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Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high nonrelapse mortality (NRM) rates, primarily from graft-versus-host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD after alloBMT. Here, we examine the impact of PTCy in patients with MM undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning. Post-transplantation GVHD prophylaxis consisted of cyclophosphamide (50 mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients, with neutrophil and platelet recovery at a median of 15 and 16 days, respectively. The cumulative incidences of acute grades 2 to 4 and grades 3 and 4 GVHD were .41 and .08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was .13. One patient succumbed to NRM. All cases of chronic GVHD involved extensive disease and 60% of these patients received systemic therapy with complete resolution. After alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression-free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was .46 (95% confidence interval [CI], .3 to .62) at 1 year and .56 (95% CI, .41 to .72) at 2 years. At last follow-up, 23% of patients remain without evidence of disease at a median follow-up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5-year and 10-year overall survival probabilities were 49% (95% CI, 35% to 67%) and 43% (95% CI, 29% to 62%), respectively. The use of PTCy after alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplantation maintenance strategies to improve long-term disease control. [ABSTRACT FROM AUTHOR]

Quercetin-Magnesium complex is one of the youngest alkaline rare earth metal (Magnesium) complexes with flavonoids (Quercetin) in organo-metalic family. Earlier studies describe the details of the complex formation, characterization and antioxidant study of the complex but toxicity profile is still under darkness. The present study was taken up to investigate the oral acute toxicity, 28 days repeated oral sub-acute toxicity study and genotoxicity study of Quercetin-Magnesium complex in Swiss albino mice. Quercetin-Magnesium complex showed mortality at a dose of 185 mg/kg in the Swiss albino mice. In 28 days repeated oral toxicity study, Quercetin-Magnesium complex was administered to both sex of Swiss albino mice at dose levels of 150, 130 and 100 mg/kg body weight respectively. Where 150 mg/kg dose shows increased levels of white blood cells and changes in total protein, serum creatinine and blood urea nitrogen. Histopathological study of Quercetin-Magnesium complex shows minor structural alteration in kidney at 150 mg/kg dose. No observed toxic level found in 130 mg/kg or below doses. No genotoxic effect found in any doses of the complex. Therefore 130 mg/kg or below dose level could be better for further study. [ABSTRACT FROM AUTHOR]

Quercetin (3,3′,4′,5,7-pentahydroxyflavone) one of the most abundant dietary flavonoids, has been investigated in the presence of magnesium (II) in methanol. The complex formation between quercetin and magnesium (II) was examined under UV–visible, Infra-red and 1 H NMR spectroscopic techniques. The spectroscopic data denoted that quercetin can reacts with magnesium cation (Mg +2 ) through the chelation site in the quercetin molecule. The free radical antioxidant activity of the complex with respect to the parent molecule was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. It was observed that the free radical scavenging activity of quercetin was increased after complexation of magnesium (Mg +2 ) cation. [ABSTRACT FROM AUTHOR]

Abstract: Several key observations providing evidence for the cancer stem cell hypothesis and insights into the unique biology of these cells have come from the study of multiple myeloma. These include evidence that cancer cells may be functionally heterogeneous in spite of their genetic homogeneity and that malignant progenitors share many biological features with normal adult stem cells including drug resistance and regulatory processes governing self-renewal. We review studies that have examined clonogenic cells in multiple myeloma, highlight controversies regarding the cell of origin in multiple myeloma, and discuss potential targeting strategies. [Copyright &y& Elsevier]

A proportion of patients with diffuse large B cell lymphoma (DLBCL) will fail to achieve durable remission to standard chemoimmunotherapy treatment with R-CHOP or dose- adjusted R-EPOCH regimens [1]. This benefit may be offset by an increased rate of relapse, however, leading to no significant differences in overall survival (OS) between patients receiving myeloablative conditioning (MAC) regimens and those receiving RIC regimens. 333, 1995, 1540-1545 3 E. Van Den Neste, N. Schmitz, N. Mounier, Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study. [Extracted from the article]

Background: Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT.Methods: PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2-7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103.Findings: Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths.Interpretation: These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended.Funding: Juno Therapeutics, a Bristol-Myers Squibb company. [ABSTRACT FROM AUTHOR]

[Display omitted] • N-succinylated chitosan (NCS), mangiferin (MGF) are conjugated into a nanohybrid. • The NCS-MGF conjugate particle size is measured as 100 ∼ 200 nm. • FT-IR and COSY analyses revealed hydrogen-hydrogen coupling between NCS and MGF. • The blood glucose lowered > 67% on 28 days treatment with NCS-MGF. • The NCS-MGF lowered plasma cholesterol > 37% and serum triglycerides > 61%. Mangiferin (MGF), from Mangifera indica is well reported for its hypoglycemic activity and hypolipidemic activity. However, MGF suffers therapeutic limitation due to poor solubility causing disparaging bioavailability. Herein to address this problem, we have incorporated MGF in alginate grafted N-succinylated chitosan (NSC) nanomatrix. Characterization by molecular docking, FT-IR and 2D-NMR (COSY) has revealed that MGF could reinforce interaction with NSC. The OH and CH 2 OH groups of MGF may set interactions with pyranosic OH, CH 2 OH, NH 2 (or NH-succinyl and COOH-succinyl) of NSC. The NSC-MGF nanoconjugate revealed a spherical particle geometry of 100 ∼ 200 nm size. The encapsulated MGF showed 100% release in vitro. In vivo, NSC-MGF nanoconjugate revealed blood glucose lowering from 300 mg/dL to ∼ 90 mg/dL as well as ∼ 37% lowering of total plasma cholesterol. This is well comparative to the earlier reports which acknowledged only 1 ∼ 36% lowering of plasma cholesterol with MGF. Furthermore, NSC-MGF lowered serum trigyceride to ∼ 61%, while in earlier studies, only 10 ∼ 40% serum triglycerides reduction was found with solitary MGF. [ABSTRACT FROM AUTHOR]

• MDSC subset distribution distinguishes three DLBCL immunotypes. • Standard chemoimmunotherapy reduces monocytic MDSC blood counts in DLBCL. • Persistence of polymorphonuclear MDSC after treatment worsens the patient's prognosis. The revised International Prognostic Index (R-IPI) is an important prognostic tool in diffuse large B cell lymphoma (DLBCL); however, outcomes can vary markedly within R-IPI groups, and additional prognostic markers are needed. We conducted a prospective observational study to evaluate the circulating immature myeloid (IM) cell subsets and cytokine profiles of 31 patients with newly diagnosed DLBCL before and after chemoimmunotherapy. Among circulating IM cells, myeloid-derived suppressor cells (MDSCs) were the predominant cell type (73.8% ± 26%). At baseline, circulating monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) were predominantly mutually exclusive. Patients with DLBCL clustered into three distinct immunotypes according to MDSC levels and subtype predominance: M-MDSChigh, PMN-MDSChigh, and MDSClow. The M-MDSChigh immunotype was associated with the germinal center B cell–like (GCB) subtype and elevated serum IL-8 and MIP-1α levels. PMN-MDSChigh was associated with the non-GCB subtype and elevated IL-8, MCP-1, IP-10, TNFα, and IL-1Ra levels. Standard chemoimmunotherapy partially reduced M-MDSC distribution across the MDSClow and M-MDSChigh groups. By contrast, among the MDSClow and PMN-MDSChigh groups, PMN-MDSCs persisted after treatment. Two high-risk patients with non-GCB DLBCL and MDSClow immunotype experienced early disease recurrence within 12 months of treatment completion. This study demonstrates that distinct types of MDSCs are associated with subtypes of DLBCL. MDSC levels are dynamic and may be associated with disease status. Persistence of PMN-MDSCs among high-risk patients with DLBCL may be associated with early relapse. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemic state. The α-glucosidase and α-amylase are considered two major targets for the management of Type 2 DM due to their ability of metabolizing carbohydrates into simpler sugars. In the current study, cheminformatics analyses were performed to develop validated and predictive models with a dataset of 187 α-glucosidase and α-amylase dual inhibitors. Separate linear, interpretable and statistically robust 2D-QSAR models were constructed with datasets containing the activities of α-glucosidase and α-amylase inhibitors with an aim to explain the crucial structural and physicochemical attributes responsible for higher activity towards these targets. Consequently, some descriptors of the models pointed out the importance of specific structural moieties responsible for the higher activities for these targets and on the other hand, properties such as ionization potential and mass of the compounds as well as number of hydrogen bond donors in molecules were found to be crucial in determining the binding potentials of the dataset compounds. Statistically significant 3D-QSAR models were developed with both α-glucosidase and α-amylase inhibition datapoints to estimate the importance of 3D electrostatic and steric fields for improved potentials towards these two targets. Molecular docking performed with selected compounds with homology model of α-glucosidase and X-ray crystal structure of α-amylase largely supported the interpretations obtained from the cheminformatic analyses. The current investigation should serve as important guidelines for the design of future α-glucosidase and α-amylase inhibitors. Besides, the current investigation is entirely performed by using non-commercial open-access tools to ensure easy accessibility and reproducibility of the investigation which may help researchers throughout the world to work more on drug design and discovery. [Display omitted] • α-glucosidase and α-amylase are considered two major targets for diabetes treatment. • 2D- and 3D-QSAR models were developed with diverse inhibitors of these targets. • 2D-QSAR models highlighted important structural requirements for higher inhibition. • 3D-QSAR hinted possible interactions with the proteins to guide future design. • The current work is entirely dependent on non-commercial open-access tools. [ABSTRACT FROM AUTHOR]

• Bloodless autologous hematopoietic cell transplantation may be safely performed. • Prime hemoglobin with erythropoiesis-stimulating agents before transplant. • Thrombopoietin agonists may be considered to optimize transplant success. Bloodless autologous hematopoietic cell transplantation is associated with risks of severe bleeding and profound anemia. RBC or platelet transfusions are often used to prevent these hematologic complications. However, in patients such as Jehovah's Witnesses who refuse major blood components, the lack of transfusion support is not an absolute contraindication to an autologous hematopoietic cell transplant. Pennsylvania Hospital performed the world's first bloodless hematopoietic cell transplant more than 15 years ago and has gradually improved its technique with a sizable patient population. Erythropoiesis-stimulating agents were successfully employed as part of their pretransplant regimen to prevent severe anemia. Thrombopoietin agonists' potential role in bloodless transplant is also currently being explored. Although there is limited literature, available reports in combination with physiologic reasoning may support the use of these growth factors to promote transplant success. These agents offer potential benefit and may be of utility in minimizing complications of a bloodless transplant. In this review, we summarize the available literature and offer insight into how we may incorporate growth factors to allow bloodless autologous hematopoietic cell transplantation to be an available option to patients who may otherwise be denied. [ABSTRACT FROM AUTHOR]

• We found a lower incidence of chronic GVHD in RIC haploidentical versus matched sibling donor transplantation for Hodgkin lymphoma. • We found a decreased relapse in PTCy-based haploidentical versus matched sibling donor transplantation for Hodgkin lymphoma. Classic Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of 2 reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell–replete related donor haploidentical (haplo) HCT with a post-transplant cyclophosphamide (PTCy)-based approach versus an MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008 and 2016 using either a haplo-PTCy (n = 139) or MSD/CNI-based (n = 457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR], 1.07; 95% confidence interval [CI],.79 to 1.45; P =.66) or PFS (HR,.86; 95% CI,.68 to 1.10; P =.22). Haplo/PTCy was associated with a significantly higher risk of grades II to IV aGVHD (odds ratio [OR], 1.73, 95% CI, 1.16 to 2.59; P =.007), but the risk of grades III to IV aGVHD was not significantly different between the 2 cohorts (OR,.61; 95% CI,.29 to 1.27; P =.19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR,.45; 95% CI,.32 to.64; P <.001), and a significant reduction in relapse risk (HR,.74; 95% CI,.56 to.97; P =.03). There was a statistically nonsignificant trend toward higher NRM with a haplo/PTCy approach (HR, 1.65; 95% CI,.99 to 2.77; P =.06). Haplo/PTCy-based approaches are associated with lower incidences of cGVHD and relapse, with PFS and OS outcomes comparable with MSD/CNI-based approaches. There was a leaning toward higher NRM with a haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable with MSD/CNI-based allo-HCT. [ABSTRACT FROM AUTHOR]

Highlights • Hemorrhagic cystitis occurs more frequently following haploidentical donor transplantation compared with matched related donor transplantation. • This higher frequency occurs despite the receipt of identical graft-versus-host disease prevention. • The grater susceptibility appears related to the inherent immune deficiency of HLA mismatch. ABSTRACT Hemorrhagic cystitis (HC) is a common and important complication of allogeneic hematopoietic cell transplantation (HCT). Reactivation of BK virus is its most common cause. The more intense immunosuppressive regimens administered to recipients of grafts from alternative donors have been reported to account for the increased susceptibility to HC in this population. This study compares patients undergoing HCT with either a haploidentical donor or a matched related donor, all of whom received identical immunosuppression with a post-transplantation cyclophosphamide-based regimen. The incidence of HC was significantly higher in the patients receiving a haploidentical graft (P =.01). The higher incidence of HC in haploidentical graft recipients is therefore directly related to the inherent immune deficiency that follows HLA-mismatched transplantation, independent of the intensity of pharmacologic immunosuppression. This finding carries significant clinical impact for the prevention and treatment of HC in haploidentical graft recipients. [ABSTRACT FROM AUTHOR]

Highlights • CYP3A5 polymorphisms did not impact i.v. tacrolimus exposure post-transplant. • CYP3A4 and ABCB1 polymorphisms impacted i.v. tacrolimus exposure post-transplant. • ABCB1 2677TT genotype was associated with increased risk of tacrolimus toxicity. • C YP3A4 and ABCB1 C2677T genotyping may help individualize i.v. tacrolimus dosing. • Pharmacogenomic guidelines should acknowledge differences in i.v. versus oral tacrolimus. Abstract Pharmacogenetics influences oral tacrolimus exposure; however, little data exist regarding i.v. tacrolimus. We investigated the impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on i.v. tacrolimus exposure and toxicity in adult patients receiving an allogeneic hematopoietic stem cell transplant for hematologic malignancies. Germline DNA was extracted from buccal swabs and genotyped for CYP3A4, CYP3A5, and ABCB1 polymorphisms. Continuous i.v. infusion of tacrolimus.03 mg/kg/day was initiated on day +5 post-transplant, and steady-state blood concentrations were measured 4days later. We evaluated the association between phenotypes and prevalence of nontherapeutic target concentrations (below or above 5 to 15 ng/mL) as well as tacrolimus-related toxicities. Of 63 patients, 28.6% achieved the target concentration; 71.4% were >15ng/mL, which was more common in CYP3A4 intermediate/normal metabolizers (compared with rapid) and those with at least 1 ABCB1 C2677T loss-of-function allele (P <.05). ABCB1 C2677T was significantly associated with concentrations >15ng/mL (odds ratio, 6.2; 95% confidence interval, 1.8 to 23.6; P =.004) and tacrolimus-related toxicities (odds ratio, 7.5; 95% confidence interval, 1.6 to 55.2; P =.02). ABCB1 C2677T and CYP3A4 are important determinants of i.v. tacrolimus exposure, whereas ABCB1 C2677T also impacts tacrolimus-related toxicities in stem cell transplants. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL. [ABSTRACT FROM AUTHOR]

Introduction Hospital readmissions after hematopoietic cell transplant (HCT) carry significant morbidity and mortality in HCT recipients. Herein, we describe a single institution 100-day readmission rate, its risk factors and clinical implications using post-HCT cytoxan as graft vs. host disease (GVHD) prophylaxis. Methods Data on 125 consecutive allogeneic HCT (allo-HCT) patients at Levine Cancer Institute, Charlotte, NC, between March 2014 and May 2018 were reviewed for dates of readmission, reasons for admission, patient demographics, socio-economic status and clinical outcomes. The cohort was divided into 2 groups, readmission vs. no readmission, based on admission to the hospital within 100 days of discharge from index transplantation admission. Study variables were compared between the 2 groups via a descriptive statistical analysis. Fisher's exact test and two-sample t-test were used to calculate P-values for categorical and continuous variables, respectively. Univariate and multivariate logistic regression analysis was used to assess risk factors for readmission. Overall survival (OS) after the initial hospital discharge was evaluated between patients with and without 100-day readmission using the Kaplan-Meier method and log-rank test. The cumulative incidence of non-relapse mortality (NRM) was estimated in a competing risk setting with relapse related death as a competing event. Group comparison of incidences were determined by Gray's test. The effect of readmission on NRM was evaluated in a Cox regression model. Results 52 (41.6%) of 125 allo-HCT patients were readmitted after transplantation admission. Median time to readmission from hospital discharge was 22.5 days (range: 1-96) and median length of stay (LOS) was 12 days (range: 1-70). The most common causes for readmission were infectious complications (57.7%) and GVHD (13.5%). In univariate analysis for 100-day readmission (Table 1), variables such as primary insurance payer, graft cell source, infections and GVHD during index admission, LOS, marital status and ANC recovery did not affect readmission risk, however being non-Caucasian (n=33, 26.4%) had increased odds ratio (OR) of 2.05 (p=0.081). OS was also similar between the 2 groups (P = 0.189). The incidence of NRM for patients with and without readmission was 25.1% and 6.9%, respectively (P = 0.047). Multivariate Cox regression analysis identified 100-day readmission (HR 2.96, 95% CI 1.01-8.71, P = 0.043), and LOS (HR 1.48, 95% CI 1.05-2.10, P = 0.027) as significant risk factors for NRM (Table 2). Conclusions Although readmission after allo-HCT is associated with increased NRM, we could not identify any risk factor for readmission within 100 days of discharge at our institution. We observed increased OR for readmission amongst non-Caucasian race in univariate analyses, but it did not emerge as a significant variable in multivariate analysis. [ABSTRACT FROM AUTHOR]

Assessment with 18 F-fluorodeoxy glucose (FDG)–positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non–Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with increased mortality (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), therapy failure (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL. [ABSTRACT FROM AUTHOR]

The complex formation between luteolin (L) and vanadium(IV) oxide sulphate monohydrate (VOSO 4 ·H 2 O) was examined under UV–visible, infra-red spectroscopy, mass spectroscopy and NMR techniques. The spectroscopic data indicated that luteolin reacts with vanadium oxide cation (VO +2 ) through 4-carbonyl-5-hydroxy chelation site in the two luteolin molecule. The free radical antioxidant activity of the complex with respect to the parent molecule was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2′-azinobis 3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS) methods. It was observed that the free radical scavenging activity and ferric ion reducing potential of luteolin was increased after the formation of complex with vanadium oxide (VO +2 ) cation. [ABSTRACT FROM AUTHOR]

Abstract: Immunosuppressive regimens that effectively prevent graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (allo-BMT) have been associated with an increased incidence of post-transplantation lymphoproliferative disorder (PTLD) in the first year after transplantation. We evaluated the incidence of PTLD associated with the use of high-dose post-transplantation cyclophosphamide (PTCy) as GVHD prophylaxis. Between 2000 and 2011, a total of 785 adult allo-BMT recipients were given PTCy as GVHD prophylaxis at the Johns Hopkins Hospital, including 313 patients who received PTCy as sole GVHD prophylaxis. HLA-haploidentical or unrelated donor graft transplantation was performed in 526 patients (67%). No cases of PTLD occurred during the first year after allo-BMT in this series. PTLD is a rare occurrence after allo-BMT using PTCy, even in high-risk alternative donor transplantations. [Copyright &y& Elsevier]

• The clinical outcome for older adults with ALL or ABL ineligible for multi-agent chemotherapy are poor and are a rare, unmet need. • Entinostat plus clofarabine was well tolerated but infectious and metabolic derangements were more common in the older population (vs younger). • Events of hyperglycemia and peripheral neuropathy were not appreciated with the use of Entinostat plus clofarabine. • Entinostat plus clofarabine appears to be active in older adults with de novo ALL/ABL, and further study of this combination should be considered. Despite advances in immunotherapies, the prognosis for adults with Philadelphia chromosome-negative, newly diagnosed (ND) or relapsed/refractory (R/R) acute lymphoblastic leukemia/acute biphenotypic leukemia (ALL/ABL) remains poor. The benzamide derivative entinostat inhibits histone deacetylase and induces histone hyperacetylation. The purine nucleoside analogue clofarabine is FDA-approved for R/R ALL in children 1−21 years of age. Low doses of clofarabine have been reported to induce DNA hypomethylation. We conducted a phase 1 study of low dose clofarabine with escalating doses of entinostat in adults with ND or R/R ALL/ABL. Adults ≥60 years with ND ALL/ABL or ≥21 years with R/R ALL/ABL received repeated cycles every 3 weeks of entinostat (4 mg, 6 mg or 8 mg orally days 1 and 8) and clofarabine (10 mg/m2/day IV for 5 days, days 3–7) (Arm A). Adults aged 40–59 years with ND ALL/ABL or age ≥21 years in first relapse received entinostat and clofarabine prior to traditional chemotherapy on day 11 (Arm B). Changes in DNA damage, global protein lysine acetylation, myeloid-derived suppressor cells and monocytes were measured in PBMCs before and during therapy. Twenty-eight patients were treated at three entinostat dose levels with the maximum administered dose being entinostat 8 mg. The regimen was well tolerated with infectious and metabolic derangements more common in the older population versus the younger cohort. There was no severe hyperglycemia and no peripheral neuropathy in this small study. There were 2 deaths (1 sepsis, 1 intracranial bleed). Overall response rate was 32 %; it was 50 % for ND ALL/ABL. Entinostat increased global protein acetylation and inhibited immunosuppressive monocyte subpopulations, while clofarabine induced DNA damage in all cell subsets examined. Entinostat plus clofarabine appears to be tolerable and active in older adults with ND ALL/ABL, but less active in R/R patients. Further evaluation of this regimen in ND ALL/ABL appears warranted. [ABSTRACT FROM AUTHOR]

Abstract: The role of allogeneic blood or marrow transplantation (alloBMT) for peripheral T cell lymphoma (PTCL) remains to be defined. There is growing interest in reduced-intensity conditioning (RIC) regimens and/or utilization of human leukocyte antigen haploidentical (haplo) grafts given concerns about treatment-associated toxicities and donor availability. We reviewed the outcomes of 44 consecutive, related donor alloBMTs for PTCL performed at Johns Hopkins Hospital from 1994 to 2011, including 18 RIC/haplo alloBMTs. Patients receiving RIC (n = 24) were older, with median age of 59 years (range, 24 to 70), than patients receiving myeloablative conditioning (MAC, n = 20), with median age of 46 years (range, 18 to 64), P = .01. The median age at RIC/haplo alloBMT was 60 years. The estimated 2-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 26% to 55%) and overall survival (OS) was 43% (95% CI, 28% to 59%). In older patients (≥60, n = 14), the estimated 2-year PFS and OS were 38% (95% CI, 18% to 79%) and 45% (95% CI, 24% to 86%), respectively. On unadjusted analysis, there was a tendency toward superior outcomes for alloBMT in first remission versus beyond first remission, with an estimated 2-year PFS of 53% (95% CI, 33% to 77%) versus 29% (95% CI, 9% to 45%), P = .08. On competing risk analysis, the 1-year cumulative incidence of relapse was 38% for MAC/HLA-identical alloBMTs and 34% for RIC/haplo alloBMTs. Estimated 1-year nonrelapse mortality was 10% for MAC and 8% for RIC (11% for RIC/haplo alloBMT). On unadjusted landmark analysis, patients with acute grade II-IV or chronic graft-versus-host disease (GVHD) had a 17% probability of relapse (95% CI, 0% to 39%), compared with 66% (95% CI, 48% to 84%) in patients without GVHD, P = .04. Utilization of RIC and alternative donors expands treatment options in PTCL to those who are older and unable to tolerate high-dose conditioning, with outcomes comparable with approaches using myeloablative regimens and HLA-matched donors. AlloBMT may be appropriate in first remission in select high-risk cases. [Copyright &y& Elsevier]

Background Autologous stem cell transplant (ASCT) is frequently used as a consolidative therapy option after induction treatment in fit patients with mantle cell lymphoma (MCL) with the goal of prolonging the initial response duration. Despite recent advances there remains a subset of patients who experience early disease relapse after ASCT. We examined predictors of shortened progression-free survival (PFS) and post-relapse overall survival (OS) in a cohort of patients completing ASCT in first remission. Methods We evaluated MCL patients treated at 10 US academic medical centers. Eligible patients were treated from 2000 through 2017, and we collected information on demographic, clinical, and treatment-related variables of interest. Patients were then categorized into three post-ASCT PFS groups: 0-2 years, 2-5 years, and > 5 years, with PFS determined from the date of ASCT until progression or death from any cause. Patients followed for at least 5 years post-ASCT who were relapse free were included in the > 5 sub group. Associations were examined between groups and collected characteristics using chi-squared tests for categorical patient characteristics and ANOVA for numeric patient characteristics. The Kaplan-Meier method was used to estimate overall survival (OS) for each group, using time of relapse after ASCT as the starting point. Results Of 968 total MCL patients, 242 patients completed ASCT in first remission and either had a PFS event or were relapse-free for at least 5 years post-ASCT. Patients were 80% male, and the median age was 59 (Range: 29-83). The patients were divided into groups of post-ASCT PFS 0-2 years (n=74), 2-5 years (n=75), and more than 5 years (n=93). Post-ASCT PFS was shorter in patients with stage 4 disease (p=0.022), splenomegaly at baseline (p=0.005), and a lymph node size > 5 centimeters at baseline (p=0.043). Other variables were not significantly associated with PFS, including time to transplant and use of intensive therapy. Patients with 0-2 year PFS had a shorter median OS (22.1 months, 95% CI: 13.1- 38.1 months) in comparison to 2-5 year PFS (132 months, 95% CI: 36-132 months) and 5+ year PFS not reached (95% CI: 41.2 – N.A; Figure). Conclusion Patients with higher tumor burden at baseline have a shorter post-ASCT PFS and are more likely to relapse within 2 years. As has been seen in other lymphoma subtypes, early relapse is associated with shorter OS. This represents a patient group requiring improved therapies and perhaps are the best candidates for post-ASCT maintenance or consolidation approaches. Further studies integrating minimal residual disease and molecular risk-stratification may better identify patients at high risk for early progression. [ABSTRACT FROM AUTHOR]

Topic Significance & Study Purpose/Background/Rationale Hematopoietic stem cell transplant (HCT) recipients are at risk for losing natural and acquired immunities, that can lead to post-HCT infectious complications. Post-HCT re-vaccination is considered a standard of care by FACT and NMDP. The current work is a quality improvement project to improve vaccination compliance. Programmatic deficiencies were identified and a Plan Do Study Act (PDSA) was implemented. Methods, Intervention, & Analysis A retrospective audit of recipient charts was performed for vaccination schedule completion and compliance by September 30, 2016. The audit is a snapshot of patients that have received vaccines at the scheduled intervals or completed the full vaccination schedule. Compliance was defined as completion of scheduled vaccination within 3 months of target date unless otherwise documented. Relapse, delayed, held for GVHD/immunosuppressant's or steroids, and refusal with proper documentation are considered complaint. Deceased patients within 3 months of target date were excluded. Overall compliance is defined as: at the 24-month landmark, which patients have received vaccinations at all landmarks based on the compliance guidelines. 21-months after implementing the PDSA, recipient charts were audited for vaccination schedule completion and compliance by June 30, 2018. Findings & Interpretation Identified deficiencies included an infrastructure that did not allow for vaccinations to be given in the same clinic as the patient's appointment with their transplant physician, lack of communication between the clinics, inconsistent orders and documentation, and a lack of knowledge with staff and patients. The PDSA interventions included a standardized vaccination order sheet, appointment identification, staff and patient education, reminder cards, and policy updates. After implementing the PDSA, the overall compliance has increased from 56.7% to 72% and overall completion has increased from 76% to 83.8% over a 21-month period. Discussion & Implications Vaccination compliance requires standardization of practices, effective communication, and adequate documentation when caring for post-transplant patients. Success of a post transplantation vaccination program requires unwavering commitment to provide support and oversight for effective vaccination strategies. Retrospective vaccination chart audits continue quarterly to achieve an 80% compliance rate. [ABSTRACT FROM AUTHOR]