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Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies

Abstract

Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.

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References

  1. Anderson KO, Giralt SA, Mendoza TR, Brown JO, Neumann JL, Mobley GM et al. Symptom burden in patients undergoing autologous stem-cell transplantation. Bone Marrow Transplant 2007; 39: 759–766.

    Article  CAS  PubMed  Google Scholar 

  2. Niscola P, Arcuri E, Giovannini M, Scaramucci L, Romani C, Palombi F et al. Pain syndromes in haematological malignancies: an overview. Hematol J 2004; 5: 293–303.

    Article  PubMed  Google Scholar 

  3. Niscola P, Romani C, Cartoni C, Cupelli L, Piccioni D, Dentamaro T et al. Epidemiology of pain in hospital haematological setting: an Italian survey. Leuk Res 2008; 32: 197–198.

    Article  PubMed  Google Scholar 

  4. Karlsson L, Quinlan D, Guo D, Brown C, Selinger S, Klassen J et al. Mobilized blood cells vs bone marrow harvest: experience compared in 171 donors with particular reference to pain and fatigue. Bone Marrow Transplant 2004; 33: 709–713.

    Article  CAS  PubMed  Google Scholar 

  5. Niscola P, Cupelli L, Romani C, Scaramucci L, Dentamaro T, Tendas A et al. Mucositis in patients with hematological malignancies: an overview. Haematologica 2007; 91: 222–231.

    Article  Google Scholar 

  6. Lieschke GJ, Burgess AW . Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. N Engl J Med 1992; 327: 28–35.

    Article  CAS  PubMed  Google Scholar 

  7. Isidorins A, Tani M, Bonifazi F, Zinzani P, Curti A, Motta MR et al. Phase II study of a single pegfilgrastim injection as an adjunct to chemotherapy to mobilize stem cells into the peripheral blood of pretreated lymphoma patients. Haematologica 2005; 90: 225–231.

    Google Scholar 

  8. Nosari A, Cairoli R, Ciapanna D, Gargantini L, Intropido L, Barate C et al. Efficacy of single dose pegfilgrastim in enhancing the mobilization of CD34+ peripheral blood stem cells in aggressive lymphoma patients treated with cisplatin-aracytin-containing regimens. Bone Marrow Transplant 2006; 38: 413–416.

    Article  CAS  PubMed  Google Scholar 

  9. Malerba L, Mele A, Leopardi G, Stramigioli S, Politi P, Visani G . Pegfilgrastim effectively mobilizes PBSC in a poor mobilizer multiple myeloma patient. Eur J Haematol 2006; 76: 436–439.

    Article  CAS  PubMed  Google Scholar 

  10. Martino M, Console G, Irrera G, Callea I, Condemi A, Dattola A et al. Harvesting peripheral blood progenitor cells from healthy donors: retrospective comparison of filgrastim and lenograstim. J Clin Apher 2005; 20: 129–136.

    Article  PubMed  Google Scholar 

  11. Kuendgen A, Fenk R, Bruns I, Dommach M, Schutte A, Engers R et al. Splenic rupture following administration of pegfilgrastim in a patient with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2006; 38: 69–70.

    Article  CAS  PubMed  Google Scholar 

  12. Nuamah NM, Goker H, Kilic YA, Dagmoura H, Cakmak A . Spontaneous splenic rupture in a healthy allogeneic donor of peripheral-blood stem cell following the administration of granulocyte colony-stimulating factor (g-csf). A case report and review of the literature. Haematologica 2006; 91: ECR08.

    PubMed  Google Scholar 

  13. Kroschinsky F, Holig K, Poppe-Thiede K, Zimmer K, Ordemann R, Blechschmidt M et al. Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors. Haematologica 2005; 90: 1665–1671.

    CAS  PubMed  Google Scholar 

  14. Hill GR, Morris ES, Fuery M, Hutchins C, Butler J, Grigg A et al. Allogeneic stem cell transplantation with peripheral blood stem cells mobilized by pegylated G-CSF. Biol Blood Marrow Transplant 2006; 12: 603–637.

    Article  PubMed  Google Scholar 

  15. Heary RF, Schlenk RP, Sacchieri TA, Barone D, Brotea C . Persistent iliac crest donor site pain: independent outcome assessment. Neurosurgery 2002; 50: 510–516.

    PubMed  Google Scholar 

  16. Kroschinsky F, Kittner T, Mauersberger S, Rautenberg U, Schuler U, Rutt C et al. Pelvic magnetic resonance imaging after bone marrow harvest—a retrospective study in 50 unrelated marrow donors. Bone Marrow Transplant 2005; 35: 667–673.

    Article  CAS  PubMed  Google Scholar 

  17. Ahlmann E, Patzakis M, Roidis N, Shepherd L, Holtom P . Comparison of anterior and posterior iliac crest bone grafts in terms of harvest-site morbidity and functional outcomes. J Bone Joint Surg Am 2002; 84-A: 716–720.

    Article  Google Scholar 

  18. Irving I, Cooper M, Durrant S . Sciatic nerve compression following bone marrow harvest. Bone Marrow Transplant 2000; 26: 705–706.

    Article  CAS  PubMed  Google Scholar 

  19. Yamamoto T, Nagira K, Kurosaka M . Meralgia paresthetica occurring 40 years after iliac bone graft harvesting: case report. Neurosurgery 2001; 49: 1455–1457.

    Article  CAS  PubMed  Google Scholar 

  20. Ferrucci PF, Martinoni A, Cocorocchio E, Civelli M, Cinieri S, Cardinale D et al. Evaluation of acute toxicities associated with autologous peripheral blood progenitor cell reinfusion in patients undergoing high-dose chemotherapy. Bone Marrow Transplant 2000; 25: 173–177.

    Article  CAS  PubMed  Google Scholar 

  21. Martino M, Morabito F, Console G, Irrera G, Messina G, Pucci G et al. Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Tumori 2003; 89: 385–390.

    Article  PubMed  Google Scholar 

  22. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al., Mucositis Study Section of the Multinational Association for Supportive Care in Cancer; International Society for Oral Oncology. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004; 100 (9 Suppl): 1995–2025.

    Article  PubMed  Google Scholar 

  23. Wang EH, Chen YA, Corringham S, Bashey A, Holman P, Ball ED et al. High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma. Bone Marrow Transplant 2004; 34: 581–587.

    Article  CAS  PubMed  Google Scholar 

  24. Ferrara F, Palmieri S, De Simone M, Sagristani M, Viola A, Pocali B et al. High-dose idarubicin and busulphan as conditioning to autologous stem cell transplantation in adult patients with acute myeloid leukaemia. Br J Haematol 2005; 128: 234–241.

    Article  CAS  PubMed  Google Scholar 

  25. Palumbo A, Bringhen S, Petrucci MT, Falcone A, Liberati AM, Grasso M et al. Prospective, randomized, phase III study of melphalan 200 mg/m2 (MEL200) versus melphalan 100 mg/m2 (MEL100) in newly diagnosed myeloma patients (abstract). Blood 2006; 108, 11 (Suppl, part 1): 21a.

    Google Scholar 

  26. Palumbo A, Bringhen S, Petrucci MT, Musto P, Rossini F, Nunzi M et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood 2004; 104: 3052–3057.

    Article  CAS  PubMed  Google Scholar 

  27. Wardley AM, Jayson GC, Swindell R, Morgenstern GR, Chang J, Bloor R et al. Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 2000; 110: 292–299.

    Article  CAS  PubMed  Google Scholar 

  28. Woo SB, Sonis ST, Monopoli MM, Sonis AL . A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer 1993; 72: 1612–1617.

    Article  CAS  PubMed  Google Scholar 

  29. Maloney DG, Sandmaier BM, Mackinnon S, Shizuru JA . Non-myeloablative transplantation. Hematology (Am Soc Hematol Educ Program) 2002, 392–421.

    Article  Google Scholar 

  30. Dominguez Reyes A, Aznar Martin T, Barberia Leache E, Cabrera Suarez E . Oral manifestations of graft versus host disease. Med Oral 2003; 8: 361–365.

    PubMed  Google Scholar 

  31. Cheuk DK, Lee TL, Chiang AK, Ha SY, Lau YL, Chan GC . Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation. Transpl Int 2007; 20: 73–81.

    Article  PubMed  Google Scholar 

  32. Richardson P, Guinan E . Hepatic veno-occlusive disease following hematopoietic stem cell transplantation. Acta Haematol 2001; 106: 57–68.

    Article  CAS  PubMed  Google Scholar 

  33. Fujii N, Ikeda K, Koyama M, Aoyama K, Masunari T, Kondo E et al. Calcineurin inhibitor-induced irreversible neuropathic pain after allogeneic hematopoietic stem cell transplantation. Int J Hematol 2006; 83: 459–461.

    Article  PubMed  Google Scholar 

  34. Piccirillo N, Sica S, Laurenti L, Chiusolo P, La Barbera EO, Sora F et al. Optimal timing of G-CSF administration after CD34+ immunoselected peripheral blood progenitor cell transplantation. Bone Marrow Transplant 1999; 23: 1245–1250.

    Article  CAS  PubMed  Google Scholar 

  35. Katayama Y, Deguchi S, Shinagawa K, Teshima T, Notohara K, Taguchi K et al. Bone marrow necrosis in a patient with acute myeloblastic leukemia during administration of G-CSF and rapid hematologic recovery after posttransplantation of peripheral blood stem cells. Am J Hematol 1998; 57: 238–240.

    Article  CAS  PubMed  Google Scholar 

  36. Mori A, Hashino S, Imamura M, Kahata K, Kawakami H, Shibata M et al. Bone marrow infarction due to acute graft-versus-host disease in an acute lymphoblastic leukemia patient after unrelated bone marrow transplantation. Bone Marrow Transplant 1998; 21: 615–617.

    Article  CAS  PubMed  Google Scholar 

  37. Jones AD, Maziarz R, Gilster J, Domreis J, Deveney CW, Sheppard BC . Surgical complications of bone marrow transplantation. Am J Surg 2003; 185: 481–484.

    Article  PubMed  Google Scholar 

  38. Sepulveda E, Brethauer U, Rojas J, Fernandez E, Le Fort P . Oral ulcers in children under chemotherapy: clinical characteristics and their relation with herpes simplex virus type 1 and Candida albicans. Med Oral Patol Oral Cir Bucal 2005; 10: E1–E8.

    PubMed  Google Scholar 

  39. Offidani M, Corvatta L, Olivieri A, Mele A, Brunori M, Montanari M et al. A predictive model of varicella-zoster virus infection after autologous peripheral blood progenitor cell transplantation. Clin Infect Dis 2001; 32: 1414–1422.

    Article  CAS  PubMed  Google Scholar 

  40. Leena M, Ville V, Veli-Jukka A . Visceral varicella zoster virus infection after stem cell transplantation: a possible cause of severe abdominal pain. Scand J Gastroenterol 2006; 41: 242–244.

    Article  PubMed  Google Scholar 

  41. van Burik JA, Lawatsch EJ, DeFor TE, Weisdorf DJ . Cytomegalovirus enteritis among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2001; 7: 674–679.

    Article  CAS  PubMed  Google Scholar 

  42. Cutler C, Antin JH . Chronic graft-versus-host disease. Curr Opin Oncol 2006; 18: 126–131.

    Article  PubMed  Google Scholar 

  43. Treister NS, Woo SB, O'Holleran EW, Lehmann LE, Parsons SK, Guinan EC . Oral chronic graft-versus-host disease in pediatric patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 721–731.

    Article  PubMed  Google Scholar 

  44. Spiryda LB, Laufer MR, Soiffer RJ, Antin JA . Graft-versus-host disease of the vulva and/or vagina: diagnosis and treatment. Biol Blood Marrow Transplant 2003; 9: 760–765.

    Article  PubMed  Google Scholar 

  45. Akpek G, Chinratanalab W, Lee LA, Torbenson M, Hallick JP, Anders V et al. Gastrointestinal involvement in chronic graft-versus-host disease: a clinicopathologic study. Biol Blood Marrow Transplant 2003; 9: 46–51.

    Article  PubMed  Google Scholar 

  46. Couriel DR, Beguelin GZ, Giralt S, De Lima M, Hosing C, Kharfan-Dabaja MA et al. Chronic graft-versus-host disease manifesting as polymyositis: an uncommon presentation. Bone Marrow Transplant 2002; 30: 543–546.

    Article  CAS  PubMed  Google Scholar 

  47. Socie G, Selimi F, Sedel L, Frija J, Devergie A, Esperou Bourdeau H et al. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors. Br J Haematol 1994; 86: 624–628.

    Article  CAS  PubMed  Google Scholar 

  48. Schulte C, Beelen DW, Schaefer UW, Mann K . Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study. Osteoporos Int 2000; 11: 344–353.

    Article  CAS  PubMed  Google Scholar 

  49. Koc Y, Miller KB, Schenkein DP, Griffith J, Akhtar M, DesJardin J et al. Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome. Biol Blood Marrow Transplant 2000; 6: 44–49.

    Article  CAS  PubMed  Google Scholar 

  50. Mercadante S, Villari P, Ferrera P, Bianchi M, Casuccio A . Safety and effectiveness of intravenous morphine for episodic (breakthrough) pain using a fixed ratio with the oral daily morphine dose. J Pain Symptom Manage 2004; 27: 352–359.

    Article  CAS  PubMed  Google Scholar 

  51. Miaskowski C . Biology of mucosal pain. J Natl Cancer Inst Monogr 2001, 37–40.

    Article  Google Scholar 

  52. Caraceni A, Cherny N, Fainsinger R, Kaasa S, Poulain P, Radbruch L et al. Pain measurement tools and methods in clinical research in palliative care: recommendations of an expert working group of the European Association of Palliative Care. J Pain Symptom Manage 2002; 23: 239–255.

    Article  PubMed  Google Scholar 

  53. Kim EJ, Buschmann MT . Reliability and validity of the faces pain scale with older adults. Int J Nurs Stud 2006; 43: 447–456.

    Article  PubMed  Google Scholar 

  54. Lynch M . Pain as the fifth vital sign. J Intraven Nurs 2001; 24: 85–94.

    CAS  PubMed  Google Scholar 

  55. Niscola P, Scaramucci L, Romani C, Giovannini M, Maurillo L, Del Poeta G et al. Opioids in pain management of blood-related malignancies. Ann Hematol 2006; 85: 489–501.

    Article  CAS  PubMed  Google Scholar 

  56. Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, et al., Expert Working Group of the European Association of Palliative Care Network. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol 2001; 19: 2542–2554.

    Article  CAS  PubMed  Google Scholar 

  57. Hill HF, Chapman CR, Kornell JA, Sullivan KM, Saeger LC, Benedetti C . Self-administration of morphine in bone marrow transplant patients reduces drug requirement. Pain 1990; 40: 121–129.

    Article  CAS  PubMed  Google Scholar 

  58. Chapman CR, Donaldson GW, Jacobson RC, Hautman B . Differences among patients in opioid self-administration during bone marrow transplantation. Pain 1997; 71: 213–223.

    Article  CAS  PubMed  Google Scholar 

  59. Playfor S, Jenkins I, Boyles C, Choonara I, Davies G, Haywood T, et al., United Kingdom Paediatric Intensive Care Society Sedation; Analgesia and Neuromuscular Blockade Working Group. Consensus guidelines on sedation and analgesia in critically ill children. Intensive Care Med 2006; 32: 1125–1136.

    Article  CAS  PubMed  Google Scholar 

  60. Lavi A, Efrat R, Feigin E, Kadari A . Regional versus general anesthesia for bone marrow harvesting. J Clin Anesth 1993; 5: 204–206.

    Article  CAS  PubMed  Google Scholar 

  61. Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, et al., Mucositis Study Section of the Multinational Association for Supportive Care in Cancer; International Society for Oral Oncology. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004; 100 (9 Suppl): 2026–2046.

    Article  PubMed  Google Scholar 

  62. Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 2007; 109: 820–831.

    Article  CAS  PubMed  Google Scholar 

  63. Cerchietti LC, Navigante AH, Korte MW, Cohen AM, Quiroga PN, Villaamil EC et al. Potential utility of the peripheral analgesic properties of morphine in stomatitis-related pain: a pilot study. Pain 2003; 105: 265–273.

    Article  CAS  PubMed  Google Scholar 

  64. Strupp C, Sudhoff T, Germing U, Hunerliturkoglu A, Schneider P, Niederste-Hollenberg A et al. Transdermal fentanyl during high-dose chemotherapy and autologous stem cell support. Oncol Rep 2000; 7: 659–661.

    CAS  PubMed  Google Scholar 

  65. Demarosi F, Lodi G, Soligo D, Sardella A, Volpe AD, Carrassi A et al. Transdermal fentanyl in HSCT patients: an open trial using transdermal fentanyl for the treatment of oral mucositis pain. Bone Marrow Transplant 2004; 33: 1247–1251.

    Article  CAS  PubMed  Google Scholar 

  66. Kim JG, Sohn SK, Kim DH, Baek JH, Chae YS, Bae NY et al. Effectiveness of transdermal fentanyl patch for treatment of acute pain due to oral mucositis in patients receiving stem cell transplantation. Transplant Proc 2005; 37: 4488–4491.

    Article  CAS  PubMed  Google Scholar 

  67. Stiff P, Mumby P, Miler L, Rodriguez T, Parthswarthy M, Kiley K et al. Autologous hematopoietic stem cell transplants that utilize total body irradiation can safely be carried out entirely on an outpatient basis. Bone Marrow Transplant 2006; 38: 757–764.

    Article  CAS  PubMed  Google Scholar 

  68. Lee SJ . New approaches for preventing and treating chronic graft-versus-host disease. Blood 2005; 105: 4200–4206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sari I, Altuntas F, Kocyigit I, Sisman Y, Eser B, Unal A et al. The effect of budesonide mouthwash on oral chronic graft versus host disease. Am J Hematol 2007; 82: 349–356.

    Article  CAS  PubMed  Google Scholar 

  70. Albert MH, Becker B, Schuster FR, Klein B, Binder V, Adam K et al. Oral graft vs. host disease in children—treatment with topical tacrolimus ointment. Pediatr Transplant 2007; 11: 306–311.

    Article  CAS  PubMed  Google Scholar 

  71. Carpenter PA, Hoffmeister P, Chesnut III CH, Storer B, Charuhas PM, Woolfrey AE et al. Bisphosphonate therapy for reduced bone mineral density in children with chronic graft-versus-host disease. Biol Blood Marrow Transplant 2007; 13: 683–690.

    Article  CAS  PubMed  Google Scholar 

  72. Baron R, Wasner G . Prevention and treatment of postherpetic neuralgia. Lancet 2006; 367: 186–188.

    Article  PubMed  Google Scholar 

  73. Mercadante S, Arcuri E . Opioids and renal function. J Pain 2004; 5: 2–19.

    Article  CAS  PubMed  Google Scholar 

  74. Muphy EJ . Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care 2005; 33: 311–322.

    Article  Google Scholar 

  75. Syrjala KL, Donaldson GW, Davis MW, Kippes ME, Carr JE . Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: a controlled clinical trial. Pain 1995; 63: 189–198.

    Article  CAS  PubMed  Google Scholar 

  76. Syrjala KL, Cummings C, Donaldson GW . Hypnosis or cognitive behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical trial. Pain 1992; 48: 137–146.

    Article  CAS  PubMed  Google Scholar 

  77. Nasilowska-Adamska B, Rzepecki P, Manko J, Czyz A, Markiewicz M, Federowicz I et al. The influence of palifermin (Kepivance) on oral mucositis and acute graft versus host disease in patients with hematological diseases undergoing hematopoietic stem cell transplant. Bone Marrow Transplant 2007; 40: 983–988.

    Article  CAS  PubMed  Google Scholar 

  78. Mayes S, Ferrone M . Fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain. Ann Pharmacother 2006; 40: 2178–2186.

    Article  CAS  PubMed  Google Scholar 

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Niscola, P., Romani, C., Scaramucci, L. et al. Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies. Bone Marrow Transplant 41, 757–764 (2008). https://doi.org/10.1038/bmt.2008.3

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