A new case of Acute Myeloid Leukemia with semi-cryptic t(7;21)(p22;q22)

Case report of a translocation : A new case of Acute Myeloid Leukemia with semi-cryptic t(7;21)(p22;q22)

СРАВНЕНИЕ ЭФФЕКТИВНОСТИ ХИМИОТЕРАПИИ И АЛЛОГЕННОЙ ТРАНСПЛАНТАЦИИ ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК ПРИ ОСТРОМ МИЕЛОБЛАСТНОМ ЛЕЙКОЗЕ В ПЕРВОЙ РЕМИССИИ У ВЗРОСЛЫХ

The aim of the study was to compare the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) and chemotherapy (CT) of acute myeloid leukemia (AML) in first remission (CR1), to identify factors influencing the results. We compare the efficacy alloHSCT in CR1 (n = 70) and CT (n = 52). Patients were stratified by age, the level of leucocytes, the origin of AML, cytogenetic risk group and response to induction CT. Five-years overall and disease-free survival (OS and DFS) were higher in the group alloHSCT (67 and 65 % vs 46 and 30 % (p = 0.02 and p = 0.001)). Benefits of DFS after alloHSCT was in standard and high-risk cytogenetic groups (78 % versus 29 % (p = 0.001), and 34 % vs 17 % (p = 0.007)). The risk of relapse (RR) was 24 % in patients after alloHSCT vs. 57 % for CT (p = 0.003). Comparing the RR after alloHSCT and CT depending on the cytogenetic risk groups: standard (HR0.2(CI95 %0.07 - 0.56) p = 0.002), and high (HR0.27(CI95 %0.08-0.86) p = 0.03). Additional factors affect the RR were the origin of AML (de novo) (HR0.47 (CI95 %0.3-0.74) p = 0.001), the hyperleukocytosis (HR1.91 (CI95 %1.09 - 3.32) p = 0.02), and no remission after the first course CT (HR3.32(CI95 %1.57-7.0) p = 0.002). The efficacy of alloHSCT compared with CT is higher both in standard and high-risk cytogenetic group.Цель - сравнить эффективность аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК) и химиотерапии (ХТ) при остром миелобластном лейкозе (ОМЛ) в первой ремиссии и выявить факторы, влияющие на результаты лечения. Сравнивалась эффективность в первой ремиссии ОМЛ алло ТГСК (n = 70) и ХТ (n = 52). Пациенты были разделены по возрасту, уровню лейкоцитов, происхождению ОМЛ, цитогенетическим группам риска и ответу на индукционную ХТ. Пятилетняя общая и бессобытийная выживаемость (ОВ и БСВ) были выше в группе аллоТГСК (67 и 65 % против 46 и 30 % (р = 0,02 и р = 0,001)). При анализе БСВ от цитогенетических групп риска выявлены преимущества аллоТГСК в стандартной и высокой группах риска (78 % против 29 % (р = 0,001) и 34 % против 17 % (р = 0,007)). Совокупный риск рецидива (РР) составил 24 % у пациентов после аллоТГСК против 57 % при ХТ (р = 0,003). При сравнении РР после аллоТГСК и ХТ от цитогенетических групп риска: стандартная (HR,0,2(CI95 %0,07-0,56) p = 0,002) и высокая (HR,0,27(CI95 %0,08-0,86) p = 0,03). Дополнительными факторами, оказывающими влияние на РР, были: происхождение ОМЛ (de novo) (HR,0,47(CI95 %0,3-0,74) p = 0,001), гиперлейкоцитоз в дебюте заболевания (HR,1,91(CI95 %1,09-3,32) p = 0,02) и отсутствие ремиссии после одного курса индукции (HR,3,32(CI95 %1,57 - 7,0) p = 0,002). Эффективность алло ТГСК по сравнению с ХТ выше при стандартной и высокой цитогенетических группах риска

Translocation t(1;11)(p32;q23) with MLL-EPS15 fusion gene formation in acute leukemias: a review and 6 new case reports. Approaches to minimal residual disease monitoring

We performed clinical and laboratory characterization of patients with rare translocation t(1;11)(p32;q23) leading to MLL-EPS15 fusion gene formation. Study cohort consisted of 33 primary acute leukemia (AL) cases including 6 newly diagnosed and 27 patients previously described in literature. Among study group patients t(1;11)(p32;q23) was found most frequently in infant AL cases (median age 8 months). In acute lymphoblastic leukemia (ALL) male/female ratio was 1:3, in acute myeloid leukemia (AML) it was 1:1. Additional cytogenetic aberrations in 38 % of patients were revealed. The most frequent breakpoint position in EPS15 gene was intron 1. Four different types of MLLEPS15 fusion gene transcripts were detected. Primers-probe-plasmid combination for MLL-EPS15 fusion gene transcript monitoring by realtime quantitative polymerase chain reaction (RQ-PCR) was developed and successfully applied. In 3 patients RQ-PCR was done on genomic DNA for absolute quantification of MLL-EPS15 fusion gene. High qualitative concordance rate (92 %) was noted between minimal residual disease data obtained in cDNA and genomic DNA for MLL-EPS15 fusion detection.</p

Факторы прогноза и эффективность терапии первой линии хронического лимфолейкоза: результаты 10-летнего наблюдения

Introduction.The biological heterogeneity of chronic lymphocytic leukemia (CLL) is reflected in the rate of progression, the need for therapy, and the response to treatment. Analysis of prognostic factors contributes to improving the quality of treatment and rational distribution of healthcare resources.Materials and methods. Among 890 patients with documented stage of CLL, 405 (45.5 %) received treatment. As the first-line of treatment, 173 patients received intensive regimens (FCR or BR), 6 – new agents, and 226 – all other regimens. The initial stage of the disease, mutation status of IGHV, del17p with or without complex karyotype were analyzed as prognostic markers.Results. Immunochemotherapeutic regimens were shown to be highly effective in case planned amount of treatment was completed. The combination of such prognostic parameters as the initial stage of the disease, the mutation status of IGHV, and the presence of del17p and/or complex karyotype allows us to clearly identify a group of patients with an unfavorable prognosis, for which it is advisable to use either intensive programs or new agents in the first-line therapy.Введение. Биологическая гетерогенность хронического лимфолейкоза (ХЛЛ) отражается в скорости прогрессирования, потребности в терапии и ответе на проводимое лечение. Анализ факторов прогноза способствует улучшению качества лечения и рациональному распределению ресурсов здравоохранения.Методы и материалы. Из наблюдаемых 890 пациентов с документированной стадией ХЛЛ лечение получали 405 (45,5 %). В 1-й линии 173 пациента получили интенсивные режимы (FCR или BR), 6 – таргетные препараты, 226 – все остальные режимы. В качестве прогностических маркеров анализировали исходную стадию заболевания, мутационный статус IGHV, del17p c комплексным кариотипом или без него.Результаты. Иммунохимиотерапевтические режимы показали высокую эффективность при условии выполнения запланированного объема лечения. Комбинация таких прогностических параметров, как исходная стадия ХЛЛ, мутационный статус IGHV и наличие del17p и (или) комплексного кариотипа, позволяет отчетливо выделить группу пациентов с неблагоприятным прогнозом, для которой целесообразно использовать либо интенсивные программы, либо таргетную терапию в 1-й линии

NEW SHOWINGS OF 5Q- SYNDROME BASED ON SERIAL MEASUREMENTS OF BAALC-EXPRESSING STEM CELLS BURDEN IN BONE MARROW.

Introduction: The 5q- deletion is macrocytic anemia syndrome with special clinical characteristics and relatively longer median survival with low probability of AML progression. The classification of this disease as MDS is still under debates. Molecular studies, such as tracking the leukemia-associated marker BAALC, may clarify this issue. Here we evaluated BAALC-expressing stem cells (BAALC-e SCs) in patient's with isolated 5q- syndrome and with different chromosomal abnormalities. Methods: The study includes analysis of bone marrow (BM) from 16 patients with isolated 5q deletion and 15 samples of 5q- combined with additional non-identical chromosomal abnormalities. BMs from 10 MDS patients without 5q- but carrying other cytogenetic aberrations were studied as control group. Serial measurements of BAALC-e SCs were performed by qPCR using BAALC RQ Kit (Inogene, Russia). Cytogenetic study included standard karyotyping and FISH. Results: The data analysis revealed that only 10% (2/16) of patients with isolated 5q- had BAALC gene overexpression. Further on, low BAALC-expressing stem cells were characteristic also in the group of 5q- combined with additional non-identical chromosomal aberrations (56%). Meanwhile, in control group this rate was higher (100%). Conclusions: The presented data of BAALC-e SCs burdens in patients with isolated 5q- syndrome indicate that this pathology differs from typical MDS and can be considered as ribosomopathy with low risk of transformation to MDS or AML. From this position, the biological advantages of 5q deletion syndrome are obvious as an optimal clinical model for further study of MDS and AML formation at the level of leukemia-initiating cells

A new case of t(6;8)(q27;p12) with "8p11 myeloproliferative syndrome"

Case report of a translocation : A new case of t(6;8)(q27;p12) with "8p11 myeloproliferative syndrome"