Version 1
: Received: 11 August 2023 / Approved: 11 August 2023 / Online: 14 August 2023 (09:52:50 CEST)
How to cite:
Alexandra, G.; Doran, C.; Ionescu, B.; Stancioaica, M. C.; Hirjan, R.; Tatic, A.; Cirstea, M.; Dragomir, M.; Calugaru, O.; Popa, C.; Jardan, C.; Vasilache, D.; Coriu, D. Early Complications in the Era of ATRA Plus ATO Therapy Outside of Clinical Trials‐One Center Experience during Three Years and Literature Review‐. Preprints2023, 2023080936. https://doi.org/10.20944/preprints202308.0936.v1
Alexandra, G.; Doran, C.; Ionescu, B.; Stancioaica, M. C.; Hirjan, R.; Tatic, A.; Cirstea, M.; Dragomir, M.; Calugaru, O.; Popa, C.; Jardan, C.; Vasilache, D.; Coriu, D. Early Complications in the Era of ATRA Plus ATO Therapy Outside of Clinical Trials‐One Center Experience during Three Years and Literature Review‐. Preprints 2023, 2023080936. https://doi.org/10.20944/preprints202308.0936.v1
Alexandra, G.; Doran, C.; Ionescu, B.; Stancioaica, M. C.; Hirjan, R.; Tatic, A.; Cirstea, M.; Dragomir, M.; Calugaru, O.; Popa, C.; Jardan, C.; Vasilache, D.; Coriu, D. Early Complications in the Era of ATRA Plus ATO Therapy Outside of Clinical Trials‐One Center Experience during Three Years and Literature Review‐. Preprints2023, 2023080936. https://doi.org/10.20944/preprints202308.0936.v1
APA Style
Alexandra, G., Doran, C., Ionescu, B., Stancioaica, M. C., Hirjan, R., Tatic, A., Cirstea, M., Dragomir, M., Calugaru, O., Popa, C., Jardan, C., Vasilache, D., & Coriu, D. (2023). Early Complications in the Era of ATRA Plus ATO Therapy Outside of Clinical Trials‐One Center Experience during Three Years and Literature Review‐. Preprints. https://doi.org/10.20944/preprints202308.0936.v1
Chicago/Turabian Style
Alexandra, G., Didona Vasilache and Daniel Coriu. 2023 "Early Complications in the Era of ATRA Plus ATO Therapy Outside of Clinical Trials‐One Center Experience during Three Years and Literature Review‐" Preprints. https://doi.org/10.20944/preprints202308.0936.v1
Abstract
Abstract
The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication.
This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction.
This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
