Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone.

Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p less than 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p less than 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p less than 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.     

Chemotherapy with cyclophosphamide,vincristine, cytosine arabinoside,and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL)

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness in markedly diminished in patients with prior bone marrow relapse.     

泼尼松诱导试验评估儿童急性淋巴细胞白血病预后

目的：探讨泼尼松诱导试验评估儿童急性淋巴细胞白血病(ALL)预后的价值。方法：126例ALL初治患儿按ALLXH99治疗方案行泼尼松诱导试验,口服泼尼松(60mg/m2)7d和氨甲蝶蛉加阿糖胞苷鞘内注射1次后外周血涂片计数幼稚淋巴细胞数。若幼稚淋巴细胞数<1000/μL,为泼尼松反应良好;如幼稚淋巴细胞数≥1000/μL,为泼尼松反应不良。生存分析采用KaplanMeier方法;各组生存的比较采用logrank检验;各生物学特征的比较采用χ2检验或Fisher确切概率法(双尾)。结果：110例患儿表现为泼尼松反应良好,16例患儿表现为泼尼松反应不良;5年无事件生存率(pEFS)分别为73%±5%与48%±13%,差异有统计学意义(P=0.0021)。结论：泼尼松诱导试验简单,易操作,可方便地评估早期治疗反应。     

Usefulness of cytosine arabinoside (NSC-63878) and prednisone (NSC-10023) in refractory childhood lymphoblastic leukemia

One hundred forty-three children with refractory lymphoblastic and undifferentiated leukemia (ALL/AUL) were treated with cytosine arabinoside (Ara-C) and prednisone (Pred). The dose and duration of Ara-C was escalated during induction depending on the response seen in the peripheral blood and/or bone marrow. For those achieving a remission, Ara-C was also used to determine its maintenance capabilities. Of the 143 children, 79 attained a clinical remission, 45 having a complete bone marrow remission and 34 having a partial remission. Maintenance of remission with twice weekly Ara-C was short and did not appear to depend on the amount of Ara-C given during induction. The major toxicity of Ara-C was myelosuppression.     

MicroRNA expression and activity in pediatric acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is the most common type of pediatric neoplasia. Highly heterogeneous, ALL includes several genetic subtypes with varying clinical outcome. Although, some features are well established as prognostic predictors, the details of the molecular mechanisms underlying different phenotypes are only beginning to emerge. Recently, microRNAs (miRNAs) have been shown to influence a range of physiological processes and, consequently, alterations in their expression and functions have been associated with the development of many cancers, including leukemia. This article aims to review the current state of knowledge of the role of miRNAs on the biology of childhood ALL, also including relevant findings from the adult leukemia literature.     

Relapse in childhood acute lymphoblastic leukemia after elective cessation of initial treatment: Failure of subsequent treatment with cyclophosphamide,cytosine arabinoside,vincristine and prednisone (COAP)

Although the majority of children with acute lymphoblastic leukemia (ALL) can electively stop treatment after 21/2–5 years of continuous disease-free remission, 20–25% of those patients relapse after discontinuation of therapy. We treated 15 patients whose disease recurred after stopping treatment. Fourteen of them attained complete remission, but the median duration of disease-free survival was only 11 months. In this population, the site of initial relapse, bone marrow or testicle, did not influence subsequent outcome. Patients who relapsed within six months of stopping initial therapy had shorter second remissions than those who relapsed after six months. We conclude that the combination chemotherapy utilized in this study was inadequte for the control of relapsed ALL. Future programs will have to use different drug combinations or bone marrow transplantation.     

Low- and high-risk non-T non-B and T-cell acute lymphoid leukemia (ALL) in childhood: Different duration of remission and survival

In a prospective, nonrandomized trial clinical (initial WBC and chest film) and immunological (surface immunoglobulin and rosetting with pretreated sheep red blood cells) criteria were used to stratify 69 children with previously untreated acute lymphoid leukemia (ALL). Forty of 61 evaluable patients had low-risk ALL (initial WBC ≤ 20,000/mm³, no mediastinal mass) and were treated less intensively. Twenty-one of 61 patients had high-risk ALL (initial WBC > 20,000/mm³ and/or mediastinal mass) and were treated more intensively. Of the high-risk patients 15 had non-T non-B and 6 T ALL. Sixty of 61 patients went into complete remission. After a median observation period of 27 months, 32 of 40 low-risk, 7 of 14 high-risk non-T non-B, and none of 6 high-risk T ALL patients were in continuous first remission. Thrity-six of 40 low-risk, 9 of 15 high-risk non-T non-B, and none of 6 T ALL patients were alive. Despite more intensive treatment, the duration of remission and the survival were significantly shorter in the high-risk than in the low-risk patients. Among the high-risk ALL, non-T non-B ALL did better than T ALL.     

Vincristine and prednisone vs vincristine,l-asparaginase,and prednisone for second remission induction of acute lymphocytic leukemia in children

Second remission induction rates for vincristine and prednisone alone (VP) and vincristine, L-asparaginase, and prednisone (VLP) are compared for children with acute lymphocytic leukemia. No evidence of a significant difference between the second induction complete remission rate for VP (78.6%) and VLP (73.7%) was found. Duration of first remission and prognostic group at initial diagnosis (defined on the basis of age and white blood count at initial diagnosis) are shown to be significant prognostic factors for second remission induction; and three second remission induction risk groups are defined on the basis of these two factors. Periodic reinforcement with prednisone in first remission does not appear to lower second induction complete response (CR) rates for VP. There was no evidence of a significant difference in the frequency of occurrence of severe toxicity between the VP and VLP regimens.     

Early deaths in acute lymphoblastic leukemia (ALL): Results of the Italian pediatric cooperative group for therapy of acute leukemia (AIL-AIEOP)

In this retrospective multicentric study, we report on early deaths (ie, those that occurred during the first month of treatment) in a total of 943 newly diagnosed ALL pediatric patients registered from 1976 to 1981 at 21 centers of the AIL-AIEOP. Objectives of this study were as follows: (1) to verify the incidence and the cause of early death in a wide population of children with ALL and (2) to elucidate factors associated with early death and therefore to identify “high-risk” groups of patients. Out of the 943 ALL patients, 39 (4.1%) early deaths were registered. Main causes were infection, 20 patients (51.3%); hemorrhage, 11 patients (28.3%); uric acid nephropathy, 2 patients (5.1%); cardiac failure, 3 patients (7.6%); syndrome of inappropriate antidiuretic hormone secretion, 1 patient. Two patients died during the first week of unknown cause. Thirteen factors measured at diagnosis and possibly influencing the early death rate were analyzed. Using the chi-square test, only three of these factors (age, mediastinum status, surface markers) appear to have any significant influence on the early death rate. We also tried to determine how therapy influences this process by analyzing variations in the early death rate, other factors being equal. Significant differences in the early death rates were encountered in AIEOP protocols using different induction regimens.     

Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.     

Incidence of childhood acute lymphoblastic leukemia (ALL) and population-based treatment results in Switzerland: Experiences with 507 study and 149 nonstudy patients

Of 656 patients with ALL (all types) diagnosed in Switzerland during 4 consecutive 4-year periods (1976–1979, 1980–1983, 1984–1987, 1988–1991), 507 were officially registered on protocols (“study” patients) while 149 were not (“nonstudy” patients). The mean incidence of 3.8/100,000 children <15 years/year is higher than reported for other Western countries. Evidence is presented suggesting that the 656 patients represent only approximately 90% of all children with ALL residing in Switzerland, indicating that the true incidence of ALL might even be higher. The fraction of “nonstudy” patients fell from 40% (1976–1979) to 15% (1984–1987). The rate of survival at 4 years of all patients with ALL (“study” and “nonstudy”) increased by 17% during the three consecutive periods 1976–1979, 1980–1983, and 1984–1987. As expected, a higher increase (20%) was observed in “study” patients and a statistically nonsignificant lower one (10%) in “nonstudy” patients. © 1995 Wiley-Liss, Inc.     

Low-dose adriamycin remission maintenance for advanced acute lymphoblastic leukemia: A southwest oncology group study

A low-dose maintenance schedule of adriamycin was evaluated in children with advanced acute lymphoblastic leukemia. Thirty-six evaluable patients who achieved two or more remissions were given adriamycin, 10 mg/m²/week, as a single maintenance agent. The median duration of second remission was 17 weeks, but only 5 weeks for third and fourth remission. Although the therapy was not found effective in more advanced disease, the median duration of second remission approached that obtained from various multi-agent treatment schedules. We conclude that the therapeutic efficacy of this treatment schedule makes it appealing for incorporation into multi-drug combination regimens.     

Interphase cytogenetic study of childhood acute lymphoblastic leukemia

We used the fluorescence in situ hybridization (FISH) technique and centromere-specific probes for chromosomes 1, 6, 8, 10, 12, 17, 18, X, and Y to investigate the presence and number of the respective chromosomes in interphase nuclei of 14 cases of childhood acute lymphoblastic leukemia (ALL) which were shown to be hyperdiploid by DNA flow cytometry irrespective of their cytogenetic pattern. Numerical anomalies for one or more chromosomes were detected in all 14 cases. The FISH results were compared with those obtained by conventional cytogenetic analysis. A hyperdiploid karyotype was evident in 5 cases, the others were either normal or lacking cytogenetic results because of technical failure. In the 5 cytogenetically hyperdiploid cases, 14 numerical abnormalities were observed with both techniques, whereas 4 numerical deviations were found only with FISH. In 9 other cases which had a DNA content indicating hyperdiploidy, 34 trisomies and 2 tetrasomies were detected by FISH analysis. Furthermore, in 1 case duplication of the Y chromosome and in 3 male cases duplication of the X chromosome were evident. Double-target FISH experiments in 2 patients allowed the correlation of numerical aberrations of 2 chromosomes in one and the same cell. By such analyses, detection of subpopulations of tumor cells was found to be relatively easy. Our results indicate that the FISH technique with chromosome-specific repetitive centromeric probes is a rapid, simple to use, and easy to interpret technique for the evaluation of numerical chromosomal aberrations in interphase nuclei of leukemias. © 1994 Wiley-Liss, Inc.     

Moyamoya syndrome following childhood acute lymphoblastic leukemia

BACKGROUND: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) sometimes suffer from adverse long-term sequelae. We analyzed the incidence, clinical course and prognosis of moyamoya syndrome (MoS) following childhood ALL. PROCEDURE: A total of 1,846 ALL patients were treated with four consecutive TCCSG ALL protocols (L84-11, L89-12, L92-13, and L95-14) between 1984 and 1999. We surveyed the MoS cases among these patients in the follow-up studies. RESULTS: Six patients with MoS were identified: four boys and two girls whose ages ranged from 2 years and 1 month (abbreviated as "2y1m") to 14y 1 m at diagnosis of ALL. None of the patients had central nervous system (CNS) leukemia. All six patients received prophylactic cranial irradiation with a dosage of 18 or 24 Gy. Although one patient died of brain infarction due to MoS, no leukemic relapse was observed in the group. The cumulative incidence of MoS in our series was 0.46 +/- 0.02% at 8 years. Among several clinical characteristics, use of cranial irradiation was the only factor that appeared to be significantly related to the development of MoS. CONCLUSIONS: MoS occurs with increased frequency in children treated for ALL, and might be associated with cranial irradiation. Prophylactic cranial irradiation should be used cautiously in ALL patients who can be cured by other CNS-directed therapies.     

Three dose regimens of adriamycin for induction of remission in acute leukemia in children: A Southwest oncology group study

Three therapeutic regimens (6-hr intervals for 6 doses daily for 3 days, and a single infusion) utilizing the same total dose of adriamycin for the induction of remission in children with late-stage acute leukemia were evaluated in 150 patients. Complete remission rates were 15%, 28%, and 25%, respectively. Twenty-five children who achieved complete bone marrow remissions with adriamycin therapy were treated a second time after subsequent relapses. Of these children 20% achieved second bone marrow remissions.     

Neuroanatomical abnormalities related to dexamethasone exposure in survivors of childhood acute lymphoblastic leukemia

Survivors of childhood acute lymphoblastic leukemia (ALL) treated with chemotherapy only are at risk for neurocognitive impairment. Regions of interest were identified a priori based on glucocorticoid receptor distribution, and sex‐stratified multivariable linear regression models were used to test associations between brain MRI morphology and total number of intrathecal injections, and serum concentration of dexamethasone and methotrexate. Compared with controls, ALL survivors have persistently smaller volumes in the bilateral cerebellum (P < 0.005), hippocampal subregions (P < 0.03), temporal lobe regions (P < 0.03), frontal lobe regions (P < 0.04), and parietal lobe regions (precuneus; P < 0.002). Long‐term problems with learning may be related to residual posttreatment brain differences.     

微小残留病在监测儿童急性T淋巴细胞白血病复发中的意义

目的 探讨徽小残留病(MRD)监测急性T琳巴细胞白血病患儿复发的临床指导意义.方法 采用四色流式细胞术对2006年8月1日-2008年4月1日32例急性T琳巴翻胞白血病住院患儿在治疗不同时间点进行追殊监测,分析不同MRD水平与患儿的临床反应及复发之间的关系.结果 诱导治疗第33天以及诱导治疗结束巩固治疗前(治疗12周)...