Adult Acute Lymphocytic Leukemia Study Testing Chemotherapy and Autologous and Allogeneic Transplantation

Thiébaut, Anne; Vernant, Jean Paul; Degos, Laurent; Huguet, Françoise; Reiffers, Josy; Sebban, Catherine; Lepage, Éric; Thomas, Xavier; Fière, D

doi:10.1016/s0889-8588(05)70190-8

Cited by 155 publications

(115 citation statements)

References 29 publications

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“…One is dedicated to comparative analysis of the role of stem cell transplantation (SCT) with allogeneic SCT in all patients with sibling donors 4,5,6,7 ; the other group consists of studies focused on optimization of chemotherapy with SCT only for subgroups such as Philadelphia chromosome (Ph)-positive ALL 8,9 or based on prognostic models. [10][11][12][13][14] Complete response (CR) rates ranged between 74% and 93% and the overall survival (OS) between 27% and 48%.…”

Section: Standard Treatment Of Adult Allmentioning

confidence: 99%

“…[10][11][12][13][14] Complete response (CR) rates ranged between 74% and 93% and the overall survival (OS) between 27% and 48%. No difference is evident for OS of studies focused on SCT (N = 2696), with a weighted mean of 84% for CR and 35% for OS, [4][5][6][7] and studies with riskadapted approaches (N = 2443), with mean CR rate of 83% and OS of 36%. [10][11][12][13][14]8 Notably, only a few studies included patients aged above 60 years.…”

Section: Standard Treatment Of Adult Allmentioning

confidence: 99%

“…The dexamethasone schedule has to be considered carefully since continuous application of higher doses may lead to long-term complications such as avascular bone necrosis 15 and to increased morbidity and mortality due to infections. The German Multicenter Study Group (GMALL) observed in their pilot trial 06/99 an early mortality of 16% with dexamethasone 10 mg/m² given on days 1-16 compared to 5% for an interrupted schedule (days [1][2][3][4][5][11][12][13][14] with corresponding CR rates of 76% and 82%. 16 The most frequently used anthracycline is daunorubicin (DNR).…”

Section: Standard Treatment Of Adult Allmentioning

confidence: 99%

“…Some groups scheduled autologous (auto) SCT only 25 and others a randomized comparison of auto SCT and chemotherapy. 4,6,14,26 The preferable approach for this trial design is "intentto-treat" analysis that compares patients with donors to those without donors. The hardest outcome parameter is the OS of the total patient cohort, which answers the question whether an SCT-based treatment concept can improve overall outcome.…”

Section: Stem Cell Transplantationmentioning

confidence: 99%

“…OS of studies with "genetic randomization" is not superior to chemotherapy studies (see above), which is partly due to the fact that allo sib SCT could be realized in only 11-38% of the patients. [4][5][6]14,25,26 Even if allo sib SCT yielded favorable results, due to infrequent realization the impact on overall outcome is too small.…”

Section: Stem Cell Transplantationmentioning

confidence: 99%

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Treatment of Adult Acute Lymphoblastic Leukemia

Gökbuget¹,

Hoelzer²

2006

Hematology

137

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In the early 1980s, adult acute lymphoblastic leukemia (ALL) was a rarely curable disease with overall survival < 10%. After adapting combinations employed by pediatric groups, the outcome improved to 30-40%. A period of stagnation followed with improvement only in distinct subgroups. In the past 5 years, however, striking new developments have been noticeable. Progress has been made in molecular diagnostics of ALL. Improvements to standard therapy including stem cell transplantation (SCT) have occurred and a variety of new drugs for ALL are under evaluation. Rapid diagnosis and classification of ALL is increasingly important to identify prognostic factors and molecular genetic subsets that will be the focus of "targeted" therapies as we enter the era of subset specific treatment. In the following review we will discuss treatment of adult ALL (excluding elderly patients, 1 adolescents 2 and patients with Ph/BCR-ABL positive ALL 3 ). Standard Treatment of Adult ALLIn the past decade two basic types of prospective trials have been reported in adult acute lymphoblastic leukemia (ALL) ( Table 1). One is dedicated to comparative analysis of the role of stem cell transplantation (SCT) with allogeneic SCT in all patients with sibling donors 4,5,6,7 ; the other group consists of studies focused on optimization of chemotherapy with SCT only for subgroups such as Philadelphia chromosome (Ph)-positive ALL 8,9 or based on prognostic models. [10][11][12][13][14] Complete response (CR) rates ranged between 74% and 93% and the overall survival (OS) between 27% and 48%. No difference is evident for OS of studies focused on SCT (N = 2696), with a weighted mean of 84% for CR and 35% for OS, 4-7 and studies with riskadapted approaches (N = 2443), with mean CR rate of 83% and OS of 36%. [10][11][12][13][14]8 Notably, only a few studies included patients aged above 60 years. 6,[9][10][11]13 Induction therapy Standard induction of adult ALL includes at least a glucocorticoid, vincristine, an anthracycline and probably asparaginase. In response to pediatric results that show a decreased central nervous system (CNS) relapse rate and improved survival, 15 prednisone is now being replaced by dexamethasone. The dexamethasone schedule has to be considered carefully since continuous application of higher doses may lead to long-term complications such as avascular bone necrosis 15 and to increased morbidity and mortality due to infections. The German Multicenter Study Group (GMALL) observed in their pilot trial 06/99 an early mortality of 16% with dexamethasone 10 mg/m² given on days 1-16 compared to 5% for an interrupted schedule (days 1-5,11-14) with corresponding CR rates of 76% and 82%. 16 The most frequently used anthracycline is daunorubicin (DNR). One randomized study showed a diseasefree survival of 36% for DNR at 30 mg/m² compared to 30% for idarubicin (9 mg/m²) given weekly in induction. 14 Many groups have replaced weekly applications by higher doses of DNR (45-80 mg/m²) on subsequent days. Promising results of smaller trials have...

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