Severe noninfectious acute lung injury in early phase of bone marrow transplantation


Sir: Bone marrow transplant recipients have a poor prognosis in intensive care units (ICUs), particularly in the early phase of transplantation. Several multifactorial etiologies may be responsible for respiratory failure, such as cardiogenic edema, infectious pneumonia, drug-related toxicity, alveolar hemorrhage, hematological malignancies, which may cause a relapse. The prognosis of this failure seems to be aggravated by the use of mechanical ventilation. Apart from the fact that these immunocompromised patients must have early intensive monitoring, perhaps with noninvasive ventilation, such as continuous positive airway pressure, the search for the cause of acute lung injury may be realized. Most respiratory failures occurring in the early phase of bone marrow transplantation are febrile. The first potentially treatable etiology is an infectious pneumonia. For this, the most efficient management is bronchoalveolar lavage (BAL) with viral, fungal, histological, and bacteriological examinations and quantitative cultures. Even if the discovery of the microorganism responsible for pneumonia seems to be less frequent in this group of patients and does not necessarily change the prognosis in the ICU, this search is in practice indispensable because of the possible institution of specific, appropriate treatment. In a lot of cases of marrow transplant recipients with febrile noncardiogenic respiratory failure, all microorganism typing is in vain. So the therapeutic dilemma is great, particularly when acute graft versus host disease (GVHD) or venoocclusive disease (VOD) is also suspected. Generally, most of these patients rapidly develop multiple organ failure syndrome. We reported our three-year experience of the clinical course of 24 allogeneic marrow transplant recipients (age 34 ± 8 years, Simplified Acute Physiology Score II 50 ± 10, leukocyte count 270 ± 240 g/l) who were admitted to the ICU with noncardiogenic febrile respiratory failure and no documentation of infection. The delay between ICU admission and engraftment was 11 ± 3 days, and at ICU admission, the arterial oxygen tension/fractional inspired oxygen ratio was 163 ± 57 and the lung injury score was 2.1 ± 0.56. All patients had a temporary weight gain, and pulmonary features were accompanied by confusion and liver and renal dysfunction in, respectively, 75, 96, and 71% of the patients. No patients developed septic shock. Four patients had cutaneous biopsy-proven diagnoses of GVHD and 2 patients had liver biopsy-proven diagnoses of VOD. GVHD and VOD were suspected in, respectively, 4 and 5 patients. In trying to determine the etiology of the pulmonary problems, there was no contribution from direct examination and culture of BAL fluid, which was performed in all patients. Mechanical ventilation was required in the 24 marrow transplant recipients. Eight patients with GVHD received intravenous corticosteroids (methylprednisolone 1±2 mg/kg per day in 6 patients and 5 and 7 mg/kg per day in 2 patients). Despite the negative microbial culture, all patients received empirical antibiotic therapy (betalactams, glycopeptide, amphotericin B). Altogether, 22/24 patients died of multiple organ failure. The two patients who survived had received high doses of glucocorticoids. In our experience, this group of marrow transplant recipients rapidly develop multiple organ failure after initial noncardiogenic acute lung injury. All of them had fever with no isolated microorganism. These multiple organ injuries have been linked to a generalized capillary leak syndrome [1]. Some authors have suggested that this endothelial damage was related to GVHD and other authors have shown that these complications were preceded by a release of tumor necrosis factor alpha and interleukin-2 [2, 3]. This phenomenon, which generally occurs in the engraftment period, must be related to circulating leukocytes [4]. In our study, high doses of methylprednisolone seemed to be efficacious in a small number of patients. Because of the possible proinflammatory pathogenesis of the capillary leak syndrome, anti-inflammatory treatment seems to be indicated in this type of complication of bone marrow engraftment [5]. It is true that we have no specific treatment of failures in the early phase of bone marrow transplantation. Despite the possible risk of corticoid therapy in the ICU, it may be necessary to try to stop unavoidable multiple organ dysfunction after initial respiratory failure in some marrow transplant recipients. Ongoing studies should clarify the role of mediators released by donor leukocyte cells in early noninfectious severe complications of allogeneic marrow transplantation.

DOI: 10.1007/s001340050610

Cite this paper

@article{Gruson1998SevereNA, title={Severe noninfectious acute lung injury in early phase of bone marrow transplantation}, author={Didier Gruson and Gilles Hilbert and Fr{\'e}d{\'e}ric Vargas and J. M. Boiron and Aranud Pigneux and Jossy Reiffers and Georges Gbikpi-Benissan and Jean Pierre Cardinaud}, journal={Intensive Care Medicine}, year={1998}, volume={24}, pages={536-536} }