Low circulating mannan-binding lectin levels correlate with increased frequency and severity of febrile episodes in myeloma patients who undergo ASCT and do not receive antibiotic prophylaxis

Abstract

Patients with multiple myeloma (MM) who undergo autologous stem cell transplantation (ASCT) are susceptible to severe infections. Low levels of circulating mannan-binding lectin (MBL) are associated with increased risk of infection. In this prospective study, we evaluated 100 patients who underwent ASCT regarding the effect of MBL on the incidence and severity of febrile episodes. Seventeen patients had MBL levels <500 ng/mL (11 received antibiotic prophylaxis and 6 did not). Although there was no statistical difference regarding the development of febrile episodes between patients with low and normal MBL, among 17 patients with low MBL levels, six out of eleven patients who received antibiotic prophylaxis developed a febrile episode compared with six out of six patients who did not receive antibiotic prophylaxis and developed a febrile episode. Patients with low MBL levels who responded less frequently to first line antibiotic therapy required more frequent administration of a second more advanced line of antibiotics, independently of receiving or not prophylaxis, and required prolonged hospitalization. In the univariate analysis low MBL associated with shorter OS. Our results suggest that patient with low MBL levels should receive antibiotic prophylaxis to reduce the number of febrile episodes and raise the issue of MBL replacement for these patients.

Low pre-transplant levels of mannose-binding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation

“…However, the procedure of HSCT is totally similar to the performed in a Hematology Service at present and to our knowledge, there are no extensive studies in the last years regarding the role of MBL in Allo-HSCT; in addition, our study has an important value because of a prospective cohort that included patients with myeloablative and non-myeloablative conditioning (the majority of studies on MBL and polymorphisms in patients with Allo-HSCT studied only those patients with myeloablative conditioning), this allows us to study a more heterogeneous population that is closer to the reality of the patients admitted to the Hematology Service. On the other hand, previous retrospective published studies on the role of innate immunity to infection or mortality in HSCT patients included old cohorts [14, 23], when probably viral and aspergillus prophylaxis were different to ours, with similar findings.…”

“…However, these observations were not consistent in all study cohorts [11–13]. In autologous HSCT [14–17] showed conflicting results regarding the influence of MBL2 genotype and functional MBL deficiency on infection risk. In myeloablative, total body irradiation (TBI) -conditioned transplantation-, MBL2 variants have been associated with an increased risk of infection [18].…”

“…Nonetheless, other studies involving Allo-HSCT showed contradictory results regarding the influence of MBL2 polymorphisms and MBL deficiency on infection risk [18–25]. In addition, it is difficult to compare these different studies, because of some studies focused on MBL levels while others determined MBL2 genotype, and even more because of different MBL cut-off levels and different MBL2 genotype or haplotype combinations that are considered deficient [14–25]. Furthermore, over the years, research on MBL in Allo-HSCT has addressed the question of whether or not MBL is associated with their prognosis without reaching clear conclusions [13].…”

Components of the Lectin Pathway of Complement in Haematologic Malignancies

“…Molle et al [ 108 , 109 ] found that MBL protects MM patients treated with melphalan and autologous haematopoietic stem cells transplantation (auto-HSCT) from severe infections, accompanied by septicaemia. Eleutherakis-Papaiakovou et al [ 110 ] supported that conclusion to some extent, by showing the (relatively slight) association of low (<0.5 µg/mL) MBL, with an enhanced incidence of febrile episodes in a similar group of patients. Earlier, Kilpatrick et al [ 111 ] noted more severe infections in patients with haematological malignancies when MBL serum concentration did not exceed 0.1 µg/mL.…”