Re-induction with Modified CLAG Regimen in Relapsed or Refractory Acute Myeloid Leukemia in Children Bridging to Allogeneic Hematopoietic Stem Cell Transplantation

Overview

Journal World J Pediatr

Specialty Pediatrics

Date 2019 Nov 22

PMID 31748985

Citations 5

Authors

Na Zhang

Jing-Bo Shao

Hong Li

Jing-Wei Yang

Kai Chen

Jia-Shi Zhu

Hui Jiang

Affiliations

Soon will be listed here.

Abstract

Background: The prognosis for relapsed or refractory acute myeloid leukemia (RR-AML) in children is poor, and the preferred salvage chemotherapy is unclear. One regimen is cladribine, cytarabine, and granulocyte-colony stimulating factor (CLAG), but little is known about its efficacy and safety in children with RR-AML.

Methods: We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1, 2015 and April 1, 2018, or conventional induction between August 1, 2011 and April 1, 2018. Patients were followed up to March 31, 2019. Patients underwent allogeneic stem cell transplantation (allo-SCT) or chemotherapy after the induction of complete remission (CR). The CR rate, survival, and side effects were analyzed.

Results: The CR rate for induction was 66.7% after one cycle and 75.0% after two cycles of the CLAG regimen in 12 children. The nine children who received conventional chemotherapy had a CR rate of 22.2% after one cycle and 33.3% after two cycles (P = 0.087 vs. CLAG). The 3-year event-free survival (EFS) of the CLAG group and the conventional treatment group were 44.4 ± 15.7% and 22.2 ± 13.8% (P = 0.112). The 3-year overall survival of the two groups were 59.5 ± 16.2% and 22.2% ± 13.8% (P = 0.057). The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7 ± 19.2% and 25.0 ± 21.7% (P = 0.015). A single case of chemotherapy-related death was recorded.

Conclusion: Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML. Allo-SCT after CR may improve the long-term outcome in these patients.

Citing Articles

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References

Kornblau S, Gandhi V, Andreeff H, Beran M, Kantarjian H, Koller C . Clinical and laboratory studies of 2-chlorodeoxyadenosine +/- cytosine arabinoside for relapsed or refractory acute myelogenous leukemia in adults. Leukemia. 1996; 10(10):1563-9. View

Estey E, Thall P, Andreeff M, Beran M, Kantarjian H, OBrien S . Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without.... J Clin Oncol. 1994; 12(4):671-8. DOI: 10.1200/JCO.1994.12.4.671. View

Jaglal M, Duong V, Bello C, Al Ali N, Padron E, Fernandez H . Cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) compared to standard induction in acute myeloid leukemia from myelodysplastic syndrome after azanucleoside failure. Leuk Res. 2014; 38(4):443-6. DOI: 10.1016/j.leukres.2013.12.010. View

Seymour J, Huang P, Plunkett W, Gandhi V . Influence of fludarabine on pharmacokinetics and pharmacodynamics of cytarabine: implications for a continuous infusion schedule. Clin Cancer Res. 1996; 2(4):653-8. View

Messinger Y, Boklan J, Goldberg J, Dubois S, Oesterheld J, Abla O . Combination of clofarabine, cyclophosphamide, and etoposide for relapsed or refractory childhood and adolescent acute myeloid leukemia. Pediatr Hematol Oncol. 2017; 34(4):187-198. DOI: 10.1080/08880018.2017.1360970. View

Fridle C, Medinger M, Wilk M, Seipel K, Passweg J, Manz M . Cladribine, cytarabine and idarubicin (CLA-Ida) salvage chemotherapy in relapsed acute myeloid leukemia (AML). Leuk Lymphoma. 2016; 58(5):1068-1075. DOI: 10.1080/10428194.2016.1235274. View

Park H, Youk J, Kim I, Yoon S, Park S, Lee J . Comparison of cladribine- and fludarabine-based induction chemotherapy in relapsed or refractory acute myeloid leukaemia. Ann Hematol. 2016; 95(11):1777-86. DOI: 10.1007/s00277-016-2774-z. View

Rubnitz J . Current Management of Childhood Acute Myeloid Leukemia. Paediatr Drugs. 2016; 19(1):1-10. DOI: 10.1007/s40272-016-0200-6. View

Wang L, Xu J, Tian X, Lv T, Yuan G . Analysis of Efficacy and Prognostic Factors of CLAG Treatment in Chinese Patients with Refractory or Relapsed Acute Myeloid Leukemia. Acta Haematol. 2018; 141(1):43-53. DOI: 10.1159/000493250. View

10.

Robak T, Wrzesien-Kus A, Lech-Maranda E, Kowal M, Dmoszynska A . Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000; 39(1-2):121-9. DOI: 10.3109/10428190009053545. View

11.

Inaba H, Stewart C, Crews K, Yang S, Pounds S, Pui C . Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia. Cancer. 2009; 116(1):98-105. PMC: 2920745. DOI: 10.1002/cncr.24712. View

12.

Wrzesien-Kus A, Robak T, Wierzbowska A, Lech-Maranda E, Pluta A, Wawrzyniak E . A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of.... Ann Hematol. 2005; 84(9):557-64. DOI: 10.1007/s00277-005-1046-0. View

13.

Chaleff S, Hurwitz C, Chang M, Dahl G, Alonzo T, Weinstein H . Phase II study of 2-chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a paediatric oncology group study. Br J Haematol. 2012; 156(5):649-55. DOI: 10.1111/j.1365-2141.2011.08976.x. View

14.

Rubnitz J, Razzouk B, Srivastava D, Pui C, Ribeiro R, Santana V . Phase II trial of cladribine and cytarabine in relapsed or refractory myeloid malignancies. Leuk Res. 2004; 28(4):349-52. DOI: 10.1016/j.leukres.2003.08.010. View

15.

Robak T . Purine nucleoside analogues in the treatment of myleoid leukemias. Leuk Lymphoma. 2003; 44(3):391-409. DOI: 10.1080/1042819021000035608. View

16.

Woelich S, Braun J, Schoen M, Ramlal R, Freter C, Petruska P . Efficacy and Toxicity of Induction Therapy with Cladribine, Idarubicin, and Cytarabine (IAC) for Acute Myeloid Leukemia. Anticancer Res. 2017; 37(2):713-717. DOI: 10.21873/anticanres.11368. View

17.

Zhang J, Sun Y, Zhang X, Long B, Lu Y, Li X . Treatment of High-Risk Acute Myeloid Leukemia With Cladribine, Cytarabine, Mitoxantrone, and Granulocyte Colony-Stimulating Factor Then Subsequent Bridging to Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: A Case Series. Transplant Proc. 2018; 50(1):246-249. DOI: 10.1016/j.transproceed.2017.11.019. View

18.

Creutzig U, van den Heuvel-Eibrink M, Gibson B, Dworzak M, Adachi S, De Bont E . Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood. 2012; 120(16):3187-205. DOI: 10.1182/blood-2012-03-362608. View

19.

Gordon M, Young M, Tallman M, Cripe L, Bennett J, Paietta E . Phase II trial of 2-chlorodeoxyadenosine in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group (ECOG), E5995. Leuk Res. 2000; 24(10):871-5. DOI: 10.1016/s0145-2126(00)00043-6. View

20.

Krance R, Hurwitz C, Head D, Raimondi S, Behm F, Crews K . Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases. J Clin Oncol. 2001; 19(11):2804-11. DOI: 10.1200/JCO.2001.19.11.2804. View