A mucosa oral e glandulas salivares acessorias na doença do enxerto contra o hospedeiro cronica pos transplante de medula ossea : estudo prospectivo dos primeiros 63 transplantes de medula ossea : analise comparativa com parametros clinicos e biopsia de pele Hemocentro/Unicamp

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

Chronic graft-vs-host disease (cGVHD) is an important cause of morbity and mortality after allogeneic bone marrow transplants. Lesions ofthe oral mucosa and salivary glands are common features of cGVHD, manifesting as xerostomia, lichenoid lesions or even severe mucositis. The biopsy of specimens of the oral mucosa, collected on day +100, is commonly used as a screening test for the diagnosis af cGVHD. The aim of our study was to evaluate the screening test for diagnosis of cGVHD on day +100 post BMT, the predictive factors of diagnosis for cGVHD, the incidence of skin and oral cGVHD manifestation and the use of findings of the histologycal specimens as a predictor of shorter survival in patients with cGVHD. Data were initially analyzed from 45 patients who had received unrnodified allogeneic marrow grafts in the Bone Marrow Transplantation Hospital Service / Hematology and Hemotherapy Center of the State University ofCampinas, UNICAMP, between September 1993 to May 1995 and who had survived for over 100 days. Ofthese 45 patients, 32 received grafts collected byaspiration (bone marrow - BM) and 13 peripheric bone progenitors cells (pBPC), from HLA-identical siblings. Biopsies of the skin and labial mucosa, including representative samples of minor salivary gland (MSG), were collected on day +100. A second biopsy was performed at a later time in 25 patients (BM=16, PBPC=9) who had developed or sustained signs or symptoms suggestive of cGVHD. All specimens were analised by 2 examiners (MEPC and MLC) separately for later comparison. Hom pathological staging score was used for the histological classification of the oral and salivary gland findings. Univariate and multivariate Cox proportional hazard regression models, and the Kaplan-Meir method were used to determine the overall survival. Sixty-three allogeneic BMT wesre performe~ between September 1993 and May 1995 in the Bone Marrow Service of the Hemocentro / Unicamp. Forty-five patients suvived for over 100 days and the histological findings were analised. Df these patients, 32 received bone marrow transplantation (BMT) and 13 received peripheral bane progenitor cells (PBPC). Nineteen patients were women and 26 men and the median age was 36 years (4 - 57 years old). The histological findings, obtained at the +100 day did not show any predictive value for cGVHD diagnosis. PBPC (p=0,023) transplant, acute GVHD,.sphO,0016) and female donors (p=0,031) were predictive factors for cGVHD on the 100 day post BMT. The PBPC (p=O,Ol7) transplant, acute GVHD (p=O,0016) and the leveI of cysclosporin (p=0,0031) were predictive factors for a worst prognostic of overall survival. The second time biopsies were performed from 104 to 304 days after BMT (median 195 days). Eighteen patients showed extensive cGVHD, 4 localized cGVHD and 3 no formof cGVHD. Eleven patients died after the second biopsy, 7 due to cGVHD, 3 due to leukemia relapse and one due to no transplant reason. The skin histological fmdings did not show any prognostic value. The results of histologicaloral mucosa and minor salivary gland fmdings showed statistical importance. We stratified patients into three groups of scale cGVHD severity, using the HORN pathological staging score (1, 11 and III-IV). For oral mucosa, the statistical value was p=0,02 for and the minor salivary gland it was p=0,009. Despite the small number of patients, our results suggest that severe histologic lesions in MSG specimens obtained beyond day +100 correlate with higher mortality in patients suffering from cGVHD. There is a greater frequency of lymphocyte infiltration in minor salivary gland than in the oral mucosa or skin. The histological findings on the 100 dayafter BMT, did not show any prognostic value for diagnosis of cGVHD. The female danors and the type oftransplantation showed important value in the prognostic for overall survival for BMT patients. The aGVHD, the BMT type and the sex of the donor were important factors for prognostic of cGVHD

ASSUNTO(S)

mucosa bucal glandulas salivares

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