ABSTRACT
We compared DXA whole body and lumbar spine bone mineral density (BMD) using manufacturers software with a body size correction which derived bone mineral content (BMC) for bone area in survivors of acute lymphoblastic leukemia in Saudi Arabia (n = 51, mean age 13.5 y). With no corrections, 29 patients (57%) had lumbar spine BMD Z score < -1.0 and 21 (41%) had whole body BMD Z score < -2. After correction, only 6 (12%) had lumbar spine BMC Z score < -1.0 and 4 (8%) had whole body BMC Z score < -2. Agreement between the methods was "poor" by weighted κ analysis.
Subject(s)
Absorptiometry, Photon , Body Size , Bone Density , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnostic imaging , Survivors , Adolescent , Female , Humans , Male , Prognosis , Saudi ArabiaABSTRACT
BACKGROUND AND OBJECTIVE: Because of the need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and King Fahad National Center for Children's Cancer and Research (KFNCCC&R) over a period of 18 years with a focus on patient characteristics and outcome. METHODS: During the period of 1981 to 1998, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90), and subsequently, Children's Cancer Group (CCG) protocols, and these were grouped as Era 1 (1981-1992) and Era 2 (1993-1998). RESULTS: Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotrexate (MTX) 1 g/m(2) and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 and cyclophosphamide. International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs during the post-remission period. The end-of-induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=.049). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P<.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important independent prognostic factors were intensity of therapy, poor risk category assignment and CNS disease at diagnosis. CONCLUSION: Outcome in children with ALL has improved because of intensification of treatment protocols and better supportive care.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Child , Child, Preschool , Clinical Trials as Topic , Combined Modality Therapy , Female , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Retrospective Studies , Risk Factors , Saudi Arabia , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: The purpose is to develop a real-time multiplex reverse transcription-PCR assay for detection and quantification of leukemia-specific chimeric transcripts that identify the genetic subgroups of acute lymphoblastic leukemias (ALLs) proposed by the WHO classification. EXPERIMENTAL DESIGN: Real-time multiplex assay for t(12;21), t(4;11), and t(1;19) with hypoxanthine phosphoribosyltransferase as internal standard used in tandem with a new real time quantitative-RT-PCR assay for the t(9;22). This new strategy was designed to yield an amplicon from each translocation with a distinct melting peak allowing dependable identification using only Sybr green I, without any need for expensive hybridization probes. RESULTS: We validated this method with 92 primary ALLs and identified 4 E2A-PBX1, 4 mBCR-ABL and 10 TEL-AML1. When compared with conventional RT-PCRs and Southern blot analyses, 100% concordance was obtained. During the course of these studies, we found marked variations in the levels of the TEL-AML1 transcripts in individual patients. We, therefore, extended the study to accurately and reproducibly determine TEL-AML1 mRNA levels in 47 additional patients with t(12;21). The results indicated that the level of expression of TEL-AML1 varied among individual patients, and it was independent of the WBC count. CONCLUSIONS: Our new real-time multiplex assay can be used for rapid, simple, and reliable classification of pediatric ALL. Its reproducible quantification results should also facilitate studies on minimal residual disease. The observed variation in TEL-AML1 transcript levels is of interest because it could reflect biological and/or clinical heterogeneity in the behavior of these leukemias.
