. Schubert MM, Eduardo FP, Guthrie KA, Franquin JC, Bensadoun RJ et al (2007) A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Support Care Cancer 15:1145–1154

    Article  PubMed  Google Scholar 

  13. Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D et al (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–2598

    Article  CAS  PubMed  Google Scholar 

  14. Blijlevens N, Sonis S (2007) 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

    Article  CAS  PubMed  Google Scholar 

  15. Kobbe G, Bruns I, Schroeder T, Czibere A, Warnecke J et al (2010) A 3-day short course of palifermin before HDT reduces toxicity and need for supportive care after autologous blood stem-cell transplantation in patients with multiple myeloma. Ann Oncol 21(9):1898–1904

    Article  CAS  PubMed  Google Scholar 

  16. Nooka AK, Johnson HR, Kaufman JL, Flowers CR, Langston A et al (2014) Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20(6):852–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M et al (1997) Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys 38:697–703

    Article  CAS  PubMed  Google Scholar 

  18. Silva GB, Mendonça EF, Bariani C, Antunes HS, Silva MA (2011) The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: a randomized clinical trial. Photomed Laser Surg 29:27–31

    Article  PubMed  Google Scholar 

  19. Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL et al (2013) Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 21:333–341

    Article  PubMed  Google Scholar 

  20. McGuire DB, Altomonte V, Peterson DE, Wingard JR, Jones RJ et al (1993) Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. Oncol Nurs Forum 20:1493–1502

    CAS  PubMed  Google Scholar 

  21. 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 Manag 44:64–73

    Article  Google Scholar 

  22. Barasch A, Peterson DE, Tanzer JM, D'Ambrosio JA, Nuki K et al (1995) Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer 76:2550–2556

    Article  CAS  PubMed  Google Scholar 

  23. Parulekar W, Mackenzie R, Bjarnason G, Jordan RC (1998) Scoring oral mucositis. Oral Oncol 34:63–71

    Article  CAS  PubMed  Google Scholar 

  24. Dasgupta RK, Adamson PJ, Davies FE, Rollinson S, Roddam PL et al (2003) Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma. Blood 102:2345–2350

    Article  CAS  PubMed  Google Scholar 

  25. Wong SF, Wilder-Smith P (2002) Pilot study of laser effects on oral mucositis in patients receiving chemotherapy. Cancer J 8:247–254

    Article  PubMed  Google Scholar 

  26. De Paula Eduardo F, Bezinelli LM, Da Graça Lopes RM, Nascimento Sobrinho JJ, Hamerschlak N et al (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

    Article  PubMed  Google Scholar 

  27. Lopes NNF, Plaper M, Chavantes MC, Lalla RV, Yoshimura EM et al (2009) Cyclooxygenase-2 and vascular endothelial factor expression in 5-fluoracil-induced oral mucositis in hamsters: evaluation of two low-intensity laser protocols. Support Care Cancer 17:1409–1415

    Article  PubMed  Google Scholar 

  28. Enwemeka CS (2009) Intricacies of dose in laser phototherapy for tissue repair and pain relief. Photomed Laser Surg 27:387–393

    Article  PubMed  Google Scholar 

  29. Cunha CB, Eduardo FP, Zezell DM, Bezinelli LM, Shitara PP et al (2012) Effect of irradiation with red and infrared laser in the treatment of oral mucositis: a pilot study with patients undergoing chemotherapy with 5-FU. Lasers Med Sci 27:1233–1240

    Article  CAS  PubMed  Google Scholar 

  30. Silva GB, Sacono NT, Othon-Leite AF, Mendonça EF, Arantes AM et al (2015) Effect of low-level laser therapy on inflammatory mediator release during chemotherapy-induced oral mucositis: a randomized preliminary study. Lasers Med Sci 30:117–126

    Article  PubMed  Google Scholar 

  31. Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL et al (2013) Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 21(1):333–341

    Article  PubMed  Google Scholar 

  32. Eduardo FP, Bezinelli L, Luiz AC, Correa L, Vogel C et al (2009) Severity of oral mucositis in patients undergoing hematopoietic cell transplantation and an oral laser phototherapy protocol: a survey of 30 patients. Photomed Laser Surg 27:137–144

    Article  PubMed  Google Scholar 

  33. Antunes HS, de Azevedo AM, da Silva Bouzas LF et al (2007) Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood 109:2250–2255

    Article  CAS  PubMed  Google Scholar 

  34. Knudsen LM, Hjorth M, Hippe E (2000) Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 65:175–181

    Article  CAS  PubMed  Google Scholar 

  35. Parikh GC, Amjad AI, Saliba RM, Kazmi SM, Khan ZU et al (2009) Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant 15:812–816

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S et al (2007) Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant 39:605–611

    Article  CAS  PubMed  Google Scholar 

  37. Goldschmidt H, Lannert H, Bommer J, Ho AD (2000) Multiple myeloma and renal failure. Nephrol Dial Transplant 15:301–304

    Article  CAS  PubMed  Google Scholar 

  38. Sirohi B, Powles R, Kulkarni S, Rudin C, Saso R et al (2011) Glomerular filtration rate prior to high-dose melphalan 200 mg/m2 as a surrogate marker of outcome in patients with myeloma. Br J Cancer 85:325–332

    Article  Google Scholar 

  39. Tricot G, Alberts DS, Johnson C, Roe DJ, Dorr RT et al (1996) Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res 2:947–952

    CAS  PubMed  Google Scholar 

  40. Badros A, Barlogie B, Siegel E, Roberts J, Langmaid C et al (2001) Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 114:822–829

    Article  CAS  PubMed  Google Scholar 

  41. Lyman GH, Morrison VA, Dale DC, Crawford J, Delgado DJ et al (2003) Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy. Leuk Lymphoma 44:2069–2076

    Article  CAS  PubMed  Google Scholar 

  42. Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258–2266

    Article  PubMed  Google Scholar 

  43. Jantunen E, Kuittinen T, Penttilä K, Lehtonen P, Mahlamäki E et al (2006) High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (>or=65 years) myeloma patients: comparison with younger patients treated on the same protocol. Bone Marrow Transplant 37(10):917–922

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Graziella Chagas Jaguar.

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The authors declare that they have no conflict of interest.

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There was no funding in this study.

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The A.C. Camargo Cancer Center Ethics Committee approved this study under Protocol No. 1480/13.

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This was a retrospective study. All the authors declare that identifying details (names, date of birth, identity number, and other information) of the participants that were studied will not be published in written descriptions, photographs, and genetic profiles.

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Rodrigues, G.H., Jaguar, G.C., Alves, F.A. et al. Variability of high-dose melphalan exposure on oral mucositis in patients undergoing prophylactic low-level laser therapy. Lasers Med Sci 32, 1089–1095 (2017). https://doi.org/10.1007/s10103-017-2211-0

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