#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Relapsed AML 2001/01, 02 Study for children with relapsed acute myeloid leukaemia or initially resistant disease has improved outcome


Authors: Zdráhalová K.ihash2ihash4ihash6ihash8ihash10ihash12ihash14ihash16ihash18ihash20ihash22ihash24ihash26ihash28ihash30ihash32ihash34ihash36ihash38ihash40ihash42ihash44ihash46ihash48ihash50ihash52 1 1 1 1 2 3 4 5 6 7 8 9 10 11 12,14 13 14 1 1 1 15 15 16 16 1 1 1
Authors‘ workplace: Klinika dětské hematologie a onkologie 2. LF UK a FN Motol, Praha, Klinika dětské onkologie, FN Brno, I. dětská interní klinika LF MU a FN Brno, Klinika dětského lékařství FN Ostrava, Dětská klinika LF UP a FN Olomouc, #IHA 1
Published in: Transfuze Hematol. dnes,17, 2011, No. 3, p. 113-121.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Relapse of acute myeloid leukaemia (AML) or AML initially resistant to treatment is extremely prognostically unfavourable. Between VIII/2001 and III/2009 in the Czech Republic, twenty patients aged 0-18 years with this diagnosis were treated as part of the international Relapsed AML 2001/01study. The protocol consisted of two blocks of chemotherapy based on a high-dose cytosine-arabinoside in combination with fludarabine. In the first block, patients were randomized to receive liposomal daunorubicin (DaunoXome). If there was > 20% blasts in the bone marrow after the first block or if a complete remission was not achieved after the second block, patients were considered non-responders and were excluded from the study. They were however eligible for the therapeutic study Relapsed AML 2001/02 with gemtuzumab ozogamicin (Mylotarg; GO) in monotherapy. After achieving a 2nd remission, children were indicated to undergo hematopoietic stem cell transplantation (HSCT). Two patients were treated for an initially resistant disease, 18 children for the 1st relapse of AML. In 61%, the relapse occurred early, less than 12 months from diagnosis. Six children did not respond to treatment, two died of an early death, twelve (60%) patients achieved a 2nd remission and 11 of these underwent allogeneic HSCT. In total, 6 (30%) of the children are alive with a median follow up of 5.8 years, all having undergone allogeneic transplantation (2 children after the 2nd HSCT). For the whole group, the event free survival probability (EFS) at 5 years is 18 ± 9%, the overall survival (OS) probability is 34 ± 11%. Treatment in the Relapsed AML 2001 study improved the prognosis of children with relapsed AML in the Czech Republic compared to the previous period 1993-2001 (n=22 children, OS 14%).

Key words:
acute myeloid leukemia, relapse, resistance, Relapsed AML 2001, children


Sources

1. Creutzig U, Zimmermann M, Ritter J, et al. Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia 2005; 19: 2030-42.

2. Kaspers GJ, Creutzig U. Pediatric acute myeloid leukemia: international progress and future directions. Leukemia 2005; 19: 2025-9.

3. Lie SO, Abrahamsson J, Clausen N, et al. Long-term results in children with AML: NOPHO-AML Study Group—report of three consecutive trials. Leukemia 2005; 19: 2090-100.

4. Entz-Werle N, Suciu S, van der Werff ten Bosch J, et al. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia 2005; 19: 2072-81.

5. Ravindranath Y, Chang M, Steuber CP, et al. Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia 2005; 19: 2101-16.

6. Smith FO, Alonzo TA, Gerbing RB, Woods WG, Arceci RJ; Children’s Cancer Group. Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children’s Cancer Group: CCG 251, CCG 213 and CCG 2891. Leukemia 2005; 19: 2054-62.

7. Starý J, Vávra V, Gajdoš P, et al. Druhá celostátní léčebná studie AML-BFM 98 zvýšila úspěšnost v dosažení remise a zlepšila celkové přežití dětí s akutní myeloidní leukemií v České republice. Transfuz Hemat dnes 2008; 14: 166-74.

8. Starý J, Gajdoš P, Blažek B, et al. Sjednocení léčby dětí s akutní myeloidní leukemií v České republice podle protokolu AML-BFM 93. Čas Lek čes 2004; 143: 257-63.

9. Stahnke K, Boos J, Bender-Götze C, Ritter J, Zimmermann M, Creutzig U. Duration of first remission predicts remission rates and long-term survival in children with relapsed acute myelogenous leukemia. Leukemia 1998; 12: 1534-8.

10. Sander A, Zimmermann M, Dworzak M, et al. Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials. Leukemia 2010; 24: 1422-8.

11. Aladjidi N, Auvrignon A, Leblanc T, et al. Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology. J Clin Oncol 2003; 21: 4377-85.

12. Abrahamsson J, Clausen N, Gustafsson G, et al. Improved outcome after relapse in children with acute myeloid leukaemia. Br J Haematol 2007; 136: 229-36.

13. Webb DK, Wheatley K, Harrison G, Stevens RF, Hann IM. Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial. MRC Childhood Leukaemia Working Party. Leukemia 1999; 13: 25-31.

14. Rubnitz JE, Razzouk BI, Lensing S, Pounds S, Pui CH, Ribeiro RC. Prognostic factors and outcome of recurrence in childhood acute myeloid leukemia. Cancer 2007; 109: 157-63.

15. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. New Engl J Med 2009; 361: 1249-59.

16. Fleischhack G, Hasan C, Graf N, Mann G, Bode U. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol 1998; 102: 647-55.

17. Gill PS, Espina BM, Muggia F, et al. Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin. J Clin Oncol 1995; 13: 996-1003.

18. Van der Velden VHJ, te Marvelde JG, Hoogeveen PG, et al. Targeting of the CD33-calicheamicin immunoconjugate GO in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal cells. Blood 2001; 97: 3197-204.

19. van der Burg M, Beverloo HB, Langera AW, et al. Rapid and sensitive detection of all types of MLL gene translocations with single FISH probe set. Leukemia 1999; 13: 2107-13.

20. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81.

21. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50: 163-70.

22. Creutzig U, Zimmermann M, Lehrnbecher T, et al. Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98. J Clin Oncol 2006; 24: 4499-506.

23. Creutzig U, Zimmermann M, Bourquin J-P, et al. t(8;21) in childhood AML: Improved outcome by an intensified induction with HAM – Results from studies AML-BFM 98 and -2004. J Clin Oncol 2011 – přijato do tisku

24. Gassas A, Ishaqi MK, Afzal S, et al. A comparison of the outcomes of children with acute myelogenous leukemia in either first or second complete remission (CR1 vs CR2) following allogeneic hematopoietic stem cell transplantation at a single transplant center. Bone Marrow Transplant 2008; 41: 941-5.

25. Balgobind BV, Raimondi SC, Harbott J, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009; 114: 2489-96.

26. Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 1998; 92: 2322-33.

27. Zwaan CM, Reinhardt D, Zimmerman M, et al. Salvage treatment for children with refractory first or second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin: results of a phase II study. Br J Haematol 2010; 148: 768-76.

28. Arceci RJ, Sande J, Lange B, et al. Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia. Blood 2005; 106: 1183-8.

29. Brethon B, Yakouben K, Oudot C, et al. Efficacy of fractionated gemtuzumab ozogamicin combined with cytarabine in advanced childhood myeloid leukaemia. Br J Haematol 2008; 143: 541-7.

30. Fagioli F, Zecca M, Locatelli F, et al. Allogeneic stem cell transplantation for children with acute myeloid leukemia in second complete remission. J Pediatr Hematol Oncol 2008; 30: 575-83.

31. Goemans BF, Tamminga RY, Corbijn CM, Hählen K, Kaspers GJ. Outcome for children with relapsed acute myeloid leukemia in the Netherlands following initial treatment between 1980 and 1998: survival after chemotherapy only? Haematologica 2008; 93: 1418-20.

32. Coustan-Smith E, Ribeiro RC, Rubnitz JE, et al. Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia. Br J Haematol 2003; 123: 243-52.

33. Sievers EL, Lange BJ, Alonzo TA, et al. Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children’s Cancer Group study of 252 patients with acute myeloid leukemia. Blood 2003; 101: 3398-406.

Labels
Haematology Internal medicine Clinical oncology
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#