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Very little is known about secondary acute lymphoblastic leukaemia (s-ALL). This retrospective analysis studied a cohort of s-ALL patients treated at a single centre between 1994 and 2013, while comparing therapy-associated ALL (t...
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Very little is known about secondary acute lymphoblastic leukaemia (s-ALL). This retrospective analysis studied a cohort of s-ALL patients treated at a single centre between 1994 and 2013, while comparing therapy-associated ALL (t-ALL) and antecedent malignancy ALL (am-ALL) patients. Thirty-two patients with s-ALL were identified. The overall incidence was 94% among ALL adults while T-cell s-ALL was rare (12% of s-ALLs). The median time interval between two malignant diagnoses was 53years (range: 01-28). In contrast to previous reports, most of the s-ALLs were CD10+ and without KMT2A (MLL) abnormalities. The overall survival (OS) rates of the entire cohort at 12 and 24months from ALL diagnosis was 49% and 25%, respectively. Most patients (n=23, 72%) received prior chemo-/radio-therapy for their first malignancy (t-ALL) and only 9 (28%) did not (am-ALL). No significant difference was found in the incidence of B-/T- lineage ALL, extramedullary disease, blood count, and the rate of Philadelphia-positive ALL, nor in the rates of complete remission (P=055) and OS (P=097). This similarity, together with high incidence of family malignancy in both groups, raise the possibility that s-ALL patients may have an inherent predisposition to malignancies and a history of previous therapy may be of lesser importance in the pathogenesis of s-ALL.
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Summary Acute lymphoblastic leukaemia (ALL) remains a leading cause of non‐traumatic death in children, and the majority of adults diagnosed will succumb to the disease. Recent advances in molecular biology and bioinformatics hav...
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Summary Acute lymphoblastic leukaemia (ALL) remains a leading cause of non‐traumatic death in children, and the majority of adults diagnosed will succumb to the disease. Recent advances in molecular biology and bioinformatics have enabled more detailed genomic analysis and a better understanding of the molecular biology of ALL. A number of recurrent genomic drivers have recently been described, which not only aid in diagnosis and prognostication, but also may offer opportunities for specific therapeutic targeting. The present review summarises B‐ALL genomic pathology at diagnosis, including lesions detectable using traditional cytogenetic methods as well as those detected only through advanced molecular techniques.
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Summary Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. He...
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Summary Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T‐lymphoblastic leukaemia ( AMTL ), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T‐lymphoid lineages, such as myeloperoxidase and CD 3. This proposed diagnostic group is supported by (i) retained myeloid differentiation potential during early T cell lymphoid development, (ii) recognition that some cases of acute myeloid leukaemia ( AML ) harbour hallmarks of T cell development, such as T‐cell receptor gene rearrangements and (iii) common gene mutations in subsets of AML and T cell acute lymphoblastic leukaemia (T‐ ALL ), including WT 1, PHF 6, RUNX 1 and BCL 11B . This proposed diagnostic entity overlaps with early T cell precursor ( ETP ) T‐ ALL and T cell/myeloid mixed phenotype acute leukaemias ( MPAL s), and also includes a subset of leukaemias currently classified as AML with features of T‐lymphoblastic development. The proposed classification of AMTL as a distinct entity would enable more precise prospective diagnosis and permit the development of improved therapies for patients whose treatment is inadequate with current approaches.
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In the 1980s and 1990s, successive large, national leukaemia trials helped to determine basic treatment strategies that are effective in most children with leukaemia. In acute lymphoblastic leukaemia, the UKALL studies addressed C...
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In the 1980s and 1990s, successive large, national leukaemia trials helped to determine basic treatment strategies that are effective in most children with leukaemia. In acute lymphoblastic leukaemia, the UKALL studies addressed CNS prophylaxis, duration of therapy, and intensive treatment blocks in improving event-free survival. Sufficient patients were recruited to permit direct comparison of individual drugs and deliver the answers within a timescale relevant to clinical practice. In acute myeloid leukaemia, collaboration with UK adult trials led to results in children that were not bettered anywhere in the world. The results of these trials were improved by advances in supportive care that were highly effective in reducing treatment-related mortality. The emphasis for paediatric leukaemia studies has changed over the last decade; more attention is being paid to patient subgroups that are performing badly, such as infants, Philadelphia chromosome-positive leukaemias, and relapsed and refractory acute myeloid leukaemia. Studies of these rare patients have been made possible by increased international collaboration that has allowed patients from many different countries to enter the same clinical trials. Interest in these difficult therapeutic areas has also been stimulated by the development of new agents and treatment strategies that have come directly from improved understanding of leukaemia biology.
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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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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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Leukaemia is the single most common childhood malignancy. With modern treatment regimens, survival in acute lymphoblastic leukaemia (ALL) approaches 90%. Only about 70% of children with acute myeloid leukaemia (AML) achieve long t...
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Leukaemia is the single most common childhood malignancy. With modern treatment regimens, survival in acute lymphoblastic leukaemia (ALL) approaches 90%. Only about 70% of children with acute myeloid leukaemia (AML) achieve long term survival. Patients who relapse have a dismal prognosis. Novel therapeutic approaches are needed to improve treatment outcomes in newly-diagnosed patients with a poor prognosis and for patients with relapsed/refractory disease that have limited treatment options. One promising approach in treating haematological malignancies has been the use of monoclonal antibodies to target cell surface antigens expressed on malignant cells. Most success with monoclonal antibody therapy in the treatment of haematological malignancies has come in the setting of adult B-cell non-Hodgkin lymphoma with the addition of the anti-CD20 monoclonal antibody rituximab to standard treatment regimens. In order to further advance treatment of haematological malignancies, novel monoclonal antibodies continue to be developed that target a variety of cell surface antigens. Several antibodies continue to be investigated in childhood leukaemias. This review will discuss the development of monoclonal antibodies that target a variety of cell surface antigens for the treatment of childhood ALL and the use of the anti-CD33 antibody gemtuzumab ozogamicin in the treatment of childhood AML.
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We read with interest the tumour lysis syndrome (TLS) guidelines published by Cairo et al (2010), which updated earlier publications (Cairo & Bishop, 2004; Coiffier et al, 2008). We were particularly struck by the guidelines regarding TLS manag...
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We read with interest the tumour lysis syndrome (TLS) guidelines published by Cairo et al (2010), which updated earlier publications (Cairo & Bishop, 2004; Coiffier et al, 2008). We were particularly struck by the guidelines regarding TLS management for patients with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) and a diagnostic white blood cell count (WBC) < 100 x 109/l. The new guidelines are risk stratified by lactate dehydrogenase (LDH) and recommend prophylactic rasburicase in all ALL patients with LDH level >2x upper limit of normal (ULN). In addition, AML patients with laboratory TLS are to receive rasburicase, regardless of the presenting WBC and clinical findings. The guidelines for the prophylactic use of rasburicase also potentially include patients with hyperkalaemia and/or hyper-phosphataemia without concomitant hypemricaemia (Fig 4 and text, Cairo et al, 2010). And lastly, the recommendation for prophylactic rasburicase in the defined high-risk subgroup is stated to be a grade A recommendation, yet no systematic review is identified (Cairo et al, 2010).
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Aims-To assess the value of immunophe- notyping of acute lymphoblastic leukae- mia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess lymphoid lineage and en...
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Aims-To assess the value of immunophe- notyping of acute lymphoblastic leukae- mia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess lymphoid lineage and enable dif- ferentiation from acute myeloid leukae- mia. Methods-45 routinely processed bone Marrow biopsy specimens (formalin Fixed, paraffin embedded and mildly de- Calcified in EDTA) reported to contain Leukaemic infiltrates on the basis of cyto- Morphological and enzyme-cytochemical Analysis of bone marrow smears 922 c-ALL, 11 T-ALL, 2 B-ALL, 10 u-ALL (unclassified) were immunostained by the ABC method with a broad panel of 26 antibodies against various haemopoietic antigens.
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All newly diagnosed patients aged 60-79 years with acute lymphoblastic leukaemia (ALL) receiving induction chemotherapy with a modified paediatric-based regimen over a 7-year period were retrospectively analysed (n = 51, median ag...
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All newly diagnosed patients aged 60-79 years with acute lymphoblastic leukaemia (ALL) receiving induction chemotherapy with a modified paediatric-based regimen over a 7-year period were retrospectively analysed (n = 51, median age 65 years). The treatment regimen consisted of induction, central nervous system prophylaxis, seven cycles of intensification and 24 cycles of maintenance. BCR-ABL1 negative patients received weekly asparaginase during intensification, while BCR-ABL1+ patients received daily imatinib. Post-remission therapy was given in an outpatient setting. The complete response rate was 75%, with an induction mortality of 20%; 6% of patients had resistant disease. 37% of patients who achieved a complete remission relapsed. The estimated 5-year overall survival was 40% for BCR-ABL1 negative and 47% for BCR-ABL1+ patients (P = not significant); the 5-year disease-free survival was 57% and 39%, respectively (P = NS). The post-induction phase was generally well tolerated, with 81% able to complete the intensification phase and proceed to maintenance. In conclusion, administration of this modified paediatric-based protocol is feasible and active for elderly patients with ALL. Survival is superior to most previously reported series in this age group, but remains worse compared to younger patients. Further improvement of the toxicity profile, particularly during induction, is required to improve outcomes.
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