1 research outputs found
The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT)
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