Shifting gears to differentiation agents in acute promyelocytic leukemia with resource constraints—a cohort study

Vaid, Tejasvini; Aggarwal, Mukul; Dass, Jasmita; Dhawan, Rishi; Kumar, Pradeep; Viswanathan, Ganesh Kumar; Tyagi, Seema; Seth, Tulika; Mahapatra, Manoranjan

doi:10.1080/0284186x.2022.2109424

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…Further, using anthracyclines during induction and consolidation may increase the risk of neutropenia and infections and blood component support, which could preclude their use in LMICs. This is corroborated by the fact that in a recent real‐world study from India, 57.4% of patients had an infection at presentation and 62.5% of patients developed new neutropenic fever during induction 13 . A high incidence of infection has also been reported during consolidation therapy among Indian patients with acute myeloid leukaemia, highlighting the ongoing infection risk in patients receiving intensive chemotherapy 14 …”

Section: Discussionmentioning

confidence: 84%

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Long‐term real‐world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all‐trans retinoic acid without chemotherapy—a retrospective, single‐centre study

et al. 2022

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Summary Arsenic trioxide (ATO) and all‐trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high‐risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate‐ and high‐risk disease received a further 2 years of maintenance with ATRA, 6‐mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow‐up. The mean (SD) estimated 5‐year event‐free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5‐year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long‐term outcomes in the real‐world setting.

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Section: Discussionmentioning

confidence: 84%

“…This is corroborated by the fact that in a recent real-world study from India, 57.4% of patients had an infection at presentation and 62.5% of patients developed new neutropenic fever during induction. 13 A high incidence of infection has also been reported during consolidation therapy among Indian patients with acute myeloid…”

Section: Discussionmentioning

confidence: 99%

Long‐term real‐world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all‐trans retinoic acid without chemotherapy—a retrospective, single‐centre study

et al. 2022

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Tissue factor activates the coagulation cascade in mouse models of acute promyelocytic leukemia

et al. 2023

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Acute promyelocytic leukemia (APL) is associated with a high risk of bleeding and thrombosis. The coagulopathy involves activation of coagulation, hyperfibrinolysis and thrombocytopenia. APL cells express tissue factor (TF), which is the receptor and cofactor for factor VII/VIIa. This study had two goals. First, we measured biomarkers of activation of coagulation and fibrinolysis as well as platelet counts and bleeding in both mouse xenograft and allograft models of APL. Second, we determined the effect of inhibiting TF on the activation of coagulation in these models. We observed increased levels of plasma thrombin-antithrombin complexes (TAT), D-dimer, plasmin-antiplasmin complexes, reduced platelet counts and increased tail bleeding in both mouse models of APL. Fibrinogen levels were decreased in the xenograft model but not in the allograft model. In contrast, the red blood cell count was decreased in the allograft model but not in the xenograft model. Inhibition of APL-derived human TF with an anti-human TF monoclonal antibody reduced levels of TAT, increased the platelet count and normalized tail bleeding in the xenograft model. Inhibition of all sources of TF (APL cells and host cells) in the allograft model with a rat anti-mouse TF monoclonal antibody decreased levels of TAT but did not affect the platelet count. Our study demonstrated that TF plays a central role in the activation of coagulation in both the xenograft and allograft mouse models. These mouse models of APL can be used to investigate the mechanisms of coagulopathy in APL.

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Shifting gears to differentiation agents in acute promyelocytic leukemia with resource constraints—a cohort study

Cited by 2 publications

References 22 publications

Long‐term real‐world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all‐trans retinoic acid without chemotherapy—a retrospective, single‐centre study

Long‐term real‐world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all‐trans retinoic acid without chemotherapy—a retrospective, single‐centre study

Tissue factor activates the coagulation cascade in mouse models of acute promyelocytic leukemia

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