Gastrointestinal Complications after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in Oncohematological Patients

V.O. Sarzhevskiy, E.G. Smirnova, V.Yа. Melnichenko

N.I. Pirogov National Medical and Surgical Centre of RF MH, Moscow, Russian Federation

For citation: Sarzhevskiy V.O., Smirnova E.G., Mel’nichenko V.Ya. Gastrointestinal Complications after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in Oncohematological Patients. Klin. onkogematol. 2014; 7(3): 343–53 (In Russ.).


ABSTRACT

Different gastrointestinal disorders with different degrees of severity are diagnosed in almost all oncohematological patients receiving the high-dose chemotherapy (HDC) with autologous bone marrow transplantation (transplantation of peripheral hematopoietic stem cells). The mentioned disorders (mucositis) significantly impair the quality of life, promote the development of infectious complications, and, in some cases, can cause a lethal outcome. Authors emphasize the importance of GIT disorders due to HDC with autologous bone marrow transplantation, present etiological and pathogenetic factors of mucosites and give a detailed description of the clinical evaluation, test methods, prevention and treatment of such transplantation complications in oncohematological patients.


Keywords: high dose chemotherapy, autologous bone marrow transplantation, mucositis.

Address correspondence to: vladsar@pochta.ru

Accepted: May 26, 2014

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REFERENCES

  1. Damon L., Rugo H., Tolaney S. et al. Cytoreduction of lymphoid malignancies and mobilization of blood hematopoietic progenitor cells with high doses of cyclophosphamide and etoposide plus filgrastim. Biol. Blood Marrow Transplant. 2006; 12(3): 316–24.
  2. Bishton M.J., Lush R.J., Byrne J.L. et al. Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin disease. Br. J. Haematol. 2007; 136(5): 752–61.
  3. Milone G., Leotta S., Battiato K. et al. Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m(2) plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients. Leuk. Lymphoma 2007; 48(10): 1950–60.
  4. Lu H., Li J.Y., Ge Z. et al. High-dose etoposide with granulocyte colonystimulating factor for mobilization of autologous peripheral blood stem/progenitor cells in patients with hematologic malignancies. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006; 14(2): 397–9.
  5. Bolwell B.J., Kalaycio M., Sobecks R. et al. A multivariable analysis of factors influencing mucositis after autologous progenitor cell transplantation. Bone Marrow Transplant. 2002; 30(9): 587–91.
  6. Grazziutti M.L., Dong L., Miceli M.H. et al. Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model. Bone Marrow Transplant. 2006; 38(7): 501–6.
  7. Blijlevens N., Schwenkglenks M., Bacon P. et al. 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. 2008; 26(9): 1519–25.
  8. Blanes M., Lahuerta J.J., Gonzalez J.D. et al. Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol. Blood Marrow Transplant. 2013; 19(1): 69–74.
  9. Jantunen E., Kuittinen T., Nousiainen T. et al. BEAC or BEAM for high-dose therapy in patients with non-Hodgkin’s lymphoma? A single centre analysis on toxicity and efficacy. Leuk. Lymphoma 2003; 44(7): 1151–8.
  10. Jo J.C., Kang B.W., Jang G. et al. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma patients: comparative analysis of efficacy and toxicity. Ann. Hematol. 2008; 87(1): 43–8.
  11. Kim J.E., Lee D.H., Yoo C. et al. BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma patients: a single center comparative analysis of efficacy and toxicity. Leuk. Res. 2011; 35(2): 183–7.
  12. Dean R.M., Pohlman B., Sweetenham J.W. et al. Superior survival after replacing oral with intravenous busulfan in autologous stem cell transplantation for non-Hodgkin lymphoma with busulfan, cyclophosphamide and etoposide. Br. J. Haematol. 2010; 148(2): 226–34.
  13. Spielberger R., Stiff P., Bensinger W. et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N. Engl. J. Med. 2004; 351(25): 2590–8.
  14. Krishnan A., Palmer J.M., Tsai N.C. et al. Matched-cohort analysis of autologous hematopoietic cell transplantation with radioimmunotherapy versus total body irradiation-based conditioning for poor-risk diffuse large cell lymphoma. Biol. Blood Marrow Transplant. 2012; 18(3): 441–50.
  15. Paris F., Fuks Z., Kang A. et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001; 293: 293–7.
  16. Wearing H.J., Sherratt J.A. Keratinocyte growth factor signaling: a mathematical model of dermalepidermal interaction in epidermal wound healing. Math. Biosci. 2000; 165: 41–62.
  17. Sonis S. Pathobiology of oral mucositis: novel insights and opportunities. J. Supp. Oncol. 2007; 5: 3–11.
  18. Wardley A.M., Jayson G.C., Swindell R. et al. Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br. J. Haematol. 2000; 110(2): 292–9.
  19. Vokurka S., Bystricka E., Koza V. et al. Higher incidence of chemotherapy induced oral mucositis in females: a supplement of multivariate analysis to a randomized multicentre study. Supp. Care Cancer 2006; 14(9): 974–6.
  20. Hahn T., Zhelnova E., Sucheston L. et al. A deletion polymorphism in glutathione-S-transferase mu (GSTM1) and/or theta (GSTT1) is associated with an increased risk of toxicity after autologous blood and marrow transplantation. Biol. Blood Marrow Transplant. 2010; 16(6): 801–8.
  21. Grazziutti M.L., Dong L., Miceli M.H. et al. Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model. Bone Marrow Transplant. 2006; 38(7): 501–6.
  22. Krishna S.G., Zhao W., Grazziutti M.L. et al. Incidence and risk factors for lower alimentary tract mucositis after 1529 courses of chemotherapy in a homogenous population of oncology patients: clinical and research implications. Cancer 2011; 117(3): 648–55.
  23. Bensinger W., Schubert M., Ang K.K. et al. NCCN Task Force Report: prevention and management of mucositis in cancer care. J. Natl. Compr. Cancer Netw. 2008; 6(Suppl. 1): S1–21.
  24. Atkinson K., Champlin R., Ritz J. et al. (eds.) Clinical Bone Marrow and Blood Stem Cell Transplantation, 3rd edn. Cambridge University Press, 2004: 276–7.
  25. National Cancer Institute. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Published August 9, 2006. Available at: www.ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf.
  26. Forbes G.M., Rule S.A., Herrmann R.P. et al. A prospective study of screening upper gastrointestinal (GI) endoscopy prior to and after bone marrow transplantation (BMT). Aust. N. Z. J. Med. 1995; 25(1): 32–6.
  27. Vishny M.L., Blades E.W., Creger R.J. et al. Role of upper endoscopy in evaluation of upper gastrointestinal symptoms in patients undergoing bone marrow transplantation. Cancer Invest. 1994; 12(4): 384–9.
  28. Tsirigotis P., Triantafyllou K., Girkas K. et al. Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study. Bone Marrow Transplant. 2008; 42(5): 337–43.
  29. Avivi I., Avraham S., Koren-Michowitz M. et al. Oral integrity and salivary profile in myeloma patients undergoing high-dose therapy followed by autologous SCT. Bone Marrow Transplant. 2009; 43(10): 801–6.
  30. Blijlevens N.M., Donnelly J.P., de Pauw B.E. Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant. Bone Marrow Transplant. 2005; 35(7): 707–11.
  31. Johansson J.E., Brune M., Ekman T. The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning. Bone Marrow Transplant. 2001; 28(8): 737–42.
  32. van Kraaij M.G., Dekker A.W., Verdonck L.F. et al. Infectious gastroenteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients. Bone Marrow Transplant. 2000; 26(3): 299–303.
  33. Chakrabarti S., Collingham K.E., Stevens R.H. et al. Isolation of viruses from stools in stem cell transplant recipients: a prospective surveillance study. Bone Marrow Transplant. 2000; 25(3): 277–82.
  34. Davila M.L. Neutropenic enterocolitis. Curr. Opin. Gastroenterol. 2006; 22(1): 44–7.
  35. Ullery B.W., Pieracci F.M., Rodney J.R. et al. Neutropenic enterocolitis. Surg. Infect. (Larchmt.) 2009; 10(3): 307–14.
  36. Arango J.I., Restrepo A., Schneider D.L. et al. Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma. Bone Marrow Transplant. 2006; 37(5): 517–21.
  37. Tomblyn M., Gordon L., Singhal S. et al. Rarity of toxigenic Clostridium difficile infections after hematopoietic stem cell transplantation: implications for symptomatic management of diarrhea. Bone Marrow Transplant. 2002; 30(8): 517–9.
  38. Avery R., Pohlman B., Adal K. et al. High prevalence of diarrhea but infrequency of documented Clostridium difficile in autologous peripheral blood progenitor cell transplant recipients. Bone Marrow Transplant. 2000; 25(1): 67–9.
  39. Ramsey D.J., Schey S.A. Cytomegalovirus colitis after autologous transplantation for multiple myeloma. Br. J. Haematol. 2000; 110(4): 894–6.
  40. Cohen Y., Paltiel O., Amir G. et al. Unusual cytomegalovirus complications after autologous stem cell transplantation for large B cell lymphoma: massive gastrointestinal hemorrhage followed by a communicating hydrocephalus. Bone Marrow Transplant. 2002; 29(8): 715–6.
  41. MASCC/ISOO evidence-based clinical practice guidelines for mucositis secondary to cancer therapy. http://www.mascc.org/assets/GuidelinesTools.
  42. Yamagata K., Arai C., Sasaki H. et al. The effect of oral management on the severity of oral mucositis during hematopoietic SCT. Bone Marrow Transplant. 2012; 47(5): 725–30. doi: 10.1038/bmt.2011.171.
  43. Stiff P.J., Emmanouilides C., Bensinger W.I. et al. Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J. Clin. Oncol. 2006; 24(33): 5186–93.
  44. Abidi M.H., Agarwal R., Tageja N. et al. A phase I dose-escalation trial of high-dose melphalan with palifermin for cytoprotection followed by autologous stem cell transplantation for patients with multiple myeloma with normal renal function. Biol. Blood Marrow Transplant. 2013; 19(1): 56–61.
  45. Abidi M.H., Agarwal R., Ayash L. et al. Melphalan 180 mg/m2 can be safely administered as conditioning regimen before an autologous stem cell transplantation (ASCT) in multiple myeloma patients with creatinine clearance 60 mL/min/1.73 m2 or lower with use of palifermin for cytoprotection: results of a phase I trial. Biol. Blood Marrow Transplant. 2012; 18(9): 1455–61.
  46. Lilleby K., Garcia P., Gooley T. et al. 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. 2006; 37(11): 1031–5.
  47. Salvador P., Azusano C., Wang L. et al. A pilot randomized controlled trial of an oral care intervention to reduce mucositis severity in stem cell transplant patients. J. Pain Sympt. Manage 2012; 44(1): 64–73.
  48. Vokurka S., Bystricka E., Scudlova J. et al. The risk factors for oral mucositis and the effect of cryotherapy in patients after the BEAM and HD-l-PAM 200 mg/m(2) autologous hematopoietic stem cell transplantation. Eur. J. Oncol. Nurs. 2011; 15(5): 508–12.
  49. Antunes H.S., de Azevedo A.M., da Silva Bouzas L.F. et al. Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood 2007; 109(5): 2250–5.
  50. Silva G.B., Mendonca E.F., Bariani C. et al. The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: a randomized clinical trial. Photomed. Laser Surg. 2011; 29(1): 27–31.
  51. Schubert M.M., Eduardo F.P., Guthrie K.A. et al. 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. Supp. Care Cancer 2007; 15(10): 1145–54.
  52. Spencer A., Horvath N., Gibson J. et al. Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplant. 2005; 35(10): 971–7.
  53. Gabriel D.A., Shea T.C., Serody J.S. et al. Cytoprotection by amifostine during autologous stem cell transplantation for advanced refractory hematologic malignancies. Biol. Blood Marrow Transplant. 2005; 11(12): 1022–30.
  54. Phillips G.L. 2nd, Bernstein S.H., Liesveld J.L. et al. A Phase I trial: dose escalation of melphalan in the ‘BEAM’ regimen using amifostine cytoprotection. Biol. Blood Marrow Transplant. 2011; 17(7): 1033–42.
  55. Wasko-Grabowska A., Rzepecki P., Oborska S. et al. Efficiency of supersaturated calcium phosphate mouth rinse treatment in patients receiving highdose melphalan or BEAM prior to autologous blood stem cell transplantation: a single-center experience. Transplant. Proc. 2011; 43(8): 3111–3.
  56. Васильева В.А., Кузьмина Л.А., Клясова Г.А. и др. Опыт применения фосфата кальция у больных после высокодозной полихимиотерапии и трансплантации гемопоэтических стволовых клеток. Гематол. и транс- фузиол. 2012; 57(3): 11–3. [Vasil’eva V.A., Kuz’mina L.A., Klyasova G.A. et al. An experience in the use of potassium phosphate in patients after the high-dose polychemotherapy and transplantation of hemopetic stem cells. Gematol. i transfuziol. 2012; 57(3): 11–3. (In Russ.)]
  57. Oblon D.J., Paul S.R., Oblon M.B. et al. Propantheline protects the oral mucosa after high-dose ifosfamide, carboplatin, etoposide and autologous stem cell transplantation. Bone Marrow Transplant. 1997; 20(11): 961–3.
  58. Lockhart P.B., Brennan M.T., Kent M.L. et al. Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation. Bone Marrow Transplant. 2005; 35(7): 713–20.
  59. Costa L.J., Micallef I.N., Inwards D.J. et al. Effect of the dose per body weight of conditioning chemotherapy on severity of mucositis and risk of relapse after autologous haematopoietic stem cell transplantation in relapsed diffuse large B cell lymphoma. Br. J. Haematol. 2008; 143(2): 268–73.
  60. Eisen D., Essell J., Broun E.R. et al. Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy. Bone Marrow Transplant. 2003; 31(1): 51–5.
  61. Lovenich H., Schutt-Gerowitt H., Keulertz C. et al. Failure of anti-infective mouth rinses and concomitant antibiotic prophylaxis to decrease oral mucosal colonization in autologous stem cell transplantation. Bone Marrow Transplant. 2005; 35(10): 997–1001.
  62. Strupp C., Sudhoff T., Germing U. et al. Transdermal fentanyl during high-dose chemotherapy and autologous stem cell support. Oncol. Rep. 2000; 7(3): 659–61. 63. Pinana J.L., Montesinos P., Martino R. et al. Incidence, risk factors, and outcome of bacteremia following autologous hematopoietic stem cell transplantation in 720 adult patients. Ann. Hematol. 2014; 93(2): 299–307