Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407

Salzer, Wanda L.; Jones, Tamekia L.; Devidas, Meenakshi; Hilden, Joanne M.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce M.; Dreyer, ZoAnn E.

doi:10.1002/pbc.24132

Cited by 33 publications

(39 citation statements)

References 45 publications

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“…After the study was amended to substitute prednisone for dexamethasone, reduce the dose of daunorubicin, and enhance supportive care, the early death rate dropped to 6% for the next 141 patients. 22 Remarkably, the early death rate increased again on the successor COG trial AALL0631, with 4 of the first 26 patients (15%) dying from infections, although the only change to induction therapy was to substitute a single dose of PEG asparaginase for native E coli asparaginase. 23 Similar issues have been reported in infants with AML.…”

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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Section: Characteristics Of Infant Leukemiamentioning

confidence: 99%

Treatment of infant leukemias: challenge and promise

Brown

2013

Hematology

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“…10,47 In the COG P9407 study, an unacceptably high rate of early death from bacterial, fungal, and viral infections prompted the investigators to amend the protocol by substituting dexamethasone with prednisolone, changing the delivery of daunorubicin from 48 h continuous infusion to 30 min infusion, and introducing an enhanced supportive care guideline. 48 These amendments led to a significant reduction in early mortality rate from 13.7% to 3.5% (P = 0.036). Respiratory syncytial virus (RSV) infection can cause serious lower respiratory complications in infants, which may result in death.…”

Section: Supportive Carementioning

confidence: 99%

Recent progress in the treatment of infant acute lymphoblastic leukemia

Tomizawa

2015

Pediatrics International

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Treatment of infants with acute lymphoblastic leukemia (ALL), especially those with mixed lineage leukemia (MLL) rearrangement (MLL-r), which account for approximately 80% of cases, is still a major challenge for pediatric hematologists and oncologists worldwide. Continuing efforts by collaborative clinical study groups in Europe, North America, and Japan have rescued approximately half of the MLL-r ALL patients with intensive chemotherapy with or without allogeneic hematopoietic stem cell transplantation. Recent progress has clarified the unique mechanism of MLL-r ALL: the aberrant methylation and histone modifications via DOT1L and other related molecules by MLL fusion proteins lead to leukemogenetic gene expression, thus to overt leukemia. In order to overcome this dismal subtype of ALL, novel targeted therapy based on leukemia biology is urgently needed. Due to the extreme rarity of the disease, collaboration between the study groups in Europe (Interfant), North America (Children's Oncology Group), and Japan (Japanese Pediatric Leukemia/Lymphoma Study Group) is under way.Key words acute lymphoblastic leukemia, epigenetics, hematopoietic stem cell transplantation, infant, mixed lineage leukemia.Acute lymphoblastic leukemia (ALL), a malignant disorder of lymphoid progenitor cells, is the most common type of malignant neoplasms in children and adolescents, with approximately 444-532 cases diagnosed annually in Japan. 1 Optimal use of "old drugs", developed between the 1950s and 1970s under successive collaborative clinical trials, has improved the outcome of childhood ALL to achieve an event-free survival (EFS) rate of 80.4-87.2% and an overall survival (OS) rate of 91.8-93.5% in recently completed clinical trials. [2][3][4][5] The progress in the treatment of infant ALL (diagnosed at age <12 months), however, is lagging behind compared with the treatment of children ≥1 year: EFS and OS remain at 41.7-50.9% and 44.8-60.5%, respectively (Table 1). 9,[11][12][13] In this review, advances in the pathobiology and clinical management of ALL in infants is described. Epidemiology and characteristicsInfant ALL accounts for <5% of childhood ALL, with 20-25 new cases diagnosed annually in Japan. In children ≥1 year, ALL comprises 75-80% of all childhood leukemia because of the high peak incidence of B-lineage ALL between the age of 2 and 5 years, with a predominance in boys. In contrast, the incidence of ALL in infants is the same as that of acute myeloid leukemia (AML), with a slight predominance in girls. 1,11 Biologically and clinically, infant ALL consists of two distinct subtypes: one involves rearrangements of mixed lineage leukemia (MLL also called KMT2A), which accounts for approximately 80% of infant ALL; and the other with germline MLL. Infant ALL with rearranged MLL (MLL-r) is a highly aggressive leukemia with high white blood cell (WBC) count and frequent involvement of extramedullary sites including the central nervous system (CNS) at diagnosis. 9,11 In addition, MLL-r ALL has a very immature CD10-ne...

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“…et al, manuscript in preparation). [1][2][3] More-efficacious, better-tolerated therapies are urgent. MLL translocations, which occur in 75% of ALL in infants younger than 1 year, are associated with poor outcomes, but survival in MLL-germline (G) cases also is inferior compared with ALL in children younger than 1 year (Z.E.D.…”

Section: Introductionmentioning

confidence: 99%