A γ/δ T-cell receptor prolymphocytic leukemia and CD4-/CD8- double-negative immunophenotype in a pediatric patient.

T-cell prolymphocytic leukemia is a very rare neoplasm, peaking in the seventh decade. An extensive search failed to find any report of this malignancy in the pediatric population. The malignant cell is morphologically characterized by a high nucleocytopasmic ratio, condensed chromatin, a single nucleolus, and nongranular basophilic cytoplasm. Cells are usually positive for the α/ß and only rarely to the γ/δ T-cell receptors. Most patients follow an aggressive clinical course, only some respond to anti-CD52. We present a 6-year-old boy with T-cell prolymphocytic leukemia. The malignant cells expressed a postthymic immunophenotype (CD4/CD8) and positivity for the γ/δ T-cell receptors. The child died after 8 months despite aggressive chemotherapy, anti-CD52, and an allogeneic bone marrow transplant.

Unsupervised analysis of classical biomedical markers: robustness and medical relevance of patient clustering using bioinformatics tools.

MOTIVATION: It has been proposed that clustering clinical markers, such as blood test results, can be used to stratify patients. However, the robustness of clusters formed with this approach to data pre-processing and clustering algorithm choices has not been evaluated, nor has clustering reproducibility. Here, we made use of the NHANES survey to compare clusters generated with various combinations of pre-processing and clustering algorithms, and tested their reproducibility in two separate samples. METHOD: Values of 44 biomarkers and 19 health/life style traits were extracted from the National Health and Nutrition Examination Survey (NHANES). The 1999-2002 survey was used for training, while data from the 2003-2006 survey was tested as a validation set. Twelve combinations of pre-processing and clustering algorithms were applied to the training set. The quality of the resulting clusters was evaluated both by considering their properties and by comparative enrichment analysis. Cluster assignments were projected to the validation set (using an artificial neural network) and enrichment in health/life style traits in the resulting clusters was compared to the clusters generated from the original training set. RESULTS: The clusters obtained with different pre-processing and clustering combinations differed both in terms of cluster quality measures and in terms of reproducibility of enrichment with health/life style properties. Z-score normalization, for example, dramatically improved cluster quality and enrichments, as compared to unprocessed data, regardless of the clustering algorithm used. Clustering diabetes patients revealed a group of patients enriched with retinopathies. This could indicate that routine laboratory tests can be used to detect patients suffering from complications of diabetes, although other explanations for this observation should also be considered. CONCLUSIONS: Clustering according to classical clinical biomarkers is a robust process, which may help in patient stratification. However, optimization of the pre-processing and clustering process may be still required.

Normal hemoglobin at the age of 1 year does not protect infants from developing iron deficiency anemia in the second year of life.

BACKGROUND: Iron deficiency anemia (IDA) is the most common hematologic disorder worldwide. Measures to prevent IDA in infants have been successful with questionable sustainability. AIM: To evaluate the incidence of developing IDA in the second year of life, in infants who were nonanemic at the age of 1 year on routine blood test. METHODS: Blood samples were obtained from 193, 24-month-old toddlers, from 2 large clinics of both main sectors in Southern Israel, comparable for lower economic status. IDA was defined as hemoglobin < 11 gr% and microcytosis as mean corpuscular volume < 70 fL. RESULTS: IDA was detected in 8 of 118 Bedouins (5 males) and in 10 of 75 Jewish (6 males) infants (P < 0.01). The probability of a nonanemic child to develop IDA in the second year of life for the whole study population was 9.3% (18 of 193 infants) and significantly higher in the Jewish population (13.3.0% vs. 6.8%, P < 0.01). CONCLUSIONS: Given the difficulty of toddlers to maintain a non-IDA status, and the very low probability of iron overload, our results clearly support the need to continue iron supplementation into the second year.

The effects of guided written disclosure on psychological symptoms among parents of children with cancer.

This study examines whether structured writing about receiving a diagnosis and treatment for pediatric cancer reduces distress among highly distressed parents of children with cancer (PCWC). Eight PCWC completed measures of posttraumatic stress symptoms (PTSS) and depressive symptoms at two baselines, and again after writing, with 1-month gaps between assessments. Using a guided disclosure protocol (GDP), parents were asked to write about receiving the diagnosis first in a chronological manner, then to explicitly label their emotions at the time of diagnosis and explain the impact of the child's illness on their life. Finally, they were asked to reflect on current feelings, future coping ability, and personal growth. Although symptoms of distress did not change between baselines, significant reductions were found in PTSS from the first baseline to postwriting, but not in depression. This preliminary study suggests that the GDP may reduce PTSS in distressed PCWC.

Imatinib resistant chronic myelogenous leukemia, BCR-ABL positive by chromosome and FISH analyses but negative by PCR, in a child progressing to acute basophilic leukemia: cytogenetic follow-up.

The case of an 11-year-old child with adult-type chronic myeloid leukemia, Philadelphia (BCR-ABL) positive, reverse transcription-polymerase chain reaction negative for the major, minor, and micro breakpoints is presented. In the course of 3 years, the child failed to respond to treatment with hydroxyurea, refused all therapy for 6 months, was intolerant to alpha-interferon and progressed, while on imatinib, to acute basophilic leukemia. Subsequently he underwent successful bone marrow transplantation. A secondary cytogenetic clonal evolution, i(17q), developed during hydroxyurea treatment and a tertiary clonal evolution, +8, was detected during imatinib treatment. It is not clear to what extent the several factors (undefined BCR-ABL breakpoint, treatment avoidance, and initial treatment choices, alone or in combination) played a role in the imatinib relapse and resistance and in the disease progression. We conclude that close follow-up with frequent bone marrow sampling is crucial in order to monitor such patients for early relapse and prompt referral for bone marrow transplant.

Conversion of childhood acute lymphocytic leukemia (L2) with a double t(12;21) to juvenile myelomonocytic leukemia with a novel t(4;11)(p12;q23): a cytogenetic, morphologic, and immunophenotypic study.

Here we describe a cytogenetic and flow-cytometric study of a case in which a conversion of childhood acute lymphocytic leukemia (ALL) into juvenile myelomonocytic leukemia (JMML) occurred. A 3-year-old boy diagnosed CALLA+, pre-B-ALL with double t(12;21) (by fluorescence in situ hybridization analysis), was treated as per the BFM protocol. A cytogenetic analysis performed at 17 months into treatment showed no t(12;21) in bone marrow (BM) cells; however, a novel translocation, namely, t(4;11), involving the p12 locus on chromosome 4 and the MLL gene at 11q23 was detected in monocytes. No cytogenetic abnormalities were found either in Epstein-Barr virus-transformed B cells or in phytohemagglutinin-stimulated T-lymphoid cells. Flow-cytometric analysis demonstrated an asynchronous expression of the antigenic determinants in populations of granulocytic and monocytoid cells: 60% of monocytes expressed low levels of CD14, an unusually high level of CD15, and no CD13 or HLA-DR antigens; 74% of myeloid cells expressed no CD13. Our results indicate that the transformation from B-cell ALL to JMML in this case occurred most probably in the granulocyte-erythroid-macrophage-megakaryocyte progenitor cells without involving the lymphoid cell line. To date, the child is 10 months off therapy and asymptomatic, with t(4;11) in only 3% of the cells.