How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation

Abstract

Pulmonary complications affect up to 40% of patients with severe neutropenia lasting for more than 10 d. As they are frequently associated with fever and elevation of C-reactive protein or other signs of inflammation, they are mostly handled as pneumonia. However, the differential diagnosis is broad, and a causative microbial agent remains undetected in the majority of cases. Pulmonary side effects from cytotoxic treatment or pulmonary involvement by the underlying malignancy must always be taken into account and may provide grounds for invasive diagnostic procedures in selected patients. Pneumocystis jirovecii (in patients not receiving co-trimoxazole as prophylaxis), multi-resistant gram-negative bacilli, mycobacteria or respiratory viruses may be involved. High-risk patients may be infected by filamentous fungi, such as Aspergillus spp., but these infections are seldom proven when treatment is initiated. Microorganisms isolated from cultures of blood, bronchoalveolar lavage or respiratory secretions need careful interpretation as they may be irrelevant for determining the aetiology of pulmonary infiltrates, particularly when cultures yield coagulase-negative staphylococci, enterococci or Candida species. Non-culture based diagnostics for detecting Aspergillus galactomannan, beta-D-glucan or DNA from blood, bronchoalveolar lavage or tissue samples can facilitate the diagnosis, but must always be interpreted in the context of clinical and imaging findings. Systemic antifungal treatment with mould-active agents, given in combination with broad-spectrum antibiotics, improves clinical outcome when given pre-emptively. Co-trimoxazole remains the first-line treatment for Pneumocystis pneumonia, while cytomegalovirus pneumonia will respond to ganciclovir or foscarnet in most cases. The clinical outcome of acute respiratory failure can also be successful with proper intensive care, when indicated.

A bronchoalveolar lavage‐driven antimicrobial treatment improves survival in hematologic malignancy patients with detected lung infiltrates: A prospective multicenter study of the SEIFEM group

“…This was an observational study, because the final choice of whether to perform bronchoscopy in eligible patients was up to the local physicians. Our data show that LI was detected in about 14% of HM patients admitted to hospital, which agrees with other published data . Out of 177 eligible patients, BAL was feasible in 82% of cases within a median time from LI detection of 4 days.…”

“…Detection of lung infiltrates (LI) is a relevant concern in patients with hematologic malignancy (HM), occurring in about 12%‐15% of severely neutropenic patients and significantly affecting survival . Moreover, infectious, and less frequently non‐infectious LI occur in up to 70% and 25% of patients, respectively, undergoing allogeneic hematopoietic stem cell transplant (alloSCT) and autologous hematopoietic stem cell transplant (ASCT).…”

“…The yield was significantly higher when the BAL was performed early after LI detection (up to 87% of positive results), allowing a change in the on‐going empirical antimicrobial treatment in about 50%‐65% of patients . Nevertheless, several issues are still under debate and investigation, these include: the diagnostic yield of BAL, the gold‐standard used to properly evaluate the positive and negative predictive value of BAL, as well as the impact of using a BAL‐guided antimicrobial strategy on clinical outcome and survival . Based on these considerations, we designed a prospective multicenter study in 18 hematology institutes.…”

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

“…1,98,100,101 Considering this aspect, intravenous Foscarnet might represent a preferable option in patients with severe cytopenia, despite its not optimal safety profile and the limited availability of data about its effectiveness for the treatment of CMV infection in settings other than allo-HSCT. 102 As for prophylaxis strategies, the current guidelines do not recommend a routine…”

Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation

“…The latter indication is common after HCT 35 and in the setting of neutropenia, where 15% of patients with FN present with lung infiltrates. 36 The distribution and morphology of infiltrates can help to refine the PC differential diagnosis, although a diminished inflammatory response may alter or delay the appearance of typical findings. There are significant limitations to the sensitivity of chest radiographs for diagnosing PCs in HM and HCT patients, even when combined with clinical data.…”