Pulmonary Complications of Hematological Disorders

Patients with hematological malignancies who are treated with chemotherapeutic drugs or radiation or are recipients of bone marrow or stem cell transplant may develop a wide variety of potentially fatal infectious and noninfectious pulmonary complications. Given that diagnosis is complex and there is little time for diagnosis and treatment, these complications present a real challenge to the pulmonary and critical care practitioner. Hematological disorders may also, directly or indirectly, contribute to the appearance of lung injury in this specific clinical context.

The pathobiological bases that may explain why the lung is a “target organ” in subjects with hematological disorders are detailed in the first article by Venerino Poletti, Ulrich Costabel and Gianpietro Semenzato. They discuss the role of innate and acquired immunity, the part played by the constitutive parenchymal cells in the lung, and the potential injury due to infectious agents, drugs, and radiation.

Pulmonary infections are an important cause of morbidity and mortality in this subgroup of immunocompromised hosts. Corrado Girmenia and Pietro Martino present the clinical spectrum by which these infections may appear. They underline also that the use of chemoprophylactic therapies is at the basis of increased incidence of dimorphic fungal infections and of noncytomegalovirus viral infections.

Drug- and radiation-related lung injury is an increasing challenge for clinicians dealing with these patients and it is the cause of morbidity and mortality in patients with hematological neoplasms that are potentially curable. Philippe Camus and Ulrich Costabel review the clinical, pathological, radiographic, and physiological features of these complications. Diagnosis requires an integrated approach with data obtained by high resolution computed tomographic scan analysis, bronchoalveolar lavage, and, only rarely, biopsy. The therapeutic approaches are also presented in detail.

Graft versus host (GVH)-associated pulmonary disease and other idiopathic pulmonary complications appearing after hematopoietic stem cell transplant are among the main pulmonary causes of delayed morbidity and mortality yet are still unfamiliar to the majority of pulmonologists. Timothy R. Watkins, Jason W. Chien, and Stephen W. Crawford present the clinical profile of obliterative bronchiolitis, bronchiolitis obliterans organizing pneumonia (BOOP), engraftment syndrome, diffuse alveolar hemorrhage, and pulmonary veno-occlusive disease. They underline that these complications must now be included in the practice of pulmonary medicine rather than remaining isolated to transplant pulmonology.

Although the lung is frequently involved by disseminated lymphoma, isolated pulmonary lymphoma is rare, accounting for less than 1% of all extranodal localized disease. Three broad categories of lymphoma of the lung require recognition: large B cell type lymphoma usually associated with Epstein-Barr virus infection, also known as T cell rich B cell lymphoma and previously included under the category of the so-called lymphomatoid granulomatosis; T cell lymphoma presenting as an angiocentric process; and, finally, the most common histologic subtype, low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. Marco Chilosi, Pier Luigi Zinzani, and Venerino Poletti detail the histology, the molecular biology characteristics, and the clinicoradiological features of these entities and discuss briefly the rarer lymphoproliferative lesions presenting primarily in the lung.

Pulmonary amyloidosis may be either part of systemic amyloidosis (primary amyloidosis or associated with myeloma) or organ limited. Jean-François Cordier describes the general characteristics of amyloidosis and the pathogenetic events associated with its formation, as well as interstitial lung amyloidosis, localized pulmonary amyloidosis, and tracheobronchial amyoloidosis.

Pulmonary involvement by myeloid leukemia is relatively uncommon and seen mainly in patients with severe disease. The most common form of pulmonary involvement consists of leukemic infiltration along the lymphatics in the peribronchovascular, septal, and pleural interstitial tissue. Less common manifestations include myeloid sarcoma, leukostasis, leukemic cell lysis pneumopathy, and hyperleukocytic reaction. Tat Tee Koh, Thomas V. Colby, and Nestor L. Müller present the radiological manifestations, the histopathologic background, and the clinical significance of these forms.

Advances made in the field of chemotherapy and radiotherapy have considerably increased the survival of patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). Unfortunately, these antiblastic therapies have also increased the risk of late complications such as second tumors, especially second lung cancers. Dino Amadori and Sonia Ronconi discuss the known and hypothetical carcinogenetic events leading to an increased incidence of secondary lung carcinomas in these patients and present the relative risks associated with radiation, drugs, or hematological neoplasms per se.

Finally, Udaya B.S. Prakash addresses the pulmonary modifications and disorders associated with hemoglobinopathies, erythrocyte disorders, and hemorrhagic diatheses. In this article, the clinical spectrum of lung injury varying from mild illness to life-threatening emergencies due to sickle cell anemia and other hemoglobinopathies, acquired methemoglobinemia, erythrocyte neoplasms, coagulation defects, and platelet disorders are discussed; pathophyisiological events and therapeutical approaches are also presented in detail

In this issue of Seminars in Respiratory and Critical Care Medicine the fruits resulting from the meeting of two “noble shells (pulmonology and hematology) containing intriguing and sophisticated pearls” are presented. We hope that readers will find this review helpful in their daily practice and useful to increase their knowledge.