Outcome of Treatment in Adults With Acute Lymphoblastic Leukemia: Analysis of the LALA-94 Trial

Thomas, Xavier; Boiron, Jean Michel; Huguet, Françoise; Dombret, Hervé; Bradstock, Ken; Vey, Norbert; Kovacsovics, Tibor; Delannoy, André; Fégueux, Nathalie; Fenaux, Pierre; Stamatoullas, Aspasia; Vernant, Jean Paul; Tournilhac, Olivier; Buzyn, Agnès; Reman, Oumédaly; Charrin, C; Boucheix, Claude; Gabert, Jean; Lhéritier, Véronique; Fière, D

doi:10.1200/jco.2004.10.050

Cited by 462 publications

(420 citation statements)

References 30 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%. 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%.…”

Section: Standard Treatment Of Adult Allmentioning

confidence: 99%

Treatment of Adult Acute Lymphoblastic Leukemia

Gökbuget¹,

Hoelzer²

2006

Hematology

136

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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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Section: Standard Treatment Of Adult Allmentioning

confidence: 99%

Treatment of Adult Acute Lymphoblastic Leukemia

Gökbuget¹,

Hoelzer²

2006

Hematology

136

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“…Advances in the chemotherapeutic treatment of adult acute lymphoblastic leukemia (ALL) have resulted in complete remission (CR) rates in the range of 74-93%; however, only 35% of these patients achieve long-term disease-free survival (DFS) [1][2][3][4][5][6][7]. Because a high incidence of relapse is the main cause of treatment failure in adults with ALL, the use of allogeneic stem cell transplantation (SCT) as post-remission therapy has become a widely-accepted strategy.…”

Section: Introductionmentioning

confidence: 99%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

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The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P 5 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P 5 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P 5 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634-641,

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“…21 In this study, only 52% of the patients actually received maintenance chemotherapy. However, the most important reason for the negative finding is likely the fact that patients with standard-risk disease did not undergo autotransplantation.…”

Section: Discussionmentioning

confidence: 78%

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients

Sirohi

Powles

Treleaven

et al. 2008

Bone Marrow Transplant

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A total of 100 adults with ALL in first CR received melphalan (110 mg/m 2 ) with TBI followed by autologous marrow (n ¼ 35) or single-agent melphalan (200 mg/m 2 ) followed by autologous blood stem cells (n ¼ 65). After adequate hematologic recovery, maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone was administered for 2 years. Six patients, all TBI recipients (P ¼ 0.001), died of toxicity. In total 70 patients received 6-mercaptopurine, 53 received methotrexate and 40 received vincristine-prednisone. The cumulative incidence of relapse at 7 years was 45%. The 7-year probabilities of disease-free survival (DFS) and overall survival were 45 and 48%. Age 30 years, 44 weeks to attain remission, and karyotypes t(4;11) and t(9;22) were associated with adverse outcome. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 7-year cumulative incidences of relapse of 19, 53 and 82% (Po0.0001), and 7-year DFS probabilities of 73, 36 and 7% (Po0.0001). The 7-year probabilities of DFS for patients receiving 0, 1, 2 and 3 maintenance chemotherapy agents were 15, 29, 58 and 61% (Po0.0001). Maintenance chemotherapy intensity was an independent determinant of outcome in Cox analysis. Maintenance chemotherapy after autotransplantation reduces relapse and improves outcome in adult patients with ALL.

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Outcome of Treatment in Adults With Acute Lymphoblastic Leukemia: Analysis of the LALA-94 Trial

Abstract: Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.

Cited by 462 publications

References 30 publications

Treatment of Adult Acute Lymphoblastic Leukemia

Treatment of Adult Acute Lymphoblastic Leukemia

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients

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