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Objective: Allogeneic stem cell transplantation (allo‐SCT) may have a curative potential due to the graft versus lymphoma effect. In this study, we aimed to compare transplant outcomes between refractory‐T‐NHL (ref‐NHL) and Chemosensitive‐T‐NHL (CS‐T‐NHL). Materials and Methods: We retrospectively reviewed the records of 26 ref‐NHL and 29 CS‐T‐NHL consecutive patients who underwent allo‐SCT at our center and compared the transplant outcomes between the groups. Results: All patients were heavily pretreated with 27% of patients relapsing post‐auto‐SCT and two patients in the ref‐T‐NHL post‐allo‐SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref‐TNHL and 19% in CS‐TNHL (p =.33), with non‐relapse mortality rates of 28% and 22%, respectively (p =.52). Female patients and those with a previous auto‐SCT had lower relapse incidence (p =.045, p =.003). The 3‐year overall survival was 39% in Ref‐TNHL and 56% in CS‐TNHL (p =.15). Trends for improved progression‐free survival (PFS) and graft‐versus‐host disease relapse‐free survival (GRFS) were observed in the CS‐TNHL group (PFS: 60% vs. 30%, p =.075; GRFS: 38% vs. 21%, p =.1). Conclusion: Acknowledging the retrospective nature of our study, our results indicate that allo‐SCT has a curative potential in patients with T‐NHL even in refractory status. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to create a simple and reliable tool, the CORE HCT score, to predict the chances of non-relapse mortality (NRM) and overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HCT). Using data from 1120 adult patients who had undergone this procedure at our center between 2013 and 2020, we identified specific patient factors affecting NRM: serum albumin, serum creatinine, serum C-reactive protein, heart and lung function, and age. Factors were weighted according to their impact on NRM. The resulting CORE HCT score grouped patients into low-, medium-, and high-risk categories, showing its effectiveness across different conditions and donor types. Notably, compared with the HCT Comorbidity Index (HCT-CI), the CORE HCT score performed better in predicting NRM and OS. The findings were validated in two independent cohorts, which supports the utility of the CORE HCT score in guiding risk assessment for allo-HCT in adult patients with malignant diseases. We aimed to develop a concise objectifiable risk evaluation (CORE) tool for predicting non-relapse mortality (NRM) and overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HCT). A total of 1120 adult patients who had undergone allo-HCT at our center between 2013 and 2020 were divided into training, first, and second validation cohorts. Objectifiable, patient-related factors impacting NRM in univariate and multivariate analyses were: serum albumin, serum creatinine, serum C-reactive protein (CRP), heart function (LVEF), lung function (VC, FEV1), and patient age. Hazard ratios were assigned points (0–3) based on their impact on NRM and summed to the individual CORE HCT score. The CORE HCT score stratified patients into three distinct low-, intermediate-, and high-risk groups with two-year NRM rates of 9%, 22%, and 46%, respectively, and OS rates of 73%, 55%, and 35%, respectively (p < 0.001). These findings were confirmed in a first and a second recently treated validation cohort. Importantly, the CORE HCT score remained informative across various conditioning intensities, disease-specific subgroups, and donor types, but did not impact relapse incidence. A comparison of CORE HCT vs. HCT Comorbidity Index (HCT-CI) in the second validation cohort revealed better performance of the CORE HCT score with c-statistics for NRM and OS of 0.666 (SE 0.05, p = 0.001) and 0.675 (SE 0.039, p < 0.001) vs. 0.431 (SE 0.057, p = 0.223) and 0.535 (SE 0.042, p = 0.411), respectively. The CORE HCT score is a concise and objectifiable risk evaluation tool for adult patients undergoing allo-HCT for malignant disease. External multicenter validation is underway. [ABSTRACT FROM AUTHOR]

Background Cytomegalovirus reactivation is often diagnosed in allogeneic hematopoietic cell transplant recipients and therefore could lead to CMV-related disease, involving many organs in these immunocompromised patients. In contrast, few studies investigated CMV reactivation and end-organ disease in patients undergoing Autologous Peripheral Blood Stem Cell Transplant (ASCT) since they are considered at low risk for both reactivation and disease. Objectives The primary outcome of the analysis was to understand the difference in incidence of CMV reactivation between MM and Lymphoma patients. Secondary outcomes included the difference between MM and Lymphoma patients when considering the effect of CMV reactivation on transplant related mortality (TRM) overall survival (OS) progression free survival (PFS), risk factors for reactivation, and median time to reactivation. Study design In this report, we retrospectively compared the incidence, risk factors, and outcome of CMV reactivation in adult patients with Myeloma (MM) and Lymphoma undergoing ASCT at the American university of Beirut Medical Center in Lebanon (AUBMC). A total of 324 consecutive ASCT were performed between January 2005 and March 2016. Serial weekly monitoring for CMV quantification was done using a quantitative PCR, starting from transplantation until the hospital discharge and afterwards based on the clinical symptoms in cases of clinical suspicion of reactivation after discharge from the hospital. Results The cumulative incidence of CMV reactivation was 16% (n = 53) with a median time of 16 (range, 4–242) days after ASCT. The incidence of reactivation was significantly higher in the MM (22%) and NHL (20%) groups, when compared to the HL (4%) (P = 0.001). There was a higher incidence of CMV reactivation according to age (≥50 vs ≤50 years) with higher incidence in the older population 24% vs 10% respectively (p = 0.0043). The mean time to CMV reactivation was significantly higher in the NHL group with a mean of 53.7 days when compared to the HL and MM groups with mean 19.75 days and 12.66 (range, 4–34) days respectively (P = 0.003). Twenty-two patients (76%) and three patients (75%) patients required specific antiviral therapy in the MM group and HL groups respectively; which was significantly higher (P < 0.001) then the NHL group with 13 (65%) patients requiring specific antiviral therapy. Five patients (1.5%) developed CMV disease at a median of 60 days (range, 7–107) post ASCT: there was significant difference in the mean-time to reactivation based on disease type MM versus lymphoma 10 versus 33 days (P = 0.007). In multivariate analysis, a higher age was associated with an increased risk of CMV reactivation; MM and NHL had higher risk of CMV reactivation when compared to HL, and progressive disease at transplant was associated with increased risk of CMV reactivation. After a median follow-up of 21.5 months (range: 1–125), there was no significant impact on PFS, however there was significant decrease in OS of lymphoma patients who had CMV reactivation when compared to those without CMV reactivation (204 and 112 days respectively P = 0.045). TRM increased from 1.1% in patients with no CMV reactivation to 13% in patients with CMV reactivation (P = 0.003). Conclusion Our data suggests that CMV reactivation is not uncommon in ASCT recipients and may contribute to increase TRM. MM patients may have a higher incidence, of CMV reactivation with more anti-viral treatment requirements when compared to lymphoma patients, especially in older population. [ABSTRACT FROM AUTHOR]

The article focuses on therapies named brentuximab vedotin (BV) and nivolumab for treatment of Hodgkin lymphoma (HL). Topics include information on BV which is an anti-CD30 chimeric Immunoglobulin G1 (IgG1) monoclonal antibody conjugated through protease-cleavable linker to antimicrotubule drug monomethyl auristatin E (MMAE); use of bendamustine, a chemotherapy medication before allogeneic hematopoietic stem cell transplantation; and use of salvage nivolumab upon failure of bendamustine.

Despite advances in the treatment of acute myeloid leukemia (AML), cytotoxic chemotherapy remains the standard induction regimen. In this single center retrospective study, we assessed outcomes of 99 consecutive adult AML patients treated with a risk-adapted strategy with a median follow-up of 35.5 months. We identified 24 (24 %), 55 (56 %) and 20 (20 %) patients classified as favorable-, intermediate-, and adverse- risk group respectively, according to the European LeukemiaNet (ELN) 2017 classification. Patients either received idarubicin and cytarabine induction chemotherapy with or without FLT3 inhibitors or hypomethylating agents based on age and comorbidity. The complete response (CR) rate was 76 % (82 % and 61 % in patients aged < 60 and ≥ 60, respectively). For the whole cohort, the 3-year overall survival (OS) was 53 %, being 62 % and 30 % in patients aged < 60 and ≥ 60, respectively. The 3-year leukemia-free survival (LFS) was 54 %, with 56 % and 45 % in patients aged < 60 and ≥ 60, respectively. The 3-year LFS were 58 %, 62 % and 25 % for patients within ELN favorable-, intermediate-, and adverse-risk groups respectively. Twenty-seven (36 %) out of 75 patients with intermediate- and adverse-risk disease underwent allogeneic hematopoietic cell transplantation (allo-HCT) in first CR with 92 % of them receiving post-transplant maintenance consisting of azacitidine in 19 (76 %) patients or sorafenib in 6 (24 %) patients. Of these patients younger than 60 years, the 3-year OS and LFS were 85 % and 69 %, respectively. These results indicate an improved OS for AML patients especially in intermediate-risk category who were treated with a total therapy consisting of induction chemotherapy followed by allo-HCT and post-transplant maintenance. [ABSTRACT FROM AUTHOR]

To evaluate polymorphisms in genes of drug metabolizing enzymes and transporters involved in cyclosporine and/or voriconazole disposition among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). DNA from forty patients was genotyped using the DMETPlus array. The average ratio of cyclosporine concentration/dose (C/D in (ng/mL)/(mg/kg)) per participant's weight was computed using available trough levels and daily doses. The C/D cyclosporine ratio was significantly higher when it was administered with voriconazole as compared to when it was administered alone: median: 116.75 vs. 25.40 (ng/mL)/(mg/kg) with and without voriconazole respectively, (P < 0.001). There was also a significant association between the C/D cyclosporine ratio combined with voriconazole and the ABCB1 2677 G > T > A (rs2032582) genetic polymorphism (P = 0.05). In parallel, ABCB1 variant allele carriers had higher creatinine in combination therapy with a median creatinine (mg/dL) of 0.74 vs. 0.56 for variant allele carriers vs. reference; P = 0.003. Interestingly, CYP2C9, CYP2C19, and CYP3A5 extensive metabolizers tended to be associated with lower cyclosporine C/D ratio when combined with voriconazole, but the results were not statistically significant. To the best of our knowledge, this is the first pharmacogenetic study on the interaction between voriconazole and cyclosporine in patients undergoing allo-HCT. Results suggest that the ABCB1 2677 G > T > A genetic polymorphism plays a role in this interaction with cyclosporine related nephrotoxicity. Pre-emptive genotyping for this genetic variant may be warranted for cyclosporine dose optimization. Larger studies are needed to potentially show significant associations with more candidate genes such as CYP3A4/5, CYP2C9, and CYP2C19 , among others. [ABSTRACT FROM AUTHOR]

Background: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results.Methods: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia.Results: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively.Conclusions: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Pre‐transplant minimal residual disease (MRD) impacts negatively on post‐transplant relapse risk in acute myeloid leukemia (AML). Therapeutic drug monitoring by calculating area under the curve (AUC) was developed to optimize busulfan (Bu) exposure. Here, we compared post‐transplant outcomes after individualized versus fixed busulfan dosage in intermediate‐risk AML who achieved CR prior to allograft focusing on pre‐transplant flow‐MRD. Eighty‐seven patients (median, 56 years) with intermediate‐risk AML and pre‐transplant flow‐MRD ("different from normal") were included. Thirty‐two patients received individualized busulfan; 54 fixed dosages. Individualized dosage was adjusted in 25/32 patients: increased, n = 18/25 (72%); decreased: n = 7/25 (28%). After median follow‐up of 27 months, we observed lower 3‐year relapses (6%, 2%–19% vs. 35%, 23%–49% p = 0.02), improved 3‐year leukemia‐free survival (LFS) (78%, 54%–91% vs. 55%, 40%–70% p = 0.009) and − overall survival (OS) (82%, 60%–93% vs. 69%, 54%–81% p = 0.05) after individualized compared to fixed Bu. Non‐relapsed mortality (NRM) and acute graft versus host disease (GvHD) were not different. In multivariate analysis, fixed Bu showed unfavorable impact on OS (hazard ratio [HR] 4.6, p = 0.044), LFS (HR 3.6, p = 0.018) and relapses (HR 3.6, p = 0.033). Fixed Bu also had unfavorable impact on LFS (3.6, 1.1–12.6, p = 0.041) in pre‐transplant MRD‐positive patients. Individualized, AUC‐based, busulfan is associated with lower relapses in intermediate‐risk AML patients allografted in CR and may overcome pre‐transplant MRD‐positivity. [ABSTRACT FROM AUTHOR]

Brentuximab Vedotin (BV) is a chimeric anti-CD30 antibody, conjugated to anti-tubulin mono-methyl-auristatin. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy for 16 cycles in high risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). However, this schedule is associated with high cost and significant toxicity. Our objective is to assess the safety and efficacy of four cycles Brentuximab Vedotin as consolidation after ASCT for relapsed/refractory (R/R) HL. We identified 20 consecutive adult patients with R/R HL treated with BV for four cycles as consolidation after ASCT. The indications for BV consolidation included primary refractory disease in 12 patients (60%), early relapse in 6 patients (30%) and extra-nodal involvement in two patients (10%). After a median follow up of 27 months, five (25%) patients relapsed. The median time to relapse was 6 months. Median PFS and OS were not reached. No significant toxicities were reported. [ABSTRACT FROM AUTHOR]

Abstract Background Gastrointestinal (GI) graft versus host disease (GVHD) occurs in up to 40% of patients undergoing allogenic hematopoietic stem cell transplantation (HSCT). However, the optimal endoscopic approach is still unclear and the area of the GI tract with the highest diagnostic yield is still a topic of debate. Objective We compared the diagnostic yield of different anatomic site biopsies in the diagnosis of GI GVHD and assessed the correlation of endoscopic findings with histopathology. Methods All cases of biopsy proven GI GVHD were obtained from pathology database AUBMC between 1/1/2005 and 31/8/2017. We retrospectively analyzed the demographical, clinical and endoscopic data. Results Nineteen patients were diagnosed with GI GVHD over 17.6 years. The most common presenting symptom was severe diarrhea (18 patients, 94.7%). Combining upper endoscopy and sigmoidoscopy with biopsies had the highest diagnostic yield of 90% in diagnosing GI GVHD compared to 63.6%, 78.6% and 77.8% for upper endoscopy, sigmoidoscopy and colonoscopy respectively. In macroscopically normal mucosa, the recto-sigmoid and duodenal biopsies had the highest diagnostic yield (75%). As for the macroscopically abnormal mucosa, the highest yield was for the recto-sigmoid biopsies (100%) in lower endoscopy and duodenal biopsies in the upper endoscopy (60%). Conclusion In a patient suspected to have GI GVHD, the best endoscopic approach is the combination of upper endoscopy and flexible sigmoidoscopy with biopsies of normal as well as abnormal mucosa. It should be emphasized that normal mucosa be biopsied especially in the duodenum and recto-sigmoid for a better diagnostic yield. [ABSTRACT FROM AUTHOR]