Front Line Clinical Trials and Minimal Residual Disease Monitoring in Acute Promyelocytic Leukemia

Ammatuna, Emanuele

doi:10.1007/978-3-540-34594-7_9

Cited by 10 publications

(4 citation statements)

References 42 publications

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“…Initial MRD studies in AML were performed in adult patients by using either reverse transcription (RT)-PCR amplification of fusion transcripts (Tobal et al, 2000;Marcucci et al, 2001;LoCoco & Ammatuna, 2007), or flow cytometry (Campana et al, 1990;San Miguel et al, 2001;Venditti et al, 2003;Buccisano et al, 2006). These studies demonstrated the potential clinical usefulness of monitoring MRD in AML.…”

Section: Prognostic Significance Of Mrd In Amlmentioning

confidence: 99%

Status of minimal residual disease testing in childhood haematological malignancies

Campana

2008

Br J Haematol

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SummaryIn children with acute leukaemia, measurements of minimal residual disease (MRD) provide unique information on treatment response and have become a crucial component of contemporary treatment protocols. In acute lymphoblastic leukaemia (ALL), the most useful MRD assays are based on polymerase chain reaction (PCR) amplification of antigenreceptor genes, and on flow cytometric detection of abnormal immunophenotypes. The latter is the only MRD assay available for most patients with acute myeloid leukaemia (AML). PCR amplification of chromosomal breakpoints and fusion transcripts can also be used to track MRD in a minority of patients with ALL or AML. Because of the strong correlation between MRD levels and risk of relapse, several ongoing regimens include treatment intensification for children with higher MRD. Treatment de-intensification for patients with early MRD clearance is also being tested. In addition to their direct clinical application, MRD measurements can be used to better understand the molecular and cellular mechanisms of drug resistance in vivo. The identification of new markers of leukaemia and the use of increasingly sophisticated technologies for detection of rare cells should further facilitate routine monitoring of MRD and elucidate the features of drug-resistant leukaemic cells.

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Section: Prognostic Significance Of Mrd In Amlmentioning

confidence: 99%

Status of minimal residual disease testing in childhood haematological malignancies

Campana

2008

Br J Haematol

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“…Such treatment has been shown to be beneficial, although only in sequential clinical trials in adults. 102,159,160 Several studies in adults and children have demonstrated the effectiveness of ATRA combined with arsenic trioxid without conventional chemotherapy in refractory, relapsed, or newly diagnosed APL. 161,162 However, more safety and efficacy data need to be generated before routinely introducing arsenic in newly diagnosed APL protocols in children.…”

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confidence: 99%

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Creutzig

Heuvel‐Eibrink

Gibson

et al. 2012

Blood

489

526

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IntroductionChildhood acute myeloid leukemia (AML) is a rare and heterogeneous disease, with an incidence of 7 cases per million children younger than 15 years. In high-income countries, intensive therapy in conjunction with effective supportive care has increased survival rates to ϳ 70%. In 1990 and 2003, expert working groups made recommendations for diagnosis, outcomes, standardization of response criteria, and reporting standards for AML. 1,2 Recent improvements in identifying the molecular genetics and pathogenesis of AML have been implemented in the new World Health Organization (WHO) classification of AML. 3 These changes, and the definition of new diagnostic and prognostic markers and their associated targeted therapies, have prompted the update of earlier recommendations by an international group, on behalf of the European LeukemiaNet for AML in adults in 2010. 4 Despite broad overlap in the diagnostic and treatment recommendations for AML for children and adults, there are important differences in both the diagnostic criteria and disease management, which merit age-specific recommendations. The absence of published recommendations specific for pediatric AML motivated an international group of pediatric hematologists and oncologists (panel and participating groups see "Appendix") to develop evidence-and expert opinionbased consensus recommendations for the diagnosis and management of AML in children, incorporating emerging information on the biology of the disease. The scope of the review is presented in the "Appendix." Recommendations for specific subgroups are also included. This article discusses diagnostic procedures and initial workup, prognostic factors, response criteria, and management, and in particular focuses on differences between adults and children with AML. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From WHO classification and pediatric AMLThe recent WHO 2008 classification is applicable to both adult and pediatric AML 3,5 and has been summarized by Döhner et al. 4 The classification contains most, but not all, cytogenetic subgroups specific to children. Differences in genetic background between children and adults are given in Table 1 and discussed further in "Cytogenetics."Compared with previous classifications (European Group of Immunologic Characterization of Leukemias [EGIL], WHO 2001), 6 the new WHO classification introduced a stringently defined subclass of acute leukemias of ambiguous lineage (mixed phenotype acute leukemias [MPALs]), mainly on the basis of detailed immunophenotypic criteria (Table 2) or presence of t(9;22)(q34; q11.2)/BCR-ABL1 or t(v;11q23)/MLL rearrangement. 3,5,6 The new classification aims to create uniform subgroups defined by unifying molecular targets, which allow selection of specific treatment. Diagnostic procedures and initial workupThe minimal diagnostic requirements in childhood AML are morphology with cytochemistry, immunophenotyping, karyotyping, FISH, and specific molecular genetics in the bone marrow, which is comparable ...

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“…Therefore, studies of MRD in AML by molecular methods are limited to specifi c genetic subtypes, and most reported studies have been performed in adult patients [41][42][43]. Because leukemic cells in most patients express aberrant immunophenotypes, fl ow cytometry can be applied to study MRD across different genetic subtypes of AML.…”

Section: Mrd Studies In Patients With Amlmentioning

confidence: 99%

Role of minimal residual disease evaluation in leukemia therapy

Campana

2008

Curr Hematol Malig Rep

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In patients with acute leukemia, measurements of minimal residual disease (MRD) provide unique information on response to treatment. The most useful currently available MRD assays are polymerase chain reaction amplification of fusion transcripts and rearranged antigen-receptor genes and flow cytometric detection of aberrant immunophenotypes. Many studies in children and adults with acute lymphoblastic leukemia and acute myeloid leukemia have demonstrated a strong association between the presence of MRD and risk of relapse. Therefore, the use of information on MRD to adjust the intensity of therapy holds great potential for improving long-term clinical outcome. This article discusses the methodologies available for productive MRD testing and the clinical significance of the results.

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Front Line Clinical Trials and Minimal Residual Disease Monitoring in Acute Promyelocytic Leukemia

Cited by 10 publications

References 42 publications

Status of minimal residual disease testing in childhood haematological malignancies

Status of minimal residual disease testing in childhood haematological malignancies

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Role of minimal residual disease evaluation in leukemia therapy

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