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Post-transplant sinusoidal obstruction syndrome in adult patients with B-cell Acute Lymphoblastic Leukemia treated with pre-transplant Inotuzumab
Agrawal, V., Pourhassan, H., Tsai, N. C., Ngo, D., Koller, P., Malki, M. M. A., Salhotra, A., Ali, H., Aribi, A., Sandhu, K. S., et al
Transplantation and cellular therapy. 2023
Abstract
Sinusoidal obstruction syndrome (SOS) is potentially a life-threatening complication that can be observed after allogeneic hematopoietic cell transplantation (HCT). Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody-drug conjugate that has demonstrated high efficacy in relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), however, it is associated with increased risk of SOS among transplant recipients. Here, we aimed to examine the incidence and outcomes of SOS in 47 adult patients with R/R ALL that received inotuzumab and subsequently underwent HCT at our institution. All patients received prophylactic therapy with ursodiol, and continuous low dose heparin was administered as well to patients receiving myeloablative conditioning. SOS occurred in 12 (26%) patients post-HCT, with a median onset of 11 days (range: 3-41). SOS was graded as very severe in 50% (n=6), severe in 25% (n=3), and mild in 25% (n=3). All patients diagnosed with SOS received treatment with defibrotide for a median of 21 days (range: 3-34), with resolution of SOS in 67% (n=8) of patients. Mortality rate from SOS was 33% (n=4) and occurred with a median of 10 days from diagnosis (range: 3-31), and in patients graded as very severe (n=3) or severe (n=1). No significant difference in median duration between the last dose of inotuzumab and transplant (46 vs. 53 days, P=0.37), the use of myeloablative conditioning regimen (42% vs. 49%, P=0.75), number of lines of therapy prior to inotuzumab (P=0.79), the median number of administered cycles of inotuzumab (2 vs. 2, P=0.14), or receiving inotuzumab as the last therapy prior to HCT (67% vs. 66%, P=1.0) was observed between patients who did and did not develop SOS, respectively. Sirolimus-based graft versus host disease (GVHD) prophylaxis was utilized more frequently in the SOS group (75% vs. 29%, P<0.01), but there were no differences in the peak sirolimus level (P=0.81) or the median time to peak sirolimus level (7 vs. 3.5 days, P=0.39) between the two subgroups, respectively. In univariable analysis, only the use of sirolimus-based GVHD prophylaxis was significantly associated with increased risk of SOS (HR=7.50 [95% CI:1.7-33.6, P<0.01]). In the SOS group, the 100-day mortality rate was 33% (n=4) and median overall survival (OS) post-HCT of 4.3 months (range: 0.2 - 57.2). In the group without SOS, the 100-day mortality rate was 14% (n=5) and the median OS post-HCT was 10.7 months (range: 0.52 - 39.6). Here, we showed that SOS is prevalent in transplant recipients who were treated with inotuzumab prior to transplant, and that sirolimus-based GVHD prophylaxis was a risk factor for SOS in inotuzumab recipients in our cohort.