Chest
Volume 87, Issue 2, February 1985, Pages 237-246
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Pulmonary Complications of Bone Marrow Transplantation

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Bone marrow transplantation (BMT) for hematologic disorders is potentially curative in selected persons. These patients may be immunocompromised for months after engraftment as a consequence of chemotherapy, irradiation, acute and chronic graft-vs-host disease (GVHD), and maturing recipient marrow. Pulmonary complications commonly occur during the early and late periods after BMT and are associated with significant morbidity and mortality. The leading early-onset complication is interstitial pneumonitis, most commonly associated with cytomegalovirus infection but also related to possible toxicities from chemotherapy and irradiation. Major late-onset problems include bacterial sinopulmonary infections and obstructive airway disease thought to be associated with chronic GVHD. The exact mechanisms of lung injury are probably quite complex, and unfortunately, often cause irreversible pulmonary disease, even in the patient who has had successful transplantation. Antimicrobial prophylaxis, modified chemotherapy and irradiation dosages, and antiviral immunization have been shown to reduce the incidence of early-onset pulmonary problems. Early recognition and treatment of late-onset problems will, it is hoped, minimize respiratory limitations.

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MARROW TRANSPLANTATION

Most BMT is done in persons younger than 40 years, preferably younger than 30, because of the greatly increased incidence of complications with age.4 As seen in Table 1, patients with acute leukemia have increased survival if BMT is performed during complete remission. Also, survival is significantly better in patients with aplastic anemia who have received no transfusions than in those who have received multiple blood products. Transplantation in patients with chronic myelogenous leukemia is

INFECTIOUS PNEUMONITIS

Pulmonary infections are the single most common complication seen in BMT, occurring both early and late after engraftment (Tables 3 and 4).16,17 Cytomegalovirus (CMV) is the most frequent and most virulent organism associated with pneumonitis, with up to 90 percent mortality.16 The diagnosis of CMV pneumonitis is made from culture of lung tissue or from histologic identification of characteristic viral inclusions (intranuclear or cytoplasmic) in macrophages or pneumocytes.18 Change in serologic

NONINFECTIOUS PNEUMONITIS

“Idiopathic pneumonitis” and “interstitial pneumonitis” are terms used by many authors if infectious or other specific causes cannot be found to explain diffuse lung disease occurring after BMT.4,9,16,33 Inductive or conditioning chemotherapy, irradiation, leukemic recurrence, and transfusion reactions are each capable of causing diffuse lung injury, although chemotherapy and irradiation are usually implied diagnoses by exclusion rather than proved entities (Tables 3 and 4).

The relationship of

GRAFT-VS-HOST DISEASE

The importance of GVHD to the respiratory system has only recently been appreciated. Its significance is related to the substantial pulmonary dysfunction in patients having successful BMT and remission from hematologic malignancies.28,29,40, 41, 42 The primary abnormality involves symptomatic, and in some cases, progressive airway obstruction, which is manifested by acute bronchitis or bronchospasm (Tables 3 and 4).

Lymphocytic bronchitis was first reported as a possible pulmonary manifestation

PULMONARY VASCULAR ABNORMALITIES

The clinical significance of vascular abnormalities often found at autopsy in the pulmonary tissue after BMT is probably minimal (Table 3).32,43,45 The incidence of documented pulmonary emboli is quite low, and the emboli have been described as calcific marrow fragments without associated parenchymal damage.45 Venous thromboembolism is probably rare, because most BMT autopsy series do not comment on this entity.32,43,45 Pulmonary thrombi, however, are frequent findings in some series, occurring

DIAGNOSTIC CONSIDERATIONS

Transbronchial lung biopsy, open lung biopsy, and bronchoalveolar lavage have been used in BMT patients in the assessment of pulmonary infiltrates in these immunocompromised hosts.46,47 In a recent prospective study, 22 patients about to undergo open lung biopsy had transbronchial lung biopsy of the lung segment immediately before thoracotomy.46 Transbronchial diagnoses were similar to thoracotomy findings in 58 percent (14 of 24); five tissue samples were inadequate, and five diagnoses were

CONCLUSION

Several practical considerations that can be derived from the studies reviewed should be stressed. The BMT involves young patients with potentially curable hematologic disorders. Even with successful engraftment, pulmonary complications are very common. For months (up to one year or more) beyond engraftment, these patients should be considered to be immunocompromised hosts. Pulmonary disease involving the lung parenchyma and airways can occur both early (within weeks) and late (beyond three

REFERENCES (50)

  • J.W. Kugler et al.

    Nosocomial Legionnaires' disease: occurrence in recipients of bone marrow transplants

    Am J Med

    (1983)
  • B. Shank et al.

    Hyperfractionated total body irradiation for bone marrow transplantation: results in seventy leukemia patients with allogeneic transplants

    Int J Radiat Oncol Biol Phys

    (1983)
  • M.J. Krowka et al.

    Azathioprine-associated pulmonary dysfunction

    Chest

    (1983)
  • M.F. Tenholder et al.

    Pulmonary infiltrates in leukemia

    Chest

    (1980)
  • H.M. Shulman et al.

    Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients

    Am J Med

    (1980)
  • D.J. Winston et al.

    Alveolar macrophage dysfunction in human bone marrow transplant recipients

    Am J Med

    (1982)
  • M.H. Depledge et al.

    Lung function after bone marrow grafting

    Int J Radiat Oncol Biol Phys

    (1983)
  • H.C. Hoagland et al.

    Bone marrow transplantation in clinical hematology (editorial)

    Mayo Clin Proc

    (1982)
  • F.E. Zwaan et al.

    Bone marrow transplantation for acute nonlymphoblastic leukaemia: a survey of the European Group for Bone Marrow Transplantation (EGBMT)

    Br J Haematol

    (1984)
  • C.D. Buckner et al.

    Marrow transplantation for acute lymphoblastic leukemia

    Semin Hematol

    (1984)
  • G.W. Santos et al.

    Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide

    N Engl J Med

    (1983)
  • H.G. Prentice

    A review of the current status and techniques of allogeneic bone marrow transplantation for treatment of leukaemia

    J Clin Pathol

    (1983)
  • J.M. Rappeport et al.

    Immature T lymphocytes in the peripheral blood of bone marrow transplant recipients

    Transplantation

    (1983)
  • M.R. Wick et al.

    Immunologic, clinical, and pathologic aspects of human graft-versushost disease

    Mayo Clin Proc

    (1983)
  • A.J. Barrett et al.

    Cyclosporin A as prophylaxis against graft-versus-host disease in 36 patients

    Br Med J

    (1982)
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