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Acute myeloid leukemia (AML) is a hematologic malignancy that most frequently develops in older adults. Overall, AML is associated with a high mortality although advancements in genetic risk stratification and new treatments are leading to improvements in outcomes for some subgroups. In this review, we discuss an individualized approach to intensive therapy with a focus on the role of recently approved novel therapies as well as the selection of post-remission therapies for patients in first remission. We discuss the management of patients with relapsed and refractory AML, including the role of targeted treatment and allogeneic stem cell transplant. Next, we review non-intensive treatment for older and unfit AML patients including the use of azacitidine and venetoclax. Finally, we discuss the integration of palliative care in the management of patients with AML. [ABSTRACT FROM AUTHOR]

Objectives: Acute myeloid leukaemia (AML) is a disease of older adults, who are vulnerable to socio‐economic factors. We determined AML incidence in older adults and the impact of socio‐economic factors on outcomes. Methods: We included 3024 AML patients (1996–2016) identified from a population‐based registry. Results: AML incidence in patients ≥60 years increased from 11.01 (2001–2005) to 12.76 (2011–2016) per 100 000 population. Among 879 patients ≥60 years in recent eras (2010–2016), rural residents (<100 000 population) were less likely to be assessed by a leukaemia specialist (39% rural, 47% urban, p =.032); no difference was seen for lower (43%, quintile 1–3) vs. higher (47%, quintile 4–5) incomes (p =.235). Similar numbers received induction chemotherapy between residence (16% rural, 18% urban, p =.578) and incomes (17% lower, 17% high, p = 1.0). Differences between incomes were seen for hypomethylating agent treatment (14% low, 20% high, p =.041); this was not seen for residence (13% rural, 18% urban, p =.092). Among non‐adverse karyotype patients ≥70 years, 2‐year overall survival was worse for rural (5% rural, 12% urban, p =.006) and lower income (6% low, 15% high, p =.017) patients. Conclusions: AML incidence in older adults is increasing, and outcomes are worse for older rural and low‐income residents; these patients face treatment barriers. [ABSTRACT FROM AUTHOR]

Features for consideration of VEXAS syndrome in patients with autoinflammatory symptoms include dermatologic manifestations, myelodysplastic syndrome or monoclonal gammopathy, and vacuolation of myeloid and erythroid precursors in bone marrow. Through genomic sequencing, some patients with previously undiagnosed autoinflammatory diseases are now understood to have a new syndrome called vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. [Extracted from the article]

There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. We also review the role of oxidative phosphorylation (OxPhos) in maintaining leukemia stem cells (LSCs), how recurrent genomic alterations in AML alter downstream metabolism, and focus on how the BCL-2 pathway and the mitochondria are inextricably linked in AML. Thus, we provide an overview of the mitochondria and metabolism in the context of our new therapeutic world for AML and outline how targeting these vulnerabilities may produce novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (CHL) is the rarest post-transplant lymphoproliferative disorder (PTLD) subtype. Few cases of patients with metachronous discordant PTLD episodes including CHL-PTLD have been reported, but the incidence of and risk factors for this phenomenon are unknown. Patients with CHL-PTLD were identified from an institutional PTLD database. Of 13 patients identified with CHL-PTLD six (46%) had antecedent non-CHL-PTLD: three had polymorphic PTLD, two monomorphic PTLD, and one nondestructive PTLD. Patients with prior metachronous non-CHL-PTLD were younger at transplant and had a longer latency time to CHL-PTLD post-transplant. The prevalence of EBV seronegativity at transplant was high in both groups, but prolonged high-level EBV DNAemia only occurred in some with metachronous non-CHL-PTLD. In conclusion, patients with CHL-PTLD have metachronous non-CHL-PTLD diagnoses with discordant histology more commonly than previously recognized. Primary EBV infection with chronically elevated EBV viral loads may represent unique risk factors for CHL-PTLD following an initial non-CHL-PTLD event. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure. We aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC. A retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure. Three hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3–99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001). In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3–12.3, P < 0.01), primary graft failure (OR 36.3, 5.4–210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7–121.1, P < 0.01). Patients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2–3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased. [ABSTRACT FROM AUTHOR]

Introduction: Epstein‐Barr virus (EBV) associated smooth muscle tumors (EBV‐SMT) are a rare complication of solid organ transplantation (SOT). Incidence data related to this EBV‐SMT are limited. EBV DNA is universally present in these tumors. How these cells get infected with EBV, whether this is a result of primary EBV infection vs reactivation, and how persistent active EBV infection post‐transplant influences EBV‐SMT pathogenesis remains unknown. Methods: Among 5006 SOT recipients (474 pediatric, 4532 adult) receiving SOT at our center between Jan 1984 and Dec 2015, three cases of post‐transplant EBV‐SMT were identified. Results: All cases were pediatric heart transplants who were EBV seronegative prior to transplant, and experienced primary EBV infection with persistently elevated EBV viral loads, despite antiviral therapy. Two are deceased at 3.2 and 0.9 years post‐diagnosis, while one remains alive 6.2 years post diagnosis. The overall local incidence of post‐transplant EBV‐SMT at our institution was 0.7 (95% CI, 0.2‐1.7) per 1000 patient years, and 2.6 (95% CI, 0.6‐6.7) per 1000 patient years in pediatric heart transplants. A literature review identified 36 pediatric and 51 adult cases of post‐transplant EBV‐SMT. Conclusions: We hypothesize that pre‐transplant EBV seronegativity, followed by primary EBV infection and persistently high EBV viral loads, represents a unique risk factor for post‐transplant EBV‐SMT. Pediatric heart transplant recipients were found to be disproportionately affected by post‐transplant EBV‐SMT at our institution. [ABSTRACT FROM AUTHOR]

Myeloid and erythroid precursor vacuolation is a common dysplastic finding associated with myeloid malignancies, toxins, drug, and nutritional deficiencies. It has been described as a core morphologic feature in VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome. We sought to determine the number of cases attributable to VEXAS syndrome in bone marrow biopsies and aspirates (BAMB) reporting myeloid precursor vacuolation. We reviewed 1318 individual BAMB reports from January 2020 to July 2021 where "vacuole(s)," "vacuolation," or "vacuolated" was reported. Bone marrow biopsies with vacuolation confined to blasts or those completed as routine workup prior to stem cell transplant or post induction chemotherapy for AML (acute myeloid leukemia) were excluded. Myeloid and erythroid precursor vacuolation was noted in 219 reports representing 210 patients. The most common etiology was myelodysplastic syndrome (MDS) (38.6%), AML (16.7%), lymphoproliferative disorders and multiple myeloma (7.6%), drug or toxin exposure (5.2%) myeloproliferative neoplasm (MPN) or MPN/MDS overlap syndrome (4.3%). VEXAS syndrome was determined to be the etiology in 2.9% of patients. Two additional cases of VEXAS syndrome with bone marrow biopsies reported in the specified time frame did not explicitly report myeloid or erythroid precursor vacuolation but were identified based on clinical suspicion and repeat BAMB review. Myeloid and erythroid precursor vacuolation is a dysplastic feature attributable to VEXAS syndrome in at least 2.9% of cases. Standardized reporting of vacuolization, triaging of molecular sequencing and optimal treatment of this disorder are critical issues facing those seeing patients with suspected VEXAS syndrome. [ABSTRACT FROM AUTHOR]

Summary: Post‐transplant lymphoproliferative disorder (PTLD) may arise after solid organ transplantation, and the most common subtype resembles diffuse large B cell lymphoma (DLBCL). In DLBCL‐type PTLD, the anti‐CD20 antibody rituximab (R) may be combined with chemotherapy (R‐CHOP) or use a strategy (R‐primary; similar to the PTLD‐1 clinical trial) consisting of induction with four weekly doses of R‐alone, without any chemotherapy or sequential R‐CHOP follow‐up. Here we report on a multicentre retrospective cohort of solid organ transplant patients with DLBCL‐type PTLD that were treated with R. In 168 adults, two‐year overall survival (OS) was 63·7% [95% CI (confidence interval) 56·6–71·7%]. No difference in OS was observed, whether patients were treated with R‐CHOP versus the R‐primary strategy. In the 109 patients treated with R‐primary, multivariate analysis found that baseline IPI score and the response to R‐induction predicted OS. Patients who responded to R‐induction had durable remissions without the addition of chemotherapy. Conversely, of the 46 patients who had stable or progressive disease after R‐induction (R‐failure), those who received R‐CHOP had an only marginally improved outcome, with a two‐year OS of 45% (23·1–65·3%) vs. no R‐CHOP at 32% (14·7–49·8%). In real‐world patients, R‐failure and high IPI scores predict a poor outcome in DLBCL‐type PTLD. [ABSTRACT FROM AUTHOR]