Five-Year Follow-Up of "Total Therapy" of Childhood Lymphocytic Leukemia

Pinkel, Donald

doi:10.1001/jama.1971.03180300032007

Cited by 196 publications

(53 citation statements)

References 10 publications

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“…With the recognition that CNS relapse was common among children in bone marrow remission, presymptomatic CNS radiation and intrathecal chemotherapy were introduced into the treatment of childhood ALL. 5 During the 1970s and early 1980s, additional treatment strategies were adopted to continue this improvement in survival, including the addition of other agents such as anthracyclines and alkylating agents, along with incorporation of a delayed intensification phase of chemotherapy. Subsequently, with the emergence of adverse late effects, clinical investigations addressed the potential reduction in intensity and duration of therapy, including approaches that produced sustained CNS remissions without the use of cranial radiation.…”

Section: Introductionmentioning

confidence: 99%

Late Effects of Acute Lymphoblastic Leukemia Therapy in Patients Diagnosed at 0-20 Years of Age

Robison

2011

Hematology

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Survival rates for children with acute lymphoblastic leukemia (ALL) have increased dramatically over the past 4 decades, with 5-year survival rates of Ͼ 90% in recent trials. With the increasing number of children and adolescents cured of ALL, identifying and characterizing the occurrence of long-term adverse late effects has become increasingly important. In this young population, successful treatment of ALL is associated with increased risk of adverse outcomes such as late mortality, second neoplasms, chronic health conditions, endocrine dysfunction, and psychological function. Research efforts conducted through large survivor cohorts, such as the Childhood Cancer Survivor Study, are providing new and important insights into the very long-term consequences of ALL therapy, while providing direction for screening recommendations and intervention-based approaches for reducing late morbidity and mortality.

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Section: Introductionmentioning

confidence: 99%

Late Effects of Acute Lymphoblastic Leukemia Therapy in Patients Diagnosed at 0-20 Years of Age

Robison

2011

Hematology

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“…Accordingly, current pediatric treatment protocols advocate extensive intrathecal and systemic chemotherapy, [9][10][11] which has been associated with long-term neurologic sequelae. 11,12 Thus, more precise diagnostic and prognostic markers for CNS involvement in ALL are needed, not only to control CNS infiltration but also to avoid systemic overtreatment.…”

mentioning

confidence: 99%

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

Alsadeq

Fedders

Vokuhl³

et al. 2016

Haematologica

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C entral nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zetachain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central nervous system positivity in T-cell acute lymphoblastic leukemia (odds ratio=11.00, 95% confidence interval, 2.00-60.62). We propose zeta-chain-associated protein kinase 70, CCR7 and CXCR4 as markers of central nervous system infiltration in acute lymphoblastic leukemia warranting prospective investigation.

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“…The bone marrow showed 84% blasts morphologically and cytochemically identified as lymphoid. Treatment with vindesine/prednisone was not successful this time and therefore therapy was begun using cyclophosphamide/methotrexate and 6-mercaptopurine [14], which led to a chronic phase. During this chronic he matological phase -peripheral blood showed 9,100 leukocytes, 98,000 thrombocytes, hemoglobin 14.6 g/dl -a cerebral relapse oc curred in July 1983.…”

Section: Case Reportmentioning

confidence: 99%

Hyperdiploidy of 54 Chromosomes with Double Ph<sup>1</sup> Chromosome in Lymphoid Chronic Myelocytic Leukemic Blast Crisis

Clemm¹,

Thiel²,

Riess³

et al. 1985

Acta Haematol

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Cytogenetic analysis of bone marrow cells in a 40-year-old man revealed a mosaic of two cell lines during blast crisis: one diploid with typical Ph1 chromosome (46 XY Ph¹) and one with hyperdiploidy of 54 chromosomes with double Ph¹ chromosome, trisomy 4, 6, 8, 18, 21 and duplication of the sex chromosomes X and Y. Immunological characterization showed common acute lymphoblastic leukemia antigen in 90% of the blasts. In spite of intensive chemotherapy the patient died in a third blast crisis 15 months after the first blast crisis, 3 months after successfully treated central nervous system relapse.

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Five-Year Follow-Up of "Total Therapy" of Childhood Lymphocytic Leukemia

Cited by 196 publications

References 10 publications

Late Effects of Acute Lymphoblastic Leukemia Therapy in Patients Diagnosed at 0-20 Years of Age

Late Effects of Acute Lymphoblastic Leukemia Therapy in Patients Diagnosed at 0-20 Years of Age

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

Hyperdiploidy of 54 Chromosomes with Double Ph<sup>1</sup> Chromosome in Lymphoid Chronic Myelocytic Leukemic Blast Crisis

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