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Background: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late‐onset CHCs and nonrelapse mortality after aPBSCT. Methods: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre‐aPBSCT body composition and new‐onset grade 3–5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011–2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex‐specific z‐scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. Results: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non‐Hispanic Whites and 81% with non‐Hodgkin lymphoma. The 5‐year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%–56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50–0.96). The 10‐year cumulative incidence of NRM was 16% (95% CI, 10–22). No body composition measure was associated with NRM. Conclusions: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT. [ABSTRACT FROM AUTHOR]

Background: Blood or marrow transplantation (BMT) survivors carry a high burden of morbidity, yet health care utilization by this vulnerable population remains understudied. Patterns and predictors of various domains of health care utilization in long‐term BMT survivors were evaluated. Methods: Study participants were drawn from the Bone Marrow Transplant Survivor Study (BMTSS). Patients transplanted between 1974 and 2014 at one of three transplant centers who had survived ≥2 years after BMT and were aged ≥18 years at the time of the study were included. A BMTSS survey served as the source of data for health care utilization, sociodemographics, and chronic health conditions. Domains of health care utilization in the 2 years preceding study participation included routine checkups, BMT‐related visits, transplant/cancer center visits, emergency room (ER) visits, hospitalizations, and high health care utilization (≥7 physician visits during the 2 years before the study). Clinical characteristics and therapeutic exposures were abstracted from medical records. Results: In this cohort of 3342 BMT survivors (52% allogeneic), the prevalence of health care utilization declined over time since BMT for both allogeneic and autologous BMT survivors, such that among those who had survived ≥20 years, only 49%–53% had undergone routine checkups, 37%–38% reported BMT‐related visits, and 28%–29% reported transplant/cancer center visits. The presence of severe/life‐threatening conditions and chronic graft‐vs‐host disease increased the odds of health care utilization across all domains. Lower education, lack of insurance, and Hispanic ethnicity were associated with a lower prevalence of routine checkups and/or transplant/cancer center visits. Lower income increased the odds of ER visits but reduced the odds of hospitalizations or high health care utilization. Conclusions: This study identified vulnerable populations of long‐term BMT survivors who would benefit from specialized risk‐based anticipatory care to reduce high health care utilization, ER visits, and hospitalizations. Health care utilization (including routine medical checkups) declines with increasing time since blood or marrow transplantation, except among survivors with severe/life‐threatening chronic health conditions as well as those with chronic graft‐vs‐host disease. Lower education and lack of insurance are associated with lower health care utilization. [ABSTRACT FROM AUTHOR]

Background: Blood or marrow transplantation (BMT) is increasingly offered to older individuals with hematologic malignancies. The high prevalence of chronic health conditions in such individuals necessitates use of multiple medications. Beers Criteria represent a list of potentially inappropriate medications (PIMs) shown to increase the risk of health problems in the elderly. We sought to determine the prevalence and predictors of PIM use in older BMT survivors and identify associations with health problems. Methods: Study participants were drawn from the BMT Survivor Study, a cohort study of patients transplanted at three US transplant centers between 1974 and 2014 and surviving ≥2 years. For this report, the survivors were aged ≥65 years. Siblings served as a comparison group. Participants self‐reported sociodemographics, chronic health conditions, and medication use. Logistic regression analyses identified predictors of PIM use and associations with health problems. Results: Overall, PIM use was comparable between BMT survivors (49.4%) and siblings (49.3%) (odds ratio [OR] = 0.9; 95% CI, 0.7–1.2); however, BMT survivors were more likely to use >1 PIM (17.4% vs. 12.4%; OR = 1.5; 95% CI, 1.01–2.4) and central nervous system–related PIMs (8.3% vs. 4.3%; OR = 2.18; 95% CI, 1.17–4.09). Predictors of PIM use included presence of severe/life‐threatening chronic health conditions (OR = 1.5; 95% CI, 1.1–2.0), and chronic graft versus host disease (OR = 1.7; 95% CI, 1.1–2.7). Survivors taking >1 PIM reported more issues with vertigo (OR = 2.3; 95% CI, 1.1–4.7), balance (OR = 2.6; 95% CI, 1.7–4.1), faintness/dizziness (OR = 2.8; 95% CI, 1.8–4.6), and personal care (OR = 4.5; 95% CI, 1.4–14.8). Conclusions: This study shows the health problems associated with PIM use and identifies vulnerable populations at higher risk for PIM use, providing evidence for caution in using PIMs in high‐risk populations. Older blood or marrow transplantation survivors were more likely to use multiple potentially inappropriate medications than a sibling comparison group. Survivors with multimorbidity and/or chronic graft versus host disease were more likely to use these medications; survivors taking multiple potentially inappropriate medications reported several health problems. [ABSTRACT FROM AUTHOR]

Background: Therapy‐related myeloid neoplasms (t‐MN) are a leading cause of nonrelapse mortality after autologous peripheral blood stem cell transplantation (aPBSCT) in patients with Hodgkin lymphoma (HL) and non‐Hodgkin lymphomas (NHL). t‐MN patients treated at an earlier stage of disease evolution have a better prognosis, and this presents a need to identify patients at risk for t‐MN. Methods: Using a prospective longitudinal study design, this study evaluated peripheral blood parameters pre‐aPBSCT and on day 100, at 6 months, 1 year, 2 years, and 3 years in 304 patients treated with aPBSCT. The relation between peripheral blood parameters and subsequent development of t‐MN was examined, and nomograms were developed to identify patients at risk for t‐MN. Results: Twenty‐one patients developed t‐MN at a median of 1.95 years post‐aPBSCT. Hemoglobin, hematocrit, white blood cell, and platelet counts were lower among patients who developed t‐MN compared to those who did not; these differences appeared soon after aPBSCT, persisted, and preceded development of t‐MN. Older age at aPBSCT (hazard ratio [HR]per_year_increase = 1.08, P =.007), exposure to total body irradiation (TBI) (HR = 2.90, P =.04), and low 100‐day platelet count (HRincrease_per_unit_decline_in_PLT = 1.01, P =.002) predicted subsequent t‐MN. These parameters and primary diagnosis allowed identification of patients at high risk of t‐MN (eg, an HL patient undergoing aPBSCT at the age of 70 years with TBI and with a day 100 PLT between 100,000 and 150,000 would have a 62% probability of developing t‐MN at 6 years post‐aPBSCT). Conclusions: Abnormalities in peripheral blood parameters can identify patients at high risk for t‐MN after aPBSCT for HL or NHL, allowing opportunities to personalize close surveillance and possible disease‐modifying interventions. In this longitudinal study of patients with lymphoma treated with autologous peripheral blood stem cell transplantation, blood parameters are altered among patients who subsequently develop therapy‐related leukemia in comparison with those who do not. These differences appear soon after transplantation, persist, and precede the development of therapy‐related myeloid neoplasms. This allows the identification of those at high risk for therapy‐related leukemia and provides opportunities to personalize close surveillance and possible disease‐modifying interventions among those at highest risk. [ABSTRACT FROM AUTHOR]

Background: Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease–positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19– disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood. Methods: This study retrospectively reviewed the outcomes of adult patients with B‐cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013‐2021) and analyzed factors associated with treatment response and EMD failure. Results: The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P =.049) and no history of previous EMD (P =.019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P =.005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P =.012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD. Conclusions: A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure. Lay Summary: Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia.A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites.Most extramedullary failure cases retain CD19 expression. Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites. [ABSTRACT FROM AUTHOR]

Blinatumomab is a bispecific T cell‐engaging antibody approved for treatment of relapsed/refractory (r/r) ALL, with 40%‐50% complete response (CR)/CR with incomplete count recovery (CRi). Cytokine release syndrome (CRS) as a major adverse effect after blinatumomab therapy. Here, we evaluated the possible association between single‐nucleotide polymorphisms (SNPs) in cytokine genes, disease response, and CRS in r/r ALL patients who received blinatumomab between 2012 and 2017 at our center (n = 66), using patients' archived DNA samples. With a median duration of 9.5 months (range: 1‐37), 37 patients (56.1%) achieved CR/CRi, 54 (81.8%) experienced CRS (G1: n = 35, G2: n = 14, G3: n = 5), and 9 (13.6%) developed neurotoxicity. By multivariable analysis, after adjusting for high disease burden, one SNP on IL2 (rs2069762), odds ratio (OR) = 0.074 (95% CI: NE‐0.43, P =.01) and one SNP on IL17A (rs4711998), OR = 0.28 (95% CI: 0.078‐0.92, P =.034) were independently associated with CR/CRi. None of the analyzed SNPs were associated with CRS. To our knowledge, this is the first study demonstrating a possible association between treatment response to blinatumomab and SNPs. Our hypothesis‐generated data suggest a potential role for IL‐17 and IL‐2 in blinatumomab response and justify a larger confirmatory study, which may lead to personalized blinatumomab immunotherapy for B‐ALL. [ABSTRACT FROM AUTHOR]

Background: Blood or bone marrow transplantation (BMT) survivors with frailty are at a higher risk of subsequent mortality. Longitudinal trends in the frailty state are not known and could help identify vulnerable subpopulations at risk of subsequent adverse events. Methods: This study included a cohort of 470 autologous and allogeneic BMT recipients who had survived ≥2 years after BMT and completed a baseline questionnaire (t1) at a median of 7.3 years after BMT and a follow‐up questionnaire (t2) 13.2 years after t1. The main outcome was change in frailty state between t1 and t2. Frailty phenotype was defined as exhibiting ≥3 of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The following categories of change in frailty state were evaluated: worsened, improved, and stable. Results: Of the 470 participants, 36.4% were aged ≥60 years at t1, and 50.6% were men. The prevalence of frailty increased from 4.8% at t1 to 9.6% at t2. Worsening was observed in 18.8% of patients, and improvement was reported in 9.7%. Pre‐BMT exposure to vincristine (odds ratio [OR], 2.1; 95% CI, 1.3‐3.39) was associated with worsening. Female sex (OR, 1.5; 95% CI, 0.93‐2.4) was associated with a trend toward worsening. Pre‐BMT exposure to vincristine (OR, 2.79; 95% CI, 1.44‐5.43), a history of chronic graft‐versus‐host disease (OR, 2.58; 95% CI, 1.2‐5.5), and grade 3 and 4 chronic health conditions at t1 (OR, 2.1; 95% CI, 1.08‐4.33) were associated with frailty at t2. Conclusions: In a cohort of BMT survivors who were followed longitudinally for a median of 20.6 years from BMT, the frailty status worsened for approximately20% over a 13‐year timespan. BMT survivors who are at risk for worsening frailty could benefit from targeted interventions. In bone marrow transplantation survivors who were followed for a median of 13 years, the prevalence of frailty increased from 4.8% to 9.6%. Exposure to vincristine before bone marrow transplantation was associated with 2.1 times greater odds (95% CI, 1.3‐3.39 greater odds) of a worsening frailty state. [ABSTRACT FROM AUTHOR]

Background: The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non‐malignant diseases and may predict outcomes after autologous HCT. Methods: This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non‐Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: <43 cm/m2 [body mass index (BMI) < 25 kg/m2] or < 53 cm/m2 [BMI ≥ 25 kg/m2] and female: <41 cm/m2 [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm2 (male), ≥396.4 cm2 (female)] were assessed from single‐slice abdominal pre‐HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30‐day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan–Meier analysis and Gray's test. Results: Median age at HCT was 53.3 years (range, 18.5 to 78.1 years); 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre‐HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.3–9.8], intensive care unit admission (OR = 4.7, 95% CI 1.5–16.1), and unplanned readmission after HCT (OR = 13.6, 95% CI 2.5–62.8). Patients who were sarcopenic obese also had the highest mortality risk at 1 year [hazard ratio (HR): 3.9, 95% CI 1.1–11.0] and 5 years (HR: 2.5, 95% CI 1.1–5.5), compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese. Conclusions: Sarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT. [ABSTRACT FROM AUTHOR]

Background: Autologous blood or bone marrow transplantation (aBMT) is considered the standard of care for patients with multiple myeloma (MM). Significantly improved survival necessitates an understanding of the morbidity burden borne by the growing survivor population.Methods: The authors evaluated severe and/or life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs) in patients with MM who were treated with aBMT using the Bone Marrow Transplant Survivor Study. A total of 630 study participants had undergone aBMT for MM at 1 of 3 BMT centers, had survived ≥2 years after aBMT, and were aged ≥18 years at the time of survey completion. Survivors of aBMT identified 289 nearest-age siblings to constitute an unaffected comparison group. Scoring of CHCs was based on version 5 of the National Cancer Institute Common Terminology Criteria for Adverse Events to determine severity (with grade 3 indicating serious and grade 4 indicating life-threatening).Results: The 10-year cumulative incidence of any grade 3 to 4 CHC among survivors of aBMT was 57.6 ± 3.2%. Survivors of MM were found to be at 40% higher odds of developing grade 3 to 4 CHCs when compared with siblings (95% confidence interval [95% CI], 1.0-1.9). Among SNs, 96% were solid tumors, yielding a 10-year cumulative incidence of 13.6% ± 2.5%. Pre-aBMT exposure to cyclophosphamide (hazard ratio [HR], 3.5; 95% CI, 1.5-8.1) and immunomodulatory drugs (HR, 3.9; 95% CI, 1.5-10.1) were associated with an increased risk of solid tumors. Melanoma (10-year cumulative incidence: 3.3% ± 1.2%) and squamous cell carcinoma (10-year cumulative incidence: 5.1% ± 1.8%), were the most common SNs. Pre-aBMT exposure to cyclophosphamide (HR, 6.02; 95% CI, 1.4-26.1) and immunomodulatory drugs (HR, 7.9; 95% CI, 0.9-68.5) was associated with an increased risk of melanoma.Conclusions: The 10-year cumulative incidence of severe and/or life-threatening CHCs was found to approach 60% in long-term survivors of MM, with solid SNs constituting a large morbidity burden. The current study has provided evidence supporting the close monitoring of survivors to manage morbidity. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment in survivors of blood or bone marrow transplantation (BMT) is well documented. However, to the authors' knowledge, the clinical relevance of self-endorsed cognitive problems and their relation to objectively assessed cognitive impairment is not known.Methods: The authors assessed cognitive impairment in 378 BMT recipients (median age, 52.2 years, 40% of whom were female and 68% of whom were non-Hispanic white) and 98 healthy controls at 5 predetermined time points: at baseline (before BMT) and at 6 months, 1 year, 2 years, and 3 years after BMT. Self-endorsed cognitive problems were evaluated using the Neuropsychological Impairment Scale (NIS) and correlated with a standardized 2-hour battery of objective cognitive testing at each time point. The authors examined the magnitude of difference in self-endorsed cognitive problems between BMT recipients and healthy controls, and the rate of change in scores over time. Multivariable analyses were used to identify clinical and/or demographic variables associated with self-endorsed cognitive problems. The authors also examined the association between cognitive impairment and returning to work after BMT.Results: Compared with healthy controls, BMT recipients endorsed more cognitive problems (P < .001) at all time points, and the rate of change in NIS scores was found to be significantly greater in BMT recipients. Fatigue was associated with greater endorsement of cognitive problems at 1 year after BMT (odds ratio, 4.23; 95% CI, 2.1-8.3 [P < .001]). Overall, there was a statistically significant, modest correlation noted between self-endorsed cognitive problems and objective cognitive impairment (range, 0.401-0.445 [P ≤ .01]). Higher self-endorsed cognitive problems were associated with a 3.7-fold (P = .02) higher odds of not returning to work at 3 years after BMT.Conclusions: The results of the current study demonstrated that self-endorsed cognitive problems can help to identify vulnerable patient subpopulations for detailed cognitive assessment and possible cognitive remediation. [ABSTRACT FROM AUTHOR]

Background: Patients with non-Hodgkin lymphoma (NHL) have an increased risk of venous thromboembolism (VTE), particularly when they are receiving treatment. Blood or marrow transplantation (BMT) is recommended for relapsed/refractory NHL, and the risk of VTE after these patients undergo BMT is uncertain.Methods: Patients with NHL who survived 2 years or longer after BMT were surveyed for long-term health outcomes, including VTE. The median follow-up was 8.1 years (interquartile range, 5.6-12.9 years). The risk of VTE in 734 patients with NHL versus 897 siblings without a history of cancer and the risk factors associated with VTE were analyzed.Results: BMT survivors of NHL were at increased risk for VTE in comparison with siblings (odds ratio for allogeneic BMT survivors, 4.61; P < .0001; odds ratio for autologous BMT survivors, 1.75; P = .035). The cumulative incidence of VTE was 6.3% ± 0.9% at 5 years after BMT and 8.1% ± 1.1% at 10 years after BMT. In allogeneic BMT recipients, an increased body mass index (BMI; hazard ratio [HR] for BMI of 25-30 kg/m2 , 3.52; 95% confidence interval [CI], 1.43-8.64; P = .006; HR for BMI > 30 kg/m2 , 3.44; 95% CI, 1.15-10.23; P = .027) and a history of chronic graft-versus-host disease (HR, 3.33; 95% CI, 1.59-6.97; P = .001) were associated with an increased risk of VTE. Among autologous BMT recipients, a diagnosis of coronary artery disease (HR, 5.94; 95% CI, 1.7-20.71; P = .005) and prior treatment with carmustine (HR, 4.91; 95% CI, 1.66-14.51; P = .004) were associated with increased VTE risk.Conclusions: Patients with NHL who survive BMT are at risk for developing late occurring VTE, and ongoing vigilance for this complication is required. Future studies assessing the role of thromboprophylaxis in high-risk patients with NHL are needed. [ABSTRACT FROM AUTHOR]

Background: Blinatumomab, a bispecific T-cell-engaging (BiTE®) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab.Methods: In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT.Results: Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P = .68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status.Conclusions: Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab.Lay Summary: Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT. [ABSTRACT FROM AUTHOR]

Background: Late mortality was investigated in patients with chronic myelogenous leukemia (CML) who underwent blood or bone marrow transplant (BMT) with or without prior tyrosine kinase inhibitor (TKI) therapy.Methods: By using data from the Blood or Marrow Transplant Survivor Study, the authors examined late mortality in 447 patients with CML who underwent BMT between 1974 and 2010, conditional on surviving ≥2 years post-BMT. For vital status information, the medical records, the National Death Index, and the Accurint database were used. Standardized mortality ratios (SMRs) were calculated using general population age-specific, sex-specific, and calendar-specific mortality rates. Kaplan-Meier techniques and Cox regression were used for all-cause mortality analyses. Cumulative incidence and proportional subdistribution hazards models for competing risks were used for cause-specific mortality analyses.Results: The 10-year overall survival rate was 65.7% and 73% for those who underwent transplant with and without pre-BMT exposure to TKI therapy, respectively. Patients who underwent transplant with and without pre-BMT TKI experienced SMRs of 6.4 and 6.4, respectively (P = .8); and the SMRs were 11.6 and 8.1, respectively, for those with high-risk disease (P = .2). Independent predictors of non-CML-related mortality included chronic graft-versus-host disease (hazard ratio [HR], 2.8; 95% CI, 1.8-4.4) and busulfan/cyclophosphamide conditioning (HR, 0.5; 95% CI, 0.3-0.9; reference, total body irradiation/cyclophosphamide conditioning). The 20-year cumulative incidence of CML-related and non-CML-related mortality was 6% and 36%, respectively, for the entire cohort. Both CML-related mortality (HR, 1.0; 95% CI, 0.1-12.6) and non-CML-related mortality (HR, 1.3; 95% CI, 0.6-3.1) were comparable for those with and without pre-BMT TKI therapy.Conclusions: The similar late mortality experienced by patients with CML who undergo transplantation with or without pre-BMT TKIs suggests that allogeneic BMT can be considered in the context of TKI intolerance or nonadherence. The prevention of post-BMT non-CML-related mortality could favorably affect long-term survival. [ABSTRACT FROM AUTHOR]

We conducted a retrospective analysis of AML patients treated with the combination of VEN/HMA at our institution between June 2016 and April 2019. Furthermore, we also show a promising CR/CRi rate (38%) in patients with r/r I TP53 i m AML, which includes some patients relapsing after prior alloHCT. Most patients in our cohort received decitabine as their HMA, and this preference may have been influenced by results of a study utilising 10-day courses of decitabine in I TP53 i m myeloid neoplasms and yielding a 100% response rate (Welch I et al i , [10]). Although our preliminary results with VEN/HMA appear favourable compared to the dismal outcomes reported in I TP53 i m AML patients when treated with conventional combination chemotherapy (Grossmann I et al i , [5]; Rucker I et al i , [7]), the median LFS was relatively short, and relapses occurred frequently. [Extracted from the article]

Induction of reactive oxygen species (ROS), an important process for the cytotoxicity of various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates the NF‐E2‐related factor 2 (Nrf2) antioxidant response pathway which in turn results in induction of antioxidant enzymes that neutralize ROS. In this study, we demonstrated that Nrf2 inhibition is an additional mechanism responsible for the marked antileukemic activity in AML seen with the combination of HMAs and venetoclax (ABT‐199). HMA and venetoclax combined treatment augmented mitochondrial ROS induction and apoptosis compared with treatment HMA alone. Treatment of AML cell lines as well as primary AML cells with venetoclax disrupted HMA decitabine‐increased nuclear translocation of Nrf2 and induction of downstream antioxidant enzymes including heme oxygenase‐1 and NADP‐quinone oxidoreductase‐1. Venetoclax treatment also leads to dissociation of B‐cell lymphoma 2 from the Nrf2/Keap‐1 complex and targets Nrf2 to ubiquitination and proteasomal degradation. Thus, our results here demonstrated an undiscovered mechanism underlying synergistic effect of decitabine and venetoclax in AML cells, elucidating for impressive results in antileukemic activity against AML in preclinical and early clinical studies by combined treatment of these drugs. [ABSTRACT FROM AUTHOR]

The article discusses late mortality in blood or marrow transplant survivors with venous thromboembolism. Topics include how Haemostatic complications are commonly observed in patients undergoing blood or marrow transplantation (BMT), and are related to thrombocytopenia and immunological complications.

Background: Anthracycline-related heart failure is a leading cause of morbidity in survivors of adult-onset lymphoma. There is a paucity of information on screening for late-occurring preclinical disease, which, in turn, has limited guidelines for early detection and intervention. The objectives of this study were to examine the prevalence and risk of cardiac dysfunction, as measured by echocardiography (abnormal left ventricular systolic/diastolic function or strain), in lymphoma survivors who received treatment with anthracyclines and to evaluate the diagnostic yield of blood biomarkers in the asymptomatic setting.Methods: Lymphoma survivors who underwent hematopoietic cell transplantation (HCT) (n = 78) or received conventional therapy (non-HCT; n = 77) were compared with each other and with a group of matched controls (n = 51); the study was limited to lymphoma survivors who were >5 years from diagnosis.Results: At a median follow-up of 9.4 years after diagnosis, 1 in 5 (20.6 %) lymphoma survivors had cardiac dysfunction; the odds of having cardiac dysfunction were 6.6-fold greater (odds ratio [OR], 6.6; P = .01) among lymphoma survivors compared with matched controls. There was a dose-dependent risk of cardiac dysfunction according to the cumulative anthracycline dose (controls [referent group], 1-249 mg/m2 [OR, 4.7; P = .05], and ≥250 mg/m2 [OR, 7.6; P < .01]), but there was no difference in the prevalence of cardiac dysfunction between conventionally treated and HCT survivors. The diagnostic accuracy of cardiac blood biomarkers in the asymptomatic setting was quite poor.Conclusions: In these long-term survivors, there was a high rate of cardiac dysfunction that was independent of HCT status. The growing number of lymphoma survivors makes it imperative to identify reliable and cost-effective strategies to decrease the burden of heart failure in this population. Cancer 2018;124:850-7. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is incurable with conventional therapies. Limited retrospective data have shown durable remissions after haematopoietic cell transplantation (HCT) [allogeneic (allo) or autologous (auto)]. We conducted a multicentre retrospective study in BPDCN patients treated with allo-HCT and auto-HCT at 8 centres in the United States and Canada. Primary endpoint was overall survival (OS). The population consisted of 45 consecutive patients who received an allo-HCT (n = 37) or an auto-HCT (n = 8) regardless of age, pre-transplant therapies, or remission status at transplantation. Allo-HCT recipients were younger (50 (14–74) vs. 67 (45–72) years, P = 0·01) and had 1-year and 3-year OS of 68% [95% confidence interval (CI) = 49–81%] and 58% (95% CI = 38–75%), respectively. Allo-HCT in first complete remission (CR1) yielded superior 3-year OS (versus not in CR1) [74% (95% CI = 48–89%) vs. 0, P < 0·0001]. Allo-HCT outcomes were not impacted by regimen intensity [3-year OS for myeloablative conditioning = 61% (95% CI = 28–83%) vs. reduced-intensity conditioning = 55% (95% CI = 28–76%)]. One-year OS for auto-HCT recipients was 11% (95% CI = 8–50%). These results demonstrate efficacy of allo-HCT in BPDCN, especially in patients in CR1. Pertaining to auto-HCT, our results suggest lack of efficacy against BPDCN, but this observation is limited by the small sample size. Larger prospective studies are needed to better define the role of HCT in BPDCN. [ABSTRACT FROM AUTHOR]

Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto- HCT) is effective for younger patients with mantle cell lymphoma ( MCL). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyper CVAD/ MTX/ ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) ( RH) versus rituximab plus bendamustine ( RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto- HCT. Fifty-three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2-year progression-free survival ( PFS) was 81% vs. 82% and overall survival ( OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi-centre transplant trials in MCL. RB achieved a 2-year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL. [ABSTRACT FROM AUTHOR]

The article discusses a study that examined the association between breast implants and incident T-cell lymphomas in the California Teachers Study (CTS) cohort comprised of female public school professionals who enrolled in 1995 to 1996. Results indicate a positive association between breast implants and anaplastic large cell lymphoma (ALCL) risk. Possible reasons for the study's discordance with previous studies include differences in population sampling and insufficient sample size.

Invasive mold infections (IMI) are life-threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT) and are mostly caused by Aspergillus species and Mucorales. We examined whether elevated serum ferritin prior to HSCT was associated with increased risk of IMI after allogeneic HSCT. Elevated serum ferritin was defined as values ≥1000 ng/mL. Pretransplant ferritin levels were available for 477 transplants. Nine developed IMI at day 30 and 21 had IMI at day 100 for a cumulative incidence of 1.9% and 4.4%, respectively. Among the high ferritin group, eight of 220 transplant cases (3.6%) developed an IMI within 30 d after HSCT compared with one of 257 (0.4%) in the low ferritin group ( P = 0.01). Fourteen of 220 (6.4%) and seven of 257 transplant cases (2.7%) in the high and low ferritin groups, respectively, had developed an IMI by day 100 after HSCT ( P = 0.07). Nine of 53 (17%) patients with grades III and IV acute GVHD and iron overload experienced IMI, when compared to three of 37 (8.1%) with high-grade aGVHD, but no iron overload. Among patients without aGVHD, those with elevated ferritin had a 2.7% incidence of IMI compared with 0.9% for patients without elevated ferritin. There was a marginally significant difference in cumulative incidence function between high and low ferritin groups for IMI ( P = 0.06). However, elevated serum ferritin (≥1000 ng/mL) was not a significant risk factor for IMI in a multivariate competing risk regression model after adjusting for aGVHD. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade has emerged as a potent new tool in the war on cancer. However, only a subset of cancer patients benefit from this therapeutic modality, sparking a search for combination therapies to increase the fraction of responding patients. We argue here that inhibition of protein phosphatase 2A (PP2A) is a promising approach to increase responses to immune checkpoint blockade and other therapies that rely on the presence of tumor‐reactive T cells. Inhibition of PP2A increases neoantigen expression on tumor cells, activates the cGAS/STING pathway, suppresses regulatory T cells, and increases cytotoxic T cell activation. In preclinical models, inhibition of PP2A synergizes with immune checkpoint blockade and emerging evidence indicates that patients who have tumors with mutations in PP2A respond better to immune checkpoint blockade. Therefore, inhibition of PP2A activity may be an effective way to sensitize cancer cells to immune checkpoint blockade and cell‐based therapies using tumor‐reactive T cells. [ABSTRACT FROM AUTHOR]

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is associated with a poor response to standard chemotherapy. However, outcomes with novel antibody and cellular therapies in relapsed/refractory (r/r) Ph-like ALL are largely unknown. We conducted a single-center retrospective analysis of adult patients (n = 96) with r/r B-ALL and fusions associated with Ph-like who received novel salvage therapies. Patients were treated with 149 individual novel regimens (blinatumomab = 83, inotuzumab ozogamicin [InO] = 36, and CD19CAR T cells = 30). The median age at first novel salvage therapy was 36 years (range; 18-71). Ph-like fusions were IGH::CRLF2 (n = 48), P2RY8::CRLF2 (n = 26), JAK2 (n = 9), ABL-class (n = 8), EPOR::IGH (n = 4) and ETV6::NTRK2 (n = 1). CD19CAR T cells were administered later in the course of therapy compared to blinatumomab and InO (p < .001) and more frequently in recipients who relapsed after allogeneic hematopoietic cell transplantation (alloHCT) (p = .002). Blinatumomab was administered at an older age compared to InO and CAR T-cells (p = .004). The complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates were 63%, 72%, and 90% following blinatumomab, InO and CD19CAR, respectively, among which 50%, 50%, and 44% of responders underwent consolidation with alloHCT, respectively. In multivariable analysis, the type of novel therapy (p = .044) and pretreatment marrow blasts (p = .006) predicted the CR/CRi rate, while the Ph-like fusion subtype (p = .016), pretreatment marrow blasts (p = .022) and post-response consolidation with alloHCT (p < .001) influenced event-free survival. In conclusion, novel therapies are effective in inducing high remission rates in patients with r/r Ph-like ALL and successfully transitioning the responders to alloHCT., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)