MLL-negative infant acute lymphoblastic leukemia. Clinical characteristics and possibilities for chemotherapy optimization
https://doi.org/10.17650/2311-1267-2017-4-3-17-26
Abstract
MLL-negative (mixed lineage leukemia – MLL) acute lymphoblastic leukemia (ALL) diagnosed in the first year of life is rare. Although infant ALL is often assumed to be fatal, no studies have been published on outcome of MLL-negative infant ALL. The present study reports the clinical characteristics and outcome of 60 patients with MLL-negative infant ALL treated with the series of Moscow-Berlin (MB) protocols, a regimen with reduced chemotherapy. MLL-negative ALL by infants with age < 6 months at the diagnosis was characterized by a higher white blood cell count, splenomegaly and prevalence of girls compared with older infants. Induction failure rate was 3.4 % for the whole group of patients and was not significantly different between infants with less or more 6 month old. EFS and OS for the whole group of patients were 62 ± 7 % and 59 ± 7 % with relapse rate of 28.7 %. But relapse rate was significantly higher in MLL-negative infant ALL patients with age < 6 month compared of that of pts with age 6 month (cumulative incidence was 60.7 ± 16.5 % vs 19.1 ± 6.7 %, p < 0.005). EFS and OS of MLL-negative infant ALL patients were significantly worse compared of that for the old infants (10 ± 9% vs 79 ± 7 % for EFS). The treatment according new MB regimens significantly improve the outcomes for the whole group and also for children with < 6 months age at the diagnosis.
About the Authors
A. I. KarachunskiyRussian Federation
1 Samory Mashela St., Moscow, 117997, Russia
Yu. V. Rumyantseva
Russian Federation
1 Samory Mashela St., Moscow, 117997, Russia
S. N. Lagoyko
Russian Federation
1 Samory Mashela St., Moscow, 117997, Russia
O. I. Bydanov
Russian Federation
1 Samory Mashela St., Moscow, 117997, Russia; 43 Frunzenskaya St., Borovlyany village, Minsk district, Minsk region, 223053, Republic of Belarus;
O. V. Aleynikova
Russian Federation
32 Seraphimy Deryabinoy St., Yekaterinburg, 620149, Russia
L. G. Fechina
Russian Federation
32 Seraphimy Deryabinoy St., Yekaterinburg, 620149, Russia;
A. V. Shamardina
Russian Federation
211 Vaneeva St., Nizhny Novgorod, 603136, Russia;
O. V. Streneva
Russian Federation
32 Seraphimy Deryabinoy St., Yekaterinburg, 620149, Russia;
K. L. Kondratchik
Russian Federation
1/9 4th Dobryninskiy Per., Moscow, 119049, Russia
M. A. Postoykina
Russian Federation
27 Prosp. Ostryakova, Vladivostok, Primorsky Krai, 690078, Russia;
E. V. Inyushkina
Russian Federation
6 Karbysheva St., Balashikha, 143900, Russia
I. I. Spichak
Russian Federation
42a Blyukher St., Chelyabinsk, 454076, Russia
E. G. Mansurova
Russian Federation
1 Ostrovityanova St., Moscow, 117997, Russia
K. S. Aslanyan
Russian Federation
14 339th Strelkovoy Divizii St., Rostov-on-Don, 344015, Russia
N. I. Ponomareva
Russian Federation
117 Leninskiy Prosp., Moscow, 117997, Russia
N. V. Myakova
Russian Federation
1 Samory Mashela St., Moscow, 117997, Russia;
V. A. Filimonenkova
Russian Federation
71 Titova St., Simferopol, Republic of Crimea, 295034, Russia
A. A. Tarasenkova
Russian Federation
71 Titova St., Simferopol, Republic of Crimea, 295034, Russia
A. G. Rumyantsev
Belarus
1 Samory Mashela St., Moscow, 117997, Russia
References
1. Biondi A., Cimino G., Pieters R., Pui C.H. Biological and therapeutic aspects of infant leukemia. Blood 2000;96(1):24–33. PMID: 10891426.
2. Chessells J.M., Eden O.B., Bailey C.C., Lilleyman J.S., Richards S.M. Acute lymphoblastic leukaemia in infancy: experience in MRC UKALL trials. Report from the Medical Research Council Working Party on Childhood Leukaemia. Leukemia 1994;8(8):1275–9. PMID: 8057661.
3. Frankel L.S., Ochs J., Shuster J.J. et al. Therapeutic trial for infant acute lymphoblastic leukemia: the Pediatric Oncology Group experience (POG 8493). J Pediatr Hematol Oncol 1997;19(1):35–42. PMID: 9065717.
4. Reaman G., Zeltzer P., Bleyer W.A. et al. Acute lymphoblastic leukemia in infants less than one year of age: a cumulative experience of the Children’s Cancer Study Group. J Clin Oncol 1985;3(11):1513–21. doi: 10.1200/ JCO.1985.3.11.1513.
5. Felix C.A., Lange B.J. Leukemia in infants. Oncologist 1999;4(3):225–40. PMID: 10394590.
6. Chen C.S., Sorensen P.H., Domer P.H. et al. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood 1993;81(9):2386–93. PMID: 8481519.
7. Pui C.H., Behm F.G., Downing J.R. et al. 11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia. J Clin Oncol. 1994;12(5):909–15. doi: 10.1200/JCO.1994.12.5.909.
8. Hilden J.M., Frestedt J.L., Moore R.O. et al. Molecular analysis of infant acute lymphoblastic leukemia: MLL gene rearrangement and reverse transcriptase-polymerase chain reaction for t(4; 11)(q21; q23). Blood 1995;86(10):3876–82. PMID: 7579356.
9. Heerema N.A., Sather H.N., Ge J. et al. Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11): a report of the Children’s Cancer Group. Leukemia 1999;13(5):679–86. PMID: 10374870.
10. Pui C.H., Gaynon P.S., Boyett J.M. et al. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet 2002;359(9321):1909–15. doi: 10.1016/ S0140-6736(02)08782-2.
11. Karachunskiy A., Herold R., von Stackelberg A. et al. Results of the first randomized multicentre trial on childhood acute lymphoblastic leukaemia in Russia. Leukemia 2008;22(6):1144–53. doi: 10.1038/ leu.2008.63.
12. Karachunskiy A., Roumiantseva J., Lagoiko S. et al. Efficacy and toxicity of dexamethasone vs methylprednisolone-long-term results in more than 1000 patients from the Russian randomized multicentric trial ALL-MB 2002. Leukemia 2015;29(9):1955–8. doi: 10.1038/ leu.2015.63.
13. Карачунский А.И., Мякова Н.В., Румянцева Ю.В. и др. Результаты мультицентрового исследования лечения острого лимфобластного лейкоза у детей по программам ALL-MB-91/ALL-BFM- 90m: анализ эффективности и токсичности. Терапевтический архив 2007;79(7):19–26. [Karachunsky A.I., Miakova N.V., Rumyantseva Yu.V. et al. The results of a multicenter trial of acute lymphoblastic leukemia treatment on ALL-MB 91/ ALL-BFM 90m in children: analysis of efficacy and toxicity. Terapevticheskiy arkhiv = Therapeutic Archive 2007;79(7):19–26. (In Russ.)].
14. Румянцева Ю.В., Карачунский А.И., Алейникова О.В. и др. Эффективность протокола ALL-МВ-2002 у детей с острым лимфобластным лейкозом. Терапевтический архив 2010;82(7):11–9. [Rumyantseva Yu.V., Karachunsky A.I., Aleynikova O.V. et al. Efficiency of the ALLMB-2002 protocol in children with acute lymphoblastic leukemia. Terapevticheskiy arkhiv = Therapeutic Archive 2010;82(7): 11–9. (In Russ.)].
15. Карачунский А.И., Румянцева Ю.В., Лагойко С.Н. и др. Возрастные особенности эффективности различных глюкокортикостероидов в терапии острого лимфобластного лейкоза. Терапевтический архив 2015;87(7):41–50. [Karachunsky A.I., Rumyantseva Y.V., Lagoiko S.N. et al. Age-related characteristics of the efficacy of different glucocorticosteroids in the therapy of acute lymphoblastic leukemia. Terapevticheskiy arkhiv = Therapeutic Archive 2015;87(7):41–50. (In Russ.)]. doi: 10.17116/terarkh201587741-50.
16. Silverman L.B., McLean T.W., Gelber R.D. et al. Intensified therapy for infants with acute lymphoblastic leukemia: results from the Dana-Farber Cancer Institute Consortium. Cancer 1997;80(12): 2285–95. PMID: 9404706.
17. Reaman G.H., Sposto R., Sensel M.G. et al. Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children’s Cancer Group. J Clin Oncol 1999;17(2):445–55. doi: 10.1200/ JCO.1999.17.2.445.
18. Pui C.H., Chessells J.M., Camitta B. et al. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia 2003;17(4):700–6. doi: 10.1038/sj.leu.2402883.
19. Chessells J.M., Harrison C.J., Kempski H. et al.; MRC Childhood Leukaemia working party. Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukemia working party. Leukemia 2002;16(5):776–84. doi: 10.1038/sj. leu.2402468.
20. Ferster A., Benoit Y., Francotte N. et al. Treatment outcome in infant acute lymphoblastic leukemia. Children Leukemia Cooperative Group--EORTC. European Organization for Research and Treatment of Cancer. Blood 2000;95(8):2729–31. PMID: 10809540.
21. Borkhardt A., Wuchter C., Viehmann S. et al. Infant acute lymphoblastic leukemia – combined cytogenetic, immunophenotypical and molecular analysis of 77 cases. Leukemia 2002;16(9):1685–90. doi: 10.1038/sj. leu.2402595.
22. Biondi A, Rizzari C, Valsecchi MG, et al. Role of treatment intensification in infants with acute lymphoblastic leukemia: results of two consecutive AIEOP studies. Haematologica 2006;91(4):534–7. PMID: 16537119.
23. Sanders J.E., Im H.J., Hoffmeister P.A. et al. Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia. Blood 2005;105(9):3749–56. doi: 10.1182/blood-2004-08-3312.
24. van der Linden M.H., Valsecchi M.G., De Lorenzo P. et al. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood 2009;114(18):3764–8. doi: 10.1182/ blood-2009-02-204214.
25. Pieters R., Schrappe M., De Lorenzo P. et al. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet 2007;370(9583):240–50. doi: 10.1016/S0140- 6736(07)61126-X.
Review
For citations:
Karachunskiy A.I., Rumyantseva Yu.V., Lagoyko S.N., Bydanov O.I., Aleynikova O.V., Fechina L.G., Shamardina A.V., Streneva O.V., Kondratchik K.L., Postoykina M.A., Inyushkina E.V., Spichak I.I., Mansurova E.G., Aslanyan K.S., Ponomareva N.I., Myakova N.V., Filimonenkova V.A., Tarasenkova A.A., Rumyantsev A.G. MLL-negative infant acute lymphoblastic leukemia. Clinical characteristics and possibilities for chemotherapy optimization. Russian Journal of Pediatric Hematology and Oncology. 2017;4(3):17-26. (In Russ.) https://doi.org/10.17650/2311-1267-2017-4-3-17-26