Treatment of Adult Acute Lymphoblastic Leukemia

Abstract

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...

A decision analysis of allogeneic hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission who have an HLA-matched sibling donor

“…However, the overall survival rate is only 27-48% because of the high rate of relapse. 1 Therefore, the establishment of optimal postremission therapy is important. The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for adult patients with ALL in first remission has been demonstrated through clinical studies using genetic randomization, in which patients with a human leukocyte antigen (HLA)-matched sibling donor were allocated to the allogeneic HSCT arm, and those without a donor were placed in the chemotherapy or autologous transplantation arm.…”

The homeobox gene CDX2 is aberrantly expressed and associated with an inferior prognosis in patients with acute lymphoblastic leukemia

“…1,2 In addition, great progress has been made in understanding the biology of ALL: recently, genome-wide analyses of ALL patients showed deletions and mutations of genes associated with lymphoid development, such as LEF1, TCF, PAX5, IKAROS and NOTCH1. [3][4][5] However, for the majority of ALL cases the molecular mechanisms driving the malignant transformation are unknown.…”

Chimeric, divalent and tetravalent anti‐CD19 monoclonal antibodies with potent in vitro and in vivo antitumor activity against human B‐cell lymphoma and pre‐B acute lymphoblastic leukemia cell lines

“…49 Anti-CD20 antibodies are not effective in treating such patients, whereas anti-CD19 MAbs might be. In our study, we demonstrated that in vitro the cHD37 MAbs mediated apoptosis, ADCC and ADCP against human pre-B ALL NALM-6 and KOPN-8 cells, and in vivo, extended the MPT of SCID mice xenografted with NALM-6 cells, indicating that these MAbs should have the potential of treating humans with pre-B ALLs.…”