Management of relapsed and refractory childhood acute promyelocytic leukaemia: recommendations from an international expert panel

Abla, Oussama; Kutny, Matthew A.; Testi, Anna Maria; Feusner, James; Creutzig, Ursula; Gregory, John J.; Gibson, Brenda; Leverger, Guy; Ribeiro, Raul C.; Smith, Owen; Locatelli, Franco; Kaspers, Gertjan J. L.

doi:10.1111/bjh.14313

Cited by 15 publications

(25 citation statements)

References 83 publications

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“…However, our present data would suggest that for sustained remission, these patients should be consolidated with an auto‐SCT after they have achieved a MR. The clinical outcomes with this approach are associated with excellent results, as reported here [mean (SD) 5‐year OS and EFS of 90·3 (5·3)% and 87·1 (6·0)% respectively], and is similar to the observation in patients with relapsed APL treated with up‐front ATRA‐based regimens 4–7,20,21 . While maintenance with an ATO‐based regimen is well tolerated, the risk of subsequent relapse is very high (39·3%) compared to that seen in the group that received an auto‐SCT consolidation (8·6%).…”

Section: Discussionsupporting

confidence: 77%

“…While the number of paediatric patients in the present study was small, the available data would suggest that the results of salvage with an ATO‐based regimen followed by consolidation with auto‐SCT are similar to those seen in adults and to several previous reports 7 . As observed in adults, there was no transplant‐related mortality in children who underwent auto‐SCT.…”

Section: Discussionsupporting

confidence: 73%

“…Salvage therapies with combined ATRA and arsenic compound‐based regimens have been shown to induce a complete remission (CR) in 50–80% of patients with refractory or relapsed APL 1,3 . The available data for the management of relapsed APL are mostly in the context of relapse after conventional ATRA plus chemotherapy‐based regimens and in this setting the existing data suggests that an autologous stem cell transplant (auto‐SCT) in molecular remission (MR) is associated with better survival in comparison to ATO‐based maintenance therapy 1,4–8 …”

Section: Introductionmentioning

confidence: 99%

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Management of relapse in acute promyelocytic leukaemia treated with up‐front arsenic trioxide‐based regimens

Sharma

Ganesan

et al. 2020

Br J Haematol

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The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front-line treatment with arsenic trioxide (ATO)based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO-based up-front therapy and were also salvaged using an ATO-based regimen were evaluated. The median (range) age of patients was 28 (4-54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4Á5%) died during salvage therapy. An autologous stem cell transplant (auto-SCT) was offered to all patients who achieved MR, 35/63 (55Á6%) opted for auto-SCT the rest were administered an ATO + all-trans retinoic acid maintenance regimen. The mean (SD) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received auto-SCT versus those who did not was 90Á3 (5Á3)% versus 58Á6 (10Á4)% (P = 0Á004), and 87Á1 (6Á0)% versus 47Á7 (10Á3)% (P = 0Á001) respectively. On multivariate analysis, failure to consolidate MR with an auto-SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4Á91, 95% confidence interval (CI) 1Á56-15Á41; P = 0Á006]. MR induction with ATO-based regimens followed by an auto-SCT in children and young adults with relapsed APL who were treated with front-line ATO-based regimens was associated with excellent longterm survival.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Management of relapse in acute promyelocytic leukaemia treated with up‐front arsenic trioxide‐based regimens

Sharma

Ganesan

et al. 2020

Br J Haematol

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“…One of the most recurrent translocation in pediatric AML is t (15, 17) , which results in the fusion transcript PML-RARA and identifies a specific AML subtype, acute promyelocytic leukemia (APL), accounting for ~12% of pediatric AML (10). Among pediatric leukemias, APL is the first case where an effective targeted therapy was used, consisting of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and this successful treatment radically changed APL from a detrimental to a curable malignancy, with complete remission rate over 90% (49, 50). These successful results constantly encourage the efforts in identifying effective targeted therapies against leukemia driver mutations.…”

Section: Targeting Fusion Proteinsmentioning

confidence: 99%

Targeted Therapies for Pediatric AML: Gaps and Perspective

2019

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Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by numerous cytogenetic and molecular aberrations that accounts for ~25% of childhood leukemia diagnoses. The outcome of children with AML has increased remarkably over the past 30 years, with current survival rates up to 70%, mainly due to intensification of standard chemotherapy and improvements in risk classification, supportive care, and minimal residual disease monitoring. However, childhood AML prognosis remains unfavorable and relapse rates are still around 30%. Therefore, novel therapeutic approaches are needed to increase the cure rate. In AML, the presence of gene mutations and rearrangements prompted the identification of effective targeted molecular strategies, including kinase inhibitors, cell pathway inhibitors, and epigenetic modulators. This review will discuss several new drugs that recently received US Food and Drug Administration approval for AML treatment and promising strategies to treat childhood AML, including FLT3 inhibitors, epigenetic modulators, and Hedgehog pathway inhibitors.

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“…Unabhängig davon richtet sich die Rezidivtherapie (1) nach dem Zeitpunkt des Rezidivs (Frührezidiv < 18 Monate, Spätrezidiv 18-36 Monate und sehr spätes Rezidiv > 36 Monate nach Diagnose) und (2) nach der Primärtherapie: ATRA + Chemotherapie oder ATRA + ATO. Ein entsprechender Algorithmus wurde im Rahmen der "Internationalen Consensus Guideline COG/I-BFM" publiziert [1].…”

Section: Rezidiv-behandlungunclassified

Akute Promyelozyten-Leukämie: Neue Behandlungsstrategien mit ATRA und ATO – AML-BFM-Empfehlungen

et al. 2018

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ZusammenfassungDie Behandlung der Akuten Promyelozyten-Leukämie (APL) hat sich in den letzten Jahren deutlich geändert. Heute können APL Patienten mit Standardrisiko – (auch als Niedrigrisiko bezeichnet) ohne Chemotherapie nur mit all-trans-Retinsäure (ATRA) und Arsentrioxid (ATO) behandelt werden. Bei Hochrisikopatienten sollte eine Induktions-Chemotherapie hinzugefügt werden. Die kurativen Ergebnisse sind gut und vergleichbar mit jenen, die in der Vergangenheit mit Chemotherapie plus ATRA erzielt wurden. Toxizitäten, insbesondere infektiöse Komplikationen sind jedoch deutlich seltener. Das Hauptrisiko bleiben frühe letale Blutungen. Durch rechtzeitige Diagnose und frühe ATRA-Behandlung kann dieses Risiko reduziert werden. In der vorliegenden Übersicht werden die aktuellen Behandlungsstrategien und Empfehlungen für APL bei Kindern dargestellt und diskutiert.

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Management of relapsed and refractory childhood acute promyelocytic leukaemia: recommendations from an international expert panel

Cited by 15 publications

References 83 publications

Management of relapse in acute promyelocytic leukaemia treated with up‐front arsenic trioxide‐based regimens

Management of relapse in acute promyelocytic leukaemia treated with up‐front arsenic trioxide‐based regimens

Targeted Therapies for Pediatric AML: Gaps and Perspective

Akute Promyelozyten-Leukämie: Neue Behandlungsstrategien mit ATRA und ATO – AML-BFM-Empfehlungen

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