Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects

Arnaout, MK; Radomski, KM; Dk, Srivastava; Tong, Xin; Belt, J.; Raimondi, SC; Behm, FG; Santana, VM; Crom, WR; Mirro, Joseph; Rc, Ribeiro

doi:10.1038/sj.leu.2401906

Cited by 33 publications

(24 citation statements)

References 28 publications

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“…Between 1980 and 1997, 290 patients younger than 21 years with previously untreated, newly diagnosed AML were consecutively enrolled on four successive clinical trials (AML80, 13 AML83, 14 AML87, 15 and AML91 16 ) at St Jude Children's Research Hospital. The diagnosis of AML was based on the finding that leukemic myeloid blast cells composed more than 30% of the mononuclear cells in the bone marrow.…”

Section: Patientsmentioning

confidence: 99%

“…The AML80, 13 AML83, 14 AML87, 15 and AML91 16 protocols have been described elsewhere. Systemic therapy on the four protocols is summarized as follows.…”

Section: Treatmentmentioning

confidence: 99%

“…Consolidation therapy comprised three additional cycles of combination chemotherapy; no maintenance therapy was given. 15 On AML91, induction therapy consisted of one or two courses of 2-chlorodeoxyadenosine (2-CDA, cladribine) followed by one to two courses of daunomycin/Ara-C/VP-16. Postremission therapy consisted of bone marrow transplantation or one course of consolidation with high-dose cytarabine.…”

Section: Treatmentmentioning

confidence: 99%

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Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution's experience

Rubnitz

Tong

et al. 2003

Leukemia

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To determine the clinical significance of central nervous system (CNS) involvement at the time of diagnosis of pediatric acute myeloid leukemia (AML), we analyzed clinical features and outcomes of 290 patients treated consecutively on four institutional trials (AML80, AML83, AML87, and AML91). CNS status was classified as CNS1 (no blast cells in CSF; n ¼ 205), CNS2 (o5 WBC/ll CSF with blast cells; n ¼ 37), or CNS3 (X5 WBC/ll CSF with blast cells, or signs of CNS involvement; n ¼ 48). Patients with CNS3 status were significantly younger than others (P ¼ 0.016) and significantly more likely to have the favorable cytogenetic features t(9;11), t(8;21), or inv(16) (Po0.001). The CNS3 group had a significantly greater probability (7s.e.) of 5-year event-free survival (43.777.0%) than did the CNS1 (27.873.2%, P ¼ 0.015) and CNS2 (24.377.5%, P ¼ 0.032) groups. However, after adjustment for favorable genetic features, there was no significant difference in EFS between the CNS3 and the combined CNS1 þ CNS2 groups (P ¼ 0.075). In all, 10 of 151 patients treated on AML80 and AML83, but none of 139 treated on AML87 and AML91, had primary CNS relapse. CNS involvement had no adverse prognostic significance, and patients with CNS2 status had similar outcome to CNS1 patients in this large group of pediatric patients with AML, treated at a single institution.

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Section: Patientsmentioning

confidence: 99%

“…The AML80, 13 AML83, 14 AML87, 15 and AML91 16 protocols have been described elsewhere. Systemic therapy on the four protocols is summarized as follows.…”

Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution's experience

Rubnitz

Tong

et al. 2003

Leukemia

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“…In this review, we first summarize the findings of the initial analyses [4][5][6]8,10 and then re-examine the outcomes of these studies. We used the Kaplan-Meier method to estimate eventfree survival (EFS) and overall survival (OS) curves, and Peto and Pike's method was used to estimate the standard errors (s.e.)…”

Section: Discussionmentioning

confidence: 99%

“…The initial analysis of the AML-87 study 6 examined 58 patients. About 50% of patients entered CR with the first course of cytarabine/etoposide.…”

Section: Supplementarymentioning

confidence: 99%

Successive clinical trials for childhood acute myeloid leukemia at St Jude Children's Research Hospital, from 1980 to 2000

et al. 2005

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Despite substantial progress in the management of childhood acute myeloid leukemia (AML), only about 50% of patients are cured by intensive chemotherapy. The long-term results of clinical trials may reveal principles that can guide the development of future therapy. From 1980 to 2000, 251 patients o15 years of age with newly diagnosed AML were enrolled on one of the five consecutive St Jude AML studies. The median age of the 128 boys and 123 girls was 6.2 years; 193 were white, 45 black, and 13 of other racial groups. With the exception of one protocol (AML-83), outcomes improved in general over the two decades. The estimated 5-year event-free survival (7s.e.) was 30.875.6% for AML-80; 11.174.3% for AML-83; 35.977.4% for AML-87; 43.576.2% for AML-91; and 45.0711.1% for AML-97. Resistant or relapsed AML caused the great majority of treatment failures. Increasing the intensity of chemotherapy (AML-87) did not improve outcome, partially because of toxicity, nor did prolonging postremission therapy by adding sequential myeloablative (AML-80) or nonmyeloablative (AML-83) chemotherapy cycles. We conclude that subtype-specific therapies are needed to replace the 'one size fits all' strategy of the past two decades.

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Death during induction therapy and first remission of acute leukemia in childhood

Rubnitz

Lensing

Zhou

et al. 2004

Cancer

131

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BACKGROUND Despite improvements in supportive care, death due to treatment toxicity remains a significant problem for children treated for acute leukemia. METHODS To determine the causes of and risk factors for death unrelated to refractory leukemia, to disease recurrence, or to second malignancy, the authors reviewed the records of 1011 patients with acute lymphoblastic leukemia (ALL) and 260 patients with acute myeloid leukemia (AML) treated between 1984 and 1999 and between 1983 and 2002, respectively, at St. Jude Children's Research Hospital (Memphis, TN). Data for patients who underwent stem cell transplantation were censored at the time of transplantation. RESULTS For patients with ALL, the estimated 10‐year cumulative incidence of death was 2.9% ± 5.3%. Age was the only predictor of death. Patients with ALL 1–9 years old had a significantly lower risk of death than did younger or older patients (P = 0.002). For patients with AML, the estimated 5‐year cumulative incidence of death was 7.6% ± 1.9%. Increasing age and increasing leukocyte count were significantly associated with increased risk of death. For patients with ALL and with AML, the incidence of death remained relatively constant during the time periods studied. Infection was the most common cause of death. CONCLUSIONS In the current study, the authors determined that children ≥ 10 years of age are at increased risk of death during therapy for ALL and AML. Cancer 2004. © 2004 American Cancer Society.

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Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects

Cited by 33 publications

References 28 publications

Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution's experience

Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution's experience

Successive clinical trials for childhood acute myeloid leukemia at St Jude Children's Research Hospital, from 1980 to 2000

Death during induction therapy and first remission of acute leukemia in childhood

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