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。     

伊马替尼联合HAG方案治疗慢性粒细胞白血病急变期临床观察

目的 探讨使干扰素治疗失败的慢性粒细胞白血病(CML)急变期达完全缓解的有效方法.方法 CML急变期患者8例,Ph染色体、bcr-abl融合基因均阳性.2例出现附加染色体.每例患者急变前除应用羟基脲外,均应用过3个月以上干扰素,5例患者曾用含阿糖胞苷(Ara-C)的不同方案化疗,均未服用伊马替尼.8例急变期患者均服用伊马替尼600 mg/d,联合HAG方案[高三尖杉酯碱(HH)1～2mg/d,Ara-C 15～25mg每12h 1次,粒细胞集落刺激因子(G-CSF)200μg/m2].根据患者年龄、血常规、骨髓象决定用药剂量及时间长短.结果 2例达血液学部分缓解,6例达血液学完全缓解,继续服用伊马替尼600mg/d.6例血液学完全缓解者达遗传学缓解,生存时间6(3～9)个月,均未达分子生物学缓解.中位血液学复发时间10(3～26)个月,伊马替尼联合HAG方案治疗中位生存时间17(8～28)个月.结论 伊马替尼联合HAG方案治疗CML急变期患者安全有效.     

伊马替尼联合HAG方案治疗慢性粒细胞白血病急变期临床观察

目的 探讨使干扰素治疗失败的慢性粒细胞白血病(CML)急变期达完全缓解的有效方法.方法 CML急变期患者8例,Ph染色体、bcr-abl融合基因均阳性.2例出现附加染色体.每例患者急变前除应用羟基脲外,均应用过3个月以上干扰素,5例患者曾用含阿糖胞苷(Ara-C)的不同方案化疗,均未服用伊马替尼.8例急变期患者均服用伊马替尼600 mg/d,联合HAG方案[高三尖杉酯碱(HH)1～2mg/d,Ara-C 15～25mg每12h 1次,粒细胞集落刺激因子(G-CSF)200μg/m2].根据患者年龄、血常规、骨髓象决定用药剂量及时间长短.结果 2例达血液学部分缓解,6例达血液学完全缓解,继续服用伊马替尼600mg/d.6例血液学完全缓解者达遗传学缓解,生存时间6(3～9)个月,均未达分子生物学缓解.中位血液学复发时间10(3～26)个月,伊马替尼联合HAG方案治疗中位生存时间17(8～28)个月.结论 伊马替尼联合HAG方案治疗CML急变期患者安全有效.     

脑原发淋巴瘤8例综合治疗分析

目的分析脑原发淋巴瘤的临床特点,探讨其治疗方式。方法8例脑原发淋巴瘤中7例行手术切除,1例行立体定向活检。8例均行放射治疗,1例接受γ刀治疗,7例6MV X线常规分割照射,全脑照射30～46 Gy,病灶区剂量40～56 Gy。6例接受了化疗,行CHOP方案4例,大剂量甲氨蝶呤(MTX)为主的化疗2例,鞘注MTX 3例。结果患者近期疗效好,全组生存时间为8～47个月,中位生存期19个月。1、3年生存率分别为75.0%和31.3%。加化疗未延长生存期,予MTX化疗者生存时间较长。结论脑原发淋巴瘤预后差,全脑放疗为主要治疗方式之一,放疗与MTX为主的化疗方案的综合治疗有可能提高疗效。     

体部伽玛刀治疗胆管癌所致梗阻性黄疸的临床观察

目的 观察体部伽玛刀治疗胆管癌所致恶性梗阻性黄疸患者的症状改善情况、近期和远期疗效.方法 对76例胆管癌所致恶性梗阻性黄疸患者采用OUR-QGD体部伽玛刀治疗.单次治疗剂量为3.0 ～ 4.0 Gy,等剂量曲线为50.0％～65.0％,共计10～12次.治疗中监测肝功能、血常规及不良反应.治疗后定期随访观察患者症状的改善情况,评价近期疗效和远期生存.结果 76例患者中,69例黄疸症状明显减轻,且总胆红素及丙氨酸氨基转移酶水平较治疗前降低（P＜0.05）;客观缓解率为88.16％（67/76）,疾病控制率为90.79％（69/76）.患者中位疾病进展时间为8.8个月,中位总生存时间为13.4个月.结论 采用体部伽玛刀治疗胆管癌所致恶性梗阻性黄疸可显著改善患者的症状,提高患者的生存质量.该疗法患者不良反应小,近远期疗效均较为满意.     

碳离子束治疗皮肤恶性黑色素瘤的近期疗效

目的 评价碳离子(~(12)C~(6+))束对皮肤恶性黑色素瘤放射治疗的近期疗效和副反应.方法 13例皮肤恶性黑色素瘤患者分6批接受~(12)C~(6+)束放射治疗,其中Ⅱ_a期2例,Ⅱ_b期3例,Ⅱ_c期5例,Ⅲ_c期3例.照射总剂量60～66 GyE分6～12 d,单次剂量2.2～4.4 GyE,1次/d,连续治疗.采用RTOG标准和WHO近期疗效标准分别评价副反应和近期疗效.结果 中位随访时间为13.5个月(1～25个月),随访率为100%.13例患者中完全缓解10例,部分缓解3例,有效率为100%,中位生存时间为21.3个月(95%可信区间为18.1～24.5个月).皮肤反应0级3例,1级6例,2级2例,3级2例.血液系统副反应治疗前后无明显改变.结论 ~(12)C~(6+)束治疗皮肤恶性黑色素瘤近期疗效好,且并发症轻.     

一次大剂量M.T.X.治疗滋养叶细胞肿瘤

本文报导了应用一次大剂量氨甲喋吟(MTX)静脉内注入治疗滋养叶细胞肿瘤的方法、效果、疗效评价及药物毒性反应。并与该院在1961～1970年间应用Hentz的修改方法(即每天静注20～25毫克持续5天,间隔5～7天重复)对照。治疗方法:MTX静注按1平方米体表面积60毫克计算。每五天静注一次。一疗程总剂量在240～900毫克间(取决于疗效),一次有效剂量是80～110毫克。诊断:应用一次大剂量MTX治疗的     

非小细胞肺癌调强放化疗的近期疗效观察

目的:分析调强放疗(IMRT)联合化疗治疗局部晚期非小细胞肺癌(NSCLC)的近期疗效和毒副反应.方法:48例局部晚期不能手术或不愿手术的NSCLC患者,采用IMRT同步联合化疗综合治疗.放疗采用5～7野IMRT技术,单次剂量2.0～2,2 Gy,每周5次,中位总剂量60 Gy(54～66 Gy).所有患者均接受2个周期长春瑞滨加顺铂方案同步化疗,放疗结束后辅助2～4个周期化疗.结果:所有患者均顺利完成同步放化疗计划.放疗结束3个月后评价疗效,CR为21％(10/48),PR为60％(29/48),SD为13％(6/48),PD为6％(3/48),有效率为81％(39/48).中位随访时间为11个月(7～30个月),中位生存时间为25个月,1和2年总生存率分别为73％和39％.按RTOG标准评价放疗毒副反应,放射性食管炎Ⅰ级15例,Ⅱ级11例,Ⅲ级1例;放射性气管炎Ⅰ级14例,Ⅱ级8例,Ⅲ级3例;放射性肺炎Ⅰ级6例,Ⅱ级4例,Ⅲ级1例.结论:IMRT联合化疗对局部晚期NSCLC患者有较好的疗效,毒副反应可以被绝大多数患者耐受,对生存率的提高有待进一步研究.     

小剂量地西他滨联合CAG方案治疗老年人急性髓系白血病及中高危骨髓增生异常综合征临床分析

目的 探讨小剂量地西他滨(DAC)治疗老年人急性髓系白血病(AML)和中高危骨髓增生异常综合征(MDS)的临床价值.方法 对19例老年AML和中高危MDS患者使用小剂量DAC(10 mg/d,连用7 d)联合CAG方案[重组粒细胞集落刺激因子(G-CSF)+阿糖胞苷(Ara-C)+阿柔比星]进行治疗;1个疗程后对疗效及不良反应进行综合评估;对患者进行生存期跟踪随访.结果 1个疗程治疗后,完全缓解8例,部分缓解7例;4个疗程治疗后,完全缓解13例(68.4%),总体反应率达到78.9%(15/19),化疗相关不良反应少.随访42个月,生存12例,中位生存时间为13.5个月(3~42个月).结论 对于中高危MDS和老年AML患者,小剂量DAC联合CAG方案有较好的疗效、较高的安全性、较低的经济负担,有利于改善患者的治疗依从性.     

立体定向放射治疗颅内肿瘤139例疗效观察

目的　探讨立体定向放射治疗颅内肿瘤方法及疗效。方法　 1997年 11月至 1998年 11月间对 13 9例颅内肿瘤行立体定向放射治疗 (StereotacticRadiotherapySRT)。其中良性肿瘤 73例 ,采用 1～ 2次大剂量或体积分隔治疗 ,肿瘤周边剂量为 18～ 3 5Gy ;恶性肿瘤 66例 ,分 3～ 10次SRT治疗加全脑放疗。肿瘤周边剂量为 15～ 3 5Gy ,全脑照射 3 0～ 40Gy/4～ 4.5周。结果　全组病例随访 1～ 15个月 ,良性肿瘤生存率 10 0 % ,病灶CT显示 5 4例 ( 73 .9% ) ,肿瘤病灶影CT值降低、体积缩小或消失 ,未见严重的并发症。恶性肿瘤中位生存 9个月 ,CT显示 61例 ( 92 .4% )有效 ,其中11例 ( 16.7% )肿瘤病灶消失。结论　对体积较大或危险区的良性肿瘤 ,可采用多等中心体积分隔治疗或分两次治疗 ,并发症少 ,仍可达到较好的疗效。恶性肿瘤分次治疗加放疗 ,疗效好、合并症少见     

High-dose methotrexate in combination with interferons in the treatment of malignant pleural mesothelioma.

Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks. Natural interferon (IFN)-alpha (3 MIU days 2-10) and recombinant IFN-gamma1b (50 microg m(-2) on days 2, 6 and 10) were injected subcutaneously after each MTX dose. At the end of MTX treatment the IFNs were continued as maintenance therapy until disease progression. Seven partial responses were observed among 24 patients evaluable for response (response rate 29%, 95% confidence interval 13-51%). Median duration of response was 10 months (range 3-24 months). Median survival was 17 months and 1-year and 2-year survival rates 62% and 31% respectively. The toxicity of the chemo-immunotherapy was acceptable. Treatment was stopped in one patient who developed grade IV neurological toxicity. MTX dose reductions were rare (two patients with grade 1-2 renal toxicity). The combination of high dose MTX and IFN-alpha and IFN-gamma is active against malignant pleural mesothelioma and well-tolerated. The survival rates are encouraging.     

Central nervous system (CNS) prophylaxis in children with low risk acute lymphoblastic leukemia (ALL)

Five hundred four children with low risk acute lymphocytic leukemia (previously untreated, age 3 to 6 years with white blood counts less than 10,000/mm3 at diagnosis) were randomized into two different central nervous system prophylaxis regimens. One regimen (250 patients) consisted of cranial radiation and intrathecal methotrexate (IT MTX). The second regimen (254 patients) consisted of IT MTX only. Median follow-up time for surviving patients is currently 54 months from randomization. Life table analysis of central nervous relapse, marrow relapse, disease-free survival, and survival shows very similar outcome for both treatment groups. The results indicate that maintenance IT MTX as described in this report can be substituted for cranial radiation in children with low risk ALL.     

High‐dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high‐dose MTX on treatment‐naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high‐dose MTX (3.5 g/m²) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin‐10 concentration. Adverse events of intravitreal and systemic high‐dose MTX were mild and tolerable. With a median follow‐up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma‐free survival (CLFS) time was 51.1 months. Two‐year CLFS, which was the primary end‐point of the study, was 58.3% (95% confidence interval, 23.0–82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2‐year CLFS was 37.5% (95% confidence interval, 8.7–67.4%). In conclusion, systemic high‐dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).     

达沙替尼治疗费城染色体阳性急性淋巴细胞白血病十例并文献复习

目的：探讨二代酪氨酸激酶抑制剂达沙替尼治疗费城染色体阳性（Ph+）成年人急性淋巴细胞白血病（ALL）的疗效及安全性。方法对应用达沙替尼治疗的10例成年 Ph+ ALL 患者的临床资料进行回顾性分析并复习相关文献。结果10例应用达沙替尼治疗的 Ph+ ALL 患者均在7周内获得缓解,其中9例获得完全缓解,包括7例在13周内达完全分子学缓解。所有患者的中位总生存时间为13.8个月（5～33个月）,中位无病生存时间为10.8个月（4～25个月）。治疗过程中,发生胸腔积液3例,Ⅳ度骨髓抑制4例,血小板极度低下（＜20×109／L）6例,经对症治疗均可改善,未出现并发症致死病例,总体安全性高。结论达沙替尼治疗成年人 Ph+ ALL 的缓解率高,可提高分子生物学反应,延长患者的生存时间,且安全性高,可作为成年人 Ph+ ALL 的一线治疗。     

Adjuvant methotrexate escalated to toxicity for resectable stage III and IV squamous head and neck carcinomas--a prospective, randomized study

To determine if adjuvant methotrexate (MTX), escalated weekly to toxicity, could improve disease-free survival (DFS) and overall survival by preventing recurrent disease, 60 patients with potentially resectable stage III or IV squamous head and neck carcinomas were stratified by primary site, stage, and nutritional status, then randomized by pairs to receive or not receive adjuvant MTX. All received standard surgery and postoperative radiation therapy. Five patients were taken off study because of unresectability at the time of surgery, leaving 55 evaluable patients. There were no statistically significant imbalances in known prognostic factors between the two treatment arms. MTX was begun at 40 mg/m2 and escalated 10 mg/m2 weekly (four doses preoperatively; four doses postoperatively, preradiation therapy; eight doses postradiation therapy) to mucosal or hematologic toxicity. The median peak MTX dose achieved was 80 mg/m2. Although three patients were hospitalized with MTX toxicity, none died of MTX toxicity. No patient receiving MTX had disease progression during treatment, and there was no increase in postoperative complications. Thirty-two patients died (median survival, 19 months); 23 patients are alive with median follow-up of 43 months. There was no statistically significant difference in actuarial DFS (P = 1.0) or overall survival (P = .61). Although patients on the MTX arm appeared to have less local and regional recurrences at first recurrence (thus more distant metastases), this did not reach statistical significance (P = .06). There was no significant difference between the sites of recurrence at death or last follow-up (P = .38).     

Glucarpidase (carboxypeptidase g2) intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy

OBJECTIVE: Leucovorin and extracorporeal removal of methotrexate (MTX) have limited efficacy in delayed MTX elimination after high-dose methotrexate (HD-MTX) therapy. Glucarpidase (carboxypeptidase G2) cleaves MTX into nontoxic metabolites, but experience with this enzyme is limited in adult patients. We evaluated the effects of glucarpidase intervention in adult and elderly patients with delayed MTX elimination. PATIENTS AND METHODS: Forty-three patients (age, 18-78 years) with MTX serum concentrations (sMTX) of 1-1,187 micromol/l received glucarpidase, leucovorin rescue guided by MTX immunoassay, and standard supportive care. MTX and MTX metabolites were quantified in serum (24 patients) and urine (8 patients) by high-performance liquid chromatography. Contributory risk factors, toxicities, and survival were recorded in all patients. RESULTS: Glucarpidase was well tolerated and resulted in an immediate >97% reduction in sMTX, with a 0.2%-35% urinary recovery of the total MTX dose as inactive MTX metabolites. Forty (93%) of 43 patients had normalization (n = 25) or improvement (n = 15) of their serum creatinine. Frequent grade III-IV MTX toxicities were hematological (60%) and mucositis (35%); only eight (19%) patients developed grade III-IV nephrotoxicity. Ten (23%) of 43 patients experienced fatal complications associated with HD-MTX therapy. Patients with three or more contributory risk factors for delayed MTX elimination had a significantly poorer survival than patients with fewer than three risk factors (hazard ratio, 3.64; confidence interval, 1.14-17.54). CONCLUSIONS: Glucarpidase is well tolerated and produces a rapid inactivation of substantial amounts of MTX. However, overall results are still unsatisfactory in adult and elderly patients, suggesting that earlier recognition of delayed MTX elimination and more rapid intervention are needed.     

Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high "corrected" serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.     

High-dose methotrexate for elderly patients with primary CNS lymphoma

The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL.     

Treatment of meningeal relapse in childhood acute lymphoblastic leukemia. I. Results of craniospinal irradiation

Fourteen children were treated for isolated meningeal relapse occurring seven to 44 months (median, 14 months) after prophylactic cranial irradiation (2,400 rad/12 fractions) and intrathecal methotrexate (IT MTX, 12 mg/m2 for four doses during cranial irradiation). Eight had "high-risk" acute lymphocytic leukemia with age less than 2 years, white blood cell counts greater than 20,000, or T cell markers. Treatment for central nervous system leukemia included IT MTX (12 mg/m2 twice weekly until clearance of spinal fluid cytology) followed by craniospinal irradiation (CSI, 3,000 rad/20 fractions to the cranium and 1,800 rad/12 fractions to the spine). No maintenance IT MTX was given. Systemic chemotherapy was continued or reinstituted for a minimum of one year after CSI. No instance of second meningeal relapse has occurred. Five patients remain in secondary complete remission 66+, 54+, 36+, 26+, and 24+ months after meningeal relapse. Disease-free survival was limited by marrow relapse in eight patients (2-20 months after CSI) and testicular relapse in one. No acute toxicities were noted with CSI. Myelosuppression occurred in seven patients. Infections within two months of CSI were noted in five. No neurologic sequelae are apparent. Serial neuropsychometric studies in 10 patients revealed a significant decline in mean values on Global IQ scales. Long-term survival with acceptable toxicity is possible following aggressive, prompt treatment of meningeal relapse occurring after prophylactic cranial irradiation. Hematologic relapse remains the major obstacle to long-term disease-free survival.     

Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study.

The effectiveness of intensive post-remission chemotherapy regimens for adult patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate of disease recurrence and a substantial incidence of treatment toxicity. To evaluate a potentially more effective and less toxic approach, we conducted a multicenter phase III trial of consolidation therapies comparing the standard L10M regimen with one combining the brief, intensive L17M regimen and escalating methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with previously untreated ALL were eligible. Induction therapy included vincristine, prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate administered over 36 days. Patients who achieved complete remission (CR) were randomized to receive consolidation with either the L10M regimen or with DAT (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp. The randomization was stratified by age, WBC and Ph chromosome status. Maintenance therapy was the same in both arms. Of 353 eligible patients, 218 (62%) achieved CR and 195 were randomized. The treatment arms did not differ significantly with respect to disease-free survival (DFS; P= 0.46) or overall survival (P= 0.39). Estimated DFS at 5 years was 32% (95% confidence interval (CI) 23-42%) in the L10M arm and 25% (95% CI 16-33%) in the DAT/MTX/L-asp arm. In each arm, 4% of patients died of toxicities (infection in all but one case). Infections and nausea/vomiting were somewhat more common in the L10M arm (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some reduction in nonfatal toxicities, but no significant improvement in DFS, overall survival or non-relapse mortality when compared to the standard L10M regimen.