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As a group, acute leukaemias are the most common childhood malignancies, and continue to be an important cause of non-accident related childhood mortality. Fortunately, with modern chemotherapy the majority of children and young p...
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As a group, acute leukaemias are the most common childhood malignancies, and continue to be an important cause of non-accident related childhood mortality. Fortunately, with modern chemotherapy the majority of children and young people with leukaemia can be cured. However, this treatment comes with a significant burden for our young patients and their families. Here, we review the essential and differential diagnostics and the initial management of children with suspected leukaemia, as relevant for secondary paediatric care. We will give a short overview of current treatment protocols for childhood acute lymphoblastic and acute myeloid leukaemia. We will explain how stratification according to certain prognostic factors - most importantly response to therapy - guides treatment intensity. Using modern molecular techniques for minimal residual disease monitoring and molecular disease classification, it is increasingly possible to identify patients with a cure rate well above 90% in whom a reduction in treatment intensity may seem feasible. In addition, these techniques also allow the definition of poor-risk patients who may benefit from more intensive chemotherapy and bone-marrow transplantation. Finally, we discuss long-term follow-up of survivors of childhood leukaemia as a multidisciplinary paediatric team approach, as well as the challenges of transition into adult care.
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摘要 :
As a group, acute leukaemias are the most common childhood malignancies, and continue to be an important cause of non-accident related childhood mortality. Fortunately, with modern chemotherapy the majority of children and young p...
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As a group, acute leukaemias are the most common childhood malignancies, and continue to be an important cause of non-accident related childhood mortality. Fortunately, with modern chemotherapy the majority of children and young people with leukaemia can be cured. However, this treatment comes with a significant burden for our young patients and their families. Here, we review the essential and differential diagnostics and the initial management of children with suspected leukaemia, as relevant for secondary paediatric care. We will give a short overview of current treatment protocols for childhood acute lymphoblastic and acute myeloid leukaemia. We will explain how stratification according to certain prognostic factors - most importantly response to therapy - guides treatment intensity. Using modern molecular techniques for minimal residual disease monitoring and molecular disease classification, it is increasingly possible to identify patients with a cure rate well above 90% in whom a reduction in treatment intensity may seem feasible. In addition, these techniques also allow the definition of poor-risk patients who may benefit from more intensive chemotherapy and bone-marrow transplantation. Finally, we discuss long-term follow-up of survivors of childhood leukaemia as a multidisciplinary paediatric team approach, as well as the challenges of transition into adult care.
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l-asparaginase encapsulated within erythrocytes (GRASPA®) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 stud...
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l-asparaginase encapsulated within erythrocytes (GRASPA®) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA® for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA® (50 iu/kg: n = 6, 100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA® was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA® provided similar results to 8 × 10 000 iu/m2 intravenous injections of E. colil-ASNase. The safety profile of GRASPA® showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA®.
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MicroRNAs (miRNAs) are key to the pathogenesis of human malignancies and increasingly recognized as potential biomarkers and therapeutic targets. Haematological malignancies, being the earliest human malignancies linked to aberran...
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MicroRNAs (miRNAs) are key to the pathogenesis of human malignancies and increasingly recognized as potential biomarkers and therapeutic targets. Haematological malignancies, being the earliest human malignancies linked to aberrant miRNA expression, have consistently underpinned our understanding of the role that miRNAs play in cancer development. Here, we review the expanding roles attributed to miRNAs in the pathogenesis of different types of myeloid malignancies and highlight key findings.
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Summary The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. C...
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Summary The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB‐RC) was calculated for treatment‐naive AML patients ( n ?=?164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB‐RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB‐RC approximately doubled the likelihood of D14BM clearance (OR?=?1·81; 95% CI: 1·24–2·64, P ?<?0·005). PBB‐RC was also associated with improved CR rates (OR per 5%?=?1·97; 95% CI: 1·27–3·01, P? <?0·005) and overall survival (OS) [hazard ratio (HR) per 5%?=?0·67; 95% CI: 0·52–0·87]. African American patients had poorer OS adjusted for PBB‐RC (HR?=?2·18; 95% CI: 1·13–4·23), while race was not associated with D14BM or CR rate. PBB‐RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML.
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Aa total of 105 patients (age ≥18 years) with newly diagnosed low or intermediate risk acute promyelocytic leukaemia (APL) were treated with a standard induction and consolidation regimen including arsenic trioxide (ATO). Sixty-e...
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Aa total of 105 patients (age ≥18 years) with newly diagnosed low or intermediate risk acute promyelocytic leukaemia (APL) were treated with a standard induction and consolidation regimen including arsenic trioxide (ATO). Sixty-eight patients who were polymerase chain reaction (PCR) negative for PML-RARA post-consolidation were randomized to either 1 year of maintenance with tretinoin, mercaptopurine and methotrexate, or observation. Enrollment in this non-inferiority trial was stopped prematurely due to slow accrual. With a median follow up of 36·1 months, the overall survival of the 105 patients was 93%, and there have been no relapses in the patients randomized to maintenance or observation. These results demonstrate that cures can be expected in >90% of patients with low and intermediate risk APL and suggest that maintenance therapy may not be needed if patients are treated with an intensive post-remission regimen including ATO. This trial was registered at clinicaltrials.gov as #NCT00492856.
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