No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections

Abstract

SUMMARYChemotherapy causes neutropenia and an increased susceptibility to infection. Recent reports indicate that mannan-binding lectin (MBL) insufficiency is associated with an increased duration of febrile neutropenia and incidence of serious infections following chemotherapy for haematological malignancies. We aimed to confirm or refute this finding and to extend the investigation to the plasma ficolins, P35 (Lficolin) and the Hakata antigen (H-ficolin). MBL, L-ficolin and H-ficolin were measured in 128 patients with haematological malignancies treated by chemotherapy alone or combined with bone marrow transplantation. Protein concentrations were related to clinical data retrieved from medical records. MBL concentrations were elevated compared with healthy controls in patients who received chemotherapy, while L-ficolin concentrations were decreased and H-ficolin levels were unchanged. There was no correlation between MBL, L-ficolin or H-ficolin concentration and febrile neutropenia expressed as the proportion of neutropenic periods in which patients experienced fever, and there was no relation between abnormally low (deficiency) levels of MBL, L-ficolin or H-ficolin and febrile neutropenia so expressed. Patients with MBL £ 0·1 m g/ml had significantly more major infections than no infections within the follow-up period ( P < 0·05), but overall most patients had signs or symptoms of minor infections irrespective of MBL concentration. Neither L-ficolin nor H-ficolin deficiencies were associated with infections individually, in combination or in combination with MBL deficiency. MBL, L-ficolin and H-ficolin, independently or in combination, did not have a major influence on susceptibility to infection in these patients rendered neutropenic by chemotherapy. These results cast doubt on the potential value of MBL replacement therapy in this clinical context.

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

“…The condition with more reduced dose of chemotherapy, conventional-dose chemotherapy without stem cell support, has been demonstrated to be at an increased risk of infection or prolonged fever in several reports, 13,14 but not by others. 17,27 Considering the strong association of MBL polymorphism and major bacterial infection in our patients, it is suggested that the protective role of MBL for infection might be more pronounced in the patients receiving HDT than those with conventional chemotherapy. However, it should be taken into consideration that the controversy about the relationship of MBL deficiency and infection after chemotherapy might be caused, at least in part, by the difference in the patients' profiles, such as underlying diseases, age, ethnicity, and other unknown genetic factors, between these several studies including ours.…”

“…11,12 An association of MBL deficiency and infection is also reported in patients treated with conventional chemotherapy 13,14 or high-dose myeloablative chemotherapy followed by allogeneic stem cell transplantation, 15 which is not confirmed by others. 16,17 In the present study, we report an increased risk of major bacterial infection in patients carrying the MBL polymorphism when treated with high-dose chemotherapy (HDT) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). In addition, the allele frequencies of the MBL polymorphism in a total of 2623 healthy individuals were determined in seven different areas in Japan, which is, to our knowledge, the largest scale of study for MBL polymorphism in a single ethnic group.…”

Successful haemopoietic stem cell transplantation does not correct mannan-binding lectin deficiency

“…9 From the small subset (21/128) of those patients who were treated with allogeneic haemopoietic stem cell transplantation, six had MBL concentrations p100 ng/ml around the time of neutropenia. One of the patients had since died and another died while ethical permission was being requested to approach the donors.…”

“…9 From that previous study, six patients with barely detectable serum MBL who received an allogeneic stem cell transplant were identified. Therefore, by taking blood samples from the donors, it would be possible to establish if any of them had MBL concentrations significantly higher than the corresponding patients and, if so, by taking a further blood sample from the patients (recipients), it should be possible to establish if any patient seroconverted to a higher MBL concentration as a result of the transplant.…”

Mannose-binding lectin levels and infections in children after allogeneic hematopoietic SCT

“…[4][5][6][7][8] However, these observations are not consistent in all studied cohorts. [9][10][11] Few studies have included hematopoietic SCT (HSCT) recipients 7,8,10 or have focused on children. 4,6,9 MBL deficiency can be corrected by liver transplantation, whereas MBL deficiency can be induced by transplantation of MBL-sufficient recipients with an MBL-deficient donor liver.…”