Long-term prognosis of childhood acute promyelocytic leukaemia with arsenic trioxide administration in induction and consolidation chemotherapy phases: a single-centre experience.

The efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (As2 O3 ) as induction therapy for adult acute promyelocytic leukaemia (APL) has been documented in several clinical trials. However, the role of ATRA/As2 O3 combination in induction and consolidation therapy in children remains unclear. Here, we report the efficacy of combined treatment with As2 O3 and ATRA as induction and consolidation chemotherapy to treat newly diagnosed childhood APL. From 1998 to 2011, 43 children with newly diagnosed APL received induction and consolidation chemotherapy with ATRA and As2 O3 (Protocol B). Rates of complete remission (CR), event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) and drug toxicity were compared between children treated with Protocol B and 25 others treated previously with ATRA alone as induction chemotherapy (Protocol A). Of 43 patients treated with Protocol B, 41 (95.4%) achieved CR (two died of intracranial haemorrhage on day 10 and 14). In contrast, only 20 (80%) of 25 patients treated with Protocol A achieved CR. Thus, the CR rate was significantly lower in patients receiving induction chemotherapy with Protocol A than in those treated with Protocol B (P = 0.045, χ(2) = 6.508). Of the 41 patients who achieved CR on induction therapy with Protocol B, 40 also received consolidation therapy. Molecular relapse, but no overt morphological relapse, occurred in one patient at 25 months after diagnosis; this patient regained CR status with As2 O3 treatment. With a median follow-up period of 75 months, estimated EFS, DFS and OS rates were 92.5 ± 4.2%, 97.1 ± 2.9% and 95.3 ± 3.2%, respectively, for Protocol B. In contrast, with a median follow-up of 127 months, the EFS, DFS and OS rates at 75 months were 70.4 ± 9.4%, 76.4 ± 9.2% and 70.4 ± 9.4%, respectively, for Protocol A. Thus, patients treated with Protocol A showed significantly lower EFS (P = 0.021) and OS (P = 0.007) rates than those treated with Protocol B. Application of As2 O3 and ATRA as induction and consolidation chemotherapy resulted in excellent outcomes and improved long-term prognosis in children with newly diagnosed APL.

Cheng Y ，Zhang L ，Wu J ，Lu A ，Wang B ，Liu G ... -  《-》

Retinoic acid and arsenic trioxide for acute promyelocytic leukemia.

Lo-Coco F ，Avvisati G ，Vignetti M ，Thiede C ，Orlando SM ，Iacobelli S ，Ferrara F ，Fazi P ，Cicconi L ，Di Bona E ，Specchia G ，Sica S ，Divona M ，Levis A ，Fiedler W ，Cerqui E ，Breccia M ，Fioritoni G ，Salih HR ，Cazzola M ，Melillo L ，Carella AM ，Brandts CH ，Morra E ，von Lilienfeld-Toal M ，Hertenstein B ，Wattad M ，Lübbert M ，Hänel M ，Schmitz N ，Link H ，Kropp MG ，Rambaldi A ，La Nasa G ，Luppi M ，Ciceri F ，Finizio O ，Venditti A ，Fabbiano F ，Döhner K ，Sauer M ，Ganser A ，Amadori S ，Mandelli F ，Döhner H ，Ehninger G ，Schlenk RF ，Platzbecker U ，Gruppo Italiano Malattie Ematologiche dell'Adulto ，German-Austrian Acute Myeloid Leukemia Study Group ，Study Alliance Leukemia ... -  《-》

Long-term survey of outcome in acute promyelocytic leukemia.

Hu J ，Shen Z ，Sun H ，Wu W ，Li X ，Sun G ，Wang Z ... -  《-》

Long-term efficacy of low-dose all-trans retinoic acid plus minimal chemotherapy induction followed by the addition of intravenous arsenic trioxide post-remission therapy in newly diagnosed acute promyelocytic leukaemia.

We evaluated the efficacy of low-dose all-trans retinoic acid (ATRA) plus minimal chemotherapy for induction in newly diagnosed acute promyelocytic leukaemia (APL). Furthermore, we compared its long-term outcome with or without the addition of intravenous arsenic trioxide (ATO) in post-remission therapy. From January 2004 to September 2011, a total of 109 patients with a median age of 41 years (range 14-73) were enrolled in the study. Two arms were assigned according to post-remission protocols: ATO group cases were subsequently treated with intravenous ATO, standard chemotherapy, and ATRA. No-ATO group cases were subsequently treated with chemotherapy and ATRA only. Patients were monitored of minimal residual disease (MRD) by reverse-transcriptase polymerase chain reaction. The haematologic complete remission (CR) rate was 96.3%. The early death rate was 0.9%. At a median follow-up of 49 months (range 8-102 months), the Kaplan-Meier estimates of 5-year relapse-free survival were significantly better for patients in the ATO group than in the no-ATO group, 94.4% vs 54.8% (p = 0.0001), and the 5-year overall survival rate was 95.7% vs 64.1%, in the two groups (p = 0.003). Our data show that low-dose ATRA plus minimal chemotherapy exhibits efficacy in induction therapy for untreated APL and suggest that the addition of ATO to post-remission therapy significantly improves the long-term outcome.

Lou Y ，Qian W ，Meng H ，Mai W ，Tong H ，Tong Y ，Huang J ，Jin J ... -  《-》

Use of all-trans retinoic acid in combination with arsenic trioxide for remission induction in patients with newly diagnosed acute promyelocytic leukemia and for consolidation/maintenance in CR patients.

In the present study, 90 patients with newly diagnosed acute promyelocytic leukemia (APL) were studied for all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) combination treatment in remission induction and postremission therapy. In addition, 20 APL patients who had achieved complete remission (CR) with an ATRA-based regimen received ATRA/As(2)O(3) combination for consolidation and maintenance were also enrolled. The results showed that ATRA/As(2)O(3) combination therapy yielded a high CR rate of 93.3% and a significantly shorter time to enter CR (median: 31 days; range: 18-59 days) compared to the ATRA-based regimen (n = 72; median: 39 days; range: 25-62 days). With the ATRA/As(2)O(3) combination for CR maintaining, regardless of the way by which CR was attained, the relapse-free survival was significantly better than with an ATRA plus cytotoxic chemotherapy regimen (92.9 +/- 3.2% vs. 72.4 +/- 7.6%, for the 3-year Kaplan-Meier estimate of relapse-free survival). The drug toxicity profile showed that with the use of As(2)O(3), the incidence of hepatotoxicity was obviously high during remission induction but decreased significantly during postremission treatment. We conclude that APL patients may benefit from the early use of the combination of ATRA and As(2)O(3), in either remission induction or consolidation/maintenance.

Dai CW ，Zhang GS ，Shen JK ，Zheng WL ，Pei MF ，Xu YX ，Cao YX ，Yi Y ，Yang JJ ，Peng HL ，Zhong HY ，Li RJ ... -  《-》