Dexamethasone in patients with acute lung injury from acute monocytic leukaemia

Abstract

The use of steroids is not required in myeloid malignancies and remains controversial in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We sought to evaluate dexamethasone in patients with ALI/ARDS caused by acute monocytic leukaemia (AML FAB-M5) via either leukostasis or leukaemic infiltration.Dexamethasone (10 mg every 6 h until neutropenia) was added to chemotherapy and intensive care unit (ICU) management in 20 consecutive patients between 2005 and 2008, whose data were compared with those from 20 historical controls (1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002). ICU mortality was the primary criterion. We also compared respiratory deterioration rates, need for ventilation and nosocomial infections.17 (85%) patients had hyperleukocytosis, 19 (95%) had leukaemic masses, and all 20 had severe pancytopenia. All patients presented with respiratory symptoms and pulmonary infiltrates prior to AML FAB-M5 diagnosis. Compared with historical controls, dexamethasone-treated patients had a significantly lower ICU mortality rate (20% versus 50%; p50.04) and a trend for less respiratory deterioration (50% versus 80%; p50.07). There were no significant increases in the rates of infections with dexamethasone.In conclusion, in patients with ALI/ARDS related to AML FAB-M5, adding dexamethasone to conventional chemotherapy seemed effective and safe. These results warrant a controlled trial of dexamethasone versus placebo in AML FAB-M5 patients with noninfectious pulmonary infiltrates.

Impact of Corticosteroids on Mortality in Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis

“…On the other hand, Azoulay's study suggested that corticosteroid treatment is favorable for patients with ARDS arising from leukemic pulmonary involvement as this treatment prevents the development of lysis pneumopathy. Patients with leukemic pulmonary involvement often satisfy the AECC criteria for ARDS, although the pathophysiology is different from that of diffuse alveolar damage (19). Further research is needed to determine pathophysiology-or trigger event-specific treatment strategies.…”

“…Corticosteroids have been by far the most widely used medications for ARDS since Ashbaugh reported the first cases of this clinical entity (2)(3)(4)(5). Nonetheless, the impact of corticosteroids on the mortality of ARDS remains controversial following the publication of numerous trials and observational studies (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Meta-analyses of these studies have indicated that the use of corticosteroids has only a marginal impact in reducing mortality in ARDS cases (20)(21)(22)(23)(24)(25)(26)(27)(28), although it is clear that corticosteroids improve gas exchange, decrease the duration of mechanical ventilation and decrease the length of stay in the intensive care unit (23,25,26).…”

Commentary

“…In patients with AML and pulmonary infiltrates, infection must be suspected and treated empirically, because ARF, the leading reason for intensive care unit admission, still carries a 50% overall mortality rate despite improvements in supportive therapy. However, clinically defined respiratory events may be directly due to the leukemia-related involvement consist of leukostasis, leukemic infiltrates and lysis pneumopathy [5]. In addition to rapid cytoreduction by hydration and chemotherapy, anti-inflammatory therapy appears to be effective in improving outcomes in these patients.…”

“…Bugdaci et al reported two cases of AML M5 and M4/5 with pulmonary leukemic infiltration at initial presentation of disease. Azoulay et al showed that adding dexamethasone (10 mg every 6 hours, until leukopenia occurred) to the chemotherapy regimen in AML M5 with acute respiratory failure from leukemiarelated pulmonary involvement significantly diminished mortality [5].…”

“…In contrast to acute lymphoblastic leukemia, AML cells have usually been resistant to these agents [8]. Nevertheless, steroid therapy has been used in AML with pulmonary disease of infectious or noninfectious origin, to prevent acute respiratory distress syndrome through various mechanism, including decrease cytokine and oxidant release, blast adhesion to endothelial cells and blast degeneration within the interstitium [5].…”