The GIMEMA ALL 0183 trial: analysis of 10‐year follow‐up

Mandelli, Franco; Annino, Luciana; Rotoli, Bruno

doi:10.1046/j.1365-2141.1996.00394.x

Cited by 53 publications

(24 citation statements)

References 19 publications

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“…Again this may be explained by the younger age population in the present study (median age, 31) compared with the older age population of the ALL90 (median age, 43) and of the ALL87 (median age, 38). Although OS in the present study is not inferior to hitherto reported large-scale studies, 3,4,6,7 recent studies which include highdose Ara-C and/or high-dose MTX in the post-remission therapy report better OS. [15][16][17] Since April 2000, our National Health Insurance policy has been changed to allow us to use high-dose Ara-C.…”

Section: Figurecontrasting

confidence: 40%

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Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study

et al. 2002

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In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m 2 was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age Ͻ40 and WBC Ͻ50 000/ l; for longer OS were age Ͻ30 and WBC Ͻ30 000/ l; and for longer DFS of CR patients were FAB L1 and ALT Ͻ50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Phpositive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).

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Section: Figurecontrasting

confidence: 40%

“…The long-term remission rate of adult ALL remains at 25 to 43%, despite the CR rate of around 80%. [3][4][5][6][7][8] Thus, adult ALL is still considered as one of the intractable cancers.…”

Section: Introductionmentioning

confidence: 99%

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study

et al. 2002

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“…Both single institutions and multicenter studies have shown that aggressive induction plus more potent intensification programs with chemotherapy alone or chemotherapy plus stem cell transplantation (SCT) may improve treatment results. [1][2][3][4][5][6] Although the complete remission (CR) proportions range from 60 to 90%, the long-term DFS rates are disappointingly short. 7 Leukemic relapse in adult ALL remains a major therapeutic problem.…”

Section: Introductionmentioning

confidence: 99%

Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial

et al. 2007

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Fifty-four percent of adults with acute lymphoblastic leukemia (ALL) who entered the LALA-94 trial experienced a first relapse. We examined the outcome of these 421 adult patients. One hundred and eighty-seven patients (44%) achieved a second complete remission (CR). The median disease-free survival (DFS) was 5.2 months with a 5-year DFS at 12%. Factors predicting a better outcome after relapse were any transplant performed in second CR (Po0.0001), a first CR duration 41 year (P ¼ 0.04) and platelet level 4100 Â 10 9 /l at relapse (P ¼ 0.04). Risk groups defined at diagnosis and treatment received in first CR did not influence the outcome after relapse. The best results were obtained in a subset of patients who were eligible for allogeneic stem cell transplantation (SCT). Genoidentical allogeneic SCT was performed in 55 patients, and 3 patients received donor lymphocyte infusions. Forty-four transplantations were performed from an unrelated donor (of which four were cord blood). We conclude that most adult patients with recurring ALL could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option.

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“…48,49 The highest risk was in patients who were over 35 years of age, Ph 1 -positive, had leukocyte counts above 30 ϫ 10(9)/L, had null ALL or undifferentiated leukemia, or required longer than four weeks to achieve complete remission. A few studies specifically addressed the role of allogeneic BMT in Ph 1 -positive patients.…”

Section: Impact Of Bcr-abl On Selecting Therapy For Allmentioning

confidence: 99%

Clinical Applications of BCR-ABL Molecular Testing in Acute Leukemia

Nashed

Rao

Gulley

2003

The Journal of Molecular Diagnostics

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Recent advances in molecular genetics impact the health care and outcome of patients with acute lymphoblastic leukemia (ALL). BCR-ABL, a common molecular defect in adult ALLIn 1960, Nowell and Hungerford 1 reported the discovery of what came to be known as the Philadelphia chromosome (Ph 1 ) in association with chronic myelogenous leukemia (CML). Their short report entitled "Minute chromosome in human chronic granulocytic leukemias" was the first to demonstrate a leukemia-specific genetic abnormality. In the ensuing decades, the pathology of the Ph 1 has been studied and it is now known to represent an abnormally shortened (derivative) chromosome 22 resulting from translocation with chromosome 9.2 The t(9;22) is found in over 90% of CMLs, in a lesser proportion of acute lymphoblastic leukemias (ALL) or biphenotypic acute leukemias, and in rare cases of de novo acute myelogenous leukemia (AML).The break on chromosome 22q11.2 usually occurs in the major breakpoint cluster region (M-BCR), in the minor breakpoint cluster region (m-BCR), or rarely at other nearby sites. The break on chromosome 9q34 involves the ABL gene, named after Abelson murine leukemia virus where a viral version of the ABL gene was first discovered. The translocation brings the 5Ј end of the BCR gene into juxtaposition with the tyrosine kinase domain of the ABL gene to produce a hybrid gene retaining tyrosine kinase activity. 3Depending on whether the M-BCR or m-bcr breakpoint is involved in the translocation, transcription of the hybrid gene results in chimeric mRNA encoding a 210 kd BCR-ABL fusion protein or a 190 kd BCR-ABL fusion protein, respectively. The reciprocal ABL-BCR translocation also forms a chimeric gene that is capable of being transcribed, but the pathological significance of this reciprocal chimeric gene product is uncertain. Laboratory Tests for t(9;22)Conventional cytogenetics is the recommended test for detecting t(9;22) in newly diagnosed leukemia patients. Chromosome banding analysis has the advantage of high specificity and an ability to detect alternate or additional cytogenetic defects that are valuable in diagnosis and prognosis. However, cytogenetic analysis requires viable marrow cells or more than 10% blasts in the peripheral blood to reliably culture the cells and visualize metaphases. Occasionally fibrosis interferes with marrow aspiration, yielding few analyzable metaphase cells. The number of cells examined determines the sensitivity of karyotyping. A typical examination of 20 cells carries a sensitivity of one in 20, or 5%. Cryptic t(9;22) occurs in about 5% of CML cases and also in a small proportion of ALLs, resulting in false negative karyotypic interpretation in metaphase spreads of cells that actually contain the translocation at the molecular level.

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The GIMEMA ALL 0183 trial: analysis of 10‐year follow‐up

Cited by 53 publications

References 19 publications

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study

Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial

Clinical Applications of BCR-ABL Molecular Testing in Acute Leukemia

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