exudates and Leukemia--Myeloid

Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum. Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events.. We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre.. Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. All identified mutations were located in exon 2 and the majority were sequence-terminating insertions or deletions (66.7%), including several hitherto unreported mutations (12 out of 15).. The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort.

Topics: Cohort Studies; Down Syndrome; Exons; Female; GATA1 Transcription Factor; Gene Deletion; Genomics; Humans; Infant, Newborn; Leukemia, Myeloid; Leukemoid Reaction; Malaysia; Male; Mutation; Referral and Consultation; Remission Induction

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Female; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leukemia, Myeloid; Malaysia; Urinary Tract Infections; Young Adult

Treatment for childhood acute myeloid leukaemia (AML) consists of remission induction chemotherapy followed by postremission chemotherapy with or without bone marrow transplantation. The AML Berlin-Frankfurt-Munster (BFM)-83 protocol with induction-consolidation-maintenance chemotherapy for 2 years has been reported to result in a 6-year event-free survival (EFS) and event-free interval (EFI) of 49% and 61% respectively. A total of 174 Malaysian children were treated with this protocol between 1985 and 1999. The 5-year EFS and EFI was 30.7% and 48.0% respectively. The overall mortality from sepsis was 24%, which needs urgent address. The 5-year EFS for patients treated before 1993 and after 1993 was 18.6% and 41.3%, respectively (P = 0.04), while the EFI was 32% and 60.6% respectively (P = 0.034). The improvement seen after 1993 was related to a reduction in induction deaths for that period and probably reflected increased capability and familiarity to cope with the demands of the AML-BFM-83 protocol and accompanying complications in the treatment of AML.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Daunorubicin; Developing Countries; Disease-Free Survival; Etoposide; Female; Humans; Infant; Infant, Newborn; Leukemia, Myeloid; Malaysia; Male; Treatment Outcome

Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytogenetic abnormalities in AML patients from Southeast Asia are not available. The karyotypic patterns in AML patients from a single center in Singapore were studied and compared with reports from other regions of the world to identify possible geographic heterogeneity.. Analysis was performed on 501 consecutive de novo AML patients diagnosed according to the FAB criteria in the Singapore General Hospital. The cytogenetic findings were analyzed for possible associations between karyotypic pattern and the age, gender, ethnicity as well as morphological (FAB) subtypes.. A total of 454 patients were studied of which 275(61%) had abnormal cytogenetics(median age 48 years). The t(15;17) and trisomy 8 were the most frequent karyotypic abnormalities - seen in 52(11%) and 33(7.3%) cases, respectively. Inv(lf) and t(16;16) were uncommon, seen only in five (1.1%) cases. The abnormalities del 5/5q and del 7/7q were seen in 30(6.6%) and 32(7%) of the cases. Complex karyotypes were seen in 78(17%) of the cases.Recurrent cytogenetic abnormalities correlated with the FAB subtypes. In all, 21 novel cytogenetic abnormalities were observed.. Certain differences such as the age at presentation and frequency of recurrent balanced translocations were noted in comparison to previous reports. These point to the need for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Aneuploidy; China; Chromosome Aberrations; Chromosomes, Human; Ethnicity; Female; Humans; India; Indonesia; Karyotyping; Leukemia, Myeloid; Malaysia; Male; Middle Aged; Singapore

Topics: Busulfan; Child; Child, Preschool; Female; Humans; Leukemia, Myeloid; Malaysia; Male; Prognosis