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Chimeric antigen receptor (CAR) T-cell therapies offer encouraging results for a subset of patients with advanced hematological malignancies; 5-year progression free survival for patients who undergo CAR T-cell therapy as third line therapy is approximately 31% (Chong et al, 2021). Despite this, advance care planning (ACP) discussions with patients prior to treatment are not routinely offered. ACP discussions allow patients an opportunity to reflect on their wishes and values, and to let the people that matter to them, as well as their healthcare team, know what kind of health and personal care they wish to receive now, and in the future as their health changes.

There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P < .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P < .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P < .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

Introduction:

Introduction

Background:The optimal management of patients with primary mediastinal B-cell lymphoma (PMBCL) who experience a partial metabolic response (PMR) on FDG-PET after initial systemic therapy is unclear. This study aimed to investigate different management strategies and outcomes for PMBCL patients who achieved PMR following primary systemic therapy, utilizing a single-center retrospective design.

Background:

Background: The previous standard Canadian approach to autologous stem cell transplantation (ASCT) included CyBorD induction and single-agent lenalidomide maintenance until progression (Cote J, et al. ASH 2022: abstract 117). In an effort to improve outcomes, the current Canadian Myeloma Research Group (CMRG)–008 trial aimed to assess the efficacy and tolerance of a regimen of isatuximab-CyBorD (Isa-CyBorD) induction, stem cell mobilization/collection, high-dose melphalan with ASCT, followed by continuous maintenance with isatuximab and lenalidomide in newly diagnosed multiple myeloma (NDMM) patients eligible for transplant. We now report the first planned analysis of Isa-CyBorD induction and stem cell mobilization and collection.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

Introduction

Introduction

Introduction:Peripheral blood samples of healthy individuals may harbour detectable mutations in genes recurrently mutated in myeloid malignancies, a situation referred to as clonal hematopoiesis (CH). Risk factors for CH include increasing age as well as previous exposure to cytotoxic therapy. CH has been associated with an increased risk of overall mortality, including in the setting of autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (Gibson et al, JCO, 2017). The excess mortality is largely driven by cardio-vascular disease, but may also be additionally attributable to an increased risk of myeloid malignancies that arise through the selection of CH subclones. Herein, we aimed to investigate the prognostic implications of CH after ASCT in an independent and diversified, large cohort of lymphoma patients using ultra-deep, highly sensitive error-correction sequencing.

Introduction

Sabloff: Astellas Pharma Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Canada: Research Funding; Pfizer Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees. Laferriere:Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria; Teva Pharm: Honoraria; Taiho: Honoraria; ROCHE: Honoraria; Pfizer: Honoraria.

Background:Autologous stem cell transplantation (ASCT) as consolidation post induction is standard of care for eligible multiple myeloma patients. Multiple strategies are employed for mobilization of stem cells in ASCT. Cyclophosphamide/GCSF is an effective standard regimen. However there are reported toxicities associated with cyclophosphamide including risk of febrile neutropenia. Since plerixafor was introduced in Canada, this mobilization agent has been increasingly used as needed with GCSF at Kingston Health Science Centre (KHSC), with elimination of cyclophosphamide. There is however high cost associated with plerixafor. To date, there is no standard mobilization regimen across Canada. This retrospective study evaluates mobilization and ASCT outcomes of multiple myeloma patients who had undergone stem cell mobilization with GCSF+/-plerixafor (GP) vs cyclophosphamide/GCSF+/-plerixafor (CyGP) at KHSC. The goal is to analyze the efficacy of each regimen balanced with adverse events to guide optimal mobilization regimen choice.

Gupta: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

Kim: Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

Lipton: Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding. Kim:Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

Gupta: Incyte: Honoraria, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background:Therapy for patients (pts) with high risk AML remains unsatisfactory. Retrospective studies have demonstrated activity of fludarabine, cytarabine, GCSF and idarubicin (FLAG-IDA) and of mitoxantrone, etoposide and cytarabine (NOVE-HiDAC) as salvage therapy in pts with relapsed or refractory AML. A recent randomized trial indicated high complete remission (CR) rates with improved relapsed-free survival when FLAG-IDA is administered as frontline induction therapy (Burnett et al. J Clin Oncol 2013). Since 01/2011, we have used FLAG-IDA as a first line therapeutic option in pts with high risk AML (poor risk cytogenetics, antecedent myeloproliferative neoplasm or myelodysplastic syndrome, and/or therapy-related AML) in an attempt to improve CR rates and permit more patients with AML to advance to allogeneic hematopoietic cell transplantation (alloHCT). Prior to 2011, either 3&7 or NOVE-HiDAC was used as first line therapy in patients with AML.

No relevant conflicts of interest to declare.

Invasive pulmonary aspergillosis (IPA) is associated with considerable morbidity and mortality in patients with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Timely diagnosis of IPA is crucial, but difficult. Strategies for early detection of IPA include serum galactomannan (GM), bronchoalveolar lavage (BAL) GM and characteristic radiologic abnormalities on CT scan; however, the relative sensitivity of these diagnostic tests is unclear. We sought to determine the utility of serum GM and characteristic CT radiologic abnormalities in diagnosing IPA in patients with hematologic malignancies who had a positive BAL for Aspergillus.We performed a single center retrospective cohort study from 2010 to 2012 to determine the sensitivity serum GM (OD > 0.5) and low dose CT scan in patients with hematologic malignancies. All positive BAL GM samples and Aspergillus isolates from BAL fluid cultures from patients with acute leukemia and those undergoing HSCT were reviewed; all patients had abnormal chest CT scans consistent with pulmonary infection. IPA was classified as proven, probable or possible according to EORTC/MSG criteria. Recent low dose CT scans correlating to the date of the positive BAL GM or Aspergillus isolation were reviewed and graded: halo signs, cavities, crescents and nodules were deemed to be consistent with IPA, while other changes (e.g. ground-glass changes, consolidation) were considered non-specific.A total of 49 BAL samples were included; of these, 31 were considered probable IPA and 18 possible IPA (on the basis of non-specific radiologic findings). Most patients had either no prior or 1–2 days of mold-active antifungal agents. There were 43 cases with positive BAL GM and 11 cases of positive Aspergillus BAL isolates; 5 patients had both. Of the positive BAL GM cases, 27 (63%) were associated with radiologic findings consistent with IPA. The remaining cases were associated with non-specific radiologic findings. Of the patients with Aspergillus isolates on BAL, 55% (6/11) had radiologic features consistent with IPA, while the remaining cases had non-specific radiologic findings.We next evaluated the sensitivity of serum GM. Of 34 patients with BAL GM positivity who had concomitant serum GM testing, 4 (12%) had positive serum GM. Of 8 patients with Aspergillus species isolated on BAL who had serum GM performed, only 1 (12.5%) had positive serum GM. In contrast, 5/8 patients (63%) with Aspergillus isolates on BAL had a positive BAL GM. The combined sensitivity of serum GM was 12% (5/42).Although the majority of patients with positive BAL for Aspergillus (+GM and/or isolates) had characteristic radiologic findings on CT scan, the absence of such findings did not exclude this diagnosis, as over one third had only non-specific radiologic findings. Serum GM had very low sensitivity in this population and should not be used in isolation to diagnose IPA.No relevant conflicts of interest to declare.

High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is historically effective treatment for patients with relapsed follicular lymphoma (FL) but relapse is common possibly due to contaminated stem cell grafts or inadequate eradication of primary disease. The addition of immunotherapy to HDT/ASCT may augment “in vivo” graft purging and achieve more effective eradication of minimal residual disease (MRD) post ASCT. This may lead to improved PFS and OS.We conducted 3 sequential prospective phase 2 trials of HDT/ASCT combined with immunotherapy in patients with relapsed FL from 1997–2010. Protocol 1 (n=13) used a-interferon 3 MU/m2 SC TIW for 2 years post ASCT. Protocol 2 (n=23) used a single infusion of rituximab (R) 375 mg/m2 for ‘in vivo’ purging 3–5 days pre-stem cell collection and 2 sets of 4 weekly R at 2 and 6 months post ASCT respectively. Protocol 3 (n=32) used 3 infusions of R 375 mg/m2 pre stem cell collection, followed by a-interferon 3 MU/m2 SC TIW × 2 years + R 375mg/m2 × 6 weekly infusions post ASCT. Eligibility included adult patients age 18–65 with stage III or IV follicular lymphoma grades 1–3a in first or second relapse. Salvage chemotherapy was either CHOP or DHAP depending on prior anthracycline exposure. High dose therapy was cyclophosphamide, carmustine, and etoposide (CBV). Minimal residual disease (MRD) assessment of t(14; 18) by quantitative PCR was serially performed in blood, PBSC and marrow. Studies were REB approved and all patients gave informed consent.Sixty-eight patients from the 3 trials are included. Median age at study enrolment was 47 (30-71) and patients were a median of 31 mo (9-197) from diagnosis. 54% were male. Median FLIPI score was 2. Median # of prior chemotherapies was 1. Median number of cycles of salvage chemotherapy was 4 (2 - 10). 63 patients proceeded to ASCT. 5 patients were not transplanted either do to disease progression (2), or failed stem cell mobilization (3). Baseline characteristics of the patients enrolled in the three trials were similar, with the exception of rituximab(R) exposure in 22% of the patients in Protocol 3. 4 (6%) patients were lost to follow up.Median time to death or last follow was 84.5 mo (7-166). 32 patients (47%) relapsed and 20 (29%) have died. Median follow up times for each trial were 116, 99 and 57 mo. Actuarial median OS for Protocol 1 was 136 mo from enrolment and has not yet been reached for Protocols 2 and 3. Actuarial median PFS for Protocols 1 and 3 are 49 and 78 mo respectively and has not yet been reached for Protocol 2.MRD assessment by PCR was collected on 48 patients. Compared with study 1, the increased use of R pre SC collection improved in vivo purging by 2 logs. In Protocols 1 and 2, most still had detectable disease in the graft to a sensitivity of 1 cell/100,000. In Protocol 3, 56% had MRD negative apheresis products. 91% of 46 evaluable patients achieved molecular remission post stem cell transplant.Thirteen patients (19%) developed secondary malignancies post ASCT with a median time to malignancy of 88.5 mo (39-144). 1 patient developed 2 distinct malignancies. Secondary malignancies present were: MDS (4), AML (1), ALL (1), basal cell carcinoma (2), squamous cell carcinoma (3), thyroid cancer (1), non small cell lung cancer (1) and adenocarcinoma of unknown origin (1). Five (7%) patients transformed to DLBCL, with a median time to transformation post ASCT of 43.5 mo (17-142).The majority of patients who received rituximab immunotherapy pre and post ASCT developed persistent hypogammaglobulinemia. 17 patients (26%) developed interstitial pneumonitis or >2 respiratory complications post rituximab. 4 patients (6%) require monthly IVIG to treat recurrent respiratory infections. 10 patients (15%) developed herpes zoster <90 days post ASCT.15% and 30% of patients in Protocols 1 and 3 did not complete the 2 years of alpha-IFN post ASCT secondary to one or more of depression, fatigue or cytopenias.HDT + ASCT combined with R +/− a-IFN produces durable PFS and molecular remissions but is associated with prolonged hypogammaglobulinemia and higher rates of interstitial pneumonitis. Three infusions of R pre SC collection achieve higher rates of molecular remission. Compliance with 2 years of a-IFN added to R post ASCT is poor and may not add clinical benefits to R alone. The additional role of HDT/ASCT in the era of R-chemotherapy for FL needs to be explored.No relevant conflicts of interest to declare.

To determine the characteristics and outcomes of patients who had been massively transfused at a university affiliated trauma centre.Consecutive patients who received ≥ 10 RBC units in ≤ 24 hours at Sunnybrook Health Sciences Centre and Women's College Hospital from January 2007 to December 2008 were identified. Demographic and outcome data were extracted through the blood bank database and retrospective chart analysis.6,326 patients were transfused a total of 19,845 RBC units in 2007 and 2008 at Sunnybrook Health Sciences Centre and Women's College Hospital. 134 consecutive massive transfusions among 131 patients were identified. Patients who were massively transfused received a total of 2,284 RBC units, represented 2.1% of the total number of patients transfused and used 11.5% of the total RBC units transfused. Their median age was 66 years and 63% were men. 50% survived to discharge. Of those who survived, 50% were discharged home, 41 % were discharged to a rehabilitation facility, and 9% was discharged to another acute care facility. A single patient had poor neurological function and was ventilator dependent at discharge.The median number of units transfused in ≤ 24 hrs among patients who received massive transfusions was 18.5 RBC units, 2 pools of platelets, 8 FFP and 8 cryoprecipitate. At our institution, 1 pool of platelet equals 4 individual platelets or a single apheresis platelet. Recombinant Factor 7a was utilized in 19% of the massive transfusions. Median length of stay in hospital was 17 days. Median time to death (TTD) from the massive transfusion event was 1 day.Overall survival (OS) among patients who were transfused 10–19 units (n=107), 20–29 (n=16), ≥30 (n=11) RBC units in ≤ 24 hours were: 56%, 31%, and 55% respectively. Indications and overall survival for massive transfusion were: trauma (49%, OS 51%, TTD 0 days), cardiac surgery (22%, OS 41%, TTD 12 days), oncologic surgery (12%, OS 63%, TTD 12 days), vascular surgery (6%,OS 50%, TTD 8.5 days), GI bleed (3%, OS 50%, TTD 18 days) and other (8%, OS 55%, TTD 19 days).Patients who have been massively transfused (≥10 RBC units in ≤ 24 hours) use a disproportionate amount of blood products. Trauma, cardiac and oncologic surgeries are the most common indications for massive transfusion at Sunnybrook Health Sciences Centre and Women's College Hospital. All causes of massive transfusion had similar mortality of approximately 50% and the majority of the survivors were discharged home or to rehabilitation with preserved neurological function. Transfusions of ≥ 30 RBC units in 24 hours were not associated with worse survival outcomes. A noticeable difference between the groups was in trauma where death occurred within hours of admission, while the majority of deaths for other causes occurred between 8 and 18 days later. These findings suggest that bleeding may have been directly responsible for most trauma deaths, while complications related to bleeding may have caused the late deaths observed in the other groups. Measures for defining medical futility, other than volume of blood products transfused, need to be sought.No relevant conflicts of interest to declare.