Role of Histopathology in Management of Graft Versus Host Disease (GVHD). A Single Centre Experience.

GVHD is a major complication after allogeneic stem cell transplantation (HSCT). The median incidence of grade II-IV acute(a)GVHD is about 40%, depending on several risk factors, whereas chronic(c)GVHD occurs in more than 50% of long term survivors after HSCT.Histopathology has a critical role in obtaining diagnosis and comprehending pathophysiology of GVHD. However, clinical or technical factors may hamper histological interpretation. Aim of the present retrospective study was to optimize the role of histopathology in the management of GVHD. Recommendations of Pathology Working Group (National Institutes of Health Consensus, ASBMT, BBMT 2006) were matched with clinical-laboratory data in order to test histological sensitivity, specificity and positive predictive value (PPV).

One hundred sixty consecutive bioptical samples were performed in 68 adult patients with suggestive signs or symptoms of organ involving a/c GVHD (n=137) or as screening test in asymptomatic patients (n=23),who underwent allogeneic HSCT at our institution between Jul 1999 and Feb 2009.Median age at transplant was 50 ys (range 17-70),with a median follow-up 32 mo (3-111). Diagnoses were 89/160 acute and 16/160 chronic leukemia, 16 lymphomas, and 39 myelomas. Sixteen % of biopsies were taken from MUD transplanted patients. The source of stem cells was bone marrow in 88/160 (median TNC 2.9 × 10⁸/Kg, range 1.11-5.60), and peripheral blood in 72 (median CD34+cells 5.87 × 10⁶/Kg, range 1.17-10.15). The biopsies, were collected from organ presenting clinical signs suggestive of GVHD involvement. If more organs were simultaneously involved,the one with more severe symptoms was selected. The biopsies were performed early at the onset of the clinical manifestations, and before modification of immunosuppressive (IS) therapy. A specific form containing the main clinical data (time from transplant, type of conditioning and possible differential diagnosis) accompanied the specimens. The histopathological diagnosis was guaranteed within 24-48 hours from the collection. The 160 bioptical samples were collected from the skin (n=86), gastrointestinal tract (GI) (oral mucosa n=5, stomach n=40, or colon n=24), liver (n=4), lung (n=1).Median time from HSCT to biopsy was 968 days (range 76-3341).PPV for the following variables was calculated: conditioning therapy (reduced intensity versus standard), source of stem cell (BM versus PB),type of organ involved (skin, versus upper GI tract, versus lower GI tract), time from HSCT to biopsy (<=180 vs >180 dy) and concomitant IS at the time of biopsy.

Seventy out of 157 biopsies were negative, 9/157 suggestive for GVHD, 48/157 were diagnostic for acute GVHD (33 had histological grade <= 2, 15 > 2), and 30/157 for chronic GVHD. The sensitivity of the histopathological test was 79% in the whole group, whereas the specificity was 80%. PPV was 86%, negative predictive value was 71%. About the analyzed variables,the following had a PPV >=90% :RIC conditioning (90%),PB source (93%),samples collected from GI tract (upper tract 90%, lower 100%),time to biopsy >180 dy(90%) and absence of concomitant IS treatment (90%).The biopsies performed as screening test in asymptomatic patients had a sensitivity of 100% but a specificity of 83%, and the true positive are as frequent as the false positive results.

Conclusions: clinical data identified at the time of sampling (RIC conditioning, PBSC transplants, lower GI tract, time to biopsy >180 dy and absence of concomitant IS) may improve the power of histology. Moreover, despite of a low number of specimens, the biopsies performed as screening test seem to have no critical role in decision making.

No relevant conflicts of interest to declare.