Recurrences of acute promyelocytic leukemia in children: experience with arsenic trioxide therapy and autologous hemopoietic cell transplantation


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Abstract

Aim. To analyze the specific features of recurrences of acute promyelocytic leukemia (APL) in children after standard therapy with daunorubicin, cytosine arabinoside (Ara-C), all-trans retinoic acid (ATRA) and to develop further programmed treatment policy.
Subjects and methods. The study included 9 patients with recurrent APL. The recurrences developed significantly more frequently in a very high-risk group (patients with minimal residual disease being preserved after the intensive therapy phase). Induction used arsenic trioxide (ATO) and/or standard chemotherapy + ATRA; ATO monotherapy was in consolidation. CD34+ cells were mobilized until molecular remission was achieved with high-dose Ara-C and granulocyte colony-stimulating factor. Pretransplantation conditioning involved melfalan as a basic drug in combination with high-dose Ara-C (5 pts), treosulfan (1 pt) or bisulfan (1 pt). Six patients received gemtusumab ozogamicin, 3-9 mg/m2, at different stages of therapy.
Results. Before therapy one patient died; 8 patients achieved the second molecular remission; CD34+ cell mobilization and sampling were effective in 7 cases. Five patients were in long-term molecular remission after autologous hemopoietic stem cell transplantation (autoHSCT). Follow-up was 23-40 months. One patient is being prepared for transplantation. Following autoHSCT, another patient with a developed repeat recurrence died from complications due to related partially compatible transplantation. Visceral, including cardiological, toxicity of therapy was insignificant. In the APL-2003 protocol, overall and event-free survival rates were 93±3 and 76±6%, respectively.
Conclusion. The application of ATO and autoHSCT in recurrent APL makes it possible to achieve and preserve the second molecular remission in case of insignificant extrahematological toxicity. Russian clinics should have access to ATO.

About the authors

D D Baidildina

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

M A Maschan

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation

E V Skorobogatova

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

M E Dubrovina

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

Yu V Rumyantseva

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation

A A Maschan

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

Email: amaschan@mail.ru
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

A G Rumyantsev

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation

E V Samochatova

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow

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