De-escalated Induction Therapy and Thiotepa/Busulfan-based Autologous Stem Cell Transplantation for Primary Central Nervous System Lymphoma.

Background: Thiotepa-based autologous stem cell transplantation (ASCT) improves survival in primary central nervous system lymphoma (PCNSL), but > 30% of patients are unable to undergo ASCT following commonly used intensive induction regimens.

Methods: This retrospective population-based study included consecutive patients ≥ 18 years old with PCNSL who were intended for ASCT in Alberta, Canada between 2011 and 2022. A reduced-intensity induction protocol was further abbreviated in 2018 to decrease toxicity and expediate ASCT by incorporating rituximab, procarbazine, and only 2 doses of high-dose methotrexate and 1 cycle of high-dose cytarabine before consolidation with thiotepa-busulfan conditioning.

Canadian cancer trials group LY.17: A randomized phase II study evaluating novel salvage therapy pre-autologous stem cell transplant in relapsed/refractory diffuse large B-cell lymphoma-outcome of rituximab-dose-intensive cyclophosphamide, etoposide, cisplatin (R-DICEP) versus R-GDP.

The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi-arm randomized phase II trial evaluating novel salvage therapies compared with R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL). This component of the LY.

Overview of the Engagement Process to Develop the Future of Cancer Impact (FOCI) Report in Alberta: The Power of Collective Action.

This commentary provides a detailed overview of the extensive stakeholder engagement efforts critical to the development of the Future of Cancer Impact (FOCI) in Alberta report. The overarching aim of the FOCI report was to support informed and strategic discussions and actions that will help key stakeholders in the province prepare for a future with increasing cancer incidence and survival. Employing a comprehensive approach and a diverse range of engagement activities, insights from a wide spectrum of stakeholders were gathered and subsequently used to shape the content of the report.

Return on investment of the lymphoma diagnostic pathway implementation in Alberta, Canada.

The Lymphoma Diagnostic Pathway (LDP) was developed based upon clinical best practice guidelines and implemented in large urban centers where lymphoma treatment is provided in Alberta, Canada. A return-on-investment analysis of the implementation of this care pathway was conducted to inform future sustainability and expansion. A cohort design with propensity score matching and difference-in-difference estimation methods were used comparing both cost and return (reduced health service utilization) between patients who were diagnosed within the LDP and those who were diagnosed outside the LDP.

Incomplete chimerism following myeloablative and anti-thymocyte globulin-conditioned hematopoietic cell transplantation is a risk factor for relapse and chronic graft-versus-host disease.

Background Aims: The value of routine chimerism determination after myeloablative hematopoietic cell transplantation (HCT) is unclear, particularly in the setting of anti-thymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis.

Methods: Blood samples were collected at 3 months post-HCT from 558 patients who received myeloablative conditioning and ATG-based GVHD prophylaxis. Chimerism was assessed using multiplex polymerase chain reaction of short tandem repeats in sorted T cells (CD3+) and leukemia lineage cells (CD13+CD33+ for myeloid malignancies and CD19+ for B-lymphoid malignancies).

Improving the outcomes of secondary CNS lymphoma with high-dose thiotepa, busulfan, melphalan, rituximab conditioning and autotransplant.

Secondary central nervous system lymphoma (SCNSL) affects approximately 5% of patients with aggressive large B-cell lymphoma (LBCL) and is associated with poor outcomes. This retrospective, multicenter study included 62 consecutive patients with SCNSL intended for transplant with high-dose methotrexate (HD-MTX)-based induction followed by high-dose thiotepa, busulfan, melphalan, rituximab (TBMR) conditioning and autologous stem cell transplantation (ASCT). Median age was 58 years (range 20-75) and 52 (84%) patients had ECOG performance status >1 at diagnosis of SCNSL.

Real-World Eligibility for Second-Line Chimeric Antigen Receptor T Cell Therapy in Large B Cell Lymphoma: A Population-Based Analysis.

The ZUMA-7 trial demonstrated the superiority of second-line chimeric antigen receptor (CAR) T cell therapy over standard of care chemotherapy with or without autologous stem cell transplantation (ASCT) for relapsed/refractory (r/r) large B cell lymphoma (LBCL). We conducted a retrospective population-based analysis to determine eligibility for second-line CAR-T cell therapy in the real-world setting. Among 125 patients with r/r LBCL between 2015 and 2019, 82% progressed within 12 months of first-line chemoimmunotherapy (CIT), 40% were treated with intention-to-transplantation, 22% underwent ASCT, and 7% achieved a durable remission after ASCT.

Comparison of the Management and Short-Term Outcomes between Patients with Advanced Cancer and Other End-of-Life Conditions Presenting to Two Canadian Emergency Departments.

An increasing number of patients with end-of-life (EOL) conditions, particularly those with advanced cancer, are presenting to the emergency department (ED). To assess the characteristics, management and short-term outcomes of ED patients with advanced cancer compared to patients with other EOL conditions. A secondary analysis of a prospective cohort study.

Physician perspectives on delays in cancer diagnosis in Alberta: a qualitative study.

Background: Delays in cancer diagnosis have been associated with reduced survival, decreased quality of life after treatment, and suboptimal patient experience. The objective of the study was to explore the perspectives of a group of family physicians and other specialists regarding potentially avoidable delays in diagnosing cancer, and approaches that may help expedite the process.

Methods: We conducted a qualitative study using interviews with physicians practising in primary and outpatient care settings in Alberta between July and September 2019.

Novel synthetic drugs for the treatment of non-Hodgkin lymphoma.

: Over the past two decades, deeper understanding of B-cell signaling pathways and other mechanisms of lymphomagenesis have yielded promising targets for novel drugs in the treatment of non-Hodgkin lymphoma.: This article provides a comprehensive review of approved synthetic drugs targeting the BTK, PI3K, immunomodulation, proteasome, HDAC, EZH2, and nuclear export pathways in non-Hodgkin lymphoma. The review includes coverage of the pharmacology, efficacy, toxicity, and active areas of research for each drug.

From symptom to cancer diagnosis: Perspectives of patients and family members in Alberta, Canada.

Background: Significant intervals from the identification of suspicious symptoms to a definitive diagnosis of cancer are common. Streamlining pathways to diagnosis may increase survival, quality of life post-treatment, and patient experience. Discussions of pathways to diagnosis from the perspective of patients and family members are crucial to advancing cancer diagnosis.

Outcomes of Consecutively Diagnosed Primary Central Nervous System Lymphoma Patients Using the Alberta Lymphoma Clinical Practice Guideline Incorporating Thiotepa-Busulfan Conditioning for Transplantation-Eligible Patients.

While no widely accepted standard treatment regimen exists for primary central nervous system lymphoma (PCNSL), growing evidence supports an approach that incorporates autologous stem cell transplantation (ASCT) as consolidative therapy when feasible. In November 2011, the Alberta Hematology Tumor Team established a new clinical practice guideline (CPG) for PCNSL involving high-dose methotrexate (HDMTX)/cytarabine-based induction followed by ASCT for eligible patients using a thiotepa and busulfan (TBu) conditioning regimen that omitted cyclophosphamide from the regimen that was used before 2011. This retrospective study analyzed all 64 patients with PCNSL diagnosed consecutively in 3 Canadian centers between November 2011 and December 2017 to evaluate adherence to the 2011 CPG and associated outcomes.

Autologous transplantation as consolidation for high risk aggressive T-cell non-Hodgkin lymphoma: a SWOG 9704 intergroup trial subgroup analysis.

Phase II data suggest a benefit to autotransplantation for aggressive T-cell non-Hodgkin lymphoma (T-NHL) in first remission; randomized trials have yet to validate this. We performed a retrospective analysis of aggressive T-NHL patients in the intergroup randomized consolidative autotransplant trial (SWOG 9704). Of the 370 enrolled, 40 had T-NHL: 12 were not randomized due to ineligibility ( = 1), choice ( = 2), or progression ( = 9), leaving 13 randomized to control and 15 to autologous stem cell transplantation (ASCT).

The Adverse Consequences of Initial Watchful Waiting for Patients With Follicular Lymphoma.

Background: Patients with low tumor burden follicular lymphoma (FL) are commonly managed with watchful waiting (WW). The incidence of organ dysfunction and/or transformation at disease progression, and subsequent impact on outcomes is poorly understood.

Patients And Methods: Patients managed with WW during 1994 to 2011 were identified through the Alberta Lymphoma Database.

Autologous transplantation improves survival rates for follicular lymphoma patients who relapse within two years of chemoimmunotherapy: a multi-center retrospective analysis of consecutively treated patients in the real world.

Although chemoimmunotherapy improves outcomes for patients with follicular lymphoma (FL), approximately 20% of patients experience early disease progression within two years of treatment and subsequently poor median survival. We conducted a retrospective study to evaluate survival rates of patients with early relapse who were treated with or without autologous transplantation. Of 517 patients with FL and who received chemoimmunotherapy, 152 relapsed and survived a minimum of four months after progression, including 84 (55.

Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the development of PTLD.

Methods: We retrospectively studied 306 patients monitored for EBV DNAemia after Thymoglobulin-conditioned HCT to determine the utility of the monitoring in the management of PTLD.

Risk factors for post-transplant lymphoproliferative disorder after Thymoglobulin-conditioned hematopoietic cell transplantation.

Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG-conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy-diagnosed PTLD in the absence of EBV DNAemia monitoring (n = 266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n = 199).

A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma.

The objective of this study was to create a bioclinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group (CCTG) LY12 prospective study. In 91 cases, sufficient histologic material was available to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and phosphoSTAT3 (pySTAT3) expression. Sixty-seven cases had material sufficient for fluorescent hybridization (FISH) for and In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent digital gene expression profiling (GEP) to evaluate , and expression, and to determine cell-of-origin (COO) using the Lymph2Cx assay.

Targeting non-Hodgkin lymphoma with blinatumomab.

Management of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) remains challenging, and novel effective agents are eagerly awaited. Blinatumomab is a bispecific T-cell engager, targeting CD19. While blinatumomab's primary clinical use has been in B-cell acute lymphoblastic leukemia (B-ALL), there are increasing data for its use in B-lineage lymphomas.

Incidence of late onset neutropenia associated with rituximab use in B cell lymphoma patients undergoing autologous stem cell transplantation.

Reversible late onset neutropenia associated with rituximab has been reported with incidence rates varying from 15 to 70% in B cell lymphoma patients receiving autologous stem cell transplantation. We conducted a retrospective descriptive study at one tertiary care center in adult B cell lymphoma patients treated with rituximab and autologous stem cell transplantation between 1 January 2004 and 30 June 2014. Late onset neutropenia was defined as an absolute neutrophil count <1.

Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients.

Background: The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity.