J Korean Med Sci.  2006 Jun;21(3):406-411. 10.3346/jkms.2006.21.3.406.

Pulmonary Complications After Hematopoietic Stem Cell Transplantation

• Lim DH
• Lee J
• Lee HG
• Park BB
• Peck KR
• Oh WS
• Ji SH
• Lee SH
• Park JO
• Kim K
• Kim WS
• Jung CW
• Park YS
• Im YH
• Kang WK
• Park K

• KMID: 1778419
• DOI: http://doi.org/10.3346/jkms.2006.21.3.406

Abstract

Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome.

Keyword

Infection; Hematopoietic Stem Cell Transplantation; Graft vs. Host Disease

MeSH Terms

Transplantation, Homologous
Transplantation, Autologous
Transplantation Conditioning
Middle Aged
Male
Lung Diseases/*etiology
Lung/microbiology
Humans
Hematopoietic Stem Cell Transplantation/*adverse effects
Graft vs Host Disease
Female
Bacterial Infections/etiology
Aged
Adult
Adolescent

Reference

1. Krowka MJ, Rosenow EC 3rd, Hoagland HC. Pulmonary complications of bone marrow transplantation. Chest. 1985. 87:237–246.

2. Shorr AF, Moores LK, Edenfield WJ, Christie RJ, Fitzpatrick TM. Mechanical ventilation in hematopoietic stem cell transplantation: can we effectively predict outcomes? Chest. 1999. 116:1012–1018.

3. Matulis M, High KP. Immune reconstitution after hematopoietic stem-cell transplantation and its influence on respiratory infections. Semin Respir Infect. 2002. 17:130–139.

4. Lossos IS, Breuer R, Or R, Strauss N, Elishoov H, Naparstek E, Aker M, Nagler A, Moses AE, Shapiro M. Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study. Transplantation. 1995. 60:672–678.

5. Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang ML, Myerson D, Stevens-Ayers T, Flowers ME, Cunningham T, Corey L. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2003. 101:407–414.

6. Afessa B, Litzow MR, Tefferi A. Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001. 28:425–434.

7. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002. 34:730–751.

8. Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R, Pizzo P, Rolston KV, Shenep JL, Young LS. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis. 1997. 25:551–573.

9. Jules-Elysee K, Stover DE, Yahalom J, White DA, Gulati SC. Pulmonary complications in lymphoma patients treated with high-dose therapy and autologous bone marrow transplantation. Am Rev Respir Dis. 1992. 146:485–491.

10. Meyers JD, Flournoy N, Thomas ED. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis. 1982. 4:1119–1132.

11. Fennessy JJ. Irradiation damage to the lung. J Thorac Imaging. 1987. 2:68–79.

12. Hartsell WF, Czyzewski EA, Ghalie R, Kaizer H. 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.

13. Afessa B, Tefferi A, Litzow MR, Krowka MJ, Wylam ME, Peters SG. Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med. 2002. 166:641–645.

14. Pastores SM, Papadopoulos E, Voigt L, Halpern NA. Diffuse alveolar hemorrhage after allogeneic hematopoietic stem-cell transplantation: treatment with recombinant factor VIIa. Chest. 2003. 124:2400–2403.

15. Afessa B, Tefferi A, Litzow MR, Peters SG. Outcome of diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med. 2002. 166:1364–1368.

16. Conces DJ Jr. Noninfectious lung disease in immunocompromised patients. J Thorac Imaging. 1999. 14:9–24.

17. Robbins RA, Linder J, Stahl MG, Thompson AB 3rd, Haire W, Kessinger A, Armitage JO, Arneson M, Woods G, Vaughan WP. Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients. Am J Med. 1989. 87:511–518.

18. Kantrow SP, Hackman RC, Boeckh M, Myerson D, Crawford SW. Idiopathic pneumonia syndrome: changing spectrum of lung injury after marrow transplantation. Transplantation. 1997. 63:1079–1086.

19. Clark JG, Hansen JA, Hertz MI, Parkman R, Jensen L, Peavy HH. NHLBI workshop summary. Idiopathic pneumonia syndrome after bone marrow transplantation. Am Rev Respir Dis. 1993. 6:1601–1606.

20. Crawford SW, Hackman RC. Clinical course of idiopathic pneumonia after bone marrow transplantation. Am Rev Respir Dis. 1993. 147:1393–1400.

21. Yamaguchi N, Takatsuka H, Wakae T, Okada M, Fujimori Y, Okamoto T, Kakishita E, Hara H. Idiopathic interstitial pneumonia following stem cell transplantation. Clin Transplant. 2003. 17:338–346.

22. Ho VT, Weller E, Lee SJ, Alyea EP, Antin JH, Soiffer RJ. Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001. 7:223–229.

23. Leung AN, Gosselin MV, Napper CH, Braun SG, Hu WW, Wong RM, Gasman J. Pulmonary infections after bone marrow transplantation: clinical and radiographic findings. Radiology. 1999. 210:699–710.

24. Nichols WG, Gorey L, Gooley T, Davis C, Boeckh M. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis. 2003. 101:407–414.

25. Reed EC, Bowden RA, Dandliker PS, Lilleby KE, Meyers JD. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann Intern Med. 1988. 109:783–788.

26. Emanuel D, Cunningham I, Jule-Elysee K, Brochstein JA, Kernan NA, Laver J, Stover D, White DA, Fels A, Polsky B. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann Intern Med. 1988. 109:777–782.

27. Schmidt GM, Kovacs A, Zaia JA, Horak DA, Blume KG, Nademanee AP, O'Donnell MR, Snyder DS, Forman SJ. Ganciclovir/immunoglobulin combination therapy for the treatment of human cytomegalovirus-associated interstitial pneumonia in bone marrow allograft recipients. Transplantation. 1988. 46:905–907.

28. Snyder CL, Ramsay NK, McGlave PB, Ferrell KL, Leonard AS. Diagnostic open-lung biopsy after bone marrow transplantation. J Pediatr Surg. 1990. 25:871–876.

29. Dunagan DP, Baker AM, Hurd DD, Haponik EF. Bronchoscopic evaluation of pulmonary infiltrates following bone marrow transplantation. Chest. 1997. 111:135–141.

30. Jain P, Sandur S, Meli Y, Arroliga AC, Stoller JK, Mehta AC. Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates. Chest. 2004. 125:712–722.

31. Wong PW, Stefanec T, Brown K, White DA. Role of fine-needle aspirates of focal lung lesions in patients with hematologic malignancies. Chest. 2002. 121:527–532.