Background: T cell depletion (TCD) decreases Graft Versus Host Disease (GvHD) risk after allogeneic stem cell transplantation (alloSCT). In order to induce a Graft Versus Leukemia (GvL) effect, post-transplantation cellular interventions are applied. Combination of ex vivo and in vivo Alemtuzumab, with Thymoglobulin only for unrelated donors (UD), can obviate the need for post-transplantation prophylactic immunosuppression, enabling early cellular interventions starting at 2 months after alloSCT after clearance of circulating therapeutic antibodies. Aims: To evaluate whether early prophylactic cellular interventions after Alemtuzumab based TCD alloSCT can restore GvL effect leading to enduring relapse-free survival without chronic GvHD. Methods: AML patients who received TCD alloSCT between April 2010 and August 2016 from a 10/10 HLA matched donor after reduced intensity conditioning (6 days 50 mg/m 2 Fludarabin a day orally and 2 days Busulphan 3.2 mg/kg intravenously) were included in this analysis. TCD was performed by Alemtuzumab (20 mg ex vivo and 30 mg in vivo) with addition of 1 mg/kg Thymoglobulin in vivo for patients with UD. No standard GvHD prophylaxis nor anti leukemia chemotherapy was given after alloSCT. Goal of this strategy was to give donor derived T cell products as part of clinical trials as early as 8 weeks after alloSCT or standard unmodified donor lymphocytes (DLI) starting at 12 weeks after alloSCT in the absence of GvHD. A competing risks model was built with study T cell products, unmodified DLI, therapeutic immunosuppression (tIS) for GvHD, relapse and death as competing events. tIS was not considered a failure, since GvHD after alloSCT in this setting could be associated with GvL effect, but was not the goal of this strategy. Chronic GvHD was evaluated by measuring use of tIS in surviving relapse-free patients at 2 years after alloSCT. Long term outcomes were evaluated at 4 years, with a minimal follow-up time of 2 years after alloSCT.
Background: Myelofibrosis is a chronic myeloproliferative neoplasm characterized by progressive bone marrow fibrosis and extramedullary hematopoiesis leading to splenomegaly. Treatment typically involves chemotherapeutic agents (such as hydroxyurea, melphalan, or interferon), investigational drugs, or splenectomy. The small-molecule JAK 1/2 tyrosine kinase inhibitor ruxolitinib was shown to reduce spleen size and improve overall survival in patients with myelofibrosis. Splenomegaly is associated with significant morbidity in patients with myelofibrosis including early satiety, splenic infarct, and cytopenia due to splenic sequestration. Spleen volume measured by computed tomography (CT) is a predictor of overall survival. CT-based determination of spleen volume was traditionally calculated based on maximum and craniocaudal length, width, and thickness, and correlated with sonographic measurements. However, 3D volumetric analysis of splenic volume is a quantitative imaging biomarker that can provide increased accuracy and detect subtle changes in surface contour. Aims: We describe 3D spleen volumetry in patients with myelofibrosis receiving non-myeloablative hematopoietic stem cell transplantation (HSCT) with concurrent ruxolitinib therapy. Methods: This is a retrospective single center study of 29 patients (16 male, 13 female) with primary or secondary myelofibrosis treated with reduced-intensity allogeneic HSCT and peri-transplant ruxolitinib therapy at the City of Hope Helford Clinical Research Hospital between 2003-2017. Eligible patients were selected based on availability of abdominal CT images obtained prior to starting treatment and at least one month after transplantation. Suitable images were processed for 29 of 102 transplant patients screened. Voxel-based volumetric data was compiled with 3D imaging software (GE AW server 3.2) by contouring the spleen on serial axial images and evaluating program-generated histograms.Results: Volumetric analysis of 3D spleen volume was assessed for 29 patients with a median age of 56.6 (41 to 70 years). The median time from date of treatment to the first follow-up CT was 4 months. Median change in spleen volume was -49.8% reduction (-92.4% to +14.8%). Only two patients (6.9%) developed an increase in spleen size. There was no significant difference between genders. Summary/Conclusion: Progressive splenomegaly is common in advanced myelofibrosis, and spleen volume is a predictor of survival. The oral selective JAK 1/2 inhibitor ruxolitinib is used for symptomatic management of intermediate-2 and high-risk myelofibrosis, and leads to significant reduction in spleen size. Ruxolitinib is usually discontinued prior to HSCT. Recent studies suggest continuing ruxolitinib in the peri-transplant period may prevent tumor lysis and cytokine dysfunction due to ruxolitinib withdrawal, as well as improve bone marrow microenvironment for successful stem cell engraftment. We used quantitative imaging software to measure 3D splenic volume in patients receiving ruxolitinib therapy and u...
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