Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression. Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2-3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/10⁴ copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH. Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/10⁴ copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion. Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level.

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 4748 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 %) and 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.

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Актуальность и цели. В настоящем ретроспективном одноцентровом исследовании анализу подвергнуто влияние высокодозной химиотерапии мелфаланом с последующей трансплантацией аутологичных гемопоэтических стволовых клеток (аутоТГСК) на выживаемость пациентов со множественной миеломой (ММ) в эпоху новых индукционных режимов. Материалы и методы. В исследование включено 133 пациента с ММ в возрасте 31,2-78,2 года (медиана 55,3 года). Женщин было 66, мужчин-67. В качестве терапии первой линии 133 больных ММ получали бортезомиб-содержащие схемы, из них 74 больным в рамках консолидации выполнена высокодозная химиотерапия мелфаланом и либо одна (n = 25), либо двойная (n = 49) аутоТГСК с 2006 по 2016 г. Результаты. Общая 5-летняя выживаемость (ОВ) составила 86,5 % в группе аутоТГСК и 72,9 % в группе без ауто ТГСК (p = 0,03); 5-летняя выживаемость без прогрессирования (ВБП)-64,9 vs 39 % в группах аутоТГСК и без аутоТГСК соответственно (p = 0,0016). Частота рецидивов/прогрессирования ММ была выше в группе пациентов, не получивших аутоТГСК (52,5 vs 28,4 %; p = 0,0016). При многофакторном анализе возраст старше 60 лет определен как фактор неблагоприятного прогноза в отношении ВБП и частоты рецидивов/прогрессирования заболевания (p = 0,004 и p = 0,04 соответственно). Вариант моноклонального белка (миелома Бенс-Джонса) определен как фактор хорошего прогноза в отношении ОВ и частоты рецидивов/прогрессирования (p = 0,02 и p = 0,04 соответственно). Отсутствие полного ответа на индукционную терапию стало независимым предиктором неблагоприятного прогноза в отношении как ОВ, так и ВБП (p = 0,04 и p = 0,041 соответственно). Проведение 2-летней поддерживающей бортезомиб-содержащей терапии после аутоТГСК статистически значимо улучшало показатели 5-летней ВБП (67,4 vs 60,7 %; p = 0,03) и снижало частоту рецидивов/прогрессирования заболевания (26,1 vs 32,1 %; p = 0,05).

Background & Aims. So far there is no data presented on the effectiveness of prevention of the graft-versus-host reaction (GVH) using post-transplant cyclophosphamide (PTCy) prescribed after unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study is to evaluate the incidence of acute and chronic GVH, the transplantation-associated mortality rate, the event-free and overall survival rates, as well as the toxicity profile and the incidence of infectious complications in the study group using cyclophosphamide for GVH prevention; the other aim is to carry out a comparative analysis of the obtained results with the historical control group. Methods. 110 adult patients were enrolled in a clinical study to evaluate the effectiveness of GVH prevention, using PTCy (No. NCT02294552). In order to prevent GVH, the study group (PTCy group) received cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF). The historical control group (ATG group) consisted of 160 patients prescribed with a GVH prevention regimen including anti-thymocyte globulin (ATG), calcineurin inhibitors, and methotrexate or MMF. Peripheral blood stem cells were used as a source of the transplant. Results. The cumulative incidence of II-IV degree acute GVH (18.2 % vs. 40.4 %, respectively; p < 0.0001), III-IV degree GVH (4.5 % vs. 22.5 %, respectively; p < 0.0001), and chronic GVH (21.7 % vs. 40.6 %, respectively; p < 0.0001) was significantly lower in the PTCy group than in the ATG group. Prevention of GVH based on PTCy was associated with the reduction in transplant-associated mortality (12.7 % vs. 33.7 %, respectively; p = 0.003), increased overall survival (70.9 % vs. 44.4 %, respectively; p < 0.001), event-free survival (68.2 % vs. 38.1 %, respectively; p < 0.001) and GVH- and relapse-free survival rates (59.1 % vs. 16.3 %, respectively; p = 0.001). Prevention of GVH using PTCy (as compared to ATG) was less toxic, accompanied by a reduction in the incidence veno-occlusive disease (2.7 % vs. 10.9 %, respectively; p = 0.016), severe mucositis (69.5 % vs. 87.6 %, respectively; p < 0.001), and invasive mycosis (7.2 % vs. 29 %, respectively; p < 0.001). Conclusion. A combination of cyclophosphamide with tacrolimus and MMF is an effective regimen for GVH prevention in patients after allo-HSCT from an unrelated donor.