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白消安诱发的肺损伤

Authors
Erich W Russi, MD
Robert S Negrin, MD
Section Editors
Kevin R Flaherty, MD, MS
James R Jett, MD
Deputy Editors
Helen Hollingsworth, MD
Diane MF Savarese, MD
Translators
张亚同, 副主任药师

引言

白消安是一种烷化剂，它在过去被用于治疗慢性髓系白血病(chronic myelogenous leukemia, CML)，但现在专门用作造血干细胞移植(hematopoietic stem cell transplantation, HCT)前预处理方案的一部分。白消安是第一个被报道的与肺毒性相关的细胞毒药物[1]。已报道的肺毒性包括急性肺损伤、慢性肺间质纤维化和肺泡出血。白消安常与其他药物联用，而许多这些药物可引起肺毒性，这使得很难确定哪一种药物才是罪魁祸首。 (参见“造血干细胞移植的预处理方案”，关于‘无放疗的化疗方案’一节)

本文将总结白消安诱发的肺损伤的临床特征。其他化疗药物引起的肺毒性将单独讨论。 (参见“与全身抗肿瘤治疗有关的肺毒性：临床表现、诊断与治疗”和“抗肿瘤治疗相关的肺毒性：细胞毒性药物”和“抗肿瘤治疗相关的肺毒性：分子靶向药物”)

流行病学和危险因素

在接受白消安治疗的患者中，有症状的肺损伤的发生率被认为不到8%；儿童和成人的肺毒性发生率似乎相近[2-16]。然而，实际的发生率并不明确；关于单独使用白消安治疗CML的患者的大部分早期数据仅包含单个案例报告[3-7,9,10]。自从口服酪氨酸激酶抑制剂开始应用之后，这类治疗已不再作为标准治疗。 (参见“慢性髓系白血病的治疗概述”)

目前，白消安的应用仅限于HCT前的预处理方案。评估这类患者发生肺损伤风险的近代数据来自于一些病例系列研究，这些研究中患者在HCT前接受白消安联合其他具有骨髓抑制作用的化疗药物和/或放射治疗。各研究中的肺损伤发病率存在差异，并且可导致肺毒性的需鉴别的病因[尤其是巨细胞病毒(cytomegalovirus, CMV)肺炎]使得结果解读复杂化：

●一份报告中，78例自体HCT前接受白消安联合环磷酰胺预处理方案的患者中，有2例(2.5%)发生了肺纤维化[14]。

          

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Literature review current through: 2017-06 . | This topic last updated: 2015-12-23.
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References
Top
  1. OLINER H, SCHWARTZ R, RUBIO F, DAMESHEK W. Interstitial pulmonary fibrosis following busulfan therapy. Am J Med 1961; 31:134.
  2. Cooper JA Jr, White DA, Matthay RA. Drug-induced pulmonary disease. Part 1: Cytotoxic drugs. Am Rev Respir Dis 1986; 133:321.
  3. Smalley RV, Wall RL. Two cases of busulfan toxicity. Ann Intern Med 1966; 64:154.
  4. Heard BE, Cooke RA. Busulphan lung. Thorax 1968; 23:187.
  5. Burns WA, McFarland W, Matthews MJ. Busulfan-induced pulmonary disease. Report of a case and review of the literature. Am Rev Respir Dis 1970; 101:408.
  6. Podoll LN, Winkler SS. Busulfan lung. Report of two cases and review of the literature. Am J Roentgenol Radium Ther Nucl Med 1974; 120:151.
  7. Hankins DG, Sanders S, MacDonald FM, Drage CW. Pulmonary toxicity recurring after a six week course of busulfan therapy and after subsequent therapy with uracil mustard. Chest 1978; 73:415.
  8. Schallier D, Impens N, Warson F, et al. Additive pulmonary toxicity with melphalan and busulfan therapy. Chest 1983; 84:492.
  9. Pearl M. Busulfan lung. Am J Dis Child 1977; 131:650.
  10. Oakhill A, Green ID, Knowlson GT, et al. Busulphan lung in childhood. J Clin Pathol 1981; 34:495.
  11. Jochelson M, Tarbell NJ, Freedman AS, et al. Acute and chronic pulmonary complications following autologous bone marrow transplantation in non-Hodgkin's lymphoma. Bone Marrow Transplant 1990; 6:329.
  12. Fernandez HF, Tran HT, Albrecht F, et al. Evaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation. Biol Blood Marrow Transplant 2002; 8:486.
  13. Hänel M, Kröger N, Sonnenberg S, et al. Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma. Ann Hematol 2002; 81:96.
  14. Ulrickson M, Aldridge J, Kim HT, et al. Busulfan and cyclophosphamide (Bu/Cy) as a preparative regimen for autologous stem cell transplantation in patients with non-Hodgkin lymphoma: a single-institution experience. Biol Blood Marrow Transplant 2009; 15:1447.
  15. Brockstein BE, Smiley C, Al-Sadir J, Williams SF. Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors. Bone Marrow Transplant 2000; 25:885.
  16. Crilley P, Topolsky D, Styler MJ, et al. Extramedullary toxicity of a conditioning regimen containing busulphan, cyclophosphamide and etoposide in 84 patients undergoing autologous and allogenic bone marrow transplantation. Bone Marrow Transplant 1995; 15:361.
  17. Ringdén O, Remberger M, Ruutu T, et al. Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group. Blood 1999; 93:2196.
  18. Santos GW, Tutschka PJ, Brookmeyer R, et al. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983; 309:1347.
  19. Copelan EA, Hamilton BK, Avalos B, et al. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood 2013; 122:3863.
  20. Bredeson C, LeRademacher J, Kato K, et al. Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation. Blood 2013; 122:3871.
  21. Ginsberg SJ, Comis RL. The pulmonary toxicity of antineoplastic agents. Semin Oncol 1982; 9:34.
  22. Sostman HD, Matthay RA, Putman CE. Cytotoxic drug-induced lung disease. Am J Med 1977; 62:608.
  23. Perkins JB, Kim J, Anasetti C, et al. Maximally tolerated busulfan systemic exposure in combination with fludarabine as conditioning before allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18:1099.
  24. Vergnon JM, Boucheron S, Riffat J, et al. [Interstitial pneumopathies caused by busulfan. Histologic, developmental and bronchoalveolar lavage analysis of 3 cases]. Rev Med Interne 1988; 9:377.
  25. Limper AH. Chemotherapy-induced lung disease. Clin Chest Med 2004; 25:53.
  26. Cleverley JR, Screaton NJ, Hiorns MP, et al. Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol 2002; 57:292.
  27. Worth L, Tran H, Petropoulos D, et al. Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide. Bone Marrow Transplant 1999; 24:947.
  28. Lund MB, Brinch L, Kongerud J, Boe J. Lung function 5 yrs after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide. Eur Respir J 2004; 23:901.
  29. Padley SP, Adler B, Hansell DM, Müller NL. High-resolution computed tomography of drug-induced lung disease. Clin Radiol 1992; 46:232.
  30. Lund MB, Kongerud J, Brinch L, et al. Decreased lung function in one year survivors of allogeneic bone marrow transplantation conditioned with high-dose busulphan and cyclophosphamide. Eur Respir J 1995; 8:1269.
  31. Bruno B, Souillet G, Bertrand Y, et al. Effects of allogeneic bone marrow transplantation on pulmonary function in 80 children in a single paediatric centre. Bone Marrow Transplant 2004; 34:143.
  32. Lund MB, Brinch L, Kongerud J, Boe J. Lung function 5 yrs after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide. Eur Respir J 2004; 23:901.
  33. Costabel U, Uzaslan E, Guzman J. Bronchoalveolar lavage in drug-induced lung disease. Clin Chest Med 2004; 25:25.
  34. Ito K, Iwabe K, Okai T, et al. Rapidly progressive pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia. Intern Med 1994; 33:710.
  35. Aymard JP, Gyger M, Lavallee R, et al. A case of pulmonary alveolar proteinosis complicating chronic myelogenous leukemia. A peculiar pathologic aspect of busulfan lung? Cancer 1984; 53:954.
  36. Tsushima K, Koyama S, Saitou H, et al. Pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia. Respiration 1999; 66:173.
  37. Ohmachi K, Ogiya D, Morita F, et al. Secondary pulmonary alveolar proteinosis in a patient with chronic myeloid leukemia in the accelerated phase. Tokai J Exp Clin Med 2008; 33:146.
  38. Kobayashi S, Ishikawa M, Wakabayashi Y, et al. [Busulfan lung exacerbated during steroid therapy: a review of Japanese literature]. Rinsho Ketsueki 1990; 31:1884.
  39. Korbitz BC, Reiquam CW. Busulfan in chronic granulocytic leukemia, a spectrum of clinical considerations. Clin Med 1969; 76:16.