Factors influencing survival in pediatric acute leukemia.The SWCCSG experience, 1958–1970

George, Stephen L.; Fernbach, Donald J.; Vietti, Teresa J.; Sullivan, Margaret P.; Lane, Daniel; Haggard, Mary Ellen; Berry, D. H.; Lonsdale, Derrick; Komp, Diane M.

doi:10.1002/1097-0142(197312)32:6<1542::aid-cncr2820320634>3.0.co;2-d

Cited by 106 publications

(27 citation statements)

References 9 publications

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“…The unfavorable prognosis carried by infants less than 1 year of age was identified following analysis of prognostic features from successive trials and registry data. 6, 7, 8 This led to the strategy of risk adaptation within clinical trials, with the majority increasing the intensity of therapy delivered to infants by stratification to high-risk arms. Table 1 summarizes published outcomes for infants treated within childhood ALL studies.…”

Section: The Past: Risk-adapted Therapy On Childhood Leukemia Studiesmentioning

confidence: 99%

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 Past: Risk-adapted Therapy On Childhood Leukemia Studiesmentioning

confidence: 99%

The evolution of clinical trials for infant acute lymphoblastic leukemia

Kotecha

Gottardo

Kees

et al. 2014

Blood Cancer Journal

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“…Clinical experience suggests that patients with high tumour load are less amenable to treatment. High leukocyte counts in patients with ALL and AML are usually considered a poor prognostic sign in terms of remission induction (Crowther et al, 1975;Robinson et al, 1980;Simone et al, 1975), remission duration (Hug et al, 1983;Robinson et al, 1980;Schauer et al, 1983) and survival (Freireich et al, 1961;George et al, 1973;Simone et al, 1975). Leukapheresis prior to chemotherapy resulted in an improved rate of remission (Cuttner et al, 1983).…”

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confidence: 99%

Effects of cell density on drug-induced cell kill kinetics in vitro (inoculum effect)

Ohnuma¹,

Arkin²,

Holland³

1986

Br J Cancer

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Summary The effects of cell density on drug-induced cell kill kinetics were studied by means of clonogenic assay using 3 human leukaemia-lymphoma cell lines. Mitoxantrone, daunorubicin, doxorubicin, vincristine and bleomycin were progressively less efficacious when cell density increased (positive inoculum effects), whereas the effects of cis-platin and carboplatin were not influenced by cell density. Inoculum effects were related to the kind of chemotherapeutic agents tested, irrespective of the type of cell lines used. Preincubation of mitoxantrone or doxorubicin in the presence of cells in high density resulted in decreases in the cytocidal activity, whereas the effects of bleomycin, vincristine and cis-platin were unaffected. These results show that cell density affects the biological effect of certain chemotherapeutic agents. Inactivation of drugs by high densities of cells partially explains this phenomenon.

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“…Patients under 1 year of age are generally acknowledged to have the worst survival of any age group. 5 T h e primary purpose of the present study was to examine the prognosis and the prognostic factors for infants treated over an extended period of time at a single institution. Infants included i n this study did poorly compared to their pairmates treated i n a similar fashion during the same time period and as for their pairmates, the type of leukemia and initial white blood count were important prognostic variables with respect to survival.…”

Section: Discussionmentioning

confidence: 99%

Unfavorable prognosis of acute leukemia in infancy

Cangır

George

Sullivan

1975

Cancer

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Pretreatment characteristics of 48 infants (under 2 years of age) with leukemia treated over a period of 18 years at a single institution were studied in relation to response to therapy, extramedullary involvement, and survival. I n order to provide a basis of comparison, 45 of the infants were each paired with an older (2-9 years of age) leukemic child, who had the same race, and disease type, who was treated within the same period of time and received similar suportive care and chemotherapy, and when possible, was of the same sex. The overall median survival times of infants and their pairmates were 211 days and 445 days, respectively. Initial status of the spleen was the single significant factor in relation to the length of survival. Median survival time for infants with splenomegaly was 186 days compared to a median survival time of 414 days for infants without splenomegaly. The complete response rate was 75% for infants and 80% for the pairmates. Median duration of remission was 84 days for infants and 280 days for their pairmates. Initial peripheral leucocyte count was significantly related to the duration of remission; patients with very high leucocyte counts had the shortest remissions. The duration of remission increased throughout the period covered by this study, however, prognosis relative to pairmates remained poor. Central nervous system leukemia occurred in 44% of infants and 40% of the pairmates; incidence of CNS leukemia was much higher (70%) in infants under one year of age than in infants one year old (37%). Extramedullary leukemia occurred at other sites in 46% of the infants and 31% of the pairmates. The only pretreatment characteristic of prognostic importance for predicting extramedullary involvement was the patient's age at diagnosis.

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Factors influencing survival in pediatric acute leukemia.The SWCCSG experience, 1958–1970

Cited by 106 publications

References 9 publications

The evolution of clinical trials for infant acute lymphoblastic leukemia

The evolution of clinical trials for infant acute lymphoblastic leukemia

Effects of cell density on drug-induced cell kill kinetics in vitro (inoculum effect)

Unfavorable prognosis of acute leukemia in infancy

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