Mild to fatal course of pandemic influenza H1N1 in children with acute leukaemia

Abstract

We have read with interest the recent paper regarding the course of pandemic 2009 H1N1 infection in children with acute lymphoblastic leukaemia (ALL) (Launes et al (2010). Viral infections may have diverse haematological consequences, in addition to their variable courses in different haematological disorders, especially in patients with haematological malignancies. In our experience of the haematological consequences of pandemic influenza H1N1 virus (Unal et al, in press), we evaluated the haematological effects of this infection among 31 patients aged 2–17 years, of which seven had a diagnosis of acute leukaemia at presentation of the infection. Of these patients, four had a diagnosis of ALL and were under maintenance chemotherapy, one was a Bloom syndrome patient who had recently developed acute myeloid leukaemia (AML), another patient had Down syndrome and was recently diagnosed with AML and one patient had AML and had finished chemotherapy 3 months earlier. The patients were confirmed to have pandemic influenza H1N1 infection by two-step polymerase chain reaction from nasopharyngeal specimens obtained through nasopharyngeal aspirates. Of the seven patients with acute leukaemia, five (71%) had leukopenia, six (86%) had neutropenia and four (57%) had thrombocytopenia at the presentatation of influenza. Two of these seven patients (one ALL, one AML) developed pneumonia and recovered without ventilatory support. All of the patients received oseltamivir for 5 d, two had already been initially treated in local hospitals prior to admission. Patients with pneumonia also received antibiotics concomitantly. None of the patients deceased in the study group, which indicated a benign course of pandemic 2009 H1N1 infection in newly diagnosed and under maintenace therapy patients with ALL and AML, paralleling the results of Launes et al (2010). However, we subsequently experienced two fatal cases of pandemic 2009 H1N1 infection in our centre. One of these patients was a 5-year-old boy with newly relapsed ALL who developed pneumonia and required ventilatory support related to acute respiratory distress syndrome. The other, a 5-year-old male patient receiving maintenance treatment for ALL, developed haemophagocytic lymphohistiocytosis (HLH) during a severe course of pandemic 2009 H1N1 infection. He developed multi-organ failure, including respiratory and renal insufficiency and was put on ventilatory support, in addition to antibacterial and oseltamivir treatments. The patient’s clinical condition worsened and the HLH-2004 protocol (Henter et al, 2007) was initiated, however, this treatment also did not aid a recovery. Both of these patients were febrile with severe neutropenia and thrombocytopenia at admission for H1N1 infection. In our series of nine patients with acute leukaemia who had H1N1 infection, two had a fatal course. Pandemic 2009 H1N1 virus may have more suppressive impact on the marrow of these patients relative to the status of the affected haematological progenitors. Haemophagocytosis should be considered in the course of these patients. Our experiences indicate that the clinical course of H1N1 infection may vary from mild to severe, including HLH and fatalites at the severe end of the spectrum. The variable clinical courses may be related to additional host factors including the status of the underlying disorder and other immunological factors.