TL Gindina, NN Mamaev, ES Nikolaeva, SN Bondarenko, OA Slesarchuk, AS Borovkova, SV Razumova, OV Pirogova, AL Alyanskii, LS Zubarovskaya, BV Afanas’ev
RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician IP 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: firstname.lastname@example.org
For citation: Gindina TL, Mamaev NN, Nikolaeva ES, et al. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias with Hyperdiploid Karyotype. Clinical oncohematology. 2016;9(4):383–90 (In Russ).
Aim. To evaluate the prognostic impact of the different cytogenetic characteristics, including the modal number, the number of chromosomal aberrations in a complex karyotype, and adverse chromosomal abnormalities (ACA) (–7/7q–, –5/5q–, –17/17p–, t(6;9)(p22;q34)) on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hyperdiploid acute myeloid leukemia (H-AML).
Methods. Forty seven H-AML patients (21 women and 26 men, aged from 1 to 58 years, median — 23.9 years) were examined. The analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed.
Results. The modal number of chromosomes (MN) of 47–48 was the most common one in the karyotype which was observed in 31 (66 %) patients. High hyperdiploidy with the modal number of 49–65 was identified in 13 (28 %) patients, near-triploid and near-tetraploid karyotypes were found in 3 (6 %) patients. Quantitative chromosomal abnormalities were nonrandom. Chromosome 8 (50 %), 21 (32 %), 13 (16 %) и 22 (16 %) trisomy was the most common one. Structural chromosomal abnormalities were detected in 22 (47 %) patients, at that, ACA were found in 7 (19 %) patients. In univariate analysis, the OS and EFS after allo-HSCT differed in patients with different clinical status (remission vs. active disease; p = 0.003 and p = 0.002, respectively), different chromosomal abnormalities in hyperdiploid karyotype (ACA– vs. ACA+; p = 0.001 and p = 0.03, respectively). An additional analysis of selected patients group with a structurally complex karyotype (n = 19) showed, that patients without ACA had a higher OS than patients with ACA (p = 0.03). In multivariate analysis, the disease status (relapse) at allo-HSCT was an independent predictor of decreased OS and EFS (p = 0.004 и p = 0.006, respectively), as well as the presence of the ACA (p = 0.002 only for OS).
Conclusion. ACA were high-risk factors in H-AML patients received allo-HSCT. Therefore, the patients with formal criteria of a complex karyotype should not be automatically included in the cytogenetic unfavorable risk group.
Keywords: hyperdiploid and complex karyotypes, acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, prognosis.
Received: April 17, 2016
Accepted: May 5, 2016
- Chilton L, Hills RK, Harrison CJ, et al. Hyperdiploidy with 49-65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome. Leukemia. 2013;28(2):321–8. doi: 1038/leu.2013.198.
- Sandahl JD, Kjeldsen E, Abrahamsson J, et al. Ploidy and clinical characteristics of childhood acute myeloid leukemia: a NOPHO-AML study. Genes Chromos Cancer. 2014;53(8):667–75. doi: 1002/gcc.22177.
- Stolzel F, Mohr B, Kramer M, et al. Karyotype complexity and prognosis in acute myeloid leukemia. Blood Cancer J. 2016;6:e386. doi: 101038/bcj.2015.114.
- Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 1182/blood-2009-07-235358.
- Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354–65. doi: 1182/blood-2009-11-254441.
- 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, Barkhatov 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)]
- Schaffer L, McGovan-Jordan J, Schmid M. An International System for Human Cytogenetic Nomenclature. Basel: S. Karger; 2013. pp. 140. doi: 10.1002/ajmg.a.35995.
- Guo RJ, Atenafu EG, Craddock K, et al. Allogeneic hematopoietic cell transplantation may alleviate the negative prognostic impact of monosomal and complex karyotypes on patients with acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(5):690–5. doi: 1016/j.bbmt.2014.01.027.