• Keywords
• Hypodiploidie,
• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * diagnosis   etiology   genetics   MeSH
• Cytogenetic Analysis methods   utilization   MeSH
• Diploidy MeSH
• Child MeSH
• Drug Therapy methods   utilization   MeSH
• Transplantation, Homologous methods   utilization   MeSH
• In Situ Hybridization, Fluorescence methods   utilization   MeSH
• Medical Oncology MeSH
• Humans MeSH
• Adolescent MeSH
• Recovery of Function genetics   immunology   drug effects   MeSH
• Pediatrics MeSH
• Prednisone administration & dosage   adverse effects   therapeutic use   MeSH
• Prognosis * MeSH
• Statistics as Topic MeSH
• Bone Marrow Transplantation methods   utilization   MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Diploidy MeSH
• Erythropoietin MeSH
• Cats MeSH
• Bone Marrow physiology   MeSH
• Blood Transfusion MeSH
• Animals MeSH
• Check Tag
• Cats MeSH
• Animals MeSH

PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS: With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION: MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis   genetics   mortality   therapy   MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Time Factors MeSH
• Diploidy * MeSH
• Child MeSH
• Progression-Free Survival MeSH
• Transplantation, Homologous MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Neoplasm, Residual MeSH
• Hematopoietic Stem Cell Transplantation * adverse effects   mortality   MeSH
• Age Factors MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Comparative Study MeSH

Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10(-5) ) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, P = 1.82 × 10(-10) ). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.

• MeSH
• Genome-Wide Association Study * MeSH
• Chromosome Aberrations MeSH
• Genomics * methods   MeSH
• Humans MeSH
• Multiple Myeloma diagnosis   genetics   MeSH
• Monoclonal Gammopathy of Undetermined Significance diagnosis   genetics   MeSH
• Genomic Instability MeSH
• Disease Progression MeSH
• Comparative Genomic Hybridization MeSH
• DNA Copy Number Variations * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

We conducted a cytogenetic analysis of 642 children with de novo acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK+), complex (CK+) and hypodiploid (HK+) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK+ (n=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients, P=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%, P=0.0081). CK+ patients without MK had a better prognosis (n=47, EFS 47±8%, P=0.46) than those with MK+ (n=12, EFS 25±13%, P=0.024). HK+ (n=37, EFS 44±8% for total cohort, P=0.3) influenced outcome only when t(8;21) patients were excluded (remaining n=16, EFS 9±8%, P<0.0001). An extremely poor outcome was observed for MK+/HK+ patients (n=10, EFS 10±10%, P<0.0001). Finally, isolated trisomy 8 was also associated with low EFS (n=16, EFS 25±11%, P=0.0091). In conclusion, monosomal karyotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts.

• MeSH
• Leukemia, Myeloid, Acute diagnosis   genetics   mortality   MeSH
• Survival Analysis MeSH
• Chromosome Aberrations MeSH
• Genetic Variation * MeSH
• Genotype * MeSH
• Karyotype MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Chromosomes, Human, Pair 7 MeSH
• Monosomy MeSH
• Mutation MeSH
• Prognosis MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome. PATIENTS AND METHODS: A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE. RESULTS: By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10-4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively (P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively (P < .001). CONCLUSION: Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * MeSH
• Asparaginase * MeSH
• Infant MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   MeSH
• Polyethylene Glycols MeSH
• Prednisone adverse effects   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols adverse effects   MeSH
• Randomized Controlled Trials as Topic MeSH
• Recurrence MeSH
• Treatment Outcome MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH