E.V. Semenova, N.V. Stancheva, S.N. Bondarenko, V.N. Vavilov, D.A. Bagge, O.V. Paina, S.V. Razumova, A.S. Borovkova, T.A. Bykova, A.A. Raths, L.S. Zuborovskaya, B.V. Afanasyev
R.M. Gorbacheva Memorial Institute of Children Hematology and Transplantation, Pavlov State Medical University, Saint-Petersburg, Russian Federation
ABSTRACT
Objective: to analyze efficacy of fludarabine- and nelarabine-containing chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and adolescents with relapsed and refractory acute lymphoblastic leukemia (ALL) .
Patients and methods: Thirty three patients (pts) with relapsed and refractory ALL from 1 till 21 y.o. (median age was 11,5 y.o.) were treated by fludarabine- (n=23) and nelarabine- (n=10) containing therapy. Subsequently 24 patients underwent allo-HSCT.
Results: CR was achieved in 11(48%) of 23 pts after FLAG±IDA and 7 (70%) of 10 pts after nelarabine-containg regimens. Duration of remissions were 1-18 months (median was 4,9 months).
Overall 3-year survival (OS) after allo-HSCT in remission was 58%, OS after allo-HSCT in relapse was 8%, OS without allo-HSCT was 0%.
Conclusion: Fludarabine- and nelarabine-containing therapy can be used as bridge to allo-HSCT in children and adolescents with poor-prognosis ALL.
Кeywords: fludarabine, nelarabine, allo-HSCT, relapsed or refractory acute lymphoblastic leukemia, children and adolescents
REFERENCES
- Schrappe M., Reiter A., Ludwig W.D. et al. Improved outcome in childhood acute Lymphoblastic leukemia despite reduced use of antracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood 2000; 95(11): 3310–22.
- Silverman L.B., Gelber R.D., Dalton V.K. et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001; 97(5): 1211–8.
- Pui C.-H., Schrappe M., Ribeiro R.C., Niemeyer C.M. Childhood and adolescent lymphoid and myeloid leukemia. Hematology 2004; 84: 124–32.
- Pui C.H., Evans W.E. Treatment of acute lymphoblastic leukemia. N. Engl. J. Med. 2006; 354(2): 166–78.
- Chessells J.M., Veys P., Kempski H. et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. Br. J. Haematol. 2003; 123: 396–405.
- Nguyen K., Devidas M., Cheng S.C. et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: A Children’s Oncology Group study. Leukemia 2008; 22: 2142–50.
- Афанасьев Б.В., Зубаровская Л.С. Трансплантация гемопоэтических стволовых клеток крови. Детская онкология: Руководство. СПб., 2002: 90–108. [Afanas’ev B.V., Zubarovskaya L.S. Transplantatsiya gemopoeticheskikh stvolovykh kletok krovi. Detskaya onkologiya: Rukovodstvo (Hematopoietic stem cell transplantation. Pediatric oncology. Manual). , 2002: 90–108.]
- Румянцев А.Г., Масчан А.А. Трансплантация гемопоэтических стволовых клеток у детей: Руководство для врачей. М., 2003. [Rumyantsev A.G., Maschan A.A. Transplantatsiya gemopoeticheskikh stvolovykh kletok u detei: Rukovodstvo dlya vrachei (Hematopoietic stem cell transplantation in children. Manual for medical practitioners)., 2003.]
- McCarthy A.J., Pitcher L.A., Hann I.M., Oakhill A. FLAG (fludarabine, high-dose cytarabine, and G-CSF) for refractory and high-risk relapsed acute leukemia in children. Med. Pediatr. Oncol. 1999; 32(6): 411–5.
- Yang S.W. et al. Dual mode of inhibition of purified DNA ligase from human cells by 9-β-D-arabinosyl-2-fluoroadenine triphosphate. J. Biol. Chem. 1992; 267: 2345–9.
- Ross S.P. et al. Fludarabine: a review of its pharmacological properties and therapeutic potential in malignancy. Drug 1993; 45: 737–59.
- Gandhi V. et al. Combination of fludarabine and arabinosyl-cytosine for the treatment of chronic lymphocytic leukemia: clinical efficacy and modulation of arabinosyl-cytosine pharmacology. Cancer Chem. Pharmacol. 1994; 34: 30–6.
- Tavil B., Aytac S., Balci Y.I. et al. Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) for the treatment of children with poor-prognosis acute leukemia: the Hacettepe experience. Hematol. Oncol. 2010; 27(7): 517–28.
- Quarello P., Berger M., Rivetti E. et al. FLAG-liposomal doxorubicin (Myocet) regimen for refractory or relapsed acute leukemia pediatric patients. J. Pediatr. Hematol. Oncol. 2012; 34(3): 208–16.
- Berg S.L., Blaney S.M., Devidas M. et al. Phase II study of Nelarabine in children and young adults with refractory T-cell malignancies: a report from the Children’s Oncology Group. J. Clin. Oncol. 2005; 23(15): 3376–82.
- Commander L.A., Seif A.E., Insogna I.G., Susan R. Rheingold. Salvage therapy with nalarabine, etoposide and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma. J. Haem. 2010; 150: 345–51.
- Trotti A., Colevas A.D. et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Radiat. O 2007; 13: 176–81.