pediatric acute myeloid leukemia

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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Haploidentical hematopoietic stem cell transplantation in children with acute myeloid leukemia: evolution of method and our data

BONE MARROW TRANSPLANTATION , ,

N.N. Subbotina, I.S. Dolgopolov, A.V. Popa, V.K. Boyarshinov, R.I. Pimenov, and G.L. Mentkevich

Pediatric Oncology and Hematology Research Institute, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

This article presents the results of haploidentical stem cell transplantation in children with prognostically unfavorable AML. The study group included 18 pts at the age of 1–18. The disease status at the transplantation time was as follows: high risk AML in first remission (n=4, 22 %), more than two remissions (n=7, 39 %), no remission (n=4, 22 %), or secondary AML in remission (n=3, 17 %). All patients received reduced-intensity conditioning regimen followed by HSCT from haploidentical donors. Hematologic recovery occurred in 17 out of 18 pts in a mean time of 11 days and 12 days for WBC and platelets, respectively. One patient with no remission at the time of transplantation died from leukemia progression and infection with no signs of hematologic recovery. The regimen toxicity was mild and manageable. Acute GVHD of I/II and III degree occurred in 88 % and 6 % of pts, respectively. Chronic GVHD occurred in 85 % of pts, having been quite severe in one pt. The causes of death were infection (n=2, 11 %) or disease relapse/progression (n = 5, 28 %). Eleven pts (61 %) are still alive and disease-free. EFS is 57.5 % with a mean follow-up of 84 (1–144) months. TRM is 13.3 % with a mean follow-up of 124 months.

Keywords: pediatric acute myeloid leukemia, unfavorable prognosis, haploidentical hematopoietic stem cell transplantation.

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Cytogenetic remission as an important criterion for treatment efficacy in pediatric acute myeloid leukemia

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF MYELOID MALIGNANCIES , ,

E.W. Fleischman1, O.I. Sokova1, A.V. Popa2, V.S. Nemirovchenko2, L.N. Konstantinova1, and N.F. Metelkova1

1 Institute of Сarcinogenesis, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

2 Pediatric Oncology and Hematology Institute, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

The results of repeated karyotype analyses in the disease course in 43 children with de novo acute myeloid leukemia (AML) are presented. Patients with clonal bone marrow chromosome abnormalities at diagnosis were included. The follow-up period lasted from 4 to 79 months (median 23 months). The patient cohort was divided into two groups: the standard-risk group and high-risk group. The first group included 13 children with t(8;21)(q22;q22), inv(16)(p13;q22), and t(16;16)(p13;q22). The rest of the patients (30 cases) formed the second group. After assessment of results of bone marrow chromosome analysis at 1–3 months of the treatment, the conclusion was drawn that persistence even single cytogenetically abnormal cell at the start of morphological remission is an unfavorable prognostic sign. It is illustrated by comparison of relapse-free survival (RFS) in two groups of patients: with cytogenetic remission at the onset of morphologic remission (group 1) or with no remission (group 2). RFS was 64.1 ± 10.3 % in the first group. In the second group, one patient is at 20th month of the first CCR and four remaining patients relapsed at 3–20th months (p = 0.018). Another conclusion can be made from our data. Persistence in bone marrow cytogenetically abnormal cells at the beginning of morphological remission can be observed in patients with favorable chromosome markers and patients from other prognostic groups. This finding was prognostically unfavorable regardless of risk-group. Thus, persistence of cytogenetically abnormal cells in bone marrow at the time of morphological remission achieved is a more sensitive criterion for poor outcome than the baseline karyotype (risk groups). The facts obtained show an importance of cytogenetic analysis performance not only at diagnosis but also at the onset of morphologic remission.

Keywords: pediatric acute myeloid leukemia, chromosome markers, cytogenetic remission.

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