Portal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6‐thioguanine during maintenance therapy

Broxson, Emmett; Dole, Mukund; Wong, Raymond; Laya, Bernard F.; Stork, Linda C.

doi:10.1002/pbc.20202

Cited by 48 publications

(36 citation statements)

References 24 publications

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“…5 As a consequence, 6-MP has remained the preferred drug for maintenance therapy. Veno-occlusive disease, as reported in other studies, 21,22 did not occur in COALL patients. This was also true for trial ALL-REZ 90 for relapsed patients, in which 6-TG was used together with weekly intravenous MTX in maintenance therapy (G Henze, personal communication).…”

Section: Discussionsupporting

confidence: 76%

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

et al. 2009

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In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significantly from the first two trials conducted in the 1980s (COALL 82 and COALL 85) to the three trials conducted in the 1990s (COALL 89, 92 and 97) (P ¼ 0.001). Through all COALL studies, age X10 years and initial white blood cell count (WBC) X50 Â 10 9 /l and pro-B immunophenotype were of significant prognostic relevance. A refinement of risk assessment has been achieved by in vitro drug sensitivity testing in COALL 92 and 97. In patients with very sensitive leukaemic cells, therapy could be reduced without loss of efficacy. In COALL 97, a further improvement in risk stratification was gained by the molecular assessment of minimal residual disease (MRD) under treatment, which proved to have a superior prognostic effect when compared with in vitro drug sensitivity testing. Importantly, the gradual reduction in central nervous system (CNS) irradiation led to a decreased incidence of brain tumours as a second malignancy. In general, the prevention of treatmentrelated late effects will be one of the major issues in future studies. It remains to be shown whether prolonged infusions of anthracyclines, which have been implemented into the COALL studies after equal efficacy compared with short-time infusions was confirmed, will be associated with fewer cardiac late effects. Another way to prevent late effects may be a more refined risk assessment allowing for a reduction in cumulative treatment burden. A great challenge in the future will be to improve the overall treatment results, which very likely can only be achieved by the identification of molecularly defined subgroups to which novel, rational therapeutic strategies can be applied.

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Section: Discussionsupporting

confidence: 76%

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

et al. 2009

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“…Recognition of portal hypertension as a possible life-threatening complication of TG created an unambiguous imbalance between its risks and potential benefits. 47 Although use of TG for a short time frame early in the treatment of boys with ALL may seem an attractive therapeutic strategy, the side effects of TG limit this approach. Furthermore, the therapeutic benefit of TG may be redundant in the face of dexamethasone treatment in SR-ALL.…”

Section: Discussionmentioning

confidence: 99%

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial

Stork

Matloub

Broxson

et al. 2010

Blood

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“…In the standard-risk patients, the treatment protocols were modified from the Children's Cancer Group (CCG)-1891 34 or CCG-1952 protocols. 35 The regimen used was switched to a modified one from the CCG-1882 protocol 36 from consolidation chemotherapy, if the percentage of bone marrow leukemic blasts on day 7 was greater than 25% during induction chemotherapy. If the percentage of leukemic blasts on day 14 was still greater than 25%, the protocol used for the high-risk patients was restarted.…”

Section: Patients and Treatment Protocolmentioning

confidence: 99%

Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia

Choi

Hwang²,

Sung

et al. 2006

Blood

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Livin, a member of the inhibitor of apoptosis proteins, has been considered to be a poor prognostic marker in malignancies. However, little is known about the clinical relevance of Livin expression in childhood acute lymphoblastic leukemia (ALL). In this study, the expression of Livin was analyzed in 222 patients with childhood ALL using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a possible association with the clinical features at diagnosis and treatment outcomes. Both Livin expression rates and expression levels were higher in patients with favorable prognostic factors. The expression rate was also higher in patients with a favorable day 7 bone marrow response to induction chemotherapy (P < .001). The Livin expression was related to the absence of relapse (P < .001). Similarly, the relapse-free survival rate (؎ 95% CI) was higher in patients with Livin expression than in patients without Livin expression (97.9% ؎ 4.0% versus 64.9% ؎ 11.8%, P < .001). Multivariate analysis for relapse-free survival demonstrated that Livin expression was an independent favorable prognostic factor in childhood ALL (P ‫؍‬ .049). This study suggests that Livin expression is a novel prognostic marker in childhood ALL and thus needs to be incorporated into the patient stratification and treatment protocols. (Blood. 2007;109: [471][472][473][474][475][476][477]

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Portal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6‐thioguanine during maintenance therapy

Abstract: The evaluations of these 12 patients suggest that treatment with TG causes injury to the liver leading to PH and that thrombocytopenia and splenomegaly are clinical hallmarks of this toxicity.

Cited by 48 publications

References 24 publications

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial

Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia

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