Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT

Patient Image Data. (XLSX 19 kb

Liver Graft‐Versus‐Host Disease is associated with poor survival among allogeneic hematopoietic stem cell transplant recipients

Liver Graft‐versus‐host disease (GVHD) is common in patients with post‐transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post‐transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non‐liver GVHD” group, which consisted of other etiologies of post‐transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post‐transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non‐liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time‐varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non‐relapse mortality, and adverse relapse‐free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151888/1/ajh25575.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151888/2/ajh25575_am.pd

Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2–9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4–52.8) and the probability of overall survival was 63.8% (95% CI 54.4–72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5–15.4) and 47.3% (95% CI 38.2–56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS

Effect of cumulative dose of brentuximab vedotin maintenance in relapsed/refractory classical Hodgkin lymphoma after autologous stem cell transplant: an analysis of real-world outcomes

Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma demonstrated an improved 2-year progression-free survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse 75% of the planned total cumulative dose, cohort 2 with 51-75% of dose, and cohort 3 with ≤50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL<12, and 39% had END. Forty-four percent of patients had prior exposure to BV and 65% were in complete remission before ASCT. Only 14% of patients received the full planned BV dose. Sixty-one percent of patients discontinued maintenance early and majority of those (72%) were due to toxicity. The 2-year PFS for the entire population was 80.7%. The 2-year PFS was 89.2% for cohort 1 (n=39), 86.2% for cohort 2 (n=33), and 77.9% for cohort 3 (n=46) (P=0.70). These data are reassuring for patients who require dose reductions or discontinuation to manage toxicity

Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes

Immunotherapy for Diffuse Large B-Cell Lymphoma: Current Landscape and Future Directions

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. B-cell receptor (BCR) pathway is essential for malignant B-cell growth, survival, and proliferation. Various immune cells, including T-cells and macrophages in the tumor microenvironment (TME) contribute to tumor cell survival and pathogenesis of chemo-resistance. The presence of many targets on the malignant B-cells and in the TME has led to emergence of novel therapeutic agents. Stem cell transplant is the oldest treatment modality leveraging immune system in DLBCL. Subsequently, CD20 targeting monoclonal antibody and chimeric antigen receptor (CAR) T-cell therapy changed the treatment landscape of DLBCL. Recently, multiple novel immunotherapeutic agents have been added in the armamentarium for the management of DLBCL, and many are under development. In this review article, we will review latest updates of immunotherapeutic agents in the management of DLBCL.</jats:p

Immunotherapy for Diffuse Large B-Cell Lymphoma: Current Landscape and Future Directions

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. B-cell receptor (BCR) pathway is essential for malignant B-cell growth, survival, and proliferation. Various immune cells, including T-cells and macrophages in the tumor microenvironment (TME) contribute to tumor cell survival and pathogenesis of chemo-resistance. The presence of many targets on the malignant B-cells and in the TME has led to emergence of novel therapeutic agents. Stem cell transplant is the oldest treatment modality leveraging immune system in DLBCL. Subsequently, CD20 targeting monoclonal antibody and chimeric antigen receptor (CAR) T-cell therapy changed the treatment landscape of DLBCL. Recently, multiple novel immunotherapeutic agents have been added in the armamentarium for the management of DLBCL, and many are under development. In this review article, we will review latest updates of immunotherapeutic agents in the management of DLBCL