阿糖胞苷代谢关键酶活性与大剂量阿糖胞苷治疗时药物血浓度关系研究*

目的:通过检测急性白血病（AL）及非霍奇金淋巴瘤（NHL ）患儿骨髓单个核细胞内阿糖胞苷（Ara-C）代谢关键酶- 脱氧胞苷激酶（DCK ）、胞苷脱氨酶（CDA ）活性及静滴大剂量阿糖胞苷（HD-AraC ）后2h 外周血中Ara-C、阿糖尿苷（Ara-U）的浓度,分析DCK 、CDA 活性与外周血中Ara-C、Ara-U 血浆峰浓度的关系。探索Ara-C 的体内代谢特征,以及Ara-C 代谢关键酶活性表达对儿童恶性血液肿瘤接受HD-AraC 治疗时药物血浓度的影响。方法:采用同位素3H-Cytidine 做为放射底物检测24例患儿骨髓单个核细胞内DCK 、CDA 酶活性,同时采用高效液相色谱法（HPLC）和Ara-C、Ara-U 标准品测定静滴HD-AraC 2h 后血浆Ara-C、Ara-U 的峰浓度,统计分析DCK 、CDA 酶活性表达强弱与外周血Ara-C、Ara-U 峰浓度的相关性。结果:CDA 酶活性表达强弱明显影响Ara-C、Ara-U 的血浆峰浓度（P<0.05）:CDA 酶活性高的患儿,Ara-U 血浆峰浓度高,Ara-C 血浆峰浓度低;CDA 酶活性低的患儿,Ara-U 血浆峰浓度低,Ara-C 血浆峰浓度相对高。但是,DCK 酶活性与Ara-C、Ara-U 的血浆峰浓度未见显著性相关（P>0.05）。 结论:HD-AraC 是治疗儿童难治型恶性血液肿瘤的有效疗法,但是CDA 酶活性表达强弱将显影响患儿个体所能达到Ara-C、Ara-U 的血浆峰浓度,进而对Ara-C 疗效和骨髓抑制等治疗反应产生影响。因此,检测CDA 酶活性表达,有可能为临床适当调整药物剂量,开展个体化治疗,提供较为可靠的参考依据。      

中、大剂量阿糖胞苷治疗缓解期急性非淋巴细胞白血病的疗效探讨

目的 对中、大剂量阿糖胞苷(ID／HD Ara-C)为主的化疗方案治疗急性非淋巴细胞白血病缓解期的疗效进行研究。方法 化疗前用MTT法测定骨髓病变细胞对不同浓度Ara-C的药物敏感性,化疗时测定其血药浓度及脑脊液中药物浓度,观察疗效及毒副作用。结果 93.3％患者骨髓病变细胞对高浓度Ara-C敏感,其中28．6％对中浓度Ara-C敏感,所有患者对低浓度Ara-C不敏感。血浆中Ara-C浓度随滴注时间逐步上升,滴注结束后迅速下降,药物可顺利通过血脑脊液屏障。该治疗毒副反应轻。结论 ID／HD Ara-C治疗既可强烈清除缓解后体内残留的肿瘤细胞,又能有效预防中枢神经系统白血病,且毒副作用小,在体内代谢快,无药物累积。     

氟达拉滨联合阿糖胞苷及粒细胞集落刺激因子治疗儿童难治及复发性急性白血病

 【摘要】　目的　观察氟达拉滨（Flud）联合阿糖胞苷（Ara-C）及粒细胞集落刺激因子（G-CSF）（FLAG）方案治疗儿童难治及复发性急性白血病（AL）的疗效及患者不良反应。方法　9例复发及难治性AL患儿接受了FLAG方案治疗,Flud 每天30 mg／m2,第1天至第5天,静脉滴注30 min;Ara-C每天2 g／m2,Flud应用后4 h静脉滴注,第1天至第5天。G-CSF 5 μg?kg-1?d-1,中性粒细胞＜0.5×109／L时开始应用,用至中性粒细胞 ≥1×109／L。9例患儿中急性髓系白血病（AML）8例,急性淋巴细胞白血病（ALL）1例;难治性AL 5例,复发性AL 4例。结果　9例患儿中经1个疗程化疗达完全缓解（CR）6例,部分缓解（PR）2例,总有效（CR+PR）率 88.9 %（8／9）。6例CR患者中2例行造血干细胞移植,现均无瘤生存;患者主要不良反应是感染、骨髓抑制和胃肠道反应。结论　FLAG方案治疗儿童难治及复发性AL缓解率高,不良反应可以耐受,是治疗儿童难治及复发性AL的一个选择,为后续的造血干细胞移植提供了机会。     

去甲氧柔红霉素或柔红霉素联合阿糖胞苷诱导治疗急性髓系白血病的疗效比较

 目的　探讨去甲氧柔红霉素（IDA）+阿糖胞苷（Ara-C）（IA方案）及柔红霉素（DRA）+ Ara-C（DA方案）诱导治疗急性髓系白血病（AML）的疗效的比较。方法　回顾性分析确诊并行IA方案（IDA每天8～12 mg／m2静脉滴注,第1天至第3天;Ara-C每天100～150 mg／m2,每12 h静脉滴注1次,第1天至第7天）或DA方案（DNR每天40～50 mg／m2静脉滴注,第1天至第3天;Ara-C用法同IA方案）诱导治疗的93例AML患者的临床资料,用SPSS13.0软件包对上述两个组的完全缓解（CR）率、有效率进行分析。结果　IA组和DA组的CR率为72.5 %、47.2 %（χ2＝5.011,P＜0.05）,有效率为82.5 %、77.4 %（χ2＝0.122,P＞0.05）。结论　对于急性髓系白血病的诱导治疗,IA方案较DA方案具有更高的诱导CR率。所需要的天数分别为16.62±3.07vs18.88±4.63、16.56±4.18vs15.50±5.06、23.69±9.61vs21.76±8.68、20.87±2.45vs21.75±5.17及24.18±2.68vs24.29±6.87,粒细胞缺乏持续的天数为10.36±4.72vs12.44±7.21,上述各组P均大于0.05。结论：对于急性髓系白血病的诱导治疗,IA较DA方案有更高的CR率,而未增加骨髓的毒副作用。     

国产去甲氧柔红霉素联合阿糖胞苷和依托泊苷治疗难治性急性髓系白血病17例

 目的　观察国产去甲氧柔红霉素（IDA）联合阿糖胞苷（Ara-C）和依托泊苷（VP16）组成的IAE方案治疗难治性急性髓系白血病（AML）的疗效。方法　IDA 7 mg／m2静脉滴注连续3 d,Ara-C 100 mg／m2和VP16 100 mg／d均静脉滴注连续5 d为1个疗程。结果　17例患者中,完全缓解（CR） 9例,52.9 %;部分缓解（PR）4例,23.9 %;未缓解3例,脑出血死亡1例。结论　IAE 方案治疗难治性白血病疗效较好,主要不良反应为骨髓抑制、 粒细胞减少及血小板减少。 未发现心、肝、肾毒副作用。     

羟基喜树碱联合阿糖胞苷和三尖杉酯碱治疗急性髓性白血病15例

 目的 观察羟基喜树碱联合三尖杉酯碱和阿糖胞苷治疗初治急性髓细胞白血病（AML）（急性早幼粒细胞白血病除外）的完全缓解率（CR）。方法 羟基喜树碱联合阿糖胞苷和三尖杉酯碱治疗AML。结果 一个疗程后缓解11例（11／15）,二个疗程后缓解13例（13／15）;PR 2例（2／15）。从诊断到完全缓解所需时间为26 ~ 64 d。结论 羟基喜树碱联合阿糖胞苷和三尖杉酯碱组成的化疗方案,不良反应并没有明显增加,治疗效果有所提高,可以进一步应用观察。     

大剂量甲氨蝶呤、阿糖胞苷联合左旋门冬酰胺酶治疗复发难治性急性淋巴细胞白血病13例

 【摘要】　目的　探讨大剂量甲氨蝶呤（MTX）、阿糖胞苷（Ara-C） 联合左旋门冬酰胺酶（L-Asp）治疗复发难治性急性淋巴细胞白血病（ALL）的疗效及患者不良反应。方法　复发难治性ALL患者13例,分别接受MTX 2 g ／m2,静脉滴注,持续24 h;Ara-C 2g／m2,共2d;L-Asp 5000～10 000 U／ 次,每天或隔天1 次,共5次。结果　2个疗程后,13例患者中7例（53.8 ％）完全缓解,2例（15.4 %）部分缓解,总有效率69.2 ％。中位缓解时间9 个月。骨髓抑制较明显,肝功能损害较轻,无一例患者于化疗期间死亡,无肾损伤、胰腺炎等发生。结论　大剂量MTX 、Ara-C联合L-Asp 用于儿童或成年人复发难治性ALL 的再诱导治疗,缓解率高,耐受性好,疗效肯定。     

急性淋巴细胞白血病小鼠甲氨蝶呤化疗后血及脑组织药物浓度的对比研究

 目的　探索急性淋巴细胞白血病小鼠不同剂量甲氨蝶呤（MTX）化疗后血和脑组织药物浓度的关系。方法　4周龄清洁级普通昆明小鼠80只：建立急性淋巴细胞白血病小鼠模型,随机抽取20只小鼠经股骨取骨髓行骨髓细胞学检查作模型验证;依据MTX化疗剂量与标本采取时间点的不同将余60只急性淋巴细胞白血病小鼠分为六组,每组10只,分别为A、B、C、D、E、F组;各组均取0.5 ml血液及0.4 g脑组织,血液离心,脑组织匀浆后离心,取上清用荧光偏振免疫方法检测药物浓度。结果　A、B、C、D、E、F六组平均MTX血药浓度分别为（39.08±5.18）μmol／L、（15.86±1.02）μmol／L、（8.67±5.43）μmol／L、（68.29±5.19）μmol／L、（29.55±6.22）μmol／L、（13.98±1.12）μmol／L,组间比较差异有统计学意义（P＜0.05）;各组脑组织平均MTX浓度依次为：（1.05±0.26）μmol／L、（0.61±0.25）μmol／L、（0.48±0.25）μmol／L、（2.07±0.35）μmol／L、（1.27±0.21）μmol／L、（0.59±0.69）μmol／L,组间比较差异有统计学意义（P＜0.05）;六组血与脑组织药物浓度相关系数依次为：0.82、0.75、0.19、0.81、0.55、0.43。结论　急性淋巴细胞白血病小鼠经大剂量MTX（HD-MTX）方案化疗后,于0.5 h出现血及脑组织药物浓度峰值,5 g／m2较3 g／m2能更好地透过血脑屏障使脑组织药物浓度达到有效治疗浓度。     

国产去甲氧柔红霉素和进口柔红霉素治疗急性白血病的疗效及安全性比较

 目的　对比国产去甲氧柔红霉素（IDA）和进口柔红霉素（DNR）在急性白血病治疗中的的疗效和安全性。方法　68例急性白血病患者随机分为IDA组35 例和DNR组33例。IDA组35 例患者中,急性髓细胞白血病用IA（国产IDA、阿糖胞苷）方案治疗,急性淋巴细胞白血病用VICLP（长春新碱、国产IDA、环磷酰胺、左旋门氡酰氨酶和泼尼松）方案治疗;同期DNR组33例患者中,急性髓细胞白血病用DA（进口DNR、阿糖胞苷）方案治疗,急性淋巴细胞白血病用VDCLP（长春新碱、进口DNR、环磷酰胺、左旋门氡酰氨酶和泼尼松）方案治疗。结果　IDA组完全缓解21例,部分缓解5例,总缓解率74.2 %（26／35）,DNR组完全缓解16例,部分缓解4例,总缓解率62.3 %（20／33）,两组总缓解率差异无统计学意义（χ2＝0.89,P＝0.50）;IDA组缓解时间超过一年者占完全缓解患者的80 %（17／21）,而DNR组为37.5 %（6／16）,两组差异有统计学意义（χ2＝5.56,P＝0.02）。结论　国产IDA治疗急性白血病缓解率及长期缓解率均优于进口DNR,是疗效确切、安全可靠的抗白血病药物。     

全反式维A酸并用吡柔比星+阿糖胞苷方案诱导缓解急性早幼粒细胞白血病的临床观察

目的探讨全反式维A酸诱导缓解急性早幼粒细胞白血病治疗过程中引起的高白细胞淤滞综合征的治疗效果。方法在21例急性早幼粒细胞白血病诱导缓解治疗时，采用全反式维A酸并用小剂量吡柔比星（THP）＋阿糖胞苷（Ara-C）方案。结果21例急性早幼粒细胞白血病患者联合治疗后的完全缓解率达85．7％。无一例出现维A酸相关综合征，与单用全反式维A酸疗效相似，达到完全缓解的时间有所缩短。结论全反式维A酸并用小剂量THP＋Ar-a-C方案诱导缓解治疗急性早幼粒细胞白血病可能更安全，获得完全缓解更快。     

High-dose cytarabine treatment in acute leukemias and leukemic meningiosis: clinical aspects and pharmacokinetics

Clinical reports concerning the therapeutic effects of high dose Cytosine arabinoside (HD Ara-C) in meningeal leukemia are relatively rare. Pharmacokinetic studies, however, have indicated potentially effective concentrations of Ara-C in cerebrospinal fluid (CSF) during and after high-dose infusions of the drug given intravenously. In this report, the treatment results of HD Ara-C in 14 patients with refractory or relapsed acute leukemia are presented including those of 2 patients with meningeal leukemia. In these 2 patients as well as in 1 patient without central nervous system (CNS) leukemia, Ara-C and Ara-U concentrations in CSF and plasma were measured during a 6-day therapy with HD Ara-C (3 g/m2 q 12h 12 X). Ara-C and Ara-U levels were determined on Days 3 and 6 of therapy, each at the end of a 3-h i.v. infusion of the drug. In the 14 patients (8 with AML, 6 with ALL) treated, a total number of 17 treatment cycles were given for remission induction with doses of Ara-C ranging from 1-3 g/m2 q 12 h 6-12 X. A complete remission rate of 47% was achieved. The duration of remission ranged from 1 to 6 months. Of the 2 patients with CNS leukemia, 1 patient achieved complete remission both in CSF and in bone marrow, the other patient only in CSF. The mean concentration of Ara-C in CSF was 903 ng/ml with a ratio of 0.38 to that in plasma. Ara-C and Ara-U did not appear to accumulate in CSF or in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical effect of low-dose Ara-C in patients with refractory acute nonlymphocytic leukemia and myelodysplastic syndrome

Twenty-one patients with refractory acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndrome were treated with low-dose cytosine arabinoside (LDARC). LDARC was administered by subcutaneous injection every 12 hours at a dose of 10 mg/m2 (regimen A) or at a dose of 20 mg/m2 by continuous intravenous infusion (CIV) or continuous subcutaneous injection (CSC) (regimen B). Among 22 courses, two elderly patients with ANLL (M4 and M5) and one M4 patient with myelofibrosis obtained complete remission (CR) and three elderly patients with ANLL (one M1 and two M2) and one patient with ANLL developed from RAEB in transformation obtained partial remission (PR). The overall remission rate (CR + PR) was 31.8%. The CR durations were 2.5, 5 and 2 months, respectively. The plasma concentration of Ara-C determined in regimen B was 8.26 +/- 4.12 ng/ml. There was no difference in the plasma concentration of Ara-C between CIV and CSC. We consider that the major mode of action of LDARC lies in its cytotoxic effect, since all patients who obtained remission exhibited pancytopenia and bone marrow hypoplasia. However, in several patients, we observed transient monocytosis and granulocytosis which were considered to be suggestive evidence of differentiation of leukemia cells.     

Clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in a patient with acute non-lymphocytic leukemia with two CNS recurrences

A case of two repeated CNS recurrences of acute non-lymphocytic leukemia (M2) was treated with intermediate dose Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-lymphocytic leukemia (M2) achieved complete remission by combination chemotherapy of Behenoyl-ara-C, Daunorubicin, 6-Mercaptopurine and Prednisolone in July, 1985. He subsequently received consolidation and intensification therapy with periodical intrathecal injection of Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of Ara-C and MTX. As he also relapsed systemically, Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of Ara-C is achieved throughout the CNS by this therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of Ara-C, which is enough concentrations for its cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including Behenoyl-ara-C, an analog of Ara-C, and was resistant to the intrathecal administration of Ara-C. These findings suggest that intermediate dose Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including Ara-C, and also, in some cases, more effective than intrathecal injection of antileukemic drugs for the treatment of CNS leukemia.     

Remission induction of meningeal leukemia with high-dose intravenous methotrexate

Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.     

The role of cytosine arabinoside maintenance in acute nonlymphoblastic leukemia.

A series of 30 unselected patients with acute nonlymphoblastic leukemia (ANLL) was treated with combination chemotherapy, including three courses of cytosine arabinoside (Ara-C) by 5-day continuous i.v. infusion, vincristine i.v. weekly, and prednisone daily to complete remission. Ara-C was administered alone as a 5-day continuous i.v. infusion monthly for maintenance. Ten (33%) achieved a complete remission (CR). The remaining 30 (67%), including temporary partial remissions, hematologic improvements, inadequate trials, and early deaths, were all considered failures. The CR rate was 57% in those 17 cases receiving an adequate trial. After After 5 1/2 years' followup, the overall median survival, including cases failing to achieve CR, was 3.1 months. For those having adequate trials the median survival was 16.6 months, and for those achieving a CR, 36.6 months. Two patients are still alive, one at 55.2 months on maintenance therapy, and the other at 62.8 months, currently unmaintained.     

Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study

Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered.     

High-Dose Mercaptopurine and Intermediate-Dose Cytarabine During First Remission of Acute Myeloid Leukemia

High-dose, continuous infusion of intravenous mercaptopurine (HD 6MP) followed by intermediate-dose continuous cytarabine (ID Ara-C) has been shown to produce remissions in children with relapsed acute myeloid leukemia (AML). The purpose of this pilot study was to explore the feasibility of using this drug regimen as a component of treatment during the first remission of AML. Of 17 children with newly diagnosed AML registered in the study, 14 developed complete remission on conventional induction therapy and subsequently received the HD 6MP and ID Ara-C combination. The dosages of HD 6MP were escalated from 500 mg/m² to 1250 mg/m² in 24-hr infusions. The initial dosages of ID Ara-C were escalated from 250 mg/m² to 650 mg/m²/24 hr and from 1 day to 4 days. Conventional treatment for AML was administered simultaneously. Seven of the 14 children remain in initial complete remission for 15 to 46 months and have completed treatment. Severe pancytopenia was observed in all patients, but there were no toxic deaths and no deaths during remission. The inclusion ofHD 6MP and ID Ara-C in the treatment of AML in first remission appears to be feasible. Evaluation of its efficacy will require a comparative clinical trial.     

2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.

PURPOSE: The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia. PATIENTS AND METHODS: Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients. RESULTS: Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L). CONCLUSION: 2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.     

A case of complete remission from acute myelogenous leukemia in second relapse achieved using an intermediate-dose cytosine arabinoside (ID Ara-C) regimen

A 57-year-old-male patient with acute myelogenous leukemia in second relapse who was refractory to BHAC . AMP [behenoyl arabinosyl cytosine (BHAC), aclacinomycin, 6-mercaptopurine and prednisolone (PSL)] and BHAC . DVP [BHAC, daunomycin, vincristine and PSL] was treated with an intermediate-dose cytosine arabinoside (ID Ara-C) regimen. This schedule consisted of a 1-h infusion of Ara-C at a dose of 500 mg/m2 every 12 h for 6 d (days 3-8), in combination with doxorubicin 50 mg/m2 on day 1 and vincristine 1 mg/m2 on day 2. The patient achieved a complete remission 23 days after completion of Ara-C and was treated with ID Ara-C (Ara-C days 3-6) as a consolidation. Remission duration was only 2.5 months. Plasma Ara-C concentrations were assayed by HPLC and the peak level was 6.7 micrograms/ml. Side effects were mild nausea, vomiting, alopecia and moderate skin rash.