Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches.

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.

Mobility in Hurler syndrome.

Hurler syndrome is an autosomal recessive metabolic storage disease. Hematopoietic stem cell transplant increases life expectancy, but the effects on associated musculoskeletal abnormalities remains unclear, and long-term data are limited. We detail the follow-up of 23 patients at a mean of 8.5 years after successful hematopoietic stem cell transplant. All patients underwent clinical examination at an annual multidisciplinary clinic. Serial radiological studies were reviewed to assess development and management of hip dysplasia and genu valgum. All patients demonstrated characteristic acetabular dysplasia and failure of ossification of the superolateral femoral head. Eight patients underwent bilateral pelvic and femoral derotation (mean age at surgery, 4.4 years); 4 patients had pelvic osteotomy only. Mean preoperative acetabular angle was 34 degrees. Genu valgum of variable severity due to failure of ossification of the lateral aspect of the proximal tibial metaphysis was observed early, and 6 patients underwent medial epiphyseal stapling, decreasing tibiofemoral angle by a mean of 8 degrees. Clinically, all patients were independently mobile, with restriction of internal hip rotation being the most significant clinical finding. Valgus knees and pronated feet were a typical finding. This cohort represents one of the largest available for study, and ongoing review will clarify the progression of musculoskeletal problems and determine the effectiveness of orthopaedic intervention.