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.

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Methods:We reviewed the clinical records of MM patients diagnosed at a single institution between 1970 and 2015. One thousand one hundred sixty-one patients (591 [50.9%] male; median age at diagnosis 64 years) was the final study population. Median follow-up for alive patients was 5.4 years (range, 0.5-34.4 years). Relative survival (RS) and disease-specific incidence mortality were calculated and expressed in incidence rate ratio (IRR). Long-term survival was defined as those who lived more than 10 years after diagnosis of MM. The population was divided into three periods, which included: group A (1970 to 1985), group B (1986 to 1999) and group C (2000 to 2015). Results: The median OS (mOS) of all patients was 3.6 years (95% CI: 3.2-3.8) from diagnosis. When demographic effects of age, sex, and year of diagnosis were compensated, the RS showed a continuous improvement during the periods analyzed, more pronounced in group C. The 5-year and 10-year RS were 26% and 8% in group A, 36% and 18% in group B, and 56% and 33% in group C, p < 0.01. In the stratified analysis by age and sex, group B and C retained its prognostic value in terms of IRR compared with group A (Figure 1). The EM rate (first 60 days after diagnosis) was 5.8%; 16.5% in Group A, 5.5% in Group B, and 2.6% in Group C; p < 0.01. The most frequent causes of early mortality were disease-related (46.7%, 63.6% and 66.6%; respectively), and infectious complications (36.7%, 22.7%, and 20.0%; respectively). In the multivariate Cox proportional hazard model in patients who received novel drugs, thrombocytopenia (OR 5.07, p = 0.04), hypercalcemia (OR 11.5, p < 0.01) and high beta-2 microglobulin (OR 8.81, p < 0.01) were significantly associated with EM. Regarding long-term survival, in the multivariate analysis, clinical variables at diagnosis associated with >10-year survival were age <60 years (OR 2.23, p = 0.02), and performing ASCT (OR 4.25, p < 0.01). Summary/Conclusion:This study shows that the survival outcome has significantly improved over the last decades in all age groups, probably due to ASCT and novel drugs. The incidence of EM has decreased over time, being the most frequent causes of MM progression and infectious complications. Thrombocytopenia, hypercalcemia and high beta-2 microglobulin were associated with worst early outcomes. Finally, these data identify age <60 years, and ASCT as important predictors of longterm survival.

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).