Prognostic Factors in Children with Acute Lymphoblastic Leukemia — Part II: Multivariate Analysis —

Hiyoshi, Y; Fujimoto, T; Kuriya, Norikazu; OTANI, YASUYO; Mibu, Keiko; Yanai, Mitsuji; Sasaki, Kuniaki; Shingaki, Y; Yokoyama, Takashi; Kadoya, S

doi:10.1093/oxfordjournals.jjco.a039035

Cited by 6 publications

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“…If several blood counts were available at initial diagnosis, we used the lowest haemoglobin level and platelet count before any transfusion, and the highest white blood cell count and peripheral blast cell count. (Schaison et al, 1990) 2 2-10 3 15-50-100 NOPHO group (Gustafsson et al, 1998) 1 1-2-10 4 10-20-50-100 Japanese group (Hiyoshi et al, 1985) 4 1-4-6-10 4 5-10- 50-200 CCG 1972-1975(Robinson et al, 1980 5 2-4-6-8-10 5 5-10-20-50-100 CCG 160 (Bleyer et al, 1986) 4 1-3-6-10 2 20-50 BFM before 1981 (Bucsky et al, 1988) 5 0.5-1-1.5-2-10 NA BFM 81 (Schrappe et al, 1987) 4 1-2-10-14 3 10-50-100 BFM 86 (Reiter et al, 1994) 3 1-6-10 4 10-20-50-200 DFCI 85-01 (Schorin et al, 1994) 3 1-2-9 3 20-50-100 UKALL X (Chessells et al, 1995) 2 1-10 4 10-20-50-100…”

Section: Study Variablesmentioning

confidence: 99%

Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE)

et al. 2000

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Prognostic factors can be dichotomous by nature, but are more often either polytomous or continuous. Continuous variables are almost always used in prognostic models after categorization. Categorizing a continuous variable has adverse consequences: it requires the definition of cutpoints and implies a threshold effect: the patients immediately above and below the cut off value are supposed to be less similar than the patients at each end of the same category. Choosing a single cutpoint will result in a loss of statistical power in most instances. But many practical or bio logical reasons lead researchers to use one or several cutpoints in order to define the therapeutic classification. Different methods have been proposed to select cutpoints. One is called the optimal cutpoint method (Hilsenbeck et al, 1992). It is based on the P value of repeated univariate analyses of the same sample. This method has been rejected (Hill, 1993;Altman et al, 1994) because it artificially decreases the P value. Another possibility is to divide the sample into equal parts (thirds or quintiles for instance) on the basis of the continuous variable under study, and to evaluate the risk in each category.Quantitative prognostic variables in childhood ALL include the white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age at diagnosis. The prognostic value of these variables was identified more than 30 years ago (Tivey, Summary Many cutpoints have been proposed to categorize continuous variables in childhood acute lymphoblastic leukaemia (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age), and have been used to define therapeutic subgroups. This variation in the choice of cutpoints leads to a bias called the 'Will Rogers phenomenon'. The aim of this study was to analyse variations in the relative risk of relapse or death as a function of continuous prognostic variables in childhood ALL and to discuss the choice of cutpoints. We studied a population of 1545 children with ALL enrolled in three consecutive protocols named FRALLE 83, FRALLE 87 and FRALLE 89. We estimated the risk of relapse or death associated with different values of each continuous prognostic variable by dividing the sample into quintiles of the distribution of the variables. As regards age, a category of children under 1 year of age was distinguished and the rest of the population was divided into quintiles. The floated variance method was used to calculate the confidence interval of each relative risk, including the reference category. The relation between the quantitative prognostic factors and the risk was monotonic for each variable, except for age. For the white blood cell count (WBC), the relation is log linear. The risk associated with WBC values in the upper quintile was 1.9 times higher than that in the lower quintile. The peripheral blast cell count correlated strongly with WBC (correlation coefficient: 0.99). The risk increased with the haemoglobin level, and the risk in the up...

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Section: Study Variablesmentioning

confidence: 99%

Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE)

et al. 2000

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Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children's Cancer and Leukemia Study Group

Tsurusawa

Katano

Yamamoto

et al. 1999

Med. Pediatr. Oncol.

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Background Prevention of central nervous system (CNS) leukemia by early introduction of therapy to this sanctuary site is an essential component of modern treatment strategy for acute lymphoblastic leukemia (ALL). However, the optimal form of preventive CNS therapy remains debatable. Procedure To address this issue, we evaluated the efficacy of CNS preventive therapy for 572 children with ALL who achieved complete remission in the Children's Cancer and Leukemia Study Group (CCLSG) ALL874 (1987–1990) and ALL911 (1991–1993) studies. They received risk‐directed therapy based on age and leukocyte count. In the ALL 874 study, the non–high‐risk (low‐risk [LR] + intermediate risk [IR]) patients were randomly assigned to the conventional cranial irradiation (CRT) regimen (L874A and I874A) and the high‐dose methotrexate (HDMTX) regimen without CRT (L874B and I874B). The former patients received 18‐Gy CRT plus 3 doses of intrathecal (IT) MTX and the latter patients received 3 courses of HDMTX at 2 g/m2 plus 13 doses of ITMTX (L874B) or 4 courses of HDMTX at 4.5 g/m2 plus 1 dose of ITMTX (I874B). Results The 7‐year probabilities (± SE) of CNS relapse‐free survival were 97.3% ± 2.6% (L874A, n = 41) vs. 90.3% ± 5.3% (L874B, n = 39) (P = 0.25) in the LR patients, and 100% (I874A, n = 55) vs. 78.5% ± 6.5% (I874B, n = 54) (P = 0.002) in the IR patients. The corresponding disease‐free survival (DFS) rates were 79.4% ± 6.5% vs. 74.4% ± 7.3% (P = 0.62) in the LR group and 63.3% ± 6.8% vs. 58.3% ± 7.2% (P = 0.66) in the IR group. Thus, the HDMTX regimen could not provide better protection of CNS relapse as compared with the CRT regimen, although their overall efficacy was not significantly different. In the ALL 911 study, intensive systemic chemotherapy with extended i,t, injections of MTX plus cytarabine achieved a high CNS relapse‐free survival (98% ± 1.9% at 7 years) and a favorable DFS (85.5% ± 5% at 7 years) in the IR patients. The patients in the high‐risk (HR) group in both ALL874 and ALL911 studies received the 18‐Gy or 24‐Gy CRT with intensive systemic chemotherapy. Their 7‐year probabilities of CNS relapse‐free survival ranged from 88% to 95%, among which the T‐ALL patients had a risk of CNS leukemia, which was 3–4 times higher compared with B‐precursor ALL patients. Conclusions These results indicate that long‐term intrathecal CNS prophylaxis as well as appropriate systemic therapy for the non–high‐risk patients can provide protection against CNS relapse equivalent to that provided by cranial irradiation. Med. Pediatr. Oncol. 32:259–266, 1999. © 1999 Wiley‐Liss, Inc.

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Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811)

Koizumi

Fujimoto²,

Takeda³

et al. 1988

Cancer

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From 1981 to 1983, 131 previously untreated patients with acute lymphoblastic leukemia (ALL) standard-risk group were entered to the protocol JCCLSG-S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by treatment with prednisone (PRD) plus vincristine (VCR) or vindesine (VDS). After preventive central nervous system (CNS) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were assigned randomly to the two maintenance chemotherapies, Regimen A and Regimen B. Regimen A (intermittent regimen) consisted of PRD (120 mg/m2/day by mouth for 5 days) plus 6-mercaptopurine (6MP) (175 mg/m2/day by mouth for 5 days) plus VCR (2.0 mg/m2 intravenously) alternating biweekly with MTX (225 mg/m2 intravenously). Regimen B (continuous regimen) consisted of 6 M P (50 mg/m2/day by mouth) plus MTX (20 mg/m2/ week by mouth) combined with pulses of PRD and VCR (the same dosages as Regimen A) every 4 weeks. As the late intensification therapy (LIT), five courses of high-dose MTX (2000 mg/m2 per dose per week intravenously for three doses every 12 weeks) with leucovorin rescue were administered to all patients who were in continuous complete remission (CCR) for more than 2 years. Sixty and 55 patients, respectively, were registered in Regimen A and B. The CCR rates in Regimen A and B were 75.1% t 5.8% (mean f 1 SE) and 49.7% ? 7.3% (P < 0.01) at 4 years, and 72.1% k 6.3% and 49.7% ? 7.3% (P < 0.05) at 5 years, respectively. In Regimen B, CNS and testicular relapses increased after 3 years of CCR. In addition, the patients in Regimen B had a much higher incidence of infections than Regimen A. The LIT did not seem to have important effects on the duration of CCR. From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy.

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Prognostic Factors in Children with Acute Lymphoblastic Leukemia — Part II: Multivariate Analysis —

Cited by 6 publications

References 0 publications

Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE)

Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE)

Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children's Cancer and Leukemia Study Group

Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811)

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