早期连续强化疗加高频度强化疗治疗儿童高危急淋白血病

为提高儿童高危急淋白血病 (ＨＲ -ＡＬＬ)的缓解率及长期无病生存率 ,我院对 2 2例ＨＲ -ＡＬＬ患儿采取早期连续强化疗 (序贯用ＶＤＬＰ、ＣＴＡ、ＨＤＭＴＸ -ＣＦ ＩＴ、ＥＡ)和高频度强化治疗即缓解后第 1化疗每月 1次、第 2年每 2月 1次、第 3年 3月 1次、第 4年 4月 1次 ,第 5年 6月 1次强化治疗。所用方案ＣＯＥＰ、ＶＤＰ、ＣＯＡＰ、ＶＥＰ轮流应用。Ｌ -ＡＳＰ、ＨＤＭＴＸ -ＣＦ每年 1～ 2疗程。期间口服 6 -ＭＰ、ＭＴＸ。结果 :2 2例中 1 9例ＣＲ ,完全缓解率为 86 .7%。全部病例均有不同程度骨髓抑制 ,时间为用药后 4～ 1 4…     

大剂量氨甲蝶呤治疗急性淋巴细胞白血病的毒副作用观察

为提高小儿急性淋巴细胞白血病（ＡＬＬ）的治疗缓解率并延长其生存期,近年来,我们采用大剂量氯甲喋吟（ＨＤ－ＭＴＸ）进行化疗,现将我们观察到的毒副作用报告如下。对象和方法１．观察对象：１９９６年８月至１９９８年８月住院的ＡＬＬ患儿共１５例,其中男性９例,女性６例,均处于完全缓解（ＣＲ）期。２．ＨＤ－ＭＴＸ化疗方法：１５例患儿累计进行３０例次ＨＤ－ＭＴＸ化疗［１］,剂量为３ｇ／ｍ２,充分水化、碱化及同时应用ＶＰ（长春新碱、泼尼松）,三联鞘注（ＭＴＸ＋Ａｖａ－Ｃ＋Ｄｍｘ）,甲酞四氢叶酸钙解救在ＨＤ－ＭＴ…     

超大剂量程序化疗方案治疗小儿急性淋巴细胞白血病

超大剂量程序化疗方案治疗小儿ＡＬＬ１７例，取得良好效果。本方案是根据肿瘤细胞动力学和抗肿瘤药物作用动力学理论制定的。强调药物配伍的治疗顺序和治疗时间的程序性。ＶＡＬＰ诱道治疗：用大剂量ＭＴＸ作冲击治疗：用ＣＰＡ或ＥＭＡ作早期强化；用６－ＭＰ和ＭＴＸ作维持治疗。强调治疗开始２１周时，应用ＶＡＬＤ作再次诱道治疗。强化治疗加用大剂量Ａｒａ－ｃ冲治疗。对普通型ＡＬＬ重视晚期反复强化治疗，对高危型ＡＬＬ重视     

超大剂量程序化疗方案治疗小儿急性淋巴细胞白血病

超大剂量程序化疗方案治疗小儿ＡＬＬ１７例，取得良好效果。本方案是根据肿瘤细胞动力学和抗肿瘤药物作用动力学理论制定的。强调药物配伍的治疗顺序和治疗时间的程序性。ＶＡＬＰ诱道治疗：用大剂量ＭＴＸ作冲击治疗：用ＣＰＡ或ＥＭＡ作早期强化；用６—ＭＰ和ＭＴＸ作维持治疗、强调治疗开始２１周时，应用ＶＡＬＤ作再次诱道治疗。强化治疗加用大剂量Ａｒａ—ｃ冲治疗。对普通型ＡＬＬ重视晚期反复强化治疗，对高危型ＡＬＬ重视早期强化治疗。为了保证本方案顺理进行，必须予先克服超大剂量程序化疗产生的血液学毒性和临床学毒性。     

治疗相关性白血病一例

患儿男 ,7岁 3个月。满族。于 1996年 2月因面色苍白1个月余住我院。经骨髓象检查 :原淋 +幼淋为 0 89;骨髓流式细胞检查 :人类白细胞抗原ＤＲ (ＨＬＡ ＤＲ) (+)、ＣＤ2 (- )、ＣＤ7(- )、ＣＤ10 (+)、ＣＤ19(++)、ＣＤ2 2 (++)、ＣＤ3 4(+)。组织化学检查 :ＰＯＸ(- )、醋酸ＡＳ Ｄ萘酚不加ＮＡＦ(- )。确诊为标危急性淋巴细胞白血病Ｌ1型 (ＳＲ ＡＬＬ)。按文献 [1]给予序贯化疗 :ＶＤＬＰ方案 [长春新碱 (ＶＣＲ) 2ｍｇ/ｍ2 ,1/周 ,× 5 ;柔红霉素 (ＤＮＲ) 30ｍｇ/ｍ2 ,1/ｄ× 2 ;左旋门冬酰胺酶 (Ｌ ＡＳＰ) 10 0 0 0Ｕ/ (ｍ2 ·ｄ)…     

去甲氧柔红霉素治疗小儿肿瘤9例分析

我科采用个去甲氧柔红霉素（ＩＤ）治疗小儿白血病等恶性肿瘤和朗罕氏组织细胞增生症（ＬＣＨ）９例,取得良好的疗效,现报道如下。材料和方法１．对象（１）小儿急性淋巴细胞性白血病（ＡＬＬ）,６例：男５例、女１例。年龄从８个月～１０岁。按全国标准评定［１］高危（ＨＲ－ＡＬＬ）４例,超高危（超ＨＲ－ＡＬＬ）２例。（２）急性髓细胞性白血病（ＡＭＬ）,１例,Ｍ６型,３岁半。误诊骨髓异常增生综合征１年,已多次使用Ａｒａ－Ｃ等化疗药物,确诊Ｍ６型后,经采用ＨＯＡＰ、ＶＰ１６＋Ａｒａ－Ｃ等方案诱导治疗失败。骨髓：原始…     

大剂量氨甲喋呤治疗白血病引起严重毒副反应1例

患儿女,９岁。于９８年２月２日确诊为“急性淋巴细胞性白血病Ｌ_２型”。给予ＶＣＰ、ＶＣＤＰ、ＶＤＬＰ方案化疗,２月后骨髓完全缓解。为预防脑膜白血病行大剂量氨甲喋呤（ＭＴＸ）疗法一次（ＭＴＸ１．１克国产）。于９８年４月２５日第一次巩固化疗,方案ＣＯＡＰ,并再次给大剂量氨甲喋呤疗法一次（ＭＴＸ１．１克国产）。于９８年５月２５日第二次巩固化疗,ＣＯＤＰ化疗方案后,休息３周,行第三次大剂量氨甲喋呤治疗,剂量２克（进口）,治疗前查血常规：ＷＢＣ１．７×１０~９／Ｌ、ＲＢＣ３．９６×１０~１２／Ｌ、Ｈｂ１１４…     

“三联药”鞘注加静滴HD—MTX防治小儿中枢神经系统白身病363例疗？…

尽管化学治疗迅速发展,但许多化疗药物不易透过血脑屏障,使中枢神经系统（ＣＮＳ）成为白血病细胞的第一庇护所,中枢神经系统白血病（ＣＮＳＬ）成为急性淋巴细胞白血病（ＡＬＬ）患儿复发的最重要原因。我们对１９８６～１９９６年收治的３６３例ＡＬＬ患儿随访观察２年,结果表明：鞘注ＭＴＸ、Ａｒａ－Ｃ、Ｄｘ加静滴ＨＤ－ＭＴＸ可明显降低ＣＮＳＬ的发生率,对提高ＡＬＬ患儿的持续完全缓经（ＣＣＲ）有着十分重要的意义,而     

急性淋巴细胞白血病化疗中发生急性肾功能不全一例

患儿女 ,6岁。确诊为急性淋巴细胞白血病 (ＡＬＬ)普通型 1年 ,入院行第 2次强化治疗。给予ＶＭ2 6 Ａｒａ Ｃ(替尼泊甙 阿糖胞苷 )后休息 13ｄ ,肝肾功能、血常规均正常 (白细胞 4 5× 10 9/Ｌ)。碱化尿液 (尿ｐＨ >7 0 ) 3ｄ后 ,予以第 6次ＨＤＭＴＸ(大剂量氨甲蝶呤 )化疗并用ＣＦ(四氢叶酸钙 )解救。ＭＴＸ 3 0ｇ/ｍ2 (患儿体表面积为 0 8ｍ2 ) ,首剂 1/ 6量于第 1小时静脉滴注 ,余量 6ｈ均匀滴入 ,同时水化碱化尿液 (每日静脉给 5 %碳酸氢钠 10 0ｍｌ/ｍ2 ,1/ 5张液体 2 5 0 0ｍｌ/ｍ2 )。用ＨＤＭＴＸ的同时 ,给予ＶＤ(长春新碱 …     

大剂量MTX＋鞘内注射对儿童中枢神经系统白血病的防治与中枢毒性

自１９９３年１０月至１９９５年１２月，对６０例儿童急性淋巴细胞性白血病（ＡＬＬ）采用大剂量氯甲喋呤＋鞘骨注射＋甲酰四氢叶酸钙解救（ＨＤＭＴＸ＋ＩＴ＋ＦＣ）方法预防髓外白血病，大大降低了中枢神经系统白血病的发生率（５％）。但有１例患儿在第３次采取常规剂量和方法的ＨＤＭＴＸ＋ＩＴ＋ＦＣ化疗时，出现严重的中枢神经毒性。一旦发生ＣＮＳＬ后，即使重新加强全身化疗，头颅放疗及ＨＤＭＴＸ应用，仍出现高ＣＮＳＬ复     

PART II. SURVIVAL AFTER RELAPSE DURING UNMAINTAINED REMISSION AND AFTER SECOND CESSATION OF THERAPY

Nygaard, R. and Moe, P. J. (Department of Paediatrics, University Hospital, Trondheim, Norway). Outcome after cessation of therapy in childhood leukemia. A population-based Nordic study of 986 patients. II. Survival after relapse during unmaintained remission and after second cessation of therapy. Acta Paediatr Scand Suppl 354: 20, 1989.
This is the second part of a population-based investigation of 986 patients after discontinuation of therapy for childhood leukemia. Patients who had their first relapse after cessation of therapy ( n =206) were studied for subsequent outcome in terms of survival after relapse. The patients with ALL ( n =191) were also analyzed according to patient variables with possible influence on survival. Fifty-one (26.7%) of the patients with relapse of ALL electively stopped therapy once more, and for them subsequent survival in remission was evaluated.
The overall estimated proportion alive at five years after relapse in unmaintained remission was 0.37 and at ten years 0.28. There was no significant difference in survival after relapse for males vs. females, and this could be attributed to the fact that isolated testicular relapses carried a better chance of subsequent survival than did relapses in other sites. Age at relapse did not have any influence on survival. However, time from cessation of therapy to first relapse was of prognostic value: Patients who relapsed within 6 months had a signifcantly lower survival than did those with relapse after longer periods in unmaintained remission.
Five-year DFS was 0.57 after second cessation of therapy in patients with ALL. Our study confirms that there may be more than one chance of cure.     

The prognosis and survival of childhood acute lymphoblastic leukemia with central nervous system relapse

Central nervous system (CNS) relapse in childhood acute lymphoblastic leukemia (ALL) has been overcome by sensitive therapeutic approachs. This study was planned to present the development of CNS relapse and survival in newly diagnosed 190 ALL patients whose cases were followed in the authors' unit between March 1991 and May 2002. St. Jude Study XI protocol was given to the patients who applied between March 1991 and March 1997 (group A) (n = 122), and St. Jude Study XIII protocol was given to the patients who applied between March 1997 and May 2002 (group B) (n = 68). The patients having isolated CNS relapse in group A received craniospinal irradiation (CSI) median 3.5 months after CNS relapse (range 2-6 months), a short time after reinduction, and 2 cures of consolidation. In group B, patients having isolated CNS relapse received IT once a month and a high-dose methotrexate treatment once every 8 weeks and 3 or 4, cures later therapy CSI median 7 months after CNS relapse (range 6-8 months) was given. When the overall survival rates of the 2 groups are compared, a statistically significant higher survival rate at 5 years was determined in group B than in group A (respectively, 82.3%, 58.4%) (p < .05). When subgroups of the patients (that is, those with no relapse, isolated CNS or BM relapse, or CNS + BM relapse) were compared in both groups, it was found that survival was much higher for the ones with no relapse and with isolated CNS relapse (respectively, 87.9%, 72.7%) compared to isolated BM or CNS + BM relapse groups (respectively, 10%, 13.3%) (p < .05). In a conclusion, for children with acute lymphoblastic leukemia and an isolated CNS relapse, with delayed definitive craniospinal irradiation allowing more intensive systemic and intrathecal chemotherapy results in better overall survival than has been previously reported.     

Initial response to therapy as an important prognostic factor in acute lymphoblastic leukemia in childhood. COALL study group

Prognostic factors to estimate the risk of relapse are crucial for risk-adapted therapy in acute lymphoblastic leukemia (ALL). In a cooperative multicenter treatment study for childhood ALL (COALL-03-85) the prognostic relevance of the bone marrow (BM) blast count at day 28 was evaluated. Treatment was adjusted to the initial risk factors; patients with high risk (white blood count (WBC) greater than or equal to 25/nl, age greater than or equal to 10 years, T- or NULL-ALL) received intensified therapy consisting of rotation of 6 non cross-resistant drug combinations with 12 different agents. After 4 weeks 289/305 (94.8%) children were in complete remission (CR); one child died of infection, and 15 (14 high-risk patients) still had more than 5% blasts in the BM. Twelve of these 15 patients were in remission after 2 to 4 weeks additional treatment. Poor responders often had a high initial WBC, age above 10 years of T- or NULL-ALL. In spite of continuation of intensive therapy all children with more than 10% blasts in the BM on day 28 suffered an early relapse except 2 who were transplanted in first remission. Event-free survival for the poor responders is 0.15 compared to 0.71 (p = 0.0001) for the good responders (median observation time 48 months). In multivariate analysis remission status on day 28 was the only significant prognostic factor in high-risk patients above one year of age; traditional risk factors as initial WBC, age above 10 years, hepatosplenomegaly, and immunological subtype were of no prognostic significance in this study. (ABSTRACT TRUNCATED AT 250 WORDS)     

Extramedullary Relapse in Childhood Leukemia

As long-term survival of children with leukemia is increasing, the prophylaxis of extramedullary leukemia has become a more important part of treatment. We studied the pattern of occurrence of extramedullary leukemia in a retrospective review. This review included a total of 2317 childhood leukemia patients aged 15 years or less who had been treated at 38 institutes in Japan between 1976 and 1985. Extramedullary leukemia developed in 386 of 1,724 ALL patients (22.4%) and 63 of 544 patients with ANLL (163%). Among the ALL patients, CNS-L was the most common form and was observed in 315 cases (81.6%), followed by testicular leukemia in 89 (23.0%). In the case of ANLL, the most common form of extramedullary leukemia was CNS-L (45 cases, 71.4%), followed by cutaneous leukemia in 10 cases (15.9%). In addition, leukemia of the lymph nodes, ovaries, bones, kidneys and eyes was observed in 7, 5, 5, 4 and 4 cases, respectively. The survival rate of ALL patients with CNS-L was 40.1% for isolated relapse and 2.7% for bone marrow relapse, and no more deaths occurred after 6 years from relapse. The survival rate of patients with testicular leukemia was 40.1% for isolated relapse and 5.9% for complicating bone marrow relapse, and no deaths occurred after 7 years from relapse. Cutaneous leukemia tended to occur late in older children with ALL and early in infants with ANLL, and all these patients died. Infiltration into the kidney was observed in 4 patients, all of whom died. More than 75% of patients died after isolated relapse of leukemia of the bones, ovaries, lymph nodes and eyes. Prophylactic extramedullary leukemia therapy, of CNS-L in particular, has played an important role in the treatment of childhood leukemia. Careful development of more effective therapy and close observation of late effects are required when monitoring affected children who are still growing.     

The Prognosis and Survival of Childhood Acute Lymphoblastic Leukemia with Central Nervous System Relapse

Central nervous system (CNS) relapse in childhood acute lymphoblastic leukemia (ALL) has been overcome by sensitive therapatic approachs. This study was planned to present the development of CNS relapse and survival in newly diagnosed 190 ALL patients whose cases were followed in the authors' unit between March 1991 and May 2002. St. Jude Study XI protocol was given to the patients who applied between March 1991 and March 1997 (group A) (n = 122), and St. Jude Study XIII protocol was given to the patients who applied between March 1997 and May 2002 (group B) (n = 68). The patients having isolated CNS relapse in group A received craniospinal irradiation (CSI) median 3.5 months after CNS relapse (range 2–6 months), a short time after reinduction, and 2 cures of consolidation. In group B, patients having isolated CNS relapse received IT once a month and a high-dose methotrexate treatment once every 8 weeks and 3 or 4, cures later therapy CSI median 7 months after CNS relapse (range 6–8 months) was given. When the overall survival rates of the 2 groups are compared, a statistically significant higher survival rate at 5 years was determined in group B than in group A (respectively, 82.3%, 58.4%) (p < .05). When subgroups of the patients (that is, those with no relapse, isolated CNS or BM relapse, or CNS + BM relapse) were compared in both groups, it was found that survival was much higher for the ones with no relapse and with isolated CNS relapse (respectively, 87.9%, 72.7%) compared to isolated BM or CNS + BM relapse groups (respectively, 10%, 13.3%) (p < .05). In a conclusion, for children with acute lymphoblastic leukemia and an isolated CNS relapse, with delayed definitive craniospinal irradiation allowing more intensive systemic and intrathecal chemotherapy results in better overall survival than has been previously reported.     

Long-term survivors of acute lymphoblastic leukemia — risk of relapse after cessation of therapy

The results of cessation of therapy (COT) in 64 long-term survivors (disease-free survival of five years or more) of acute lymphoblastic leukemia (ALL) were analyzed to determine the incidence of relapse off therapy. Thirty-seven of the patients had intermittent central nervous system (CNS) prophylaxis. Total follow-up from diagnosis varied from 5.75 to 27.75 years. The median time off therapy was three years (range, 8 months to 26 years). Eighty-six percent (55/64) of the patients continue in their initial remission. Eight patients had relapse, and one patient had a morphologically different leukemia at recurrence. All the relapses occurred between five to eight years from diagnosis and the cumulative rate of relapse for this period was 0.14. There was no significant difference in the rate of relapse for those receiving CNS prophylaxis (0.08) versus those not receiving CNS prophylaxis (0.19). The difference in the relapse rates for boys (0.24) versus girls (0.04) was statistically significant (P=0.04). Isolated testicular relapse (ITR) was not seen in any of the 34 boys. The present study confirms the earlier observations by others that relapse is uncommon in ALL patients remaining in remission longer than seven to eight years. ALL patients treated with intermittent CNS prophylaxis administered throughout the period of maintenance chemotherapy appear to be at no greater risk for relapse off therapy than those treated with high-dose initial cranial irradiation and intrathecal methotrexate. The longer duration of therapy and the use of a repetitive reinduction regimen for maintainance seem to be associated with a decreased risk of ITR after discontinuation of therapy for boys and men. There appears to be a small but definite risk of “second” leukemia in the long-term survivors of leukemia.     

Use of the Ommaya reservoir in the prevention and treatment of CNS leukemia—an update

The prophylaxis of the CNS in ALL with intraventricular methotrexate therapy via an Ommaya reservoir in 18 patients resulted in a reduction of the CNS relapse rate to 11% with a 6-10+ year follow-up. This procedure proved to be safe and effective in our hands, but with newer, equally effective and less invasive methods of CNS prophylaxis now available, its use is no longer indicated. Intraventricular therapy via the Ommaya reservoir was also evaluated for its role in improving CNS remission duration after a leukemic recurrence in the CSF. The treatment of CNS relapse with intraventricular chemotherapy and low dose (600r) neuraxis radiation is encouraging. Of the ten patients treated for CNS leukemia, three are long-term (8-11+ years) survivors. Isolated CNS relapse occurred in three. The median CNS disease-free survival and the median relapse-free survival are 39 months and 21 months respectively.     

Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia

In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48+-125+ months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified.     

Liver function studies in children with acute lymphocytic leukemia after cessation of therapy

We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone + vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1–7 years prior to this study. Twenty-three patients had transfusions of packed red blood cells or fresh whole blood (1–11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids + deoxycholic acids to chenodeoxycholic acids + lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood. © 1994 Wiley-Liss, Inc.     

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.