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Post Transplant Complications

Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors

Bone Marrow Transplantation volume 25, pages 885–894 (2000)Cite this article

Abstract

We sought to define risk factors predisposing breast cancer and lymphoma patients to cardiac and pulmonary toxicity when undergoing high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR). Additionally, we evaluated in depth the predictive value of the ejection fraction measured prior to HDC in determining cardiac toxicity. In this retrospective analysis, 24 variables were examined in 138 patients undergoing HDC and ASCR from 1990 until 1995. Logistic regression models were used to model the probability of experiencing cardiac and pulmonary toxicity as a function of the 24 prognostic covariates. Cardiac toxicity occurred in 12% of patients and pulmonary toxicity in 24% of patients. Bivariate analyses showed that patients with lymphoma (as opposed to breast cancer) and those with a higher cardiac risk factor score were more likely to experience cardiac toxicity. Multivariate logistic regression models predicted lymphoma and older age to be risk factors for cardiac toxicity. History of an abnormal ejection fraction and higher doses of anthracyclines prior to HDC may also contribute to cardiac toxicity. Pulmonary toxicity occurred more commonly in lymphoma than breast cancer patients, likely due to the busulfan used in the HDC regimen. No other risk factors for pulmonary toxicity were identified. We conclude that older patients with lymphoma should be carefully evaluated prior to being accepted for HDC programs. Older patients with breast cancer may tolerate this procedure well. There is a trend towards cardiac toxicity in patients with a past history of low ejection fraction, although seemingly poor cardiac risk patients may fare well with HDC if carefully selected with the aid of a thorough cardiac evaluation. Bone Marrow Transplantation (2000) 25, 885–894.

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References

  1. Brockstein BE, Williams SF . High-dose chemotherapy with autologous stem cell rescue for breast cancer: yesterday, today and tomorrow Stem Cells 1996 14: 79–89

    Article  CAS  Google Scholar 

  2. Dillman RO, Barth NM, Nayak SK et al. High-dose chemotherapy with autologous stem cell rescue in breast cancer Breast Cancer Res Treat 1996 37: 277–289

    Article  CAS  Google Scholar 

  3. Vandenberghe EA, Goldstone AH . Autologous stem cell transplants in lymphomas Ann Med 1996 28: 137–144

    Article  CAS  Google Scholar 

  4. Stasi R, Venditti A, Del Poeta G et al. High-dose chemotherapy in adult acute myeloid leukemia: rationale and results Leukemia Res 1996 20: 535–549

    Article  CAS  Google Scholar 

  5. Droz JP, Culine S, Biron P et al. High-dose chemotherapy in germ-cell tumors Ann Oncol 1996 7: 997–1003

    Article  CAS  Google Scholar 

  6. Santos SW, Sensenbrenner LL, Bruke PJ et al. The use of cyclophosphamide for clinical marrow transplantation Transplant Proc 1972 4: 559–564

    CAS  PubMed  Google Scholar 

  7. Goldberg MA, Antin JH, Guinan EC et al. Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor Blood 1986 68: 1114–1118

    CAS  PubMed  Google Scholar 

  8. Braverman AC, Antin JH, Plappert MT et al. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens J Clin Oncol 1991 9: 1215–1223

    Article  CAS  Google Scholar 

  9. Gottdiener JS, Appelbaum FR, Ferrans VJ et al. Cardiotoxicity associated with high-dose cyclophosphamide therapy Arch Intern Med 1981 141: 758–763

    Article  CAS  Google Scholar 

  10. Shan K, Lincoff AM, Young JB . Anthracycline-induced cardiotoxicity Ann Intern Med 1996 125: 47–58

    Article  CAS  Google Scholar 

  11. Bu'Lock FA, Mott MG, Oakhill A et al. Early identification of anthracycline cardiomyopathy: possibilities and implications Arch Dis Child 1996 75: 416–422

    Article  CAS  Google Scholar 

  12. Bristow MR, Thompson PD, Martin RP et al. Early anthracycline cardiotoxicity Am J Med 1978 65: 823–832

    Article  CAS  Google Scholar 

  13. Porembka DT, Lowder JN, Orlowski JP et al. Etiology and management of doxorubicin cardiotoxicity Crit Care Med 1989 17: 569–572

    Article  CAS  Google Scholar 

  14. Quezado ZM, Wilson WH, Cunnion RE et al. High-dose ifosfamide is associated with severe reversible cardiac dysfunction Ann Intern Med 1993 118: 31–36

    Article  CAS  Google Scholar 

  15. Kandylis K, Vassilomanolakis M, Tsoussis S et al. Ifosfamide cardiotoxicity in humans Cancer Chemother Pharmacol 1989 24: 395–396

    Article  CAS  Google Scholar 

  16. Collins C, Weiden PL . Cardiotoxicity of 5-fluorouracil Cancer Treat Rep 1987 71: 733–736

    CAS  PubMed  Google Scholar 

  17. Martin M, Diaz-Rubio E, Furio V et al. Lethal cardiac toxicity after cisplatin and 5-fluorouracil chemotherapy Am J Clin Oncol 1989 12: 229–234

    Article  CAS  Google Scholar 

  18. Rowinsky EK, Eisenhauer EA, Chaudhry V et al. Clinical toxicities encountered with paclitaxel (taxol) Semin Oncol 1993 20: (Suppl. 3) 1–15

    CAS  PubMed  Google Scholar 

  19. Wood AJ . Paclitaxel (taxol) New Engl J Med 1995 332: 1004–1014

    Article  Google Scholar 

  20. Mandel EM, Lewinski U, Djaldetti M . Vincristine-induced myocardial infarction Cancer 1975 36: 1979–1982

    Article  CAS  Google Scholar 

  21. Sivanesaratnam V . Mitomycin-C cardiotoxicity Med J Aust 1989 151: 300

    CAS  PubMed  Google Scholar 

  22. Schultz-Hector S . Radiation-induced heart disease: review of experimental data on dose response and pathogenesis Int J Radiat Biol 1992 61: 149–160

    Article  CAS  Google Scholar 

  23. Benoff LJ, Schweitzer P . Radiation therapy-induced cardiac injury Am Heart J 1995 129: 1193–1196

    Article  CAS  Google Scholar 

  24. Stewart JW, Fajardo LF, Gillette SM et al. Radiation injury to the heart Int J Radiat Oncol Biol Phys 1995 31: 1205–1211

    Article  CAS  Google Scholar 

  25. Lopez-Jimenez J, Cervero C, Munoz A et al. Cardiovascular toxicities related to the infusion of cryopreserved grafts: results of a controlled study Bone Marrow Transpl 1994 13: 789–793

    CAS  Google Scholar 

  26. Yellowlees P, Greenfield C, McIntyre N . Dimethylsulphoxide-induced toxicity Lancet 1980 8202: 1004–1006

    Article  Google Scholar 

  27. Hertenstein B, Stefanic M, Schmeiser T et al. Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant J Clin Oncol 1994 12: 998–1004

    Article  CAS  Google Scholar 

  28. Bearman SI, Petersen FB, Schor RA et al. Radionuclide ejection fractions in the evaluation of patients being considered for bone marrow transplantation: risk for cardiac toxicity Bone Marrow Transplant 1990 5: 173–177

    CAS  PubMed  Google Scholar 

  29. Durant JR, Norgard MJ, Murad TM et al. Pulmonary toxicity associated with bischloroethylnitrosourea (BCNU) Ann Intern Med 1979 90: 191–194

    Article  CAS  Google Scholar 

  30. Blum RH, Carter SK, Agre K . A clinical review of bleomycin – a new antineoplastic agent Cancer 1973 31: 903–914

    Article  CAS  Google Scholar 

  31. Krowka MJ, Rosenow EC, Hoagland HC . Pulmonary complications of bone marrow transplantation Chest 1985 87: 237–246

    Article  CAS  Google Scholar 

  32. Chan CK, Hyland RH, Hutcheon MA . Pulmonary complications following bone marrow transplantation Clin Chest Med 1990 11: 323–332

    CAS  PubMed  Google Scholar 

  33. Twohig K, Matthay R . Pulmonary effects of cytotoxic drugs other than bleomycin Clin Chest Med 1990 11: 31–54

    CAS  PubMed  Google Scholar 

  34. Todd NW, Peters WP, Ost AH et al. Pulmonary drug toxicity in patients with primary breast cancer treated with high-dose combination chemotherapy and autologous bone marrow transplantation Am Rev Resp Dis 1993 147: 1264–1270

    Article  CAS  Google Scholar 

  35. Przepiorka D, Dimopoulos M, Smith T et al. Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for marrow transplantation: risk factors for early regimen-related toxicity Ann Hematol 1994 68: 183–188

    Article  CAS  Google Scholar 

  36. Carlson K, Backlund L, Smedmyr B et al. Pulmonary function and complications subsequent to autologous bone marrow transplantation Bone Marrow Transplant 1994 14: 805–811

    CAS  PubMed  Google Scholar 

  37. Quakeck K . The lung as a critical organ in marrow transplantation Bone Marrow Transplant 1994 14: (Suppl. 4) S19–S28

    Google Scholar 

  38. Hartsell WF, Czyzewski EA, Ghalie R et al. Pulmonary complications of bone marrow transplantation: a comparison of total body irradiation and cyclophosphamide to busulfan and cyclophosphamide Int J Radiat Oncol Biol Phys 1995 32: 69–73

    Article  CAS  Google Scholar 

  39. Nichols DG, Walker LK, Wingard JR et al. Predictors of acute respiratory failure after bone marrow transplantation in children Crit Care Med 1994 22: 1485–1491

    Article  CAS  Google Scholar 

  40. 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: 329–331

    CAS  PubMed  Google Scholar 

  41. Behar S, Graff E, Reicher-Reiss H et al. Low total cholesterol is associated with high total mortality in patients with coronary heart disease Eur Heart J 1997 18: 52–59

    Article  CAS  Google Scholar 

  42. Bokemeyer C, Berger CC, Kuczyk MA, Schmoll HJ . Evaluation of long-term toxicity after chemotherapy for testicular cancer J Clin Oncol 1996 14: 2923–2932

    Article  CAS  Google Scholar 

  43. Fiorenza AM, Branchi A, Cardena A et al. Serum cholesterol levels in patients with cancer. Relationship with nutritional status Int J Clin Lab Res 1996 26: 37–42

    Article  CAS  Google Scholar 

  44. Hosmer DW Jr, Lemeshow, S . Applied Logistic Regression John Wiley: New York 1989

    Google Scholar 

  45. Lawless JF, Singhal K . ISMOD: an all-subsets regression program for generalized linear models. I. Statistical and computational background Comp Meth Prog Biomed 1987 24: 117–124

    Article  CAS  Google Scholar 

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Acknowledgements

The authors gratefully thank LP Schumm and R Mick for their statistical analyses and advice, Sheila Dertz for her data management assistance, and Elis Perez for her secretarial assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Hematology/Oncology, University of Chicago, IL, USA

    BE Brockstein, C Smiley & SF Williams

  2. Section of Cardiology, University of Chicago, IL, USA

    J Al-Sadir

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  1. BE Brockstein
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  2. C Smiley
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  3. J Al-Sadir
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  4. SF Williams
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Appendix 1

Appendix 1

Table 9

Table 9 Coronary heart disease risk factor prediction worksheets (Score worksheet) (modified from Framingham heart study)
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Brockstein, B., Smiley, C., Al-Sadir, J. et al. Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors. Bone Marrow Transplant 25, 885–894 (2000). https://doi.org/10.1038/sj.bmt.1702234

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