Gastrointestinal involvement in chronic graft-versus-host disease: A clinicopathologic study

AbstractThe original histopathologic description of chronic graft-versus-host disease (CGVHD) of the gastrointestinal (GI) tract was from autopsy series. There is little information on the evaluation of living patients with CGVHD and GI symptoms. We reviewed data on 40 consecutive patients with CGVHD and persistent GI symptoms who underwent endoscopic examinations. The diagnosis of CGVHD in these 40 patients was made on the basis of clinical criteria and confirmed by histology of other involved organs in 70%. Patients had progressive (in 19 patients, or 48%), quiescent (in 11, or 27%) or de novo–type (in 10, or 25%) onset of their CGVHD. Four groups were defined based on the following histologic criteria: (1) consistent with acute GI GVHD if there was marked apoptosis with or without cryptitis, (2) suggestive of acute GI GVHD if there was scattered apoptosis with or without cryptitis, (3) suggestive of chronic GI GVHD if there were at least 2 histologic indicators of chronicity such as fibrosis and significant crypt distortion, and (4) no histologic evidence of GVHD. Results of microbiologic, radiologic, and malabsorption studies, if performed, were also retrieved. Median time from diagnosis of CGVHD to GI endoscopy was 4.5 months (0-109 months). The major GI symptoms at the time of endoscopy were diarrhea, abdominal pain/cramping, nausea/vomiting, weight loss, dysphagia, and early satiety. The endoscopic examination was nonspecific for the diagnosis of GI GVHD except for diffuse mucosal sloughing. Based on the histologic criteria in 22 patients with biopsies, 13 cases (59%) were considered to have acute GI GVHD, and 3 cases (14%) were felt to show possible chronic GI GVHD; changes of both acute and chronic GVHD were seen in 6 (27%) cases. GI dysmotility was diagnosed in 7 (18%) patients, including 2 of the patients who had histologic changes suggestive of chronic GVHD. Other causes of the GI symptoms included infection, drug side effect, and malabsorption. In conclusion, GI involvement by acute GVHD appears to be a major cause of persistent GI symptoms in patients with chronic GVHD. An isolated form of chronic GI GVHD confirmed by histology is an uncommon phenomenon in the actual clinical setting. © 2003 American Society for Blood and Marrow TransplantationBiology of Blood and Marrow Transplantation 9:46-51 (2003

Classic and Overlap Chronic Graft-versus-Host Disease (cGVHD) Is Associated with Superior Outcome after Extracorporeal Photopheresis (ECP)

The National Institutes of Health (NIH) classification of graft-versus-host disease (GVHD) is a significant improvement over prior classifications, and has prognostic implications. We hypothesized that the NIH classification of GVHD would predict the survival of patients with GVHD treated with extracorporeal photopheresis (ECP). Sixty-four patients with steroid refractory/dependent GVHD treated with ECP were studied. The 3-year overall survival (OS) was 36% (95% confidence interval [CI] 13-59). Progressive GVHD was seen in 39% of patients with any acute GVHD (aGVHD) (classic acute, recurrent acute, overlap) compared to 3% of patients with classic chronic GVHD (cGVHD) (P=.002). OS was superior for patients with classic cGVHD (median survival, not reached) compared to overlap GVHD (median survival, 395 days, 95% CI 101 to not reached) and aGVHD (delayed, recurrent or persistent) (median survival, 72 days, 95% CI 39-152). In univariate analyses, significant predictors of survival after ECP included GVHD subtype, bilirubin, platelet count, and steroid dose. In multivariate analyses overlap plus classic cGVHD was an independent prognostic feature predictive of superior survival (hazard ratio [HR] 0.34, 95% CI 0.14-0.8, p=.014). This study suggests that NIH classification can predict outcome after ECP for steroid refractory/dependent GVHD

Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria

Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD

New‐onset posttransplant diabetes mellitus after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide

Abstract Haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplant cyclophosphamide (PTCY) is utilized for patients with hematological disorders but without conventional donors. The effects of new‐onset posttransplant diabetes mellitus (PTDM) following haplo‐HCT are unknown. We examined PTDM incidence and outcomes after haplo‐HCT with PTCY. Patients without diabetes receiving haplo‐HCT (n = 64) were analyzed for PTDM diagnosis (defined as blood glucose ≥ 200 mg/dL). By day 100, 14 (22%) patients developed PTDM (median, 18 days). Hyperglycemia (blood glucose ≥ 200 mg/dL) preceded corticosteroids in 11 (79%) individuals. PTDM patients had increased death/relapse (P = .029). PTDM occurs frequently, precedes corticosteroids, and leads to inferior outcomes following haplo‐HCT. PTDM prophylaxis/treatment may improve HCT survival