Annette Poon

Hyperkalaemia during massive blood transfusion in paediatric craniofacial surgery

Children undergoing major craniofacial surgery (MCFS) often require transfusion in excess of one blood volume. Therefore they were the subject of a retrospective review which looked at the longitudinal trend of plasma potassium concentration [K+] during surgery. Ten of eleven children had a statistically significant increase in plasma potassium concentration during their intraoperative course and in five the potassium concentration exceeded 5.5 mmol · L−1. This was in contrast to the stable intraoperative plasma [K+] observed in a control group which did not receive blood transfusion. All MCFS children received a blood transfusion with red blood cell concentrates (RBCconc). The age of the units of RBCconc which had been transfused was 16.1 ± 8.4 days. The amount of extracellular potassium in 28 units of RBCconc was determined in order to estimate the amount of free potassium (Kdose) which the MCFS group received. The plasma [K+] in units of RBCconc < 1 week of age was < 20 mmol · L−1, whereas in units aged > 2 weeks it was > 40 mmol · L−1. The estimated Kdose was 0.2–1.6 mmol · kg−1. We concluded that the amount of extracellular potassium in units of RBCconc was clinically important and may give rise to hyperkalaemia during massive blood transfusion.RésuméIl faut souvent transfuser massivement les enfants subissant une reconstruction crâniofaciale majeure. Nous avons revu le profil kaliémique intra-opératoire de onze d’entre eux. Chez dix, la kaliémie augmentail de façon statistiquement significative pendant l’intervention et chez cinq, elle dépassait 5,5 mmol · L−1 alors que la kaliémie intra-opératoire demeurait stable chez les enfants non transfusés d’un groupe contrôle. Lors des reconstructions, tous les enfants avaient été transfusés avec des culots globulaires récoltés en moyenne 16,1 ± 8,4 jours auparavant. Nous avons mesuré la concentration plasmatique de potassium de 28 culots globulaires et avons trouvé qu’elle était inférieure à 20 mmol · L−1 dans les culots récoltés moins d’une semaine plus tôt et de plus de 40 mmol · L−1 dans ceux de deux semaines et plus. Nous avons ainsi pu estimer que les enfants avaient reçu entre 0,2 et 1,6 mmol · kg−1 de potassium. Les culots globulaires contiennent donc une quantité appréciable de potassium, susceptible d’amener de l’hyperkaliémie lors de transfusions massives.

A practical, comprehensive classification for pediatric myelodysplastic syndromes: the CCC system.

Purpose Pediatric myelodysplastic syndromes (MDS) are biologically diverse. The French-American-British (FAB) classification of adult forms of MDS is not always applicable because many pediatric patients do not fit into any of the categories. To circumvent the FAB schema and other flawed formats, the authors developed a practical classification system for childhood MDS. Patients and Methods The authors analyzed 40 children with MDS diagnosed in Toronto between 1988 and 1998 to test the utility of the classification. Children were classified according to three main features: category, cytology, and cytogenetics. Results Using this system the authors were able to classify all 40 patients; about half could not be unclassified by FAB. Patients could also be longitudinally classified by serial analysis to show progression of disease. Juvenile myelomonocytic leukemia was excluded because of its known myeloproliferative pathogenesis. Chronic myelomonocytic leukemia, which almost never occurs in children, was also omitted. Also excluded were other chronic myeloproliferative disorders and any cytopenias without malignant potential. Conclusions Based on these data, the CCC system appears to have prognostic potential; children with advanced class and cytogenetic abnormalities had a poorer outcome. The authors urge international adoption of this system for uniformity in clinical practice and reporting purposes.

Reticulated platelet counts in the diagnosis of acute immune thrombocytopenic purpura.

Purpose: Bone marrow aspiration is often performed to diagnose childhood acute immune thrombocytopenic purpura (ITP) because no non-invasive investigation to confirm the diagnosis is routinely available. Reticulated platelets (RPs)—young platelets characterized by a high RNA content—increase with increased platelet production and may be useful in the diagnosis of ITP. Methods: To assess the role of RP counts in distinguishing ITP, we compared counts from 15 consecutive patients with ITP with counts from 20 patients with acute lymphoblastic leukemia (ALL), 10 with aplasia, and 27 healthy normal children. Whole blood in edetic acid (EDTA) was labelled with a platelet-specific monoclonal antibody and incubated with thiazole orange (TO). A standard gate was set to achieve a fluorescence value of 1.3 ± 0.5% for control lyophilized platelets. Results: Patients with ITP had a mean (± 1 standard deviation) RP level of 32.9 ± 10.2%; patients with ALL, 6.6 ± 3.1%; patients with aplasia, 3.4 ± 2.0%; and normal patients, 7.9 ± 2.9%. The difference in RPs between the ITP group and the ALL, aplasia, and normal groups was highly significant (p <0.0001 each), with no significant difference between the non-ITP groups (p = 0.12). Conclusions: Measuring RPs by this simple whole-blood cytometric technique discriminated very well between the acute ITP and non-ITP groups. This test has a strong positive predictive value and may prove very useful in the assessment of childhood acute ITP and the screening of candidates for bone marrow aspiration.

Regional cancer cytogenetics: A report on 1,143 diagnostic cases

The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.

Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: potential role of cytokines in clinical manifestations.

A permanent cell line, HSC-M1, was established from a child with advanced CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features included irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, neutrophilia, and bone marrow erythrophagocytosis. While HSC-M1 cells exhibited an immunophenotype characteristic of ALCL of T-cell lineage, the cell line also demonstrated features of monocyte-macrophage lineage. Cytogenetic and polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and involved bone marrow demonstrated the characteristic non-random chromosomal translocation t(2;5)(p23;q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immunosorbent assays showed increased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M 1 cells of some of these cytokines was demonstrated, the production of others was only detectable after stimulation with exogenous CD30 ligand. With few exceptions, there was good correlation between serum cytokine levels and cytokines produced by HSC-M1 cells. These findings indicate that cytokine production is a feature of ALCL cells and that some of the clinical manifestations in ALCL may result from cytokines produced by either the malignant or accessory cells.

Refractoriness to platelet transfusions in children with acute leukemia

Purpose We evaluated the incidence of clinically significant refractoriness to platelet transfusions in children with acute leukemia. Patients and Methods We reviewed the complete transfusion records up to July 1993 of all 213 patients diagnosed with acute leukemia at our institution over the 4-year period 1987 to 1990. The transfusion protocol called for all patients requiring transfusion of red cell and/or platelet concentrates to initially receive components that were not leukocyte reduced. Patients suspected clinically to be refractory to platelets were tested for anti-human leukocyte antigen (HLA) antibodies and those that tested positive were switched to HLA-matched platelets. Results Of 184 patients diagnosed with acute lymphoblastic leukemia (ALL), 133 (72%) required platelet support, whereas all 29 patients with acute myeloid leukemia (AML) were transfused with platelets. The incidence of clinically suspected refractoriness to non-leukocyte- reduced platelets, which was confirmed by a positive test for anti-HLA antibodies and which resulted in a switch to HLA-matched platelets, was nine of 29 (31%) for patients with AML but only three of 133 (2.3%) for patients with ALL. Conclusions The results of this study indicate that clinically significant platelet refractoriness requiring transfusion of HLA-matched platelets occurs infrequently in childhood ALL. For this group of patients, use of leukocyte-depleted cellular components for the purpose of preventing platelet refractoriness cannot be justified. This approach may be appropriate for children with AML.

Secondary acute non-lymphocytic leukemia with monosomy 7 arising 9 years after acute lymphoblastic leukemia in childhood

We report a case of pediatric acute non-lymphocytic leukemia (ANLL) with monosomy 7 occurring in a child successfully treated for acute lymphoblastic leukemia (ALL) nine years earlier. Acquired monosomy 7 is currently recognized as a distinct therapy-related cytogenetic abnormality which nonrandomly occurs as a late complication of cytotoxic therapy used in the treatment of both malignant and nonmalignant disease. Most commonly, this occurs as a disorder of bone marrow morphology and function characterized as a myelodysplastic syndrome (MDS) or ANLL. This case report emphasizes the need for continued evaluation of long-term survivors of childhood cancer to identify and minimize therapy-related side effects without compromising successful management.

Revised Practical, All Inclusive 1999 Classification Of Pediatric Myelodysplasias (Ccc System)

Revised Practical, All Inclusive 1999 Classification Of Pediatric Myelodysplasias (Ccc System)