pediatric acute leukemias

Analysis of Karyotype Aberrations in Children and Adolescents with Post-Transplantation Relapses of Acute Leukemia

BONE MARROW TRANSPLANTATION , ,

T.L. Gindina, N.N. Mamaev, E.N. Nikolaeva, I.A. Petrova, S.N. Bondarenko, A.L. Alyanskii, N.V. Stancheva, O.A. Slesarchuk, M.Yu. Aver’yanova, L.S. Zubarovskaya, B.V. Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Nikolaeva EN, et al. Analysis of Karyotype Aberrations in Children and Adolescents with Post-Transplantation Relapses of Acute Leukemia. Clinical oncohematology. 2015;8(4):420–427 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-420-427

ABSTRACT

Aim. To analyze the karyotype aberrations at the relapse after allogeneic HSCT (alloHSCT) in children and adolescents with acute leukemias, in order to evaluate their relation with disease-free survival and overall survival (OS) rates after the relapse and to identify prognostic groups of patients based on clinical and cytogenetic characteristic of a tumor.

Methods. Cytogenetic investigations were performed in 30 children and 15 adolescents (26 males and 19 females aged from 1.2 to 21 years; median age 10 years) with a post-transplant relapse (PTR) of acute myeloid leukemia (n = 29) and acute lymphoblastic leukemia (n = 16). The analysis of aberrating chromosomal abnormalities was performed by comparison of the karyotypes in relapse with those before the alloHSCT.

Results. Karyotype aberrations in PTR were observed in 29 (64 %) patients. 2 and more abnormal cytogenetic clones were observed in 10 (34 %) patients with PTR. Additional chromosomal aberrations acquired in PTR were related primarily to chromosomes 1, 11 and 19. OS after the relapse was higher in patients with alloHSCT performed during the remission and with one abnormal cytogenetic clone in PTR. Based on this, we formed three prognostic groups: the first group consisted of 8 (18 %) patients with 2 adverse factors and median 40-day OS after relapse; the second group included 20 (44 %) patients with 1 adverse factor and median OS after PTR equal to 152 days, and the 4-year survival was 16 %; the third group included 17 (38 %) patients without the above negative factors and median OS after relapse equal to 549 days, and the 4-year survival was 31 %. The multivariate analysis showed that the number of abnormal cytogenetic clones in leukemic population is an independent predictor of OS after PTR.

Conclusion. The presence of leukemic population of ³ 2 abnormal cytogenetic clones is the most important prognostic factor affecting the OS in PTR patients. Since the clonal evolution of the karyotype may be associated with the use of cytotoxic drugs in the therapy of acute leukemia in children and adolescents with indications for alloHSCT, the latter should be done as soon as possible and non-myeloablative conditioning regimen should be preferred.

Keywords: pediatric acute leukemias, post-transplantation relapses, clonal cytogenetic evolution.

Received: June 13, 2015

Accepted: November 8, 2015

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REFERENCES

  1. Schmidt-Hieber M, Blau I, Richter G, et al. Cytogenetic studies in acute leukemia patients relapsing after allogeneic stem cell transplantation. Cancer Genet Cytogenet. 2010;198(2):135–43. doi: 10.1016/j.cancergencyto.2010.01.005.
  2. Bacher U, Haferlach T, Alpermann Т, et al. Comparison of cytogenetic clonal evolution patterns following allogeneic hematopoietic transplantation versus conventional treatment in patients at relapse of AML. Biol Blood Marrow Transplant. 2010;16(12):1649–57. doi: 10.1016/j.bbmt.2010.06.007.
  3. Kawamata N, Ogawa S, Seeger K, et al. Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia. Int J Oncol. 2009;34(6):1603–12. doi: 10.3892/ijo_00000290.
  4. Lee J, Jang P, Chung N, et al. Treatment of children with acute myeloid leukaemia who relapsed after allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2013;160(1):80–6. doi: 10.1111/bjh.12074.
  5. Lawler S, Khokhar M, Davies H, et al. Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts. Cancer Genet Cytogenet. 1990;47(1):249–63. doi: 10.1016/0165-4608(90)90034-8.
  6. Yuasa M, Uchida N, Kaji D, et al. Prognostic significance of the cytogenetic evolution after the hematopoietic stem cell transplantation in adult acute myeloid leukemia. Blood. 2013;122(21):1391.
  7. Cho Y, Chi H, Park S, et al. Comparative analysis of cytogenetic evolution patterns during relapse in the hematopoietic stem cell transplantation and chemotherapy settings of patients with acute leukemia. Blood. 2013;122(21):1320.
  8. Гиндина Т.Л., Мамаев Н.Н., Бондаренко С.Н. и др. Сложные хромосомные нарушения у больных с посттрансплантационными рецидивами острых лейкозов: клинические и теоретические аспекты. Клиническая онкогематология. 2015;8(1):69–77.
    [Gindina TL, Mamaev NN, Bondarenko SN, et al. Complex chromosomal aberrations in patients with post-tranplantation relapses of acute leukemias: clinical and theoretical aspects. Klinicheskaya onkogematologiya. 2015;8(1):69–77. (In Russ)]
  9. Гиндина Т.Л., Мамаев Н.Н., Бархатов И.М. и др. Сложные повреждения хромосом у больных с рецидивами острых лейкозов после аллогенной трансплантации гемопоэтических стволовых клеток. Терапевтический архив. 2012;8:61–6.
    [Gindina TL, Mamaev NN, Barhatov IM, et al. Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations. Terapevticheskii arkhiv. 2012;8:61–6 (In Russ)]
  10. Schaffer L, McGovan-Jordan J, Schmid M. An International System for Human Cytogenetic Nomenclature. Basel: S. Karger; 2013.
  11. Gindina T, Mamaev N, Bondarenko S, et al. Complex aberrant karyotype in patients with post-transplant relapses of acute myeloid and lymphoid leukemias evaluated by serial cytogenetic assays, including mFISH. Blood. 2014;124(21):5313.