Introduction Intensive “pediatric oriented” treatment with heavy cytostatic load, incorporation of allogeneic HSCT is now considered a backbone approach in adult ALL therapy. Highly myelosuppressive treatment is more toxic and less reproducible, so RALL has initiated non-intensive but non- interruptive protocol “ALL-2009”and started a prospective multicenter trial for adult Ph-negative ALL based on: 1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in bone marrow after 7 days of prephase; 2) de-intensified but non-interruptive treatment with doses modification according to the myelosuppression with total treatment duration of 127 weeks; 3) prolonged implication of L-asparaginase (total proposed dose 590.000 IU/m2); 4) autologous hematopoietic stem cell transplantation (HSCT) after non-myeloablative BEAM conditioning followed by prolonged maintenance – for T-cell ALL patients. Allo-BMT was an option for high risk patients with sibling donors. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Methods and patients From Jan 2009, till June 2014, 30 centers enrolled 250 pts: median age 30 years (15-60 years), 115f/135 m; in 2,4% phenotype was unknown (n=6), B-lineage ALL - 63,2% (n=158), T-lineage ALL - 34% (n=85), biphenotypic - 0,4% (n=1). Cytogenetics was available in 62,4% of patients (n=156) and 41% of them (n=64) had normal karyotype (NK). 25,2% of patients (n=63) were in the standard risk (SR) group (WBC <30 for B-lineage, <100 for T-lineage; EGIL BII-III, T-III; LDH < 2N; no late CR; t(4;11)-negative), 59,2% (n=148) - in the high risk (HR) group (WBC >30 for B-lineage, >100 for T-lineage; EGIL BI, T-I-II-IV; LDH > 2N; late CR; t(4;11)-positive), 39 patients were not qualified by risk group. The analysis was performed in June 2014. The median time of follow-up was 26,1 mo. Results Prednisolone was replaced with dexamethazone after prephase in 68,1% of patients (135 of 198). The portion of non-responders to PRD in SR and HR groups was 54% and 67%, respectively (p=0,06). CR rate in 228 available for analysis patients was 87% (n=198), induction death occurred in 10,5% (n=24), resistance was registered in 2,5% (n=6). The majority of CR patients (91%) achieved it after prephase (7,1%, n=16) and the 1st phase of induction (83,9%, n=164). Late responders constituted 9% (n=18). None of those factors (PRD sensitivity, initial risk group, immunophenotype, late response) influenced overall (OS) or disease-free survival (DFS). OS rate in older ALL patients (>30) was substantially less than in younger ones (52,7% vs 73,6%, p=0,0009). DFS was comparable - 61,2% vs 71,5%, p=0,1. 24 of 75 (32%) CR T-ALL patients underwent autologous BMT after BEAM conditioning at a median time of 6 mo from CR and proceeded to further maintenance. No relapses were registered in this group so far. Allogeneic BMT was performed only in 14 patients (Ò-ALL-7, B-ALL-7) on the protocol. Totally 47 patients (20,6%) relapsed (16 with T-lineage, 31 with B-lineage ALL). At 48 mo OS for the whole group constituted - 65,6%, DFS - 69,3%. OS and DFS differed in B-ALL patients with NK in comparison with abnormal karyotype: 80% vs 57%,(p=0,01) and 81% vs 61%, respectively (p=0,02), but not in T-ALL patients. Conclusions Our data demonstrate that the proposed treatment approach is rather effective and reproducible. OS and DFS did not depend on various common risk factors (initial risk group, WBC, LDH, immunophenotype, late response, PRD resistance). The only independent risk factor for OS was age (>30 y). In B-cell ALL abnormal karyotype became an independent adverse risk factor for OS, DFS, relapse incidence. Fig.1 Overall survival (A) according to age in the whole cohort and disease-free survival (B) in B-cell ALL according to karyotype Table 1 (A) OS in different age groups (B) DFS in B-cell ALL Figure Figure. (A) OS in different age groups Figure Figure. (B) DFS in B-cell ALL Disclosures No relevant conflicts of interest to declare.
гематологии и переливания крови Росмедтехнологий, гематологическая клиника; 2 ГОУ ВПО Кировская государственная медицинская академия Росздрава, институт последипломного образования, кафедра анестезиологии и реаниматологии с курсом скорой медицинской помощи
The effects of GSTM1 and GSTT1 gene deletion ("zero") polymorphisms on the risk of chronic myeloid leukemia development and progress and on response to imatinib monotherapy were studied in the representatives of the Russian nationality in the Vyatka region of Russia. Homozygotic carriership of GSTT1 "zero" allele was associated with a 3.66 times higher risk of chronic myeloid leukemia development in residents of the Vyatka region (OR=3.66, 95% CI=2.12-6.30; p<0.0001). Combinations of the "zero" GSTM1 and GSTT1 genotypes were risk factors indicating the probable disease progress and failure of high cytogenetic response after 12 months of imatinib therapy (400 mg daily).
ФГУ «Кировский научно-исследовательский институт гематологии и переливания крови Росмедтехнологий», г. КировРезюме. Исследованы показатели клеточного и гуморального иммунитета у 45 больных множе-ственной миеломой до применения химиотерапии. Установлено, что в общей группе больных на-рушено соотношение Т-и В-лимфоцитов за счет увеличения количества CD3-лимфоцитов при уменьшении CD20-клеток, снижены количество HLA-DR лимфоцитов, процент фагоцитирующих нейтрофилов, уровень IgM и титр комплемента, увеличено число CD8-клеток, повышена активность сывороточного лизоцима и β-лизинов. Иммунные нарушения оказались менее выраженными у боль-ных с I стадией заболевания и при варианте Бенс-Джонса. Высокодозная химиотерапия способство-вала усугублению нарушений, прежде всего, Т-звена иммунитета. Полученные данные свидетель-ствуют о необходимости регулярного иммунологического мониторинга больных миеломой с целью индивидуального подхода к назначению иммунокорригирующей терапии. A study of cell and humoral immune indices was carried out in forty-five pre-treated patients with multiple myeloma. Imbalance in T:B lymphocyte ratio was revealed, due to increased CD3 + cells and decreased CD20 + cell levels. Accordingly, lowered levels of HLA-DR-lymphocytes, high CD8 cell scores, low percentages of phagocytizing neutrophils, decreased IgM and complement titers, increased serum lysozyme and β-lysine activities were observed. Immune disorders in the patients with II and III stage disease were much more frequent, as compared to stage I, and they depended on immune variant of myeloma. Minimal immune defects were noted in cases with Bence Jones variant. High-dose chemotherapy resulted into more expressed immune disorders, mainly, altered T-cell immunity. These data are indicative for a necessity of a regular immunological monitoring, aiming for administration of immunocorrective therapy. (Med. Immunol., vol. 11, N 6, pp 571-576) ВведениеМножественная миелома (ММ) -наиболее часто встречающаяся опухоль из группы им-муноглобулинсекретирующих лимфом, имеет многовариантный характер течения, отражаю-щий особенности поражения костного мозга, костей, а также специфику продукции опухоле-выми клетками моноклональных иммуноглобу-линов и их фрагментов [1]. Не вызывает сомне-ния и факт, что заболевание протекает на фоне вторичной иммунной недостаточности, кли-ническим проявлением которой является под-верженность больных ММ смешанным инфек-циям [7]. Способствующими факторами служат активация эндогенной инфекции, расширение входных ворот вследствие повреждения кожи,
5,3 (0,8-18,0) мес, а общей выживаемости -25,4 (0,8-47,1) 5.3 (0.8-18.0) months and median overall survival was 25.4 (0.8-47.1) months. Hematologic toxicity was in 53.2 % of patients.
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