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

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 (i.t.) 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.     

Treatment of ALL in children. Results and side effects with a modification of protocol memphis VII (author's transl)]

42 patients with ALL were treated according to the following protocol: induction with vincristine + prednisone (+/- L-asparaginase), CNS-prophylaxis with cranial irradiation (2400 rads) and intrathecal methotrexate, maintenance for 3 years with 6-MP 50 mg/m2/d p.o. + MTX 75-150 mg/m2/2 wk i.v. X 4, alternating in a cyclic fashion with 6-MP 50 mg/m2/d p.o. + cyclophophshamide 600 mg/m2/2 wk i.v. X 4. The observation time is 24-67 (median 49) months. The actuarial complete remission curve shows 40% continuous complete remissions at 36 months and 30% at 60 months.--The frequency and temporal distribution of typical infectious complications are presented. The incidence of varicella was comparable to that in a southgerman normal control group (5,7% per year). During treatment there were two zoster manifestations per one varicella case, the incidence of zoster being 1 case per 106 patient-months, viz 11,4% per year.     

Intermediate-dose methotrexate and intravenous 6-mercaptopurine chemotherapy for children with acute lymphoblastic leukemia who did not respond to initial induction therapy

PURPOSE: To determine the complete remission rate of children with acute lymphoblastic leukemia (ALL) who were not induced into remission by initial therapy, when subsequently treated with intermediate-dose methotrexate and intravenous 6-mercaptopurine. PATIENTS AND METHODS: Children with B-precursor ALL who did not achieve initial remission after 4 or 6 weeks of standard three- or four-drug induction chemotherapy were entered on study. Therapy consisted of three doses at weekly intervals of methotrexate 1,000 mg/m2 over 24 hours followed by 6-mercaptopurine 1,000 mg/m2 over 8 hours 20 minutes. Patients achieving a partial remission could receive two additional weekly courses of methotrexate and 6-mercaptopurine. Initially, patients received weekly intrathecal chemotherapy, but the study was amended to include intrathecal therapy only at week 1. RESULTS: Nineteen patients were entered on study. All were evaluable for toxicity and response. There were seven complete remissions, four partial remissions, six patients with no response, and two children with progressive disease, for an overall complete remission rate of 37%. One patient was removed from the study after the second course of methotrexate and 6-mercaptopurine because of renal failure. Two patients had neurologic toxicity resulting in a study amendment. No patients subsequently experienced neurologic toxicity. CONCLUSIONS: Intermediate-dose intravenous methotrexate and intravenous 6-mercaptopurine can induce remission in some patients with ALL who experience initial induction failure. Features predicting complete remission, however, could not be identified.     

Effective multi-agent chemotherapy for advanced abdominal lymphoma and FAB L3 leukemia of childhood

Between June 1981 and May 1988, 51 children with diffuse undifferentiated, advanced (Murphy Stage III and IV) intra-abdominal non-Hodgkin′s lymphoma were treated on an intensive multi-drug chemotherapy protocol without irradiation to the primary tumour. Therapy was completed for Stage III disease at one year, but Stage IV patients continued with a further year of therapy until January 1986, when it was reduced to one year. Central nervous system (CNS) prophylaxis consisted of eight doses of intrathecal MTX for all children, and 24 Gy cranial irradiation for Stage IV patients only. There were 42 patients with Stage III disease (III A n = 29 and III B n = 13) and nine patients with Stage IV disease, of whom eight had extensive bone marrow and extramedullary disease (FAB L3 ALL). No patient had CNS disease at presentation. Forty-eight of 51 children (94%) achieved a complete remission. Two children died during remission induction therapy and eleven children relapsed, mostly within eight months of diagnosis. All patients have completed therapy. Failure free survival is 76% for Stage III and 67% for Stage IV patients, with a median followup of 90 and 64 months, respectively. Subdividing Stage III patients into Stage III A and III B did not show significantly different survival (P = 0.9), but the number of patients in Stage III B is small. These results compare favourably with the most effective published protocols, and toxicity has been manageable. © 1993 Wiley-Liss, Inc.     

Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia

In 1971, Cancer and Leukemia Group B (CALGB) mounted a study of acute lymphocytic leukemia (ALL) that compared the effects of the two steroid hormones dexa-methasome and prednisone. Six-hundred-forty-six children and adolescents with ALL were randomized to receive either prednisone or dexamethasone as part of their remission induction therapy. The 493 evaluable patients who achieved complete remission received the same steroid as pulses throughout remission. Specific central nervous system (CNS) therapy was randomized to either six injections of intrathecal methotrexate (IT MTX) alone or to six injections of IT MTX with cranial radiation (2,400 cGy). Both cranial radiation and dexamethasone offered increased protection against CNS relapse as the first site of failure over IT MTX alone. There were 30 CNS relapses among 238 patients (12.6%) receiving cranial radiation plus IT MTX, whereas there were 70 CNS relapses among 225 (P < 0.001) (22.5%) in those who received IT MTX alone. Similarly, there were 33 CNS relapses among 231 (14.3%) children treated with dexamethasone, whereas there were 67 CNS relapses among 262 (25.6%) treated with prednisone (P = 0.017). Both steroids appeared equal in protecting the bone marrow. Recent national studies have shown significant improvements in preventing CNS relapse over the results in the present report. However, this finding warrants further investigation and, with further documentation, could lead to the substitution of prednisone by dexamethasone to aid further in preventing CNS relapse. This may be particularly important in patients at higher risk for CNS relapse.     

CT scans of long-term survivors of various childhood malignancies

Forty-two children with various systemic malignancies in continuous remission for 1 to 3 years after the completion of chemotherapy had CT scans with normal ventricular dimensions, similar to a noncancer “control” population. Seventeen of these patients had acute lymphocytic leukemia (ALL) treated either with prophylactic cranial irradiation and intrathecal methotrexate [7] or intrathecal methotrexate alone [10] and the remaining 25 patients had soft tissue sarcomas. Sixteen other patients with sarcomatous meningitis had enlarged ventricles while on chemotherapy. Nine had ALL. Seven had soft tissue sarcomas, none of whom received any prior CNS irradiation or intrathecal chemotherapy. In this retrospective study no evidence of hydrocephalus or significant white matter hypodensity was detected in long-term survivors of childhood cancer, regardless of whether prophylactic intrathecal chemotherapy and/or cranial irradiation was given. Direct involvement of the CNS with meningeal cancer was the most important association with ventriculomegaly.     

Immunocompetence and prognosis in children with acute lymphoblastic leukemia: combination of two different maintenance therapies.

Intensive chemotherapy in patients with leukemia produced immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with "favorable immunocompetence" only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with "unfavorable immunocompetence," 15 relapsed and 8 remain in complete remission from 9 to 26 months.     

Immunocompetence and prognosis in children with acute lymphoblastic leukemia: Combination of two different maintenance therapies

Intensive chemotherapy in patients with leukemia produces immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with “favorable immunocompetence” only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with “unfavorable immunocompetence,” 15 relapsed and 8 remain in complete remission from 9 to 26 months.     

CRANIAL COMPUTED TOMOGRAPHY DURING TREATMENT OF CHILDHOOD LYMPHOCYTIC LEUKEMIA

ABSTRACT. Twenty-three children with acute lymphocytic leukemia (ALL) were examined by computed tomography (CT) of the head on two occasions more than 11 months apart. The first CT was performed at the time of diagnosis in 11 children, who were re-examined while still in their first complete remission. They had received prophylactic central nervous system (CNS) treatment consisting of intrathecal methotrexate supplemented by irradiation in 7 cases and intermediate dose methotrexate in 4 cases. Twelve children were receiving treatment for CNS relapse. This included therapeutic irradiation and intrathecal methotrexate. Abnormal CT developed in 7 children. Three CT scans demonstrated areas of decreased attenuation coefficient, one with intracerebral calcifications. In 5 patients, dilatation of the ventricles and cortical sulci had developed. AU CT abnormalities occurred in children in remission after CNS relapse. These results indicate that prophylactic treatment including cranial irradiation with 24 Gy and low cumulative doses of methotrexate is a safe procedure. Patients with CNS leukemia are at risk of developing CNS abnormalities, when they receive treatment with cranial irradiation and methotrexate. The risk is not correlated with age or sex of the child, the duration of the disease, the dose of irradiation or the cumulative dose of methotrexate.     

Treatment of recurrence of acute myeloid leukemia in childhood. A retrospective analysis of recurrence in the AML-BFM-83 study]

Complete remission (CR) rates of 80% are achieved with the AML-BFM protocols but one third of patients relapse within the first three years. There are few reports of treatment of relapsed childhood AML, and these deal with the evaluation of new drugs for frontline therapy. We performed a retrospective analysis to investigate how patients previously treated with the AML-BFM-83 protocol were treated after relapse and how many long term remissions were achieved. 48 of 139 patients relapsed after having achieved complete remission with the AML-BFM-83 protocol which consists of continous infusion of ARA-C 100 mg/m2 day 1-2, ARA-C 200 mg/m2 day 3-8, Daunorubicin 60 mg/m2 day 3, 4, and 5, and VP-16 150 mg/m2 day 6, 7, and 8, and an 8 week consolidation therapy consisting of Prednisolone, Thioguanine, Vincristine, ADR, ARA-C, Cyclophosphamide, intrathecal ARA-C and cranial irradiation followed by maintenance therapy. Duration of first remission ranged from 1.5 months to 66.3 months. Excluding 5 children with either isolated or combined extramedullary relapses and another 4 patients for missing data, 39 children were evaluable. 20 children received no therapy or palliative therapy while 16 patients received chemotherapy and another 3 children were transplanted in relapse. Although 9 different intensive chemotherapy regimens were used for reinduction, a high number (12 of 16 = 75%) of second complete remissions was achieved. Several therapeutic options were used to maintain a second remission: regular maintenance therapy (7 patients), allogeneous bone marrow transplantation (BMT) (2 patients), autologous BMT (3 patients).(ABSTRACT TRUNCATED AT 250 WORDS)     

急性淋巴细胞白血病患儿亚甲基四氢叶酸还原酶基因多态性与大剂量甲氨蝶呤不良反应的相关性

目的探讨急性淋巴细胞白血病(ALL)患儿亚甲基四氢叶酸还原酶(MTHFR)基因677位点多态性与大剂量甲氨蝶呤(HDMTX)体内排泄及不良反应的相关性。方法 2008年3月-2010年2月在本院儿科中心和血液内科住院的完全缓解并接受HDMTX治疗的40例ALL患儿,在接受HDMTX治疗前应用PCR-限制性酶切片段长度多态性(RFLP)技术检测MTHFR基因C677T多态性,在HDMTX静脉输注开始后24 h、48 h应用荧光偏振免疫法(FPIA)测定其血浆MTX水平,密切观察ALL患儿HDMTX化疗后的不良反应,对化疗不良反应进行分级。对MTHFR677的基因多态性与MTX不良反应及HDMTX 48 h的MTX水平(MTX-48 h)的相关性进行分析。结果在有HDMTX相关不良反应的ALL患儿中,肝损害和骨髓抑制发生率最高。MTHFR C677T有肝脏损害的基因型分布频率由低到高为CC型40.0%,TT型60.0%,CT型80.0%,CT基因型者肝脏损害发生的风险是CC基因型者的6倍(OR=6.00,95%CI:1.05～34.32,P=0.044);677CT+TT基因型者肝脏损害发生的风险是CC基因型者的4.13倍(OR=4.13,95%CI:1.02～16.67,P=0.047)。MTHFR C677T基因型与骨髓抑制无明显相关性。携有MTHFR突变基因型(CT+TT)患者的48 hMTX血药质量浓度明显高于携带MTHFR野生型基因CC者(P=0.006)。结论 MTHFR 677位基因型可作为ALL患儿HDMTX化疗不良反应和药物体内排泄的有效预测指标。     

COMPUTED TOMOGRAPHIC FINDINGS OF THE BRAIN IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA AFTER CENTRAL NERVOUS SYSTEM PROPHYLAXIS WITHOUT CRANIAL IRRADIATION

Abstract. Nineteen children in primary remission of acute lymphocytic leukemia (ALL) were investigated by computed tomographic (CT) scans of the brain 2 to 64 (mean 19) months after the central nervous system (CNS) prophylaxis was finished. The CNS prophylaxis consisted of high dose Methotrexate (HDM) intravenously combined with 6–8 doses of Methotrexate intrathecally. Two children received only Methotrexate intrathecally as CNS prophylaxis. In addition three children with ALL who had CNS leukemia were investigated by CT scans of the brain. Only one abnormal CT scan was found among the nineteen asymptomatic children, and one of the three patients with CNS relapse had slightly dilatated subarachnoidal spaces. These results compared with other reports in literature in which the CNS prophylaxis has consisted of intrathecal Methotrexate and cranial irradiation, suggest that there are fewer abnormal CT findings of the brain in patients not receiving cranial irradiation as part of CNS prophylaxis.     

Isolated cerebral calcifications after prophylactic treatment of cerebromeningeal involvement of acute lymphoblastic leukemia: relation of psycho-intellectual sequelae

Intracranial calcifications were demonstrated by CT scan in 5 children after complete remission of acute lymphoblastic leukemia (ALL). Initial treatment included prophylactic irradiation of central nervous system and intrathecal methotrexate. Behavioral abnormalities or learning difficulties were clinically apparent in all children at the time of the radiologic examination. Isolated intracranial calcifications represent one of possible cerebral sequelae that are to be found in 53% of children receiving treatment for ALL. No fine correlation between direct toxic effect of methotrexate or, post-radiation lesion, and neuro-psychological sequelae can be done. In an attempt to avoid some of this sequelae, suppression of cranial irradiation from ALL treatment protocols is now studied.     

The results of high risk children's acute lyrnphoblastic leukemia total therapy. A report from the Polish children's leukemia/lymphoma study group

The study evaluates the efficacy of seven drug systemic therapy and three drug intrathecal treatment in children with acute lymphoblastic leukemia (ALL). Three hundred and thirty-five children with ALL treated at six hematological centers in Poland were divided into two groups: standard group and high risk group according to the BFM score method. Ninety-two children estimated as high risk patients diagnosed between 1978 and 1981 were treated according to the Polish Children's Leukemia/Lymphoma Study Group (PCLSG) program adopted from LSA₂L₂ regimen. The patients received prednisone, vincristine, adriamycin and cyclophosphamide as remission induction treatment, followed by cytarabin and 6-thioguanine given as consolidation therapy. The central nervous system prophylaxis consisted of cranial irradiation and intrathecal methotrexate, cytarabin and hydrocortisone. In maintenance phase, three different drug combinations were given as intermittent therapy. The total duration of therapy was 2.5 years. The life table analysis showed a 38% disease free survival and 50% complete continuous remission (CCR) for the total group of patients. A relatively high incidence of CNS relapse was observed. These results indicated that the regimen applied was not satisfactorily effective for the increased risk of ALL. Three of seven evaluated prognostic indices—age, mediastinal mass and cytochemical features—were significantly associated with probability of survival of the patients with protocol applied. Some other therapy proposals are discussed.     

急性淋巴细胞白血病并中枢神经系统白血病的诊断与治疗

目的：探讨急性淋巴细胞白血病（ALL）并中枢神经系统白血病（CNSL）的诊断与治疗及影响发病和预后的因素。方法：对1990－1999年收治117例临床资料进行回顾分析。结果：CNSL发生距确诊ALL的中位数时间为8个月,高危型组发生率（54．85）明显高于标危型组（23．7％）。31例CNSL中以脑脊液（CSF）异常作出诊断远比临床症状多。CNSL治疗效果显示,大剂量氨甲喋呤＋三联鞘注＋四组（CR＋IT）相当。结论：为避免诊断假阳性造成的过度治疗,CSF仅有幼稚细胞而白细胞计数政党者诊断CNSL应慎重,HDMTX＋IT＋FC是治疗CNSL的有效措施。     

Cyclic combination chemotherapy for acute lymphoblastic leukemia recurring after elective cessation of therapy

Cyclic combination chemotherapy was administered to 26 patients with acute lymphoblastic leukemia who had relapsed in the bone marrow greater than or equal to 6 months after elective cessation of therapy. Each patient had been in initial continuous complete remission for 36-111 months (median, 47 months). Prednisone, vincristine, and doxorubicin induced second complete remissions in all patients within 1 month. Continuation therapy consisted of alternating 6-week courses of 6-mercaptopurine/methotrexate and vincristine/cyclophosphamide with intervening reinforcement courses of prednisone/doxorubicin, for a total of 18 months. All patients received 4 weeks of late intensification therapy with the same agents used for remission reinduction. Periodic intrathecal methotrexate was given as reprophylaxis for subclinical central nervous system leukemia. The estimated rate of continuous failure-free survival at 5 years is 31% +/- 17% (2 SE). Eight patients remain free of leukemia for 42 + to 65+ months after completing therapy a second time. Adverse second events included 11 hematologic, 1 testicular, and 3 meningeal relapses. Patients who relapsed at more than 12 months after the completion of initial treatment have had significantly longer second remissions than patients whose first remissions were shorter (p = .04). None of the other six factors we analyzed showed predictive strength. These end results indicate that intensive cyclic continuation chemotherapy, as described here, will secure durable second remissions in approximately one-third of the children with late bone marrow relapses.     

Remission maintenance of adult acute lymphoblastic leukemia.

This report describes the results of a study of central nervous system (CNS) prophylaxis and combination chemotherapy for the maintenance of remission in adult acute lymphoblastic leukemia. Adults with acute lymphoblastic leukemia who achieved complete remission were treated with 2,400 rads cranial irradiation and intrathecal methotrexate for CNS prophylaxis followed by continuation systemic chemotherapy with oral methotrexate, 6-mercaptopurine and cyclophosphamide. There were no CNS relapses following treatment. One-half of the patients relapsed within 11 months, with 5 patients remaining in remission for 27+ to 31+ months. The toxicity was acceptable with no treatment-related deaths. This regimen is capable of producing long remissions in a significant proportion of adults with acute lymphoblastic leukemia and appears to be effective in reducing the incidence of CNS relapse. It has the additional advantage of ease of administration and can be largely administered in the community.     

两种不同方案治疗儿童急性淋巴细胞白血病疗效分析

目的：比较两种治疗方案对小儿急性淋巴细胞白血病(ALL)治疗的近期完全缓解率(CR)与持续完全缓解(CCR),探讨影响小儿ALL长期生存的有关因素。方法：根据化疗方案所用药物不同将44例患儿分为2组：一般化疗组(A组),诱导治疗采用VCP(长春新碱、环磷酰胺、强的松),庇护所预防使用二联鞘注(甲氨喋呤、地塞米松),维持治疗使用6 巯嘌呤与甲氨喋呤,加强强化用VCP及COAP(长春新碱、环磷酰胺、阿糖胞苷、强的松)交替;强烈化疗组(B组),按照1993年广西北海会议制定的小儿急性白血病诊疗建议进行序贯治疗,其中大剂量甲氨喋呤(HD-MTX)采用每次 1.5～2.0 g/m2及三联鞘注(甲氨喋呤、阿糖胞苷、地塞米松)。结果：两种方案经过4周治疗44例患儿均获CR,但达到CR的时间A组为(3.83±0.41)周,长于B组(3.00±0.82)周(P0.05)。结论：强烈化疗组不仅近期完全缓解所用时间短,而且在CCR及预防疾病复发上明显优于一般化疗组,虽然强烈化疗后合并各种感染的机会增多,但只要积极采取相应的预防措施,取得家长的密切配合可以使其发生率降低。     

Computed tomographic findings of the brain in children with acute lymphocytic leukemia after central nervous system prophylaxis without cranial irradiation.

Nineteen children in primary remission of acute lymphocytic leukemia (ALL) were investigated by computed tomographic (CT) scans of the brain 2 to 64 (mean 19) months after the central nervous system (CNS) prophylaxis was finished. The CNS prophylaxis consisted of high dose Methotrexate (HDM) intravenously combined with 6--8 doses of Methotrexate intrathecally. Two children received only Methotrexate intrathecally as CNS prophylaxis. In addition three children with ALL who had CNS leukemia were investigated by CT scans of the brain. Only one abnormal CT scan was found among the nineteen asymptomatic children, and one of the three patients with CNS relapse had slightly dilatated subarachnoidal spaces. These results compared with other reports in literature in which the CNS prophylaxis has consisted of intrathecal Methotrexate and cranial irradiation, suggest that there are fewer abnormal CT findings of the brain in patients not receiving cranial irradiation as part of CNS prophylaxis.     

The results of high risk children's acute lyrnphoblastic leukemia total therapy. A report from the Polish children's leukemia/lymphoma study group

The study evaluates the efficacy of seven drug systemic therapy and three drug intrathecal treatment in children with acute lymphoblastic leukemia (ALL). Three hundred and thirty-five children with ALL treated at six hematological centers in Poland were divided into two groups: standard group and high risk group according to the BFM score method. Ninety-two children estimated as high risk patients diagnosed between 1978 and 1981 were treated according to the Polish Children's Leukemia/Lymphoma Study Group (PCLSG) program adopted from LSA₂L₂ regimen. The patients received prednisone, vincristine, adriamycin and cyclophosphamide as remission induction treatment, followed by cytarabin and 6-thioguanine given as consolidation therapy. The central nervous system prophylaxis consisted of cranial irradiation and intrathecal methotrexate, cytarabin and hydrocortisone. In maintenance phase, three different drug combinations were given as intermittent therapy. The total duration of therapy was 2.5 years. The life table analysis showed a 38% disease free survival and 50% complete continuous remission (CCR) for the total group of patients. A relatively high incidence of CNS relapse was observed. These results indicated that the regimen applied was not satisfactorily effective for the increased risk of ALL. Three of seven evaluated prognostic indices—age, mediastinal mass and cytochemical features—were significantly associated with probability of survival of the patients with protocol applied. Some other therapy proposals are discussed.