Abstract
We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3′-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery.
Highlights
Hematological cancers derive from various cells of the immune system
The aim of our investigation was to estimate possible association of complement-activating collectins (MBL, CL-LK) and associated serine proteases with cancer (MM, LYMPH) itself and with hospital infections after chemotherapy followed by auto-hematopoietic stem cell transplantation (HSCT)
In addition to mannose-binding lectin (MBL), we have extended our investigations to include CL-LK and MASP-2 since those factors are relevant to collectin-mediated complement activation
Summary
Multiple myeloma (MM), a plasma cell malignancy, is relatively common It more often affects males than females and is usually diagnosed at age >55 years. Complement is a complex system of numerous components that constitutes a crucial branch of the immune response It protects from a variety of infections and takes part in clearance of host cells undergoing apoptosis, necrosis or neoplastic transformation. The aim of our investigation was to estimate possible association of complement-activating collectins (MBL, CL-LK) and associated serine proteases with cancer (MM, LYMPH) itself and with hospital infections after chemotherapy followed by auto-HSCT. Peterslund et al [34] found a strong relationship between MBL deficiency and serious infections in a relatively small group of patients suffering from hematological malignancies (n = 54, including 18 with MM and 13 with NHL). In addition to MBL, we have extended our investigations to include CL-LK and MASP-2 since those factors are relevant to collectin-mediated complement activation
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