Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies
- Authors: Parovichnikova EN1, Savchenko SA1, Klyasova GA1, Isayev VG1, Sokolov AN1, Kulikov SM1, Ustinova EN1, Gribanova EO1, Ryzhko VV1, Khorosko ND1, Kravchenko SK1, Galstyan GM1, Konstantinova TS2, Zagoskina TP2, Zyuzgin IS2, Kaplanov KD2, Moskov VI2, Sokolova IV2, Anchukova LV2, Lapin VA2, Loginov AB2, Tumakov VA2, Korobkin AV2, Milyutina GI2, Samoilova OS2, Tikunova TS2, Pristupa AS2, Kondakova EV2, Domnikova NP2, Gavrilova LV2, Obidina NA2, Porokhina OV2, Rekhtman GB2, Mashchuk VN2, Khuazheva NK2, Kaporskaya TS2, Golubeva ME2, Maksimov AG2, Ploskikh MA2, Menshakova SN2, Maltsev VI2, Rossiyev VA2, Pilipenko GI2
-
Affiliations:
- Hematology Research Center, Russian Academy of Medical Sciences, Moscow
- Research Group of 32 Hematology Centers from 26 cities and towns of Russia
- Issue: Vol 82, No 7 (2010)
- Pages: 5-11
- Section: Editorial
- URL: https://journals.rcsi.science/0040-3660/article/view/30585
- ID: 30585
Cite item
Full Text
Abstract
Materials and methods. The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients.
Results. The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30109/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses).
Conclusion. The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.
About the authors
E N Parovichnikova
Hematology Research Center, Russian Academy of Medical Sciences, Moscow
Email: elenap@blood.ru
Hematology Research Center, Russian Academy of Medical Sciences, Moscow
S A Savchenko
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
G A Klyasova
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
V G Isayev
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
A N Sokolov
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
S M Kulikov
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
E N Ustinova
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
E O Gribanova
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
V V Ryzhko
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
N D Khorosko
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
S K Kravchenko
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
G M Galstyan
Hematology Research Center, Russian Academy of Medical Sciences, MoscowHematology Research Center, Russian Academy of Medical Sciences, Moscow
T S Konstantinova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
T P Zagoskina
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
I S Zyuzgin
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
K D Kaplanov
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
V I Moskov
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
I V Sokolova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
L V Anchukova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
V A Lapin
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
A B Loginov
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
V A Tumakov
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
A V Korobkin
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
G I Milyutina
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
O S Samoilova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
T S Tikunova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
A S Pristupa
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
E V Kondakova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
N P Domnikova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
L V Gavrilova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
N A Obidina
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
O V Porokhina
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
G B Rekhtman
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
V N Mashchuk
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
N K Khuazheva
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
T S Kaporskaya
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
M E Golubeva
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
A G Maksimov
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
M A Ploskikh
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
S N Menshakova
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
V I Maltsev
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
V A Rossiyev
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
G I Pilipenko
Research Group of 32 Hematology Centers from 26 cities and towns of RussiaResearch Group of 32 Hematology Centers from 26 cities and towns of Russia
References
- Rowe J. Optimal induction and post remission therapy for AML in first remission. In: Hematology 2009: ASH education program book. Washington, 2009; 396-405.
- Burnett A. K., Hills R. K., Wheatley K. et al. A sensitive risk score for directing treatment in younger patients with AML. Blood (ASH Annual Meeting Abstracts) 2006; 108: Abstr. 18.
- Buchner Th., Berdel W. E., Haferlach C. et al. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: A study by the German Acute Myeloid Leukemia Cooperative Group. J. Clin. Oncol. 2009; 27: 61-69.
- Савченко В. Г., Паровичникова Е. Н., Клясова Г. А. и др. Итоги двух с половиной лет работы Российского многоцентрового исследования по лечению острых миелоидных лейкозов взрослых. Тер. арх. 1995; 7: 21-24.
- Parovichnikova H., Savchenko V., Kliasova G. et al. 7+3 versus 7+3+VP-16 as remission induction in AML patients under the age of 60 years: preliminary results of Russian multicenter trial. In Buchner T. et al., eds. Acute leukemias VI. Berlin; 1997; 837-845.
- Савченко В. Г., Паровичникова Е. Н., Клясова Г. А. и др. Итоги проводимых в течение 7 лет клинических многоцентровых исследований по лечению острых миелоидных лейкозов взрослых. Тер. арх. 1999; 7: 13-20.
- Савченко В. Г., Паровичникова Е. Н., Менделеева Л. П. и др. Многоцентровая кооперация - основа прогресса в лечении лейкозов. Тер. арх. 2005; 7: 5-11.
- Zittoun R. A., Mandelli F., Willemze R. et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N. Engl. J. Med. 1995; 332 (4): 217-223.
- Harousseau J. L., Cahn J. Y., Pignon B. et al. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. Blood. 1997; 90 (8): 2978-2986.
- Harousseau J. L., Pignon B., Chevalier M. P. et al. Comparison of intensive chemotherapy and autologous transplantation as post remission therapy in adult acute myeloid leukemia. Update of the GOELAM 1 trial. In: Acute leukemias VIII. Berlin; Heidelberg: Springer-Verlag; 2001. 661-664.
- Cassileth P., Harrington D. P., Appelbaum F. R. et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N. Engl. J. Med. 1998; 339: 1649-1656.
- Slovak M., Kopecky K. J., Cassileth P. et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest oncology group/ eastern cooperative oncology group study. Blood. 2000; 96 (13): 4075-4083.
- Mayer R. J., Davis R. B., Schiffer C. A. et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N. Engl. J. Med. 1994; 331: 896-903.
- Клясова Г. А., Сперанская Л. Л., Миронова А. В. и др. Возбудители сепсиса у иммунокомпрометированных больных: структура и проблемы антибиотикорезистентности (результаты многоцентрового исследования). Гематол. и трансфузиол. 2007; 1: 11-19.
- Pagano L., Caira M., Candoni A. et al. The epedemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006; 91 (8):1068-1075.
- Клясова Г. А., Петрова Н. А., Паровичникова Е. Н. и др. Инвазивный аспергиллез легких. Тер. арх. 2005; 7: 65-71.
- Сornet M., Fleury L., Maslo C. et al. Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. J. Hosp. Infect. 2002; 51 (4): 288-296.
![](/img/style/loading.gif)