Serum amyloid A protein concentration in bone marrow transplantation for /B thalassaemia

Aims: To investigate whether serum amyloid A protein (SAA) and C-reactive protein (CRP) concentrations could be used in the management of fi thalassaemic patients undergoing bone marrow transplantation (BMT). Methods: Serum SAA and CRP concentrations were determined in paired samples from 66 patients with Ii thalassaemia before and after BMT. Serum SAA concentrations were determined by an enzyme linked immunoassay (EIA); serum CRP concentrations were determined by a nephelometric assay. Results: Serum SAA concentrations before transplantation were significantly higher in the group that subsequently rejected the transplant than the group without complications. SAA concentrations increased after BMT in acute graft versus host disease (GvHD) and rejection. No significant increase in SAA or CRP was found in chronic GvHD. Increases in serum in SAA and CRP concentrations were not related to concomitant infection episodes. Conclusions: The different acute phase response in acute GvHD and rejection compared with chronic GvHD suggests that different immunopathogenic mechanisms are responsible. Laboratorio di Immunologia e Genetica, Istituto di Ricerca CodivillaPutti, Bologna M Uguccioni E Lalli A Facchini Patologia Medica I, Universiti di Bologna R Meliconi G Gasbarrini Divisione Ematologica di Muraglia, Centro Trapianto Midollo Osseo, Ospedale di Pesaro, Pesaro S Nesci C Delfini G Lucarelli Istituto di Citomorfologia CNR, Chieti, Italy E Lalli Correspondence to: Dr Riccardo Meliconi, I Patologia Medica, Policlinico S.Orsola, via Massarenti 9, 40138 Bologna, Italy. Accepted for publication 1 October 1991 Acute phase proteins, and in particular, serum amyloid A protein (SAA) and C-reactive protein (CRP), are currently used to monitor infections and inflammatory processes. Increased serum CRP concentrations after bone marrow transplantation (BMT), carried out for haematological disease other than ,B thalassaemia, have been found in patients with bacterial infections or acute graft versus host disease (GvHD) complicated by infections. But conflicting data about serum CRP concentrations have been reported in acute GvHD without infection.'2 In chronic GvHD without infection episodes no increase in serum CRP has been found.' SAA is a high density lipoprotein associated plasma protein that is mainly produced in the liver in response to stress or inflammation. It is regulated by the action of cytokines such as interleukin-I (IL-1), interleukin-6 (IL-6), and tumour necrosis factor (TNF).45 Extrahepatic expression of SAA has been shown in virtually all tissues and particularly in those with a recognisable macrophage population.6 The rise in SAA blood concentrations that occurs during acute events is the most intense and rapid of all the acute phase proteins. Little information about serum SAA concentrations after BMT is available. Some studies have been carried out on serum SAA concentrations during renal and liver transplantations which suggest that SAA may be a marker of rejection.78 In addition to GvHD, graft failure is one of the events that can occur in # thalassaemic transplant recipients. Different factors have been analysed before transplantation to assess their possible influence on outcome. Age, number of transfusions before transplantation, sex of donor/recipient, blood group, removal of spleen, HLA type, and cell dose did not significantly influence the outcome of the transplantation in terms of rejection. In the period immediately after transplantation no precipitating factors for rejection have been identified.9 Methods Among the series of 222 patients reported elsewhere,101' we randomly selected patients, according to the outcome of BMT'0: 17 with acute GvHD; 11 with chronic GvHD; 23 that rejected the transplantation; and 15 disease free survivors. Of these 66 patients, 22 had received less than or up to 100 transfusions and 44 more than 100 transfusions. The spleens of 16 of these patients had been removed before BMT. Liver biopsy had been carried out in 55 as part of liver disease assessment before BMT. The presence of siderosis and fibrosis was evaluated by semiquantitative scoring: absent, mild, moderate and severe; 15 patients presented with chronic active hepatitis and 13 with chronic persistent hepatitis; none had cirrhosis. Serum samples were obtained from all patients (mean 31 (SEM) 6) days before BMT and seven to 380 days after transplantation. In patients with GvHD or graft rejection the sample taken after BMT was obtained at the onset of BMT complications. Blood samples were obtained from each patient between 0700 and 0900 hours and left to clot at room temperature. Serum samples were stored at -70°C until analysis. The BMT preparative regimen has been described previously." EVALUATION AFTER BMT Infection was diagnosed on the basis of clinical evaluation, and blood samples were drawn 348 group.bmj.com on July 8, 2017 Published by http://jcp.bmj.com/ Downloaded from