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Objectives: Dysregulation of BCL‐2 family members has been reported in acute lymphocytic leukemia (ALL), with various BH3‐dependencies of the leukemic clone. We conducted a multicenter retrospective cohort of patients with relapsed/refractory B or T ALL, with ven‐chemotherapy or ven‐navitoclax combinations, to assess efficacy and safety. Methods: Seventeen patients were included in the analysis, median age was 32 years, with 6 B‐ALL and 11 T‐ALL patients. Nine patients received venetoclax combined with chemotherapy, and 13 patients received venetoclax in combination with navitoclax, vincristine and asparaginase, of which 5 were already exposed to venetoclax in previous lines. Results: ORR was 55% and 46% among the ven‐chemotherapy and the ven‐navitoclax‐chemotherapy, respectively. Most of the responders proceeded to an allogenic bone marrow transplant in both cohorts. The most common adverse effects of the ven‐navitoclax combination were infectious complications and hepatotoxicity. Conclusions: Our data demonstrated the possible efficacy of ven‐chemotherapy and ven‐navitoclax in r/r ALL with moderate toxicity. [ABSTRACT FROM AUTHOR]

Objectives: Define clinical and laboratory attributes of acute myeloid leukemia (AML) patients with long‐term survival exceeding five years and compare them with AML patients succumbing to disease within 2 years of diagnosis. Methods: A retrospective analysis of AML patients alive at least five years from the time of initial diagnosis. Baseline clinical data were compared with patients who died within 2 years of diagnosis. Results: The long‐term cohort consisted of 93 patients treated in 2007–2016 with a median follow‐up duration of 7.7 years (range 5–13.6 years). European LeukemiaNet (ELN) 2017 favorable risk patients accounted for 60% of the cohort. All long‐term survivors achieved remission following induction chemotherapy. Multivariate analysis showed that compared with 132 patients experiencing death within 2 years of diagnosis, long‐term survivors were more likely to be of younger age [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.9–0.95; p < 0.001], have a lower initial WBC count (OR, 0.58; 95% CI, 0.43–0.79; p = 0.0004), undergo an allogeneic stem cell transplantation (OR, 7.95; 95% CI, 3.07–20.59; p < 0.0001), and harbor favorable risk cytogenetics (OR, 0.03; 95% CI, 0.006–0.23; p = 0.0004). Conclusions: Long‐term survival of AML is seen in a distinct demographic and biologic patient subset. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL). METHODS: The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo‐HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018. RESULTS: The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2‐year leukemia‐free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100‐day incidence of grade 2 through 4 acute graft‐vs‐host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia‐free survival (64.9% vs 47.3%; P =.019) and OS (75.5% vs 53.5%; P =.006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P =.047). The incidence of relapse, GVHD‐free/relapse‐free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22‐0.89; P =.022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26‐0.86; P =.014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes. CONCLUSIONS: The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2‐year OS of 75% and, most recently, an NRM rate of only 17%. In patients with acute lymphocytic leukemia who undergo haploidentical transplantation with posttransplantation cyclophosphamide prophylaxis, significant improvements in leukemia‐free survival and survival are observed in more recently transplanted patients. A nonrelapse mortality rate of 17% is reported in recently transplanted patients with acute lymphocytic leukemia who receive posttransplantation cyclophosphamide prophylaxis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the current role of bisantrene, an anthracene with anthracycline‐like activity which was shown in earlier studies to be effective therapy in relapsed/refractory acute myeloid leukemia with no discernible cardiotoxicity, in the treatment of patients with R/R AML. Methods: This phase 2, single‐center study (NCT03820908) enrolled adult R/R AML to receive bisantrene (250 mg/m2 daily for 7 days) which was administered via an intravenous infusion over 2 hours on days 1‐7. Disease assessment included routine blood work and bone marrow studies. Results: In all, 10 patients were enrolled with a median of 3 lines of prior therapy including seven patients who had relapsed following allogeneic stem cell transplantation. The most frequently reported grade ≥3 treatment‐attributed hematologic AE was thrombocytopenia, whereas the most frequently reported grade ≥3 treatment‐attributed non‐hematologic AE was mucositis. Of the 10 patients, one (10%) achieved a complete remission and three patients achieved a partial remission resulting in an overall response rate of 40%. Next‐generation sequencing of patient samples identified a wide array of mutations associated with activated signaling, splicing, and epigenetic modification. Conclusions: In view of the observed low toxicity, a follow‐up study combining bisantrene with complementary anti‐leukemic therapy is planned. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myeloid leukemia (AML) are surviving longer. There are no data on changes in myocardial mechanics from standard of care low‐dose anthracycline‐based induction chemotherapy in older patients with AML. The aim of this study was to demonstrate the potential utility of strain imaging in detecting early changes in left ventricular function in this patient population after induction chemotherapy. Methods: Thirty two patients enrolled in the ECOG‐ACRIN E2906 study (cytarabine and daunorubicin vs clofarabine [Genzyme/Sanofi]) from 2011 to 2014 were evaluated retrospectively. Two‐dimensional transthoracic echocardiography (TTE) imaging with Doppler and two‐dimensional speckle‐tracking echocardiography (2DSTE) using EchoInsight software (Epsilon imaging) were performed before and after induction chemotherapy. Results: Eighteen patients received cytarabine and daunorubicin (7 + 3) and 14 received clofarabine. The clofarabine group was older than the 7 + 3 cohort (67.8 ± 4.0 vs 63.7 ± 3.8, P = .007). There were no other significant differences in cardiac risk factors between groups. The 7 + 3 group had a decrease in average peak systolic global longitudinal (−19.1 ± 2.8 to −17.2 ± 3.0, P = .01) and circumferential strain (−29.4 ± 6.3 to −23.9 ± 4.3, P = .011). These changes were not demonstrated in the clofarabine group and were not associated with a decline in left ventricular ejection fraction (LVEF). Conclusions: In older AML patients, standard cytarabine and daunorubicin chemotherapy causes early changes in global longitudinal and circumferential strain not seen with clofarabine therapy. These findings demonstrate subclinical left ventricular dysfunction after exposure to low cumulative doses of anthracycline‐based induction chemotherapy and may help us better identify those patients at risk for adverse long‐term cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Summary: Assessment of minimal residual disease (MRD) is being routinely used to assess response in patients with acute myeloid leukaemia (AML). While it is well established that pre‐transplant positive MRD studies predict for relapse in patients transplanted either from matched sibling donors or matched unrelated donors, it is currently unknown whether MRD has comparable prognostic value in haploidentical stem cell transplantation (haplo‐SCT). To this end we performed a retrospective analysis using the Acute Leukaemia Working Party/European Society of Blood and Marrow Transplantation multicentre registry. All adult AML patients with known MRD status at transplant who underwent a first T‐cell replete haplo‐SCT while in remission between 2006 and 2016 were included. Two hundred and sixty‐five MRD‐negative and 128 MRD‐positive patients were assessed. In multivariate analysis, MRD‐negative patients experienced lower relapse incidence and better leukaemia‐free survival (LFS) compared to MRD‐positive patients. Subset analysis for MRD‐positive patients revealed that patients with donors positive for cytomegalovirus experienced decreased relapse rates as well as increased survival. A 6‐month landmark analysis suggests that the clinical benefit of pre‐transplant MRD negativity in terms of relapse, overall survival and LFS is realized at this time point. Pre‐transplant MRD status is potentially a pivotal prognosticator of outcome in AML patients undergoing T‐cell replete haplo‐SCT. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The recently introduced Bayer wide-range C-reactive protein (wr-CRP) assay might be relevant for the real-time low-cost and online determination of inflammatory bowel disease (IBD) activity. Our aim was to examine whether wr-CRP can substitute for the Dade Behring high sensitivity C-reactive protein (hs-CRP) assay in IBD patients. METHODS: A total of 71 patients with IBD, of whom 48 had Crohn's disease CD and 23 had ulcerative colitis (UC) with various intensities of disease activity participated in the study. The CRP of patients who were under treatment at the Department of Gastroenterology and Liver Diseases were measured using both wr-CRP and the hs-CRP. RESULTS: A significant ( r = 0.995; P < 0.001) correlation was noted between the hs-CRP and wr-CRP measurements for the whole sample as well as for the two diseases, CD ( r = 0.994; P < 0.001) and UC ( r = 0.997; P < 0.001), which were analyzed separately. CONCLUSION: The Bayer wr-CRP assay might be a useful low-cost and real-time inflammation-sensitive biomarker in patients with IBD. [ABSTRACT FROM AUTHOR]

Objective: To assess the expression of heparanase in the different stages leading to endometrial cancer.Methods: The 38 examined specimens included adenocarcinoma, hyperplasia, and normal endometrium specimens. Heparanase, estrogen, and progesterone receptor expressions were analyzed immunohistochemically and the intensity was scored.Results: Secretory normal endometrium and simple hyperplasia specimens expressed the lowest mean values of expression (1.00 and 0.63, respectively); the complex hyperplasia specimens and G2 endometrioid adenocarcinoma showed the highest values of expression (2.33 and 2.71, respectively). A linear trend (P=0.005) of heparanase expression was observed when comparing the normal endometrium and simple hyperplasia group with the complex hyperplasia+G1 carcinoma group and the G2+G3 carcinoma group. Evaluation of atrophic and inactive endometrium compared with papillary serous carcinomas yielded no significant differences. We found no significant correlation between heparanase expression and estrogen receptor or progesterone receptor expression.Conclusion: Heparanase expression was tightly regulated in endometrial tumorigenesis. [ABSTRACT FROM AUTHOR]

Summary Patients with FLT3‐mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard‐of‐care for patients with R/R FLT3‐mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt‐ven) improves outcomes as compared with gilteritinib monotherapy. We included patients treated with gilteritinib (n = 19) and gilt‐ven (n = 17) for R/R AML after intensive chemotherapy. Gilteritinib and gilt‐ven groups did not differ in terms of mCRc rates (53% and 65%, p = 0.51) and realization of allogeneic haematopoietic stem‐cell transplantation (HSCT, 47% and 35%, p = 0.5). Overall survival (OS) was comparable between groups, although a trend towards better OS was seen with gilt‐ven (12‐month OS 58.8% [95% CI 39.5%–87.6%]) versus gilteritinib (42.1% [95% CI 24.9%–71.3%] for gilteritinib). Early salvage with gilt‐ven versus any other gilteritinib‐based approach was associated with the best outcome (p = 0.031). Combination therapy was associated with increased haematological toxicity. In summary, gilt‐ven did not improve remissions or HSCT‐realization rates in patients with R/R FLT3‐mutated AML as compared with gilteritinib and was associated with increased haematological toxicity. Although OS did not differ, a trend towards better survival was suggested with gilt‐ven and a survival benefit was shown for gilt‐ven approach when sequenced early for salvage. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of rearrangement of 11q23/mixed-lineage leukemia (MLL) in acute myeloid leukemia (AML) after the application of fludarabine, cyclophosphamide, and rituximab (FCR).