complex karyotype

Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities

BONE MARROW TRANSPLANTATION , , , ,

TL Gindina, NN Mamaev, SN Bondarenko, ES Nikolaeva, IA Petrova, OA Slesarchuk, AS Borovkova, SV Razumova, AL Alyanskii, LS Zubarovskaya, BV 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, Bondarenko SN, et al. Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities. Clinical oncohematology. 2016;9(3):271-78(In Russ).

DOI: 10.21320/2500-2139-2016-9-3-271-278

ABSTRACT

Aim. To evaluate the prognostic significance of the complex karyotype including del(5q), –7, del(7q) abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. Forty-four AML patients with chromosome 5 and/or 7 abnormalities (22 women and 22 men, aged from 1.2 to 67 years, median 31.2 years) were examined. 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. Prior to allo-HSCT, the complex karyotype (with three or more chromosomal abnormalities) was observed in 19 (43 %) patients, the monosomal karyotype was in 8 (18 %) patients. Univariate analysis demonstrated that OS and EFS differed in patients from different age groups (³ 18 vs. < 18 years; p = 0.01 and p = 0.05, respectively), with different disease status at transplantation (1 remission vs. other clinical status; p = 0.1 and p = 0.008, respectively), with and without complex karyotype (СK– vs. CK+; p = 0.05 and p = 0.002, respectively), with and without monosomal karyotype (МK– vs. MK+; p = 0.009, only for EFS), and with different stem cells source (bone marrow vs. other source; p = 0.03 only for OS). Multivariate analysis confirmed that age of 18 years and more (p = 0.02 and p = 0.01, respectively), active disease at allo-HSCT (p = 0.04 and p = 0.005, respectively), complex karyotype (p = 0.04 и p = 0.0008, respectively) and stem cell source other than bone marrow (p = 0.02 only for OS) were independent predictors of OS and EFS deterioration.

Conclusion. The study demonstrates that chromosome 5 and/or 7 abnormalities as a part of the complex karyotype is high-risk factor in AML patients undergoing allo-HSCT (unlike the monosomal karyotype), that requires the special therapeutic approach.

Keywords: acute myeloid leukemias, complex karyotype, chromosome 5 and 7 abnormalities, allogeneic hematopoietic stem cell transplantation, prognosis.

Received: March 5, 2016

Accepted: April 5, 2016

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REFERENCES

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    [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;84(8):61–6. (In Russ)]
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Complex Karyotype in Pediatric Acute Myeloid Leukemia

MYELOID TUMORS , ,

EV Fleishman1, OI Sokova1, AV Popa1, II Kalinina2, LN Konstantinova1

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Elena Vol’fovna Fleischman, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)323-57-22; e-mail: flesok@yandex.ru

For citation: Fleishman EV, Sokova OI, Popa AV, et al. Complex Karyotype in Pediatric Acute Myeloid Leukemia. Clinical oncohematology. 2015;8(2):151–60 (In Russ).

ABSTRACT

Objective. To evaluate the clinical relevance of the complex karyotype in pediatric practice.

Methods. In this study, we investigated the karyotype of 521 patients with de novo AML (299 children and 222 adults). Among them 34 pediatric patients and 25 adults had various complex karyotypes.

Results. Certain differences of complex karyotypes between pediatric and adult AML were revealed. Some peculiarities of marker sets were also found: in children, such high-risk markers as monosomy 5 and del(5q) as well as monosomy 7 and del(7q) were less frequent than in adults. Monosomal complex karyotypes were less common in children. Specific distribution of blast cell morphological types was observed in pediatric AML with complex karyotypes. Unlike AML with noncomplex karyotype, where the M2 type was found in almost a half (47.9 %) of patients, in patients with 3 and more chromosome aberrations its incidence was 11.8 % only (p = 0,000). However, incidence of M5 and rare M0 and M7 types in patients with complex karyotype was higher than in the others. RFS in patients with a complex karyotype was similar to that of remaining patients in the high-risk group: 38.4 ± 9.9 % and 30.6 ± 8.8 %, respectively. The OS rate of patients with a complex karyotype was practically identical to that of intermediate-risk group patients: 48.0 ± 10.0 % and 48.0 ± 10.0 %, respectively. There was a comparatively high 10-year survival rate (RFS and OS were higher than 30 %) in the pediatric high-risk group. Ten of 25 (40 %) patients with complex karyotype survived five years and 7 of them persisted in complete remission for more than 10 years. Five-year survival in adults from high-risk group is up to 15 %.

Conclusion. Analysis of data on survival of pediatric AML does not answer a question in which prognostic group (high or intermediate-risk) cases of AML with complex karyotypes without high-risk chromosome markers must be included.

Keywords: pediatric acute myeloid leukemia, chromosome aberrations, complex karyotype.

Received: November 26, 2014

Accepted: February 2, 2015

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Complex Chromosomal Aberrations in Patients with Post-Transplantation Relapses of Acute Leukemias: Clinical and Theoretical Aspects

MYELOID TUMORS , ,

TL Gindina, NN Mamaev, SN Bondarenko, NV Semenova, EN Nikolaeva, ME Vlasova, NV Stancheva, OA Slesarchuk, VN Vavilov, EV Morozova, AL Alyanskii, BV Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: tatgindina@gmail.com

For citation: Gindina TL, Mamaev NN, Bondarenko SN, et al. Complex Chromosomal Aberrations in Patients with Post-Transplantation Relapses of Acute Leukemias: Clinical and Theoretical Aspects. Clinical oncohematology. 2015;8(1):69–77 (In Russ).

ABSTRACT

Objective. To analyze the incidence of a complex karyotype in patients with post-transplantation relapses of acute myeloid leukemias and to evaluate preliminary treatment results before and after bone marrow transplantation in order to elaborate optimal approaches to the treatment of this disease.

Methods. Cytogenetic investigations (including fluorescent in situ hybridization [FISH]) were performed in 100 patients (53 males, 47 females aged from 1 to 60; median — 23 years) with post-transplantation relapses of acute myeloid leukemias (AML) (n = 61) and acute lymphoblastic leukemia (ALL) (n = 39).

Results. Aberrant karyotypes were found in 90 % of AML and 97 % of ALL patients. The incidence of acute leukemias (AL) with complex karyotypes (CK) was significantly higher in ALL patients than that in the AML group (67 % vs 36 %; p = 0.002). At that, the percentage of CK with 4 and more chromosome abnormalities per cell in ALL patients aged 1–18 years was also significantly higher than that in AML patients (60 % vs 30 %; p = 0.03). Besides, this difference was observed in the CK+ proportion between ALL and AML groups. Transplantation was performed during the active phase of the disease (i.e. after remission) in 75 % vs 55 %, respectively (p = 0.003).

Conclusions. Serial cytogenetic investigations showed that CKs before transplantation and in PTR are closely related, thus confirming their clonal nature. Therefore, it may be assumed that karyotype complication achieved by the PTR can be caused by both chemotherapy performed at early stages of acute leukemia and pre-transplant conditioning regimes. In this case, further increase of the chemotherapeutic intensity in order to prevent and treat expected PTRs in patients with CK+ acute leukemias seems to be unreasonable. In this connection, infusion of donor lymphocytes, administration of hypomethylating agents or medicines with target mechanism of action should be used for management of AML patients during the post-transplant period.

Keywords: acute leukemias, post-transplantation relapses, complex karyotype.

Received: September 2, 2014

Accepted: November 13, 2014

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