Optimal treatment intensity in children with Down syndrome and myeloid leukaemia: data from 56 children treated on NOPHO-AML protocols and a review of the literature

Abstract Children with Down syndrome (DS) and myeloid leukaemia have a significantly higher survival rate than other children, but they also experience considerable treatment-related toxicity. We analysed data on 56 children with DS who were treated on the Nordic Society for Paediatric Haematology and Oncology-acute myeloid leukaemia (NOPHO-AML)88 and NOPHO-AML93 protocols and reviewed the literature. In the dose-intensive NOPHO-AML88 protocol, 8 out of 15 patients (53%) experienced an event. In the less dose-intensive NOPHO-AML93 protocol, 7 out of 41 patients (17%) had an event. Therapy was reduced in 29 patients (52%) with in average 75% and 67% of the scheduled dose of anthracycline and cytarabine, respectively. Treatment-related death occurred in seven who all received full treatment. Relapse and resistant disease occurred at a similar rate in those receiving full and reduced treatment. Review of major series of myeloid leukaemia of DS showed no clear relationship between dose and survival; however, it appears that both a reduction in treatment dose and a less intensively timed treatment regimen improved the outcome. Further studies are needed to define the optimal regimen for treating myeloid leukaemia of DS

Unidentified actor as Hassan, an unidentified actor as the Caliph and the soldiers in the J.C. Williamson London production of Hassan and how he came to make the golden journey to Samarkand, act 5 scene 1 The garden, 1923 [picture] /

From: Hassan : and how he came to make the golden journey to Samarkand / James Elroy Flecker ; arranged for the stage by Basil Dean ; music by Frederick Delius.; Condition: Damage on edges.; Inscriptions: "Caliph ordering Hassan to see the torture"--Handwritten, on verso.; Part of the collection: J.C. Williamson collection of photographs.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn3805710; No programs held in PROMPT collection

Improved outcome after relapse in children with acute myeloid leukaemia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldIn the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122 patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival were duration of first complete remission (CR1) and stem cell transplantation (SCT) in CR1. In early relapse (<1 year in CR1), survival was 21 +/- 5% compared with 48 +/- 6% in late relapse. For children receiving re-induction therapy, survival in early relapse was 29 +/- 6% and 51 +/- 6% in late. Patients treated in CR1 with SCT, autologous SCT or chemotherapy had a survival of 18 +/- 9, 5 +/- 5 and 41 +/- 5%, respectively. Survival was 62 +/- 6% in 64 children given SCT as part of their relapse therapy. A significant proportion of children with relapsed AML can be cured, even those with early relapse. Children who receive re-induction therapy, enter remission and proceed to SCT can achieve a cure rate of 60%

Treatment stratification based on initial in vivo response in acute myeloid leukaemia in children without Down's syndrome: results of NOPHO-AML trials.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThree consecutive protocols for childhood acute myeloid leukaemia (AML) have been used in the Nordic countries since 1984: the Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML84 was of moderate intensity, NOPHO-AML88 of high intensity with upfront loading and aggressive consolidation. NOPHO-AML93 utilized the same treatment blocks as NOPHO-AML88, but after the first block those children with a hypoplastic non-leukaemic bone marrow were allowed to recover from aplasia. Poor responders received intensified induction therapy. Between January 1993 and December 2000, 219 children without Down's syndrome were entered on NOPHO-AML93. Compared with NOPHO-AML88, the event-free survival (EFS) at 7 years increased from 41% to 49% (P = 0.06) and 7-year overall survival increased from 47% to 64% (P < 0.01). Toxic death during induction was reduced from 10% to 3%. Survival was similar in patients receiving stem cell transplantation or chemotherapy only in first remission. The major prognostic factors in NOPHO-AML93 were response to therapy and cytogenetics. A total of 67% of patients achieved remission after the first induction course and showed an EFS of 56% compared with 35% in those not in remission (P < 0.01). Cytogenetic results were obtained in 95% of patients. Patients with t(9;11) (p22;q23) (n = 16) experienced a significantly better EFS (86%) than other cytogenetic groups. The overall outcome was improved by employing the previous toxic protocol with different timings, and through individualizing therapy according to the initial response of the patient

Acute leukaemia in children with Down syndrome: a population-based Nordic study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldTo determine the epidemiology and outcome of children with Down syndrome (DS) diagnosed with acute leukaemia in the Nordic countries, data registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) population-based leukaemia registry were analysed. Of 3494 children with acute leukaemia diagnosed between July 1984 and December 2001, 136 patients (3.9%) with DS were identified. 2.1% of the children with acute lymphoid leukaemia (ALL) and 14.0% of the children with acute myeloid leukaemia (AML) had DS. In ALL, DS patients had similar age and sex distribution and no major differences in blood counts compared with non-DS children. None of the DS patients had T cell leukaemia. Outcome was inferior to that of non-DS children and treatment results did not improve over time. In AML, DS patients showed a significant female predominance and all but one were <5 years old. DS patients with AML had significantly lower platelet and white blood cell counts and two-thirds were type M7 as according to the French-American-British classification. None of the patients <5 years of age had typical AML cytogenetic aberrations. Outcome was far better in the DS group. DS patients treated for AML after 1992 had an excellent outcome (probability of event-free survival, 83 +/- 6%). The high proportion of female DS patients with AML is unexplained. The differing treatment results in AML versus ALL need further evaluation and represent a challenge for the coming years