Low Dose Unfractionated Heparin (UFH) Prophylaxis Is a Feasible Strategy for the Prevention of Hepatic Sinusoidal Obstruction Syndrome (SOS) after Myeloablative Adult Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Hepatic SOS is a serious complication after allogeneic HSCT with a reported incidence of 14%. While prophylaxis is widely used, there is no uniform consensus on the optimal strategy. Low dose UFH has been utilized & recent guidelines published by Dignan, et al suggest alternatives prophylaxis strategies. However, the benefit of UFH and potential risk of bleeding needs further evaluation. 490 adult allograft recipients received myeloablative conditioning (MAC) for hematologic malignancies between 01/2003-12/2013 [359 (73%) acute leukemia/ MDS, 44 (9%) lymphoma, 53 (11%) multiple myeloma, 34 (7%) CML/ myeloproliferative disorder]. MAC comprised busulfan (n=243; 50%), total body irradiation (n = 233; 48%), or other (n=14; 3%). 402 pts (82%) received CD34+ selected T-cell depleted (TCD) allografts (402, 82%). All patients (pts) received SOS prophylaxis with low dose UFH 100 units/kg/24 hrs by continuous IV from admission through d+21 or engraftment. Pts with history of prior allograft, non-malignant/refractory disease, concurrent ursodiol prophylaxis, or therapeutic anticoagulation were excluded. The median age was 51 (range 21-65) yrs, and 268 (54%) were male. During the 10 year study period, 14 pts developed hepatic SOS [d+100 incidence of 2.9% (95%CI: 1.6-4.6)]. Age & HLA-match did not influence SOS development (Table). The incidence of hepatic SOS was higher in unmodified versus TCD grafts recipients, p ≤ 0.001, and pts with hepatitis B/C exposure, p = 0.033. Due to the low SOS incidence, adjusted multivariate analysis was not conducted. Median time to SOS onset was 30 days (range 5-57). Six pts received supportive care & 8 defibrotide. Of those, 7 developed severe SOS resulting in multi-organ failure (5 supportive care, 2 defibrotide). 3/14 of these pts are alive at last follow-up (7 deaths due to SOS). Grade II-IV bleeding occurred in 26/490 pts (5%) [4 (0.8%); grade 3-4]. D+100 incidence of grade II-IV and III-IV liver acute GVHD was 1.4% (95%CI: 0.6-2.8) and 0.4% (95%CI: 0.1-1.4), respectively. D+100 TRM was 9.8% (95%CI: 7.4-12.6). To our knowledge, this is the largest analysis evaluating the use of low dose UFH for the prevention of hepatic SOS in pts receiving MAC allogeneic HSCT. UFH is well tolerated when used as prophylaxis for hepatic SOS. Incidence of SOS in our study was low; including recipients of TCD allografts. Low dose UFH prophylaxis can be considered in select patients who cannot tolerate oral route. Further prospective studies comparing UFH to other prophylaxis methods are warranted.TableUnivariate analysis of variables associated with SOS.Variable(95% CI)p-valueAge (years)0.620<403.5(1.2-8.2)≥402.7(1.4-4.7)HLA-match0.787 8/82.7(1.4-4.8) ≤7/83.2(1.1-7.5)Graft<0.001 TCD1.0(0.3-2.4) Unmodified11.4(5.8-19.0)Conditioning0.353 Busulfan-based2.1(0.8-4.5) TBI-based3.4(1.6-6.4)Hepatitis B & C Serologies0.033 Negative2.1(1.1-3.7) Positive14.3(0.5-49.1) Open table in a new tab