Assessing the yield and safety of endoscopy in acute graft-vs-host disease after hematopoietic stem cell transplant

Table 1 Baseline demographics and clinical characteristics

Demographics and clinical characteristics	n = 195
Age (yr), median (range)	56 (17-78)
Female, n (%)	101 (51.8)
Time since HSCT in days, median (range)	27 (9-98)
Hematologic disorder, n (%)1
AML	80 (41.0)
B-ALL	34 (17.4)
MDS	30 (15.4)
Myelofibrosis	13 (6.7)
Presenting symptoms, n (%)1
Diarrhea	144 (73.9)
Nausea/vomiting	107 (54.9)
Abdominal pain	50 (25.6)
Gross endoscopic findings, n (%)1
Edema/erythema	108 (55.4)
Gastritis	84 (43.1)
Ulcerations/erosions	56 (28.7)
Colitis	39 (20.0)
Esophagitis	27 (13.9)
Duodenitis	26 (13.3)
Normal	25 (12.8)
Pathologic findings, n (%)1
Mild GVHD	133 (68.2)
Chronic inflammation	41 (21.0)
Moderate GVHD	36 (18.5)
Ulceration/erosion	25 (12.8)
Severe GVHD	16 (8.2)
Location of pathologic findings, n (%)1
Sigmoid colon	118 (60.5)
Stomach	105 (53.9)
Rectum	103 (52.8)
Duodenum	94 (48.2)
Pre-procedure lab values, median (range)
Hemoglobin (g/dL)	9.0 (6.7-14.4)
Platelets (× 103/µL)	80 (16-388)
ANC (× 103/µL)	2.6 (0.0-23.0)
INR	1.0 (0.9-1.7)
BUN	14 (2-78)
Creatinine	0.70 (0.28-3.32)
Pre-procedure transfusions, n (%)
1 or more units of platelets transfused	78 (40.0)
1 or more units of pRBCs transfused	55 (28.2)
1 or more units of FFP transfused	3 (1.5)
Immunosuppressant use within 1-wk pre-procedure, n (%)1
Tacrolimus	164 (84.1)
Sirolimus	115 (59.0)
Mycophenolate	70 (35.9)
Methylprednisone	55 (28.2)
Hydrocortisone	49 (25.1)

¹Only the most common findings were included in this table. FFP: Fresh frozen plasma/cryoprecipitate; pRBCs: Packed red blood cells; BUN: Blood urea nitrogen; INR: International normalized ratio; ANC: Absolute neutrophil count; AML: Acute myelogenous leukemia; B-ALL: B-cell acute lymphoblastic leukemia; MDS: Myelodysplastic syndromes; GVHD: Graft-vs-host disease; HSCT: Hematopoietic stem cell transplant.

Table 2 Yield of performing different endoscopic modalities in detecting graft-vs-host disease in patients with different presenting symptoms

Endoscopic procedure	Confirmed GVHD in patients with any symptom, % (n)	Confirmed GVHD in patients presenting with diarrhea, % (n)	Confirmed GVHD in patients presenting with nausea/vomiting, % (n)	Confirmed GVHD in patients presenting with abdominal pain, % (n)
EGD (n = 45)	66.7 (30/45)	85.7 (6/7)1	70.6 (24/34)	57.1 (8/14)
FS (n = 57)	77.2 (44/57)	76.8 (43/56)	87.5 (7/8)2	76.9 (10/13)
Colonoscopy (n = 4)	75.0 (3/4)	75.0 (3/4)	-	100.0 (1/1)
EGD + FS (n = 83)	83.1 (69/83)	84.9 (62/73)	85.9 (55/64)	90.5 (19/21)
EGD + colonoscopy (n = 6)	50.0 (3/6)	50.0 (2/4)	0 (0/1)	100.0 (1/1)

¹Three of six patients who presented with diarrhea and underwent esophagogastroduodenoscopy with confirmed graft-vs-host disease (GVHD) also had nausea/vomiting at time of presentation.

²Seven of seven patients who presented with nausea/vomiting and underwent FS with confirmed GVHD also had diarrhea at time of presentation. EGD: Esophagogastroduodenoscopy; FS: Flexible sigmoidoscopy; GVHD: Graft-vs-host disease.

Table 3 Gross endoscopic findings and concurrent presence of mild, moderate, and severe graft-vs-host disease

Endoscopic finding	Patients with GVHD, % (n)	Sensitivity (%)	Specificity (%)	Patients with mild GVHD, % (n)	Patients with moderate GVHD, % (n)	Patients with severe GVHD, % (n)
Normal1	84.0 (21/25)	14.1	91.3	100.0 (21/21)	4.8 (1/21)	0 (0/21)
General findings1
Edema/erythema	82.4 (89/108)	59.7	58.7	88.8 (79/89)	30.3 (27/89)	12.4 (11/89)
Ulceration/erosion	80.4 (45/56)	30.2	76.1	77.8 (35/45)	40.0 (18/45)	26.7 (12/45)
Friability	90.9 (10/11)	6.7	97.8	80.0 (8/10)	30.0 (3/10)	20.0 (2/10)
Nodule	80.0 (4/5)	2.7	97.8	100.0 (4/4)	50.0 (2/4)	25.0 (1/4)
Specific findings2
Gastritis	84.5 (60/71)	72.3	78.6	95.0 (57/60)	16.7 (10/60)	1.7 (1/60)
Duodenitis	66.7 (14/21)	16.1	88.9	78.6 (11/14)	21.4 (3/14)	21.4 (3/14)
Colitis	97.1 (33/34)	30.3	93.0	57.6 (19/33)	42.4 (14/33)	24.2 (8/33)
Esophagitis	66.7 (14/21)	70.0	94.3	100.0 (14/14)	0 (0/14)	0 (0/14)

¹We did not localize these endoscopic findings to a particular segment of the gastrointestinal (GI) tract. Diagnostic yield, sensitivity, and specificity calculated were for finding graft-vs-host disease (GVHD) anywhere in the GI tract.

²Patients in the “Specific Findings” category had endoscopic evidence of inflamed mucosa in a specific segment of the GI tract along with biopsy taken from this segment. Diagnostic yields, sensitivities, and specificities calculated were for finding histopathological evidence of GVHD in this specific segment of the GI tract. GVHD: Graft-vs-host disease.

Table 4 Utility of biopsying various segments of the gastrointestinal tract in patients presenting with diarrhea, nausea/vomiting, and abdominal pain

Presenting symptom and biopsy location1	Histological evidence of GVHD in location, % (n)
Diarrhea (n = 144)
Upper GI tract	95.7 (67/70)
Esophagus	51.9 (14/27)
Stomach	82.1 (55/67)
Duodenum	87.1 (61/70)
Lower GI tract	99.1 (109/110)
Ileum	100.0 (2/2)
Cecum	100.0 (1/1)
Ascending colon	100.0 (4/4)
Transverse colon	75.0 (3/4)
Descending colon	91.7 (11/12)
Sigmoid colon	93.5 (101/108)
Rectum	94.0 (94/100)
Nausea/vomiting (n = 107)
Upper GI tract	97.5 (77/79)
Esophagus	51.6 (16/31)
Stomach	84.6 (66/78)
Duodenum	87.3 (69/79)
Lower GI tract	96.8 (60/62)
Ileum	-
Cecum	-
Ascending colon	-
Transverse colon	-
Descending colon	100.0 (6/6)
Sigmoid colon	90.2 (55/61)
Rectum	91.1 (51/56)
Abdominal pain (n = 50)
Upper GI tract	89.3 (25/28)
Esophagus	66.7 (8/12)
Stomach	89.3 (25/28)
Duodenum	85.7 (24/28)
Lower GI tract	96.8 (30/31)
Ileum	100.0 (1/1)
Cecum	100.0 (1/1)
Ascending colon	100.0 (2/2)
Transverse colon	100.0 (1/1)
Descending colon	100.0 (4/4)
Sigmoid colon	87.1 (27/31)
Rectum	86.7 (26/30)

¹Denominators represent all patients with presenting symptom, biopsy obtained from specified location in the gastrointestinal (GI) tract, and histological evidence of graft-vs-host disease in tissue obtained anywhere in the GI tract. GI: Gastrointestinal; GVHD: Graft-vs-host disease.

Table 5 Complications in thrombocytopenic and neutropenic patients

Complication	Non-thrombocytopenic patients	Thrombocytopenic patients	Non-neutropenic patients1	Neutropenic patients1
Any-cause mortality within 1 wk of endoscopy, n (%)	0/128 (0)	0/67 (0)	0/170 (0)	0/25 (0)
Adverse outcomes excluding death, n (%)	3/128 (2.3)	1/67 (1.5)	3/170 (1.8)	1/25 (4.0)
Bleeding within 1 wk of endoscopy	1/128 (0.8)	1/67 (1.5)	1/170 (0.6)	1/25 (4.0)
Infection within 1 wk of endoscopy	2/128 (1.6)	0/67 (0)	2/170 (1.2)	0/25 (0)
Perforation within 1 wk of endoscopy	1/128 (0.8)	0/67 (0)	1/170 (0.6)	0/25 (0)
Adverse outcomes including death within 1 wk, n (%)2	3/128 (2.3)	1/67 (1.5)	3/170 (1.8)	1/25 (4.0)

¹Thrombocytopenia was defined as a pre-procedure platelet count ≤ 50 × 10³/µL or ≤ 75 × 10³/µL and ≥ 1 units of platelet transfused. Neutropenia was defined as a pre-procedure absolute neutrophil count < 1000 cells/µL.

²P = 1.000 for thrombocytopenic vs non-thrombocytopenic patients and P = 0.425 for neutropenic vs non-neutropenic patients.