Venocclusive Disease of the Liver Is Associated with the Early Development of Post-Transplant Microangiopathy in Allogeneic Stem Cell Transplantation.

Abstract

Thirty-three patients were followed prospectively for the development of venocclusive disease (VOD) of the liver and Post-Transplant Microangiopathy (PTM) on days 0,7,14,21,30,60,90 following allogeneic stem cell transplantation. The grading system of Zeigler, ZR et al (Bone Marrow Transplant, 1995) was used to categorize patients with the clinical syndrome of PTM. The diagnosis of venocclusive disease was made using the criteria of Jones, RJ, (Transplantation, 1987). Patients with and without VOD had similar peak grades of PTM, that ranged for Grade 2 – 4. However, the development of PTM occurred earlier in those with VOD. Data regarding the development of PTM is shown in the Table below as medians and 10th and 90th percentiles. Patients following allogeneic SCT without evidence of PTM have a median % fragmented cells of 1.4% (10th and 90th percentiles of 0.2 and 3.6%). Median LDH elevations expressed as x ULN in patients following allogeneic SCT (without evidence of PTM) were 0.5 ( 10th and 90th percentiles of 0.5–1.0).When compared with patients without VOD, patients with VOD experienced earlier an earlier onset and a higher grade of PTM. The sequence of events is an increase in bilirubin assoicated with an elevation of the LDH level at day 7 followed by the recognition of grade 2 or higher PTM by day 14. There is also an increase in fragmented cells differentiating the two groups by day 21. By day 28, those patients with VOD who have survived have similar LDH and fragmented cell levels as those that did not have VOD. We conclude that PTM that occurs less than or equal to day 21 post-SCT represents regimen toxicity and often accompanies the diagnosis of VOD.ParameterWith VOD N=15Without VOD N=18PDay to Development of PTM14 (7–31)33 (21–58)<0.001Day to peak PTM18 (14–32)43 (7–112)0.02LDH x ULN Day 71.0 (0.5–2.1)0.6 (0.5–0.8)0.02LDH x ULN Day 141.5 (0.7–3.7)0.7 (0.5–2.5)<0.01LDH x ULN Day 212.3 (0.7–12.2)0.9 (0.7–1.6)0.01% FC Day 216.7 (1.8–17)2.0 (0.2–3.8)<0.01Bilirubin (mg/dl) Day 73.3 (1.2–6.5)1.0 (0.5–2.7)<0.001