Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia.

INTRODUCTION: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. METHODS: We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP-ALL aged 1-9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient-specific primers were designed for each patient and used in semi-nested polymerase chain reaction for the detection of preleukemic clones at birth. RESULTS: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis. CONCLUSION: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card-positive versus Guthrie card-negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events.

[Importance of psychological support for families of children with cancer].

INTRODUCTION: A family of a child with cancer needs continuous help and support from medical and other professionals, relatives, friends and community at the moment of making diagnosis and during the treatment. The goal of this study was to find out the most frequent sources of individual or community based psychological support, reported by parents of children suffering from malignant diseases. We focused on the help received at the moment of making diagnosis and within the first and second year of treatment. MATERIAL AND METHODS: We analyzed data obtained by a questionnaire specially designed for parents of children suffering from different malignancies. The poll was conducted from April 2007 till October 2009 at the Hematology/Oncology Department of Children's Hospital of Novi Sad and it included 72 parents of both sexes, whose children were treated at our Department in the period from 2007 to 2009. The children were of different age. RESULTS: The parents selected the following forms of support as the most important: support given by the emotional partner and other family members (together with sick and healthy child), communication with and accessibility of hospital stuff (physicians at the first place, but also psychologists, nurses, other parents, support groups...). They also expressed their need for contacting friends, relatives and other close people. The selected forms of support are extremely important for the patients (regardless of age) and for their family. All forms of organized and professionally conducted psycho-social support of patients and their family result in higher quality of psychological survival during the treatment and further rehabilitation of patients after rejoining their primary social environment. CONCLUSION: Family is the primary and the most important social surrounding within which disease both happens and is resolved. Adequate support can help family to overcome such crises, thus leading to the positive outcome.

[Allergic complications of L-asparaginase therapy in children with acute lymphoblastic leukaemia].

INTRODUCTION: L-asparaginase (L-ASP) is one of the most effective medications for the treatment of acute lymphoblastic leukaemia (ALL) in children, and allergic reactions to the therapy are considered the most significant side effects. OBJECTIVE: The aim of this study was to determine the prevalence and type of allergic reactions, as well as to identify potential risk factors for the development of allergic reactions during L-ASP therapy in children with ALL. METHODS: The study encompassed 70 patients under 18 years of age, who were treated at the Institute for Child and Youth Healthcare of Vojvodina, Novi Sad in the period January 2000 - June 2009. We analyzed the frequency and type of allergic reactions during the administration of L-ASP, the onset of allergic reaction in relation to the phase of therapy of underlying disease, as well as the prevalence of allergic reactions in relation to drug administration method. RESULTS: Allergic reaction manifested in 17 patients (24%). In 14 patients (82%) allergic reaction to L-ASP manifested as urticaria, bronchospasm or anaphylaxis, whereas a mild local reaction was observed in only three patients (18%). In a group treated, according to the high-risk protocol, the prevalence of allergic reactions was statistically significantly higher in the intermediate-risk group of patients (p < 0.01), i.e. statistically significantly more frequent, as compared to the standard-risk group of patients (p < 0.05). The majority of patients (11; 65%) developed allergic reactions to the 9th dose of L-ASP, i.e. the first dose during the reinduction phase. The time interval between the last L-ASP dose in the induction phase and the 1st dose in the reinduction phase was at least four weeks. With respect to administration method, the majority of patients (16; 94%) developed allergic reaction after intravenous application of L-ASP. CONCLUSION: Potential risk factors for the development of allergic reaction to L-ASP are a high-risk therapy group, intravenous administration route and repeated application of the drug after at least four-week cessation period.

[Biphenotypic acute leukaemia: case reports of two paediatric patients].

INTRODUCTION: Biphenotypic acute leukaemia is an uncommon type of leukaemia whose blasts co-express myeloid and B-or T-lymphoid antigens. CASE REPORT: We describe two cases of paediatric patients with biphenotypic acute leukaemia. A four-year-old female patient was found to have myeloid and B-lymphoid associated antigens in the same blast cells. Cytogenetic analysis showed a Philadelphia (Ph) positivity t (9;22) (q34;q1l1 with rearrangements of M.bcr-Abl (p210). She was treated with combined acute myeloid leukaemia/acute lymphoblastic leukaemia induction therapy followed by autologous stem cell transplantation. The patient died due to the complications of stem cell transplantation procedure. Another patient was a 20-month-old girl with myeloid and T-lymphoid associated antigens in the blast cells and with normal karyotype. She received acute myeloid leukaemia induction therapy. She has never achieved remission. DISCUSSION: Immunophenotype is essential to establish the diagnosis of biphenotypic acute leukaemia according to the scoring system adopted by the European Group of Immunological Classification of Leukaemia. There is no agreement about uniformity in treatment for the patients with this type of leukaemia. Biphenotypic acute leukaemia is a high risk leukaemia which requires a more intensive treatment. CONCLUSION: Therapy for every patient with biphenotypic acute leukaemia should depend on their immunophenotype and gene rearrangement profiles.