Pulmonary Complications of Marrow Transplantation

M arrow transplantation, once undertaken only after failure of all other forms of therapy, is currently an accepted approach to treatment of malignant diseases such as acute and chronic leukemias, lymphomas and selected solid tumors, as well as nonmalignant conditions, such as aplastic anemia, thalassemia and immunodeficiency syndromes.’ The success of marrow transplantation is, in part, limited by complications of the cyto-reductive conditioning regimens, the immunologic sequelae of engraftment of allogeneic lymphoid cells, and infections during immunosuppression.t3 Frequently, these complications are manifested by pulmonary involvement. As transplant units are developed at centers throughout the world, increasing numbers of physicians are involved in the care of these patients and inevitably confront difficult decisions in the diagnostic approach to pulmonary complications in marrow recipients. Experience with acute pulmonary complications in a wide spectrum of immunocompromised patients has resulted in diagnostic principles that can clearly be applied in the setting of marrow transplantation.4’5 However, there are special considerations in marrow recipients which distinguish these patients from other immunocompromised hosts and help focus attention on the most likely diagnoses in individual patients. The purpose of this commentary is to discuss these considerations in developing a differential diagnosis and diagnostic approach to acute lung diseases in marrow recipients. First, while the spectrum of acute pulmonary complications following marrow transplantation is not unique, the relative frequency of specific lung diseases in marrow transplant recipients differs from that encountered in other immunocompromised . ,0 Cytomegalovirus (CMV) pneumonia and idiopathic pneumonia account for the vast majority of diffuse nonbacterial pneumonias in marrow recipients. The prominence of serious viral infections may be in part due to the essentially total ablation of virus-specific immunity by the intense pre-transplant conditioning. Although Pneumocystis carinii pneumonia is a major concern in other immunocompromised patients, especially those with the acquired immune deficiency syndrome (AIDS), the prophylactic administration of trimethoprim-sulfamethoxazole prior to marrow transplant and following engraftment has virtually eliminated the disease in marrow recipients.6 These antibiotics may also have reduced the incidence of Gram-negative and pneumococcal pneumonia. Similarly, the prompt use of broad spectrum antibiotics in febrile patients during the period of neutropenia has greatly reduced the incidence of bacterial pneumonia. Bronchopneumonia is found in less than 2 percent of open lung biopsies at the Fred Hutchinson Cancer Research Center7 Secondly, some commonly encountered extrapulmonary post-transplant complications are associated with characteristic pulmonary disorders that can be presumptively diagnosed and treated. For example, aspiration is a frequent cause of basilar infiltrates in the setting of severe oral mucositis and narcotic analgesia following marrow transplantation. Similarly, pleural effusion is frequently associated with hepatic venoocclusive disease. In such instances, invasive diagnostic procedures to search for other causes may not be indicated. Finally, major pulmonary complications associated with marrow transplantation occur in relatively welldefined time periods after the onset of profound immunosuppression associated with the conditioning regimen.6’8 For example, pulmonary edema (both cardiogenic and non-cardiogenic) is frequently encountered in the first few weeks after marrow transplantation. CMV is uncommon during this interval, but it is the main cause of pneumonia in the subsequent weeks. The risk fur specific infections can be further related to a sequence of post-transplant events including neutropenia, marrow engraftment, posttransplantation immunosuppression therapy and graftversus-host disease.6 These considerations are often helpful in arriving at a difl rential diagnosis and in planning diagnostic strategy. In deciding upon a diagnostic approach, it is also important to distinguish between focal and diffuse lung involvement. Regardless of the interval since transplantation, focal lung infiltrates have a higher likelihood of yielding a specific (usually infectious) diagnosis than do diffuse infiltrates and usually warrant empiric antibiotic therapy or a definitive diagnostic procedure. When bacterial bronchopneumonia is not a major clinical consideration, we advocate prompt pursuit of a definitive diagnosis. We have successfully used percutaneous fine needle aspiration to recover Aspergillus in six of eight patients with fucal lung infection. Several factors may have attributed to this success rate without complications. All of the patients had peripheral lesions and platelet counts above 30,000/cu mm. They were not in respiratory distress and were able to cooperate with the procedure, and the aspiration was carried out by an experienced radiologist using fluoroscopic guidance. Open lung