Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

Abstract

BackgroundCorticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and MethodsAdult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1-8 and 15-22, either dexamethasone 8 mg/m 2 or prednisolone 60 mg/m 2 . Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. ResultsBetween August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75-1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76-1.40). The 6-year cumulative incidences of relapse were 49.8% and 53.5% (Gray's test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray's test: P=0.07). ConclusionsIn the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone. (ClinicalTrials.gov Identifier: NCT00002700)

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

“…The reasons for excluding 15 articles are shown in Figure 1. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Characteristics of included studies are presented in Table 1 (patients in trial Risk of bias assessment has been hampered by the fact that four of the eight studies, so far, have only published preliminary data in form of conference abstracts (AIEOP-BFM ALL 2000 and ALL-BFM 2000, respectively; COG AALL0232, EORTC 58951). Considering all trials, allocation generation and concealment information were available for one and two trials, respectively.…”

Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood

“…This might reflect differences in the definition and detection methods of ON but also disparities in the studied cohorts such as size and type of the cohort, inclusion criteria (notably the percentage of adolescents) and the treatments received (mainly the cumulative steroid dose). Corticosteroids are essential for the treatment of pediatric ALL [10][11][12] and have been identified as the main cause of ON in this context. However, few studies were designed to understand the effect of the cumulative steroid dose as a quantitative variable on the risk of ON and, to our knowledge, none of them have tried to identify a steroid dose threshold.…”

Age-related characteristics of the efficacy of different glucocorticosteroids in the therapy of acute lymphoblastic leukemia

“…Поэтому в новом исследовании ALL-MB 2002 наряду с общими задачами улучшения со-проводительной терапии и ведения пациентов в периоде индукции решено применить различные режимы стеро-идной терапии и проанализировать, позволит ли исполь-зование метилпреднизолона (MePRED) в дозе 60 мг/м 2 вместо DEXA (6 мг/м 2 ) снизить смертность во время ин-дукции, обеспечивая при этом эквивалентную бессобы-тийную выживаемость (БСВ) и воздействие на централь-ную нервную систему (ЦНС). Мы также исследовали воз-растные различия по эффективности различных ГКС у детей с ОЛЛ, так как имеющиеся в литературе данные весьма противоречивы [2,3]. С учетом наиболее благо-приятного дозового соотношения ГКС 10:1 [4] пациенты в нашем исследовании во время индукционной терапии по-лучали DEXA (6 мг/м 2 ) или MePRED (60 мг/м 2 ) в зависи-мости от того, в какую группу попали при рандомизации.…”

“…Однако мы обнаружили, что у подростков БСВ выше, а кумулятивный риск развития ре-цидивов ниже в группе пациентов, получавших MePRED. Кроме того, не отмечено даже тенденции к уменьшению количества системных рецидивов при использовании DEXA в нашем или сопоставимых исследованиях у взрос-лых [2]. Улучшение раннего ответа на терапию (8-й день) и уменьшение частоты развития изолированных рециди-вов поражения КМ при использовании MePRED свиде-тельствуют о худшем системном антилейкемическом эф-фекте DEXA in vivo -даже в нашем соотношении 10:1 или ниже, как продемонстрировано в исследовании DFCI (Dana Farber Cancer Institute) [20].…”