%0 Journal Article %J Br J Haematol %D 2015 %T Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort. %A Randi, Maria L %A Geranio, Giulia %A Bertozzi, Irene %A Micalizzi, Concetta %A Ramenghi, Ugo %A Tucci, Fabio %A Notarangelo, Lucia D %A Ladogana, Saverio %A Menna, Giuseppe %A Giordano, Paola %A Consarino, Caterina %A Farruggia, Piero %A Zanazzo, Giulio A %A Fiori, Giovanni M %A Burnelli, Roberta %A Russo, Giovanna %A Jankovich, Momcilo %A Peroni, Edoardo %A Duner, Elena %A Basso, Giuseppe %A Fabris, Fabrizio %A Putti, Maria C %K Adolescent %K Adult %K Amino Acid Substitution %K Child %K Child, Preschool %K Cohort Studies %K Female %K Hematologic Neoplasms %K Humans %K Infant %K Janus Kinase 2 %K Male %K Mutation, Missense %K Neoplasm Proteins %K Thrombocythemia, Essential %X

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25·8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74·2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

%B Br J Haematol %V 169 %P 584-9 %8 2015 May %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/25716342?dopt=Abstract %R 10.1111/bjh.13329 %0 Journal Article %J Blood %D 2014 %T Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study. %A Conter, Valentino %A Valsecchi, Maria Grazia %A Parasole, Rosanna %A Putti, Maria Caterina %A Locatelli, Franco %A Barisone, Elena %A Lo Nigro, Luca %A Santoro, Nicola %A Aricò, Maurizio %A Ziino, Ottavio %A Pession, Andrea %A Testi, Anna Maria %A Micalizzi, Concetta %A Casale, Fiorina %A Zecca, Marco %A Casazza, Gabriella %A Tamaro, Paolo %A La Barba, Gaetano %A Notarangelo, Lucia Dora %A Silvestri, Daniela %A Colombini, Antonella %A Rizzari, Carmelo %A Biondi, Andrea %A Masera, Giuseppe %A Basso, Giuseppe %K Adolescent %K Antineoplastic Combined Chemotherapy Protocols %K Child %K Child, Preschool %K Combined Modality Therapy %K Female %K Hematopoietic Stem Cell Transplantation %K Humans %K Infant %K Male %K Neoplasm, Residual %K Precursor Cell Lymphoblastic Leukemia-Lymphoma %K Radiotherapy %K Remission Induction %K Treatment Outcome %X

The outcome of high-risk (HR) acute lymphoblastic leukemia patients enrolled in the AIEOP-BFM ALL 2000 study in Italy is described. HR criteria were minimal residual disease (MRD) levels ≥10(-3) at day 78 (MRD-HR), no complete remission (CR) at day 33, t(4;11) translocation, and prednisone poor response (PPR). Treatment (2 years) included protocol I, 3 polychemotherapy blocks, delayed intensification (protocol IIx2 or IIIx3), cranial radiotherapy, and maintenance. A total of 312 HR patients had a 5-year event-free survival (EFS) of 58.9% (standard error [SE] = 2.8) and an overall survival of 68.9% (SE = 2.6). In hierarchical order, EFS was 45.9% (4.4) in 132 MRD-HR patients, 41.2% (11.9) in 17 patients with no CR at day 33, 36.4% (14.5) in 11 patients with t(4;11), and 74.0% (3.6) in 152 HR patients only for PPR. No statistically significant difference was found for disease-free survival in patients with very HR features [MRD-HR, no CR at day 33, t(4;11) translocation], given hematopoietic stem cell transplantation (HSCT) (n = 66) or chemotherapy only (n = 88), after adjusting for waiting time to HSCT (5.7 months). Patients at HR only for PPR have a favorable outcome. MRD-HR is associated with poor outcome despite intensive treatment and/or HSCT and may qualify for innovative therapies. The study was registered at www.clinicaltrials.gov as #NCT00613457.

%B Blood %V 123 %P 1470-8 %8 2014 Mar 6 %G eng %N 10 %1 http://www.ncbi.nlm.nih.gov/pubmed/24415536?dopt=Abstract %R 10.1182/blood-2013-10-532598 %0 Journal Article %J Pharmacogenomics %D 2014 %T TNF-α SNP rs1800629 and risk of relapse in childhood acute lymphoblastic leukemia: relation to immunophenotype. %A Franca, Raffaella %A Rebora, Paola %A Athanasakis, Emmanouil %A Favretto, Diego %A Verzegnassi, Federico %A Basso, Giuseppe %A Tommasini, Alberto %A Valsecchi, Maria Grazia %A Decorti, Giuliana %A Rabusin, Marco %K Adolescent %K Antineoplastic Agents %K Child %K Child, Preschool %K Drug Resistance, Neoplasm %K Female %K Genotype %K Humans %K Infant %K Leukemia, Lymphocytic, Chronic, B-Cell %K Male %K Phenotype %K Precursor Cell Lymphoblastic Leukemia-Lymphoma %K Precursor T-Cell Lymphoblastic Leukemia-Lymphoma %K Recurrence %K Risk Assessment %K Steroids %K Tumor Necrosis Factor-alpha %X

AIM: In the AIEOP-BFM ALL (Associazione Italiana Ematologia Oncologia Pediatrica-Berlin Frankfurt Münster acute lymphoblastic leukemia) 2000 protocol, 70% of relapsed patients had favorable prognostic features and fell within less intensive polychemotherapeutic regimens, suggesting the need for better assessing lower risk stratification.

MATERIALS & METHODS: A novel two-phase study design selected 614 children to be genotyped for TNF-α SNP rs1800629 (-308G>A). A weighted Cox model was applied to evaluate the SNP effect on hazard of relapse, adjusting for immunophenotype, risk group, age and gender and including interaction terms.

RESULTS: Significant interaction was found with immunophenotypes (p = 0.0007, with minor allele genotypes being adverse genetic markers in B-cell acute lymphoblastic leukemia and protective ones in T-cell acute lymphoblastic leukemia), and also with risk protocols (p = 0.0041, with minor allele genotypes as prognostic factor of relapse for standard risk patients [only one T-cell acute lymphoblastic leukemia in the subgroup analyzed]).

CONCLUSION: The presence of at least one A allele in TNF-α SNP rs1800629 should suggest a closer monitoring in B-cell acute lymphoblastic leukemia standard risk patients.

%B Pharmacogenomics %V 15 %P 619-27 %8 2014 Apr %G eng %N 5 %1 http://www.ncbi.nlm.nih.gov/pubmed/24798719?dopt=Abstract %R 10.2217/pgs.13.249