Infectious complications in patients with acute promyelocytic leukaemia treated with the AIDA regimen

Abstract

Infections represent a frequent complication of chemotherapy used for acute myeloid leukaemia (AML) and are associated with important toxicity frequently leading to treatment discontinuation. Acute promyelocytic leukaemia (APL) is a unique AML subset requiring tailored therapy including all-trans retinoic acid and anthracycline-based chemotherapy. We analysed in this study the incidence and type of infections complicating the clinical course of 89 consecutive APL patients receiving the AIDA protocol at a single institution. A total of 179 febrile episodes were registered during induction and consolidation, 52% of which were of unknown origin. Infections were clinically and microbiologically documented in 10.6 and 37.4% of cases, respectively. Coagulase-negative staphylococci represented the major cause of septicaemia (28%) and were more frequently isolated during induction, whereas viridans group streptococci, the second pathogen most frequently isolated from blood (27%), represented the principal pathogen detected during consolidation and were significantly associated with mucositis. Gram-negative bacteria accounted for 33.3% of all blood isolates. Fungal infections were only occasionally observed. Bloodstream infections in APL patients were compared with those documented in 271 consecutive patients affected by other subtypes of AML. The incidence of total septicaemia episodes, of staphylococcal bacteraemias and of fungaemias was significantly higher in patients with other AMLs. Empirical antibiotic therapy with ceftriaxone plus amikacin was effective in 73% of APL cases, most of the remaining cases being successfully managed by the addition of teicoplanin. One single death apparently related to infectious complication was recorded. Overall, infections led to antileukaemic treatment withdrawal in six patients, five of whom currently remain in haematologic remission for 13-106 months. These results indicate that a particular pattern of infections is observed in APL patients receiving ATRA plus anthracyclinebased chemotherapy and that these appear to be effectively counteracted by standard management. Leukemia (2003) 17, 925-930.

Concentração de cálcio no dialisato e hipercalcemia na DRC

“…21 The ATRA dose prescribed for the patient is unusually indicated for those with APL. [9][10][11]13 However, the patient's symptoms together with the negative culture tests in the urine and the hemoglobinuria caused the suspicion of ATRA syndrome. ATRA was immediately suspended and replaced by corticosteroid therapy.…”

“…12 Therefore, patients with APL on ATRA therapy may need antifungal therapy. [13][14][15] Since its discovery, in 1955, amphotericin B (AB) 16,17 remains as the antimicrobial of choice for this practice, as well as for the treatment of confirmed systemic fungal infections. 16,18 However, AB is associated with chronic and acute adverse effects, especially nephrotoxicity, which may cause renal damage and electrolytic disorder (hypokalemia and hypomagnesemia).…”

Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso

“…12 Assim, pacientes com LPA em tratamento com ATRA podem necessitar de terapia antifúngica. [13][14][15] A anfotericina B (AB), desde sua descoberta em 1955, 16,17 permanece o antimicrobiano de escolha para essa prática assim como para o tratamento de infecções fúngicas sistêmicas confirmadas. 16,18 Todavia, a AB está associada com efeitos adversos crônicos e agudos, especialmente a nefrotoxicidade que pode refletir em dano renal e distúrbio eletrolítico (hipocalemia e hipomagnesemia).…”

Risk of invasive fungal infection in patients affected by acute promyelocytic leukaemia. A report by the SEIFEM‐D registry

“…Few IFIs in APL have been reported in clinical trials (de la Serna et al, 2008;Iland et al, 2012), and only four cases (4Á5%) of non-fatal IFI were reported (one pulmonary mycetoma, two hepatosplenic candidiasis and one candidaemia) in a series of 89 APL patients treated with the AIDA protocol (ATRA + idarubicin) (Girmenia et al, 2003), while in a paediatric series of 33 APL, only two patients (6Á1%) experienced fungal infection (Cellot et al, 2013).…”

“…Patients with acute promyelocytic leukaemia (APL) are usually considered at lower risk for developing an infectious complication (Girmenia et al, 2003), principally because current treatments are mainly based on the induction of myeloid differentiation rather than the highly myeloablative properties of standard chemotherapy used in patients with acute myeloid leukaemia (AML). This prospective study, conducted in 33 locations throughout Italy, evaluated the incidence of invasive fungal infection (IFI) and the clinical characteristics in patients with APL compared to patients affected by other AML subtypes treated with intensive chemotherapy.…”