Towards targeted therapy for infant acute lymphoblastic leukaemia

Stam, Ronald W.; Boer, Monique L. den; Pieters, Rob

doi:10.1111/j.1365-2141.2005.05909.x

Cited by 30 publications

(50 citation statements)

References 125 publications

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“…Our results could have been affected by the preferential participation of surviving cases if the factors under study affect prognosis. However, none of the variables investigated here has been associated with survival (4,5). In addition, because proxy interview was the object of data collection, deceased cases were eligible for the study; 27% of cases were not living at the time of maternal interview.…”

Section: Discussionmentioning

confidence: 99%

“…The 5-year survival rate for infant leukemia of f45% is considerably lower than that for leukemia at older ages (3). Presence of an MLL rearrangement is an important predictor of survival for infants with acute lymphoblastic leukemia (ALL); in a recent review, event-free survival was <15% and >50% among MLL + and MLL À cases, respectively (4). The prognostic importance of MLL rearrangements in infant acute myelogenous leukemia (AML) is less clear (5).…”

Section: Introductionmentioning

confidence: 99%

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Birth Characteristics, Maternal Reproductive History, and the Risk of Infant Leukemia: A Report from the Children's Oncology Group

Spector

Davies

Robison

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Leukemias with MLL gene rearrangements predominate in infants (<1 year of age), but not in older children, and may have a distinct etiology. High birth weight, higher birth order, and prior fetal loss have, with varying consistency, been associated with infant leukemia, but no studies have reported results with respect to MLL status. Here, we report for the first time such an analysis. During 1999 to 2003, mothers of 240 incident cases (113 MLL + , 80 MLL À , and 47 indeterminate) and 255 random digit dialed controls completed a telephone interview. Odds ratios and 95% confidence intervals for quartile of birth weight, birth order, gestational age, maternal age at delivery, prior fetal loss, prepregnancy body mass index, and weight gain during pregnancy were obtained using unconditional logistic regression; P for linear trend was obtained by modeling continuous variables. There was a borderline significant linear trend of increasing birth weight with MLL + (P = 0.06), but not MLL À (P = 0.93), infant leukemia. Increasing birth order showed a significant inverse linear trend, independent of birth weight, with MLL + (P = 0.01), but not MLL À (P = 0.18), infant leukemia. Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies. (Cancer Epidemiol Biomarkers Prev 2007;16(1):128 -34)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Birth Characteristics, Maternal Reproductive History, and the Risk of Infant Leukemia: A Report from the Children's Oncology Group

Spector

Davies

Robison

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…New therapeutic targets have to be identified by unraveling the biology of MLL-rearranged ALL. Phase 1/2 trials with FLT3 inhibitors 20 are currently being initiated in infant MLL-rearranged ALL.…”

Section: Org Frommentioning

confidence: 99%

Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol

Linden

Valsecchi

Lorenzo

et al. 2009

Blood

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Acute lymphoblastic leukemia (ALL) diagnosed in the first month of life (congenital ALL) is very rare. Although congenital ALL is often assumed to be fatal, no studies have been published on outcome except for case reports. The present study reports the outcome of 30 patients with congenital ALL treated with the uniform Interfant-99 protocol, a hybrid regimen combining ALL treatment with elements designed for treatment of acute myeloid leukemia. Congenital ALL was characterized by a higher white blood cell count and a strong trend for higher incidence of MLL rearrangements and CD10-negative B-lineage ALL compared with older infants. Induction failure rate was 13% and not significantly different from that in older infants (7%, P ‫؍‬ .14), but relapse rate was significantly higher in congenital ALL patients (2-year cumulative incidence [ IntroductionAcute lymphoblastic leukemia (ALL) in infants (up to 1 year of age) is known to be biologically different from ALL in older children diagnosed with ALL. ALL in infants is more often associated with a higher tumor load at diagnosis, 1,2 a rearrangement in the mixed lineage leukemia (MLL) gene, and very immature B-cell phenotype (pro-B ALL) without CD10 expression. 1-3 Infant ALL cells are more resistant to several standard chemotherapeutic agents, 3,4 and the disease is also characterized by a poorer prognosis compared with older children. [5][6][7][8][9][10][11][12][13][14] Congenital ALL is diagnosed at birth or within the first month of life and is very rare. Although it is assumed to be inevitably fatal and the toxicity of the chemotherapeutic agents in these very young infants is unclear, to the best of our knowledge, no series have been published on congenital ALL except for case reports. Bresters et al 15 reviewed 24 patients with congenital ALL diagnosed over 25 years who were described in case reports: all patients died.We recently reported the results of a large international collaborative trial, Interfant-99, in infants younger than 1 year with ALL. 14 Here, we detail the outcome and characteristics of 30 patients with congenital ALL who received uniform therapy with curative intent. Methods PatientsThe Interfant-99 trial design, the inclusion criteria, and recruitment methods have been published earlier. 14 Individual study groups obtained ethics approval from all participating institutions, and patient informed consent was obtained in accordance with the Declaration of Helsinki. Of the 518 infants diagnosed with ALL, which account for approximately 3% of the ALL population, 35 patients were younger than 1 month, confirming the rarity of congenital ALL (ϳ 2 children per every 1000 with ALL). The present study reports on 30 cases that were treated with Interfant-99 (Figure 1). ProceduresEnrolled patients were stratified into standard-risk and high-risk groups on the basis of their response to 1 week of daily systemic prednisone (at a dose of 60 mg/m 2 ) and 1 intrathecal dose of methotrexate. Patients were classified as standard risk if their peripheral bloo...

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“…www.bjournal.com.br considering the MLL translocation to be the first genetic hit undoubtedly arising in utero, but yet displaying N region-positive DJ H junctions, it is very likely that an exquisitely short latency period for only limited mutagenic events is further required (14,32). Furthermore, it was recently found that the receptor tyrosine kinase FLT3 is highly expressed in MLL-rearranged ALL as compared with other leukemias (6).…”

Section: Other Molecular Markersmentioning

confidence: 99%

Acute leukemia in early childhood

Emerenciano

Koifman

Pombo‐de‐Oliveira

2007

Braz J Med Biol Res

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Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL /AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months) has detected TEL /AML1 +ve (N = 9), E2A/PBX1 +ve (N = 4), PML /RARA +ve (N = 4), and AML1/ETO +ve (N = 2) cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07), OR = 2.27 (95%CI = 1.56-3.31) and OR = 9.08 (95%CI = 2.95-27.96)], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

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Towards targeted therapy for infant acute lymphoblastic leukaemia

Cited by 30 publications

References 125 publications

Birth Characteristics, Maternal Reproductive History, and the Risk of Infant Leukemia: A Report from the Children's Oncology Group

Birth Characteristics, Maternal Reproductive History, and the Risk of Infant Leukemia: A Report from the Children's Oncology Group

Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol

Acute leukemia in early childhood

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