Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with <i>MLL</i> gene rearrangements: A report from the Japan infant leukemia study group

Tomizawa, Daisuke; Koh, Katsuyoshi; Hirayama, Masahiro; Miyamura, Takako; Hatanaka, Michiki; Saikawa, Yoshiro; Ishii, Eiichi

doi:10.1002/pbc.21975

Cited by 42 publications

(37 citation statements)

References 22 publications

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“…Another key conclusion from these studies was the need for more effective postremission therapy, as a high proportion of relapse (61.7%, n =21/34) occurred before HSCT. 39 Age <6 months was the only independent prognostic factor associated with inferior outcome for MLL -rearranged infants (5-year EFS 27.8% <6 months vs 52.9% ⩾6 months) with CNS disease at diagnosis identified on univariate analysis. 37 Compared with the germline group, univariate analysis demonstrated that MLL -rearranged infants were significantly younger, had higher WBC counts, increased frequency of CNS disease and CD10 negativity at diagnosis.…”

Section: The Present: Infant-specific Collaborative Group Protocolsmentioning

confidence: 85%

The evolution of clinical trials for infant acute lymphoblastic leukemia

Kotecha

Gottardo

Kees

et al. 2014

Blood Cancer Journal

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Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified international trial.

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Section: The Present: Infant-specific Collaborative Group Protocolsmentioning

confidence: 85%

The evolution of clinical trials for infant acute lymphoblastic leukemia

Kotecha

Gottardo

Kees

et al. 2014

Blood Cancer Journal

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“…The low rates of second remission reported by the Japanese Pediatric Leukemia Study Group (JPLSG) in patients relapsing after treatment for infant ALL are consistent with this hypothesis. 21 …”

Section: Characteristics Of Infant Leukemiamentioning

confidence: 99%

Treatment of infant leukemias: challenge and promise

Brown

2013

Hematology

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Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its unique biology that is increasingly pointing the way toward novel therapeutic approaches. This review highlights the key clinical, pathologic, and epidemiologic features of infant leukemia, including the high frequency of mixed lineage leukemia (MLL) gene rearrangements. The state of the art with regard to current approaches to risk stratified treatment of infant leukemia in the major international cooperative groups is discussed. Finally, exciting recent discoveries elucidating the molecular biology of infant leukemia are reviewed and novel targeted therapeutic strategies, including FLT3 inhibition and modulation of aberrant epigenetic programs, are suggested.

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“…Hematopoietic stem cell transplantation can be an effective treatment for certain types of malignant diseases involving bone marrow cancer, mainly leukemia, lymphoma, or myeloma [1][2][3][4][5]. For any transplant in which stem cells come from a donor, it is necessary to ensure a close matching of the human leukocyte antigen (HLA) genetic components as their constituent gene products play vital roles in immune response.…”

Section: Introductionmentioning

confidence: 99%