Search

This article examines the use of tyrosine kinase inhibitor (TKI) therapy as a maintenance treatment after chimeric antigen receptor (CAR) T-cell therapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who cannot undergo allogeneic hematopoietic cell transplantation (alloHCT). The study presents a case series of seven patients who received CAR-T cells for relapsed/refractory Ph+ ALL and subsequently received TKI maintenance. The article discusses the patients' characteristics and outcomes, emphasizing the need for further research and data on this approach. The study suggests that TKI maintenance therapy after CAR-T may be beneficial, particularly in patients who achieve complete molecular remission (CMR) and have no evidence of minimal residual disease (MRD). The authors recommend larger prospective trials to confirm the effectiveness and safety of TKI maintenance therapy post-CAR-T, and to explore its potential application to other subtypes of ALL. [Extracted from the article]

Summary: Therapy‐related acute lymphoblastic leukaemia (tr‐ALL) is a disease entity attributed to previous exposure to chemotherapy and/or radiation for antecedent malignancy. There is observed female predominance for tr‐ALL, likely due to high prevalence and excellent curable rate for non‐metastatic breast cancer as well as the frequent use of carcinogenic agents as part of adjuvant therapy. Here, we reviewed 37 women with diagnosis of ALL following breast cancer treatment with focus on cytogenetic categorization. Philadelphia chromosome positivity (Ph+), KMT2A alterations and other cytogenetic change groups were observed in 32%, 22% and 46% of patients respectively. Median overall survival (OS) and relapse‐free survival (RFS) were 19.4 and 12.9 months, overall while both OS and RFS were superior in tr‐ALL with Ph+ disease compared to KMT2Ar and other cytogenetics respectively. Seventeen (45.9%) patients underwent consolidative allogeneic haematopoietic cell transplantation (alloHCT) in CR1 out of which 4 (24%) relapsed following transplant. Both OS and RFS were superior in the KMT2Ar cytogenetics group following alloHCT. Ph chromosome represents the largest genetic entity of tr‐ALL following breast cancer therapy, and it may be associated with superior survival outcomes while KMT2Ar may be associated with poorer outcomes that can perhaps be mitigated by alloHSCT. [ABSTRACT FROM AUTHOR]

Introduction: In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild-to-moderate COVID-19 at high risk for disease progression. Methods: We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021. Results: Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab-imdevimab. Four (11%) patients were hospitalized due to COVID-19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID-19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS-CoV-2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7-138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12-42). We observed a significant difference in hospitalization among patients who received a HCT versus non-HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01). Conclusions: This study demonstrates that SARS-CoV-2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients. [ABSTRACT FROM AUTHOR]

The 1-year OS for HCT patients (21 patients) was 85% (95% CI 61-95%) compared to 41% (95% CI 16-65%) in non-HCT patients in cCR (14 patients). The 1-year LFS in patients who underwent HCT (21 patients) was 67% (95% CI 41-84%) I versus i 33% (95% CI 10-57%) in non-HCT patients in cCR (14 patients). [Extracted from the article]

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]

The swimming performance of juvenile rock carp (Procypris rabaudi, Tchang) subjected to repeated fatigue exercise was studied using a flume‐type respirometer at 20°C. The critical swimming speed (Ucrit) and oxygen consumption rate (MO2) of juvenile rock carp were measured during two successive stepped velocity tests, following a 60 min rest interval. Ucrit of rock carp was giving a recovery ratio (Rr) of 92.64%, and exertion exercise decreases Ucrit. When MO2 was plotted as a linear function of U, the slope for trial 1 was 1.06 and 1.50 for trial 2, indicating a decreasing in swimming efficiency. The maximum metabolic rate (MMR) increased from 17.06 ± 1.14 mmol O2/(kg·hr) to 19.14 ± 1.23 mmol O2/(kg·hr), and the exercise post oxygen consumption rate (EPOC) increased from 9.00 to 9.65 mmol O2/kg. Repeated fatiguing exercise increased both the aerobic and anaerobic cost of reaching Ucrit, but anaerobic metabolism accounted for a larger proportion in the trial 2. The data investigation on the swimming performance and the physiological response to fatigue provide important design criteria for fishways. [ABSTRACT FROM AUTHOR]