SUPPLEMENTARY DATA

for

Prognostic factors and outcomes of severe gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation

Cristina Castilla-Llorente MD1*; Paul J. Martin, MD1,2; George B. McDonald, MD1,2; Barry E. Storer, PhD1,2; Frederick R. Appelbaum, MD1,2; H. Joachim Deeg, MD1,2; Marco Mielcarek, MD1,2; Howard Shulman, MD1,2; Rainer Storb, MD1,2; Richard A. Nash, MD1,2**

Supplementary Table 1. Data collected for this study*

Parameter / Description / Stages/Grades /
Gut GVHD stage / A peak stage was assigned based on volume of diarrhea and clinical signs. / Stage 0 - ≤500 ml;
Stage 1 - 500-1000 ml;
Stage 2 - 1000-1500 ml;
Stage 3 - >1500 ml;
Stage 4 - severe abdominal pain (cramps)† or melena.
Skin GVHD stage / A peak stage was assigned based on the extent and severity of the rash. / Stage 0 - No involvement;
Stage 1 - <25%;
Stage 2 - 25-50%;
Stage 3 - >50%; Stage 4 - Generalized erythema with bullae.
Liver GVHD
stage / A peak stage was assigned based on the level of serum bilirubin and exclusion of other causes of abnormalities in serum bilirubin. / Stage 0 - <2 mg/dl;
Stage 1 - 2.0-3.0 mg/dl;
Stage 2 - 3.1-6.0 mg/dl;
Stage 3 - 6.1-15 mg/dl;
Stage 4 - >15 mg/dl
Upper GI symptoms / Presence or absence of any of anorexia, nausea or vomiting.
Gastrointestinal bleeding / Presence or absence of frank red blood or melena in the stools.
Endoscopic grades of GVHD in upper and lower gastrointestinal tract / Endoscopic grading was based on the visual findings at endoscopy previously described16,40 / Grades 0 - normal appearance;
Grade 1 - edematous or erythematous changes; no ulcerations or erosions;
Grade 2 - friable mucosa, focal erosions or ulcerations;
Grade 3 - extensive confluent erosions or ulcerations.
Histopathological grades of upper and lower gastrointestinal
GVHD / As previously described16,26,41 if more than one endoscopy was performed in the same 14-day interval, the highest grade for GVHD histology was assigned. / Grade 0 - normal mucosa; Grade 1 - presence of apoptosis without crypt (or basilar gland) loss;
Grade 2 - individual crypt (or basilar gland) loss;
Grade 3 - contiguous areas of crypt (or basilar gland) loss with or without presence of focal regenerative hyperplasia;
Grade 4 - complete loss of crypts (or basilar glands).
Grade of GVHD based on abdominal CT imaging / The grades were based on the extent of involvement. / Grade 0 - Normal; Grade 1 - Regional wall thickening in either the small or large intestine;
Grade 2 - Extensive wall thickening in both the small and large intestine 38.
Infections / Infections of the gastrointestinal tract confirmed by cultures or biopsy including cytomegalovirus, C. Difficile or other infections.
GVHD treatment: / Immunosuppressive agents used for treating GVHD were noted for each of the 14-day intervals including any relevant change in the dose of corticosteroids or the addition of other systemic therapies. Data on the use of topical therapies was not collected.
Serum albumin / The nadir of serum albumin was noted for each consecutive 14-day interval (mg/L).
RBC transfusion / Number of red blood cell units transfused for each 14-day interval.
Total parenteral nutrition (TPN) / The number of days on TPN in each 14-day interval.
Hospitalization / The number of days for which hospitalization was required for supportive care.

*Each parameter was collected as either presence/absence or peak/nadir values for each 14-day interval from 14 days before onset of stages 3-4 gut GVHD.

†

Cramps were defined as abdominal pain requiring intravenous narcotics.

Supplementary Table 2. Survival at 6 and 12 months according to the number of risk factors

Number of
Risk Factors* / Number of
Patients / 6 Month Overall
Survival (%) / 12 Month Overall
Survival (%)
0 or 1 / 18 / 83 / 72
2 / 30 / 73 / 57
3 / 35 / 26 / 11
4 / 33 / 0 / 0

*Risk factors for overall survival were identified in the multivariate analysis and are: 1) serum bilirubin >3.0 mg/dL, 2) corticosteroid-resistant, 3) patient >18 years of age at transplant and 4) gastrointestinal bleeding. Overall survival decreases as the number of risk factors for poor outcome are increased.

BMT REVISED MS# BMT-2013-533.R1 12/17/2013 12:18 PM 1