The peripheral portacath provides safe and convenient venous access in pediatric and adolescent patients.

INTRODUCTION: Adolescent patients with chronic conditions rely on permanent venous access for safe treatment and supportive care. Traditionally this is provided by a central venous access device (CVAD) e.g. Hickmann catheter or totally implanted subcutaneous port or also called Port-a-Cath (PaC). We reviewed the patient experience, safety and feasibility of insertion of peripheral inserted implanted subcutaneous port (peripheral PaC). METHODS: Medical records of patients who underwent insertion of peripheral PaC under ultrasound guidance at our institution since between 2012-2017 were reviewed to ascertain specific details including duration of insertion and complication rate. Short structured questionnaires were used to assess nursing and patient satisfaction. RESULTS: Twenty eight peripheral PaC were inserted at our institution. There were 17 female and 11 male patients aged between 12.3 and 18.7 years (median = 16.1). Six were inserted under local anesthetic (LA) in patients who were not fit for general owing to mediastinal mass or lung disease. At the time of analysis 2 PaCs remained in situ with a median duration of 8 months (range 3-48). Removal of 26 PaCs was under LA in 15 cases and under GA in 11. Complications were observed in 9 cases but only necessitated early removal or replacement in 3 cases (displacement and disconnection) and repositioning in 1 case. Thrombosis was seen in 2 patients who required systemic anticoagulation but had complete resolution. CONCLUSION: This study shows that the use of peripheral PaC is safe. The feedback from patients and nursing staff supports the use of the peripheral PaC. We are exploring additional patient groups that might benefit from this device.

Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization.

Chromosomal abnormalities are important for the classification and risk stratification of patients with acute lymphoblastic leukemia (ALL). However, approximately 30% of childhood and 50% of adult patients lack abnormalities with clinical relevance. Here, we describe the use of array-based comparative genomic hybridization (aCGH) to identify copy number alterations (CNA) in 58 ALL patients. CNA were identified in 83% of cases, and most frequently involved chromosomes 21 (n=42), 9 (n=21), 6 (n=16), 12 (n=11), 15 (n=11), 8 (n=10) and 17 (n=10). Deletions of 6q (del(6q)) were heterogeneous in size, in agreement with previous data, demonstrating the sensitivity of aCGH to measure CNA. Although 9p deletions showed considerable variability in both the extent and location, all encompassed the CDKN2A locus. Six patients showed del(12p), with a common region encompassing the ETV6 gene. Complex CNA were observed involving chromosomes 6 (n=2), 15 (n=2) and 21 (n=11) with multiple regions of loss and gain along each chromosome. Chromosome 21 CNA shared a common region of gain, with associated subtelomeric deletions. Other recurrent findings included dim(13q), dim(16q) and enh(17q). This is the first report of genome-wide detection of CNA in ALL patients using aCGH, and it has demonstrated a higher level of karyotype complexity than anticipated from conventional cytogenetic analysis.

Protracted dormancy of pre-leukemic stem cells.

Cancer stem cells can escape therapeutic killing by adopting a quiescent or dormant state. The reversibility of this condition provides the potential for later recurrence or relapse, potentially many years later. We describe the genomics of a rare case of childhood BCR-ABL1-positive, B-cell precursor acute lymphoblastic leukemia that relapsed, with an acute myeloblastic leukemia immunophenotype, 22 years after the initial diagnosis, sustained remission and presumed cure. The primary and relapsed leukemias shared the identical BCR-ABL1 fusion genomic sequence and two identical immunoglobulin gene rearrangements, indicating that the relapse was a derivative of the founding clone. All other mutational changes (single-nucleotide variant and copy number alterations) were distinct in diagnostic or relapse samples. These data provide unambiguous evidence that leukemia-propagating cells, most probably pre-leukemic stem cells, can remain covert and silent but potentially reactivatable for more than two decades.

Clonal origins of ETV6-RUNX1⁺ acute lymphoblastic leukemia: studies in monozygotic twins.

Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned that shared clonal rearrangements of IG or TCR genes by concordant ALL in twins would be informative about the fetal cell type in which clonal advantage is elicited by ETV6-RUNX1. Five pairs of twins were analyzed for all varieties of IG and TCR gene rearrangements. All pairs showed identical incomplete or complete variable-diversity-joining junctions coupled with substantial, subclonal and divergent rearrangements. This pattern was endorsed by single-cell genetic scrutiny in one twin pair. Our data suggest that the pre-leukemic initiating function of ETV6-RUNX1 fusion is associated with clonal expansion early in the fetal B-cell lineage.

CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage.

Switches from the lymphoid to myeloid lineage during B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment are considered rare and thus far have been detected in MLL-rearranged leukemia. Here, we describe a novel BCP-ALL subset, switching BCP-ALL or swALL, which demonstrated monocytosis early during treatment. Despite their monocytic phenotype, 'monocytoids' share immunoreceptor gene rearrangements with leukemic B lymphoblasts. All swALLs demonstrated BCP-ALL with CD2 positivity and no MLL alterations, and the proportion of swALLs cases among BCP-ALLs was unexpectedly high (4%). The upregulation of CEBPα and demethylation of the CEBPA gene were significant in blasts at diagnosis, prior to the time when most of the switching occurs. Intermediate stages between CD14(neg)CD19(pos)CD34(pos) B lymphoblasts and CD14(pos)CD19(neg)CD34(neg) 'monocytoids' were detected, and changes in the expression of PAX5, PU1, M-CSFR, GM-CSFR and other genes accompanied the switch. Alterations in the Ikaros and ERG genes were more frequent in swALL patients; however, both were altered in only a minority of swALLs. Moreover, switching could be recapitulated in vitro and in mouse xenografts. Although children with swALL respond slowly to initial therapy, risk-based ALL therapy appears the treatment of choice for swALL. SwALL shows that transdifferentiating into monocytic lineage is specifically associated with CEBPα changes and CD2 expression.