Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

Lazarus, Hillard M.; Richards, Susan; Chopra, Raj; Litzow, Mark R.; Burnett, Alan Kenneth; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, Ian; Rowe, Jacob M.; Goldstone, Anthony H.

doi:10.1182/blood-2005-11-4666

Cited by 211 publications

(177 citation statements)

References 26 publications

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“…18 Besides the mature B-cell phenotype, 19 only a few factors have been associated with an increased risk for CNS relapse in adults with ALL. In a recent study, Lazarus et al 20 reported that a T-cell phenotype, high presenting leukocyte counts and the presence of a mediastinal mass were associated with CNS leukemia at diagnosis. Despite intensified chemotherapy and craniospinal irradiation (24 Gy cranial and 12 Gy spinal), or hematopoietic stem cell transplantation with 13.2 Gy fractionated total-body irradiation in approximately half of the patients, those with CNS leukemia at diagnosis had a significantly higher risk for any type of CNS relapse, isolated or combined (11.9% vs. 5.6%), and a poorer survival rate (29% vs. 38% at 5 years) compared with all other patients.…”

Section: Risk Factors For Cns Relapsementioning

confidence: 99%

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Pui

2006

Hematology

105

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Improved treatment for acute lymphoblastic leukemia (ALL) has virtually eliminated testicular relapse. However, the control of central nervous system (CNS) leukemia remains a therapeutic challenge in childhood ALL, partly because of the late complications arising from cranial irradiation. In most current pediatric protocols, cranial irradiation (12 to 18 Gy) is given to 5% to 25% of patients—those with T-cell ALL, overt CNS disease (CNS3 status) or high-risk cytogenetics. CNS control is a less urgent concern in adults with ALL, in whom systemic relapse remains the major problem. With current approaches, approximately 2% to 10% of patients can be expected to develop CNS relapse. Children with B-cell precursor ALL who have a late CNS relapse (after an initial remission of 18 months or more) and did not receive cranial irradiation have an excellent outcome after retrieval therapy, with a 5-year event-free survival (EFS) rate approaching that in newly diagnosed patients. Innovative treatment options are needed for children who develop CNS relapses after a short initial remission or after receiving cranial irradiation, and in any adults with CNS leukemia at diagnosis or relapse.

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Section: Risk Factors For Cns Relapsementioning

confidence: 99%

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Pui

2006

Hematology

105

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“…1,2 Although the international ALL Medical Research Council (MRC) UKALL XII/Eastern Cooperative Oncology Group (ECOG) E2993 trial reported a worse outcome for ALL adults with CNS leukemia, the Leucé mies Aiguë s Lymphoblastiques de l 0 Adulte (LALA) trials and a Southwest Oncology Group study 1,3 found no significant variation in survival according to CNS disease status. However, the outcome of CNS patient subgroups reported in the MRC trial was not statistically different in event-free survival (EFS) compared with other patients and the CNS subgroup of patients had a significantly high WBC count at diagnosis compared with CNS-negative ALL patients.…”

Section: Introductionmentioning

confidence: 99%

Treatment of adult ALL with central nervous system involvement at diagnosis using autologous and allogeneic transplantation: a study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Chantepie

Mohty

Tabrizi

et al. 2012

Bone Marrow Transplant

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To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central nervous system involvement at diagnosis, we retrospectively analyzed 90 patients who underwent autologous HSCT (auto-HSCT group; n ¼ 27) or allogeneic HSCT (allo-HSCT group; n ¼ 63) and reported to the Socié té Franc¸aise de Greffe de Moelle et de Thé rapie Cellulaire registry between 1994 and 2008. At the time of transplantation, 67 patients (74%) were in first CR, 15 (17%) in CRX2 and 8 (9%) with progressive disease. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33% for the auto-HSCT groups, respectively (P ¼ NS). The TRM at 5 years was 29.8% for the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis, a time for transplantation of o12 months, the remission status at transplantation, the use of high-dose TBI and the number of the transplant were all determined to be prognostic factors for improved DFS and OS probabilities.Using multivariate analysis, we demonstrated that both the use of high-dose TBI and the remission status had a favorable impact on OS. Although the DFS and OS were better in the allo-HSCT group, the differences were not statistically significant.

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“…46 In adults with ALL, CNS leukemia at diagnosis has been associated with a significantly higher risk for CNS relapse in large trials, although no differences were observed in 5-year EFS or DFS rates compared with subgroups without CNS leukemia at presentation. 162,163 CNS leukemia at diagnosis was associated with significantly decreased 5-year OS rate in one trial (29% vs. 38%; P = .03) 162 but not in another trial (35% vs. 31%). 163 Factors associated with increased risks for CNS leukemia in adults include mature B-cell immunophenotype, T-cell immunophenotype, high presenting WBC counts, and elevated serum lactate dehydrogenase (LDH) levels.…”

Section: Cns Involvement In Allmentioning

confidence: 99%

“…163 Factors associated with increased risks for CNS leukemia in adults include mature B-cell immunophenotype, T-cell immunophenotype, high presenting WBC counts, and elevated serum lactate dehydrogenase (LDH) levels. 23,162 CNS-directed therapy may include cranial irradiation, intrathecal chemotherapy (e.g., methotrexate, cytarabine, corticosteroids), and/or highdose systemic chemotherapy (e.g., methotrexate, cytarabine, mercaptopurine, L-asparaginase). 1,27,46 Although cranial irradiation is an effective treatment modality for CNS leukemia, it can be associated with serious adverse events, such as neurocognitive dysfunctions, secondary malignancies, and other long-term complications.…”

Section: Cns Involvement In Allmentioning

confidence: 99%

Acute Lymphoblastic Leukemia

Alvarnas

Brown

Aoun

et al. 2012

J Natl Compr Canc Netw

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The inaugural NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) were developed as a result of meetings convened by a multidisciplinary panel of experts in 2011. These NCCN Guidelines provide recommendations on the diagnostic evaluation and workup for ALL, risk assessment, risk-stratified treatment approaches based on the Philadelphia chromosome status and age (adults vs. adolescents/young adults), assessment of minimal residual disease, and supportive care considerations. It is recommended that patients be treated at specialized centers with expertise in the management of ALL. (JNCCN 2012;10:858-914) NCCN Categories of Evidence and ConsensusCategory 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

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Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

Cited by 211 publications

References 26 publications

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Treatment of adult ALL with central nervous system involvement at diagnosis using autologous and allogeneic transplantation: a study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Acute Lymphoblastic Leukemia

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