Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies

Abstract

Aim. To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009.
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, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

G A Klyasova

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

V G Isayev

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

A N Sokolov

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

S M Kulikov

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

E N Ustinova

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

E O Gribanova

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

V V Ryzhko

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

N D Khorosko

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

S K Kravchenko

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

G M Galstyan

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

Hematology Research Center, Russian Academy of Medical Sciences, Moscow

T S Konstantinova

Research Group of 32 Hematology Centers from 26 cities and towns of Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research 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 Russia

Research Group of 32 Hematology Centers from 26 cities and towns of Russia

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Copyright (c) 2010 Parovichnikova E.N., Savchenko S.A., Klyasova G.A., Isayev V.G., Sokolov A.N., Kulikov S.M., Ustinova E.N., Gribanova E.O., Ryzhko V.V., Khorosko N.D., Kravchenko S.K., Galstyan G.M., Konstantinova T.S., Zagoskina T.P., Zyuzgin I.S., Kaplanov K.D., Moskov V.I., Sokolova I.V., Anchukova L.V., Lapin V.A., Loginov A.B., Tumakov V.A., Korobkin A.V., Milyutina G.I., Samoilova O.S., Tikunova T.S., Pristupa A.S., Kondakova E.V., Domnikova N.P., Gavrilova L.V., Obidina N.A., Porokhina O.V., Rekhtman G.B., Mashchuk V.N., Khuazheva N.K., Kaporskaya T.S., Golubeva M.E., Maksimov A.G., Ploskikh M.A., Menshakova S.N., Maltsev V.I., Rossiyev V.A., Pilipenko G.I.

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