Action potential simulation (APS) in patients with fibromyalgia syndrome (FMS): a controlled single subject experimental design.

OBJECTIVES: Action potential simulation (APS) is becoming a popular method of pain reduction. Nevertheless, little is known about the efficacy of this relatively new treatment. The aim of this study was to investigate whether APS helps to reduce pain, improves patients' perception of daily functioning and social participation in patients with fibromyalgia syndrome (FMS). MATERIALS AND METHODS: Ten patients with FMS according to the American College of Rheumatology (ACR) criteria entered this double blind crossover single-case study. In a period of 20 weeks, the patients underwent two treatment periods of 4 weeks, one with verum and one with placebo, at random, in a double blind fashion. Outcome measures were evaluated on a weekly basis. Primary outcome measure was pain measured with the Fibromyalgia Impact Questionnaire (FIQ) questions 4 and 5, the number of tender points and the total tender point pain intensity score. Both visual inspection and statistical analysis were done to analyse the data from this single-subject design. RESULTS: Performing visual inspection and statistical analysis, no positive results of the APS treatment were found in this study. Remarkable is the fact that placebo APS had significantly better results than verum APS. CONCLUSIONS: In this single-case study with ten patients (all female), APS was not a helpful method to reduce pain, to improve patients' perception of daily functioning and social participation in patients with FMS.

Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.

PURPOSE: Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial. PATIENTS AND METHODS: Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54. RESULTS: Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (> 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR. CONCLUSION: Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL.

Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group.

PURPOSE: In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. PATIENTS AND METHODS: Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. RESULTS: At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC. CONCLUSION: The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.

Chemotherapy for bone marrow relapse of childhood acute lymphoblastic leukemia.

Results of the BMF study group trials ALL-REZ 83 and 85 for relapsed acute lymphoblastic leukemia (ALL) are presented. For children with late marrow relapse, remission rates of about 90% were seen in both studies. In children treated for early marrow relapse, the remission rate in study ALL-REZ 85 was superior (86% vs 62%). The probability of event-free survival for all patients and for those with early marrow relapse was also statistically significant (P less than 0.05). Children with T-cell ALL had an extremely unfavourable prognosis in both studies.

Partial trisomy 1q, an uncommon chromosomal aberration in erythroleukemia.

A 2 years 4 months old boy with erythroleukemia (FAB-M6) and Down's syndrome is described. Chromosome analysis of bone marrow leukemic blasts revealed apart from the trisomy 21 a partial trisomy of the long arm of chromosome 1:1q23-->1qter in all cells and trisomy 8 mosaicism. To the best of our knowledge this is the first time that a partial trisomy of chromosome 1 in association with erythroleukemia has been described. Previous reports of other hematologic malignancies with aberrations of chromosome 1 indicate that the breakpoint 1q23 is nonrandom and that trisomies of chromosome 1 plays a crucial role in the course of development of hematologic malignancies. This could probably also be true for erythroleukemias.

[Practical pain control in pediatric oncology. Recommendations of the German Society of Pediatric Oncology and Hematology, the German Association for the Study of Pain, the German Society of Palliative Care, and the Vodafone Institute of Children's Pain Therapy and Palliative Care]. / Praktische Schmerztherapie in der pädiatrischen Onkologie. Empfehlungen der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH), der Deutschen Gesellschaft zum Studium des Schmerzes (DGSS), der Deutschen Gesellschaft für Palliativmedizin (DGP) und des Vodafone-Stiftungsinstituts für Kinderschmerztherapie und Pädiatrische Palliativmedizin an der Vestischen Kinder- und Jugendklinik Datteln -- Universität Witten/Herdecke (IKP).

In pediatric oncology, optimal pain control is still a challenge. A structured pain history and the regular scoring of pain intensity using age-adapted measuring tools are hallmarks of optimal pain control. Psychological measures are as important as drug therapy in the prophylaxis or control of pain, especially when performing invasive procedures. Pain control is oriented toward the WHO multistep therapeutic schedule. On no account should the pediatric patient have to climb up the "analgesic ladder" - strong pain requires the primary use of strong opioids. Give opioids preferably by the oral route and by the clock - short-acting opioids should be used to treat breakthrough pain. Alternatives are i.v. infusion, patient-controlled analgesia, and transdermal applications. Constipation is the adverse effect most often seen with (oral) opioid therapy. Adverse effects should be anticipated, and prophylactic treatment should be given consistently. The assistance of pediatric nurses is of the utmost importance in pediatric pain control. Nurses deliver the basis for rational and effective pain control by scoring pain intensity and documenting drug administration as well as adverse effects. The nurses' task is also to prepare the patient for and monitor the patient during painful procedures. It is the responsibility of both nurse and doctor to guarantee emergency intervention during sedation whenever needed. In our guideline we comment on drug selection and dosage, pain measurement tools, and documentation tools for the purpose of pain control. Those tools may be easily integrated into daily routine.

[Initial results of a study of the treatment of children with ALL recurrences]. / Erste Ergebnisse einer Studie zur Behandlung von Kindern mit ALL-Rezidiven.

Ninety-five children and adolescents with their first relapse of ALL were treated in the multicentric prospective trial ALL-REZ BFM 83. Treatment was stratified with respect to time and site of relapse. The overall remission rate was 86.3%. In the group of patients with early relapse only 44/56 children (78.6%) achieved a second remission, whereas the remission rate was 97.4% (38/39) in patients with late relapse. The 2 year probabilities of a sustained second complete remission are 0.65 +/- 0.10, 0.33 +/- 0.09 and 0.71 +/- 0.14 for patients with late, early and isolated CNS relapses, respectively. The poorest prognosis was observed in children with early marrow relapse (0.16 +/- 0.13 after one year).

[Practice of pain control in paediatric oncology--recommendations of the quality-monitoring group of the German Society for Paediatric Oncology and Haematology (GPOH)]. / Praktische Schmerztherapie in der Kinderonkologie. Auszüge aus den Empfehlungen der Qualitätssicherungsgruppe der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH).

In paediatric oncology, optimal pain control is still a challenge.A structured pain history and the regular scoring of pain intensity using age-adapted measuring tools are hallmarks of optimal pain control. Psychological measures are as important as drug therapy in prophylaxis or control of pain, especially when performing invasive procedures. Pain control is oriented on the WHO analgesic ladder. On no account the paediatric patient should have to climb up the 'analgesic ladder'- strong pain requires the primary use of strong drugs. Opioids should be given by the oral route and by the clock - short acting opioids should be used to treat break-through pain. Alternatives are IV infusion and patient-controlled analgesia. Constipation is the adverse effect most often seen with (oral) opioid therapy. Adverse effects should be anticipated, and prophylactic treatment should be given consistently. The assistance of paediatric nurses is of utmost importance in paediatric pain control. Nurses' deliver the basis for rational and effective pain control by scoring pain intensity and documenting drug administration as well as adverse effects. The nurses task is also to prepare the patient for and monitor the patient during painful procedures. It is the responsibility of both nurse and doctor to guarantee emergency intervention during sedation whenever needed. In our paper we comment on drug selection and dosage, pain measurement tools, and documentation tools for the purpose of pain control. Those tools may be easily integrated into daily routine.

[Ototoxicity of cisplatin in children with malignant diseases]. / Ototoxizität von Cisplatin bei Kindern mit malignen Erkrankungen.

Ten out of 20 children with malignant diseases who received cisplatin in combination with other drugs developed hearing impairment primarily at the higher and rarely also at the lower frequencies. The CDDP-ototoxicity was found to be dose-related and irreversible. Audiometric abnormalities were symmetrical and bilateral. Two patients had symptomatic hearing impairment. Ototoxicity was more severe with higher individual and higher cumulative doses. CNS-irradiation increases the ototoxic effect of CDDP. Audiometric testing at the beginning of chemotherapy and during chemotherapy is important to find out preexisting disturbances of hearing function and to recognize early developing hearing loss.

[Biclonal leukemia O-ALL/AMoL) with 11;19 translocation and trisomy X in an 8-month-old girl]. / Biklonale Leukämie (O-ALL/AMoL) mit 11;19 Translokation und Trisomie X bei einem 8 Monate alten Mädchen.

Biclonal leukemia was diagnosed in an 8 months old girl, combining lymphoblastic (FAB L1) and monoblastic (FAB M 5) phenotypes which were classified as O-ALL and AMol by immunological examination of surface-antigens. Chemotherapy for one cell type resulted in predominance or relapse of the other one. Chromosomal abnormalities diagnosed in the lymphoblastic clone consisted of translocation t(11;19)(q23;p13) and triple X. The breakpoint 11q23 neighbouring one well known oncogene (ets) is not strictly associated with special leukemic phenotypes. But it is often found in infants and usually correlated with a poor prognosis. The data of 18 patients with hybrid leukemias registered in the BFM studies strongly support the fatal course of the disease. 12 months after diagnosis approximately 1 out of 10 children is expected to survive disease-free.

[Successful chemotherapy in a primary cerebral centroblastic non-Hodgkin's lymphoma in childhood]. / Erfolgreiche Chemotherapie bei einem primär zerebralen zentroblastischen Non-Hodgkin-Lymphom im Kindesalter.

Primary lymphomas of the central nervous system (CNS) are rare diseases. Often these tumors are surrounded by glia cells and may, therefore, be misdiagnosed as 'astrocytomas' with accompanying reactive lymphocytosis. A 15-year old patient was irradiated to the posterior cranial fossa and the brain stem because of a supposed astrocytoma. Five months after completion of radiotherapy he presented two lesions each in the right and left cerebral hemisphere. Repeated biopsy led to a revision of the primary diagnosis in favor of a B-cell Non-Hodgkin lymphoma (centroblastic type). After cyclic polychemotherapy including high-dose methotrexate and cytosine-arabinoside he entered a complete remission. No further radiotherapy was given. So far, 18 months after discontinuating therapy, the patient has been in complete remission and is in an excellent physical condition.

[Long-term infusion of L-asparaginase--an alternative to intramuscular injection?]. / Langzeitinfusion von L-Asparaginase--eine Alternative zur intramuskulären Injektion?

Nine children of the ALL-REZ BFM 87 and 90 trial received L-Asparginase (L-ASP) as a continuous infusion for 48-72 hs (i.e. 25 therapy cycles). Seven patients had had an allergic reaction towards an i.m. application (i.m., 29 therapy cycles). Two further patients got L-ASP initially as continuous infusion. The i.m. applications were carried out 19 times with Erwinia and 10 times with E. coli-Asparaginase, the continuous infusions 15 times with Erwinia and 10 times with E. coli-Asparaginase. In case of four patients continuous infusions of the same L-ASP type (E. coli or Erwinia) was well tolerated, after there had been an allergic reaction after i.m. application. Allergic reactions after i.m. application occurred during 10 courses as local painful erythema, during five courses as urticaria, during four courses as a general exanthema during one course as difficult breathing and during a further course as drop in blood pressure. After continuous infusion of L-ASP urticaria and difficult breathing occurred once and a transient exanthema two times. There was no anaphylactic reaction in any case. These data show that i.m. application of L-ASP causes no life-threatening side effects but allergic reactions (local pain and swelling) which clearly impaired general condition. Continuous infusion is a pharmacologically equivalent alternative with less impairment of the patients' general condition.

[Severe renal impairment of methotrexate elimination after high dose therapy]. / Schwere renale Methotrexat-Ausscheidungsstörung nach Hochdosis-Therapie.

Even in patients with normal renal function, high-dose methotrexate therapy (HDMTX) may be followed by extremely prolonged MTX elimination through alkaline diuresis is performed correctly. By inquiry in Germany, Austria and Switzerland for HDMTX infusions with MTX plasma concentration 42 h after start of exposure (MTX-42) higher than 5 mumol/l (microM), we analyzed data from 21 patients in whom impairment of renal methotrexate elimination had received 5 g/m2.24h, 3 had received 12 g/m2.4h. They presented with MTX-48 serum level between 1.7 and 1404 microM. There was no recognizable causative factor. As early signs for impaired elimination, we identified enhanced vomiting during MTX infusion in 8/21, elevated steady-state-MTX in 11/15, and a rise of serum creatinine greater than 50% in 14/16 patients in whom respective data were available. Creatinine rose to a maximum of 1.0-4.9 mg/dl within 1-4 days in 19/21 patients (accompanied by diuresis problems in only 5 patients) and normalized within 3-17 days in all but two patients. Creatinine maximum correlated weakly with MTX-48 (r = 0.34) and with extrarenal toxicity. 8 patients had normal (WHO 0-II degree), 8 other had intensified (III-IV degrees) but not critical extrarenal MTX toxicity with calcium folinate (CF) doses of 0.2-1.6 mg/kg.microM MTX q 6 h started 28-54 h after beginning of MTX exposure. 5 patients had unusual toxicity. 2 patients suffered from severe but reversible encephalopathies with CF doses of 0.05 and 1 mg/kg.microM MTX q 6 h started after 51 and 36 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermediate dose methotrexate is as effective as high dose methotrexate in preventing isolated testicular relapse in childhood acute lymphoblastic leukemia.

PURPOSE: We evaluated the influence of three different dosages of methotrexate (MTX) during consolidation on the incidence of testicular relapse in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: One thousand one hundred forty-four boys with newly diagnosed ALL, enrolled in three consecutive trials of the Berlin-Frankfurt-Münster group (ALL-BFM 81, 83, 86), were retrospectively evaluated for the influence of MTX on testicular relapse-free interval. The basic treatment design was similar in all trials. No intravenous MTX was used in trial ALL-BFM 81 in the group who received cranial irradiation (CRT) except for a part of standard risk patients. Four courses of intermediate dose MTX (IDM) (0.5 g/m2) were introduced for all patients in trial ALL-BFM 83 (IDM group), which were replaced by high dose MTX (HDM) (5 g/m2) in trial ALL-BFM 86 (HDM group). The media observation time was > 9 years. RESULTS: The cumulative incidence of isolated testicular relapses was significantly higher in the CRT group as compared to the IDM and HDM groups (6.7% versus 2.5% and 2.3%, p = 0.02 and 0.01). HDM decreased neither the incidence nor the rate of isolated testicular relapses any further. Event-free survival (EFS) for boys was similar between trial ALL-BFM 81 and 86 (64% versus 69%, p = 0.35), but differed significantly between trials ALL-BFM 83 and 86 (61% versus 69%, p = 0.0078). CONCLUSION: The introduction of IDM reduced the incidence of isolated testicular relapses significantly by a factor two, but had no significant influence on overall survival. HDM did not result in a more effective prevention of testicular relapses, but resulted in better systemic control and hence better survival than IDM.

[Effect of 7S immunoglobulin substitution on the incidence and course of infection in cytostatic drug treated patients]. / Einfluss der 7S-immunoglobulin substitution auf die Häufigkeit und den Verlauf von Infektionen bei zytostatisch behandelten Patienten.

This retrospective analysis evaluates the effect of intravenously administered immunoglobulin against infections occurring during bone marrow depression after cancer chemotherapy in 85 children with leukemia and lymphoma. There was no statistical difference between patients with and without immunoglobulin administration neither when immunoglobulins were used prophylactically nor therapeutically in addition to antibodies during episodes of infection. Duration of fever, duration of antibiotic therapy, maximum of temperature, white blood cell counts, and kind of infections were comparable in 84 fever episodes in patients who had received immunoglobulin therapeutically and 69 fever episodes in patients who had not. This study supports the aspect that immunoglobulin administration does not have preventive or therapeutic efficacy on infections during cancer chemotherapy in children.

[Long-term experiences with central venous catheters in pediatric oncology]. / Langzeiterfahrungen mit zentralvenösen Kathetern in der pädiatrischen Onkologie.

93 central venous catheters (77 Broviac und 16 ports) were inserted in 79 children with malignant diseases between 1980 and 1988. The median duration of use for Broviac was 5.8 months (0.2-24 months) and for ports 7.5 months (0.8-44 months). The total duration of use was 14 658 days for Broviac catheters and 5970 days for ports. The most frequent complications were dislogements, obstructions and infections. They were observed in 19 out of 77 Broviac catheters (25%) and in 5 out of 16 ports (31%). Because of complications 17 out of 93 catheters were prematurely removed. Complication rates were not significantly different in both systems. The incidence of infections in Broviac catheters was 5% or 0.27 per 1000 days of use, respectively, which is lower than reported by other studies. The consistency in catheter-care procedures can decrease the rates of complications.

Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin-Frankfurt-Münster) Relapse Study Group.

Presymptomatic central nervous system (CNS) treatment in children with a late isolated first bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL) was based on intermediate-dose systemic and intrathecal (IT) methotrexate (MTX) in the multicenter trial, ALL-REZ BFM 85. Because this was associated with an excess of overt second CNS relapses, cranial radiotherapy (cRT) plus prolonged triple IT therapy with MTX, cytarabine, and prednisone was instituted during the course of the subsequent trial, ALL-REZ BFM 87. Results of children with or without cRT, but otherwise identical chemotherapy, are presented here. Between April 1985 and March 1990, 93 children with their first late isolated BM relapse of ALL were entered on protocols ALL-REZ BFM 85M and ALL-REZ BFM 87. An intensive 6-month phase of multiagent chemotherapy that included 8 courses of systemic MTX (1 g/m2) plus IT MTX was followed by 2 years of conventional maintenance therapy with daily 6-thioguanine and biweekly MTX. Children with bone marrow transplantation excluded, 73 were in complete remission at the end of intensive polychemotherapy, 40 of whom received fractionated cRT plus triple IT therapy during the following 6 months; 11 did not receive cRT but prolonged triple IT; 22 received neither cRT nor prolonged triple IT. Except for a higher percentage of children who had received cRT in front-line protocols (29 of 33 v 20 of 40), the patient groups without or with salvage cRT were comparable. Of 33 children without salvage cRT, 26 relapsed, compared with 21 of 40 who had received cRT (P < .05). The difference was solely attributable to second relapses with CNS involvement (10 of 33 v 1 of 40; P < .01). Estimated 6-year event-free survival rates were .18 for children without cRT and .46 for children with cRT (P < .01). In patients without cRT, no impact of prolonged IT therapy could be shown. The data suggest that second CNS prophylaxis with cRT and prolonged triple IT therapy in children with late isolated BM relapse of ALL is effective in preventing CNS relapses, in reducing the overall relapse rate, and in increasing the overall survival rate.

Erythroblastopenia in two patients after splenectomy and polychemotherapy.

Acquired erythroblastopenia is a rare disorder of the hematopoietic system associated with viral infections, autoimmune diseases, and drugs. We report on two patients who became anemic due to maturation-arrest at the proerythroblast level, without alterations of white blood cell or platelet counts. Both patients had been splenectomized and had undergone chemotherapy for nephroblastoma or Hodgkin's disease, respectively, at the same pediatric oncology unit. Erythropoietin levels were elevated in both patients. Antibodies against specific viruses, particularly parvovirus B 19, could not be detected in patient sera. Both patients responded to infusions of 7 S immunoglobulin with a rapid increase of the reticulocyte counts. In both cases, complete clinical remission was observed after a duration of 5 months. Heat-inactivated serum obtained during the acute phase and after remission as well was found to be inhibitory for normal bone marrow granulocyte and erythrocyte progenitor growth in vitro. The simultaneous appearance of this rare disorder in two otherwise unrelated patients treated at the same unit prompts speculations about a viral etiology.

Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group.

Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment.

Syndrome of the posterior and anterior root in a late isolated CNS relapse of c-ALL. Case report.

A 15 year-old girl who had c-ALL diagnosed in 1982 was presented in our clinic suffering from an ascended flaccid paresis and dysaesthesia of both legs. These are typical symptoms of polyradiculitis of the nerve roots L2-S2. A lumbal puncture revealed a pleocytosis with lymphoblasts which were up to 40% CD10 (cluster of differentiation) up to 70% CD19 and TdT (terminal transferase) positive. The diagnosis of late isolated CNS relapse was made. It is assumed that local residual infiltrations of leukemic cells into the nerve roots L2-S2 got into cell cycle and caused these rare CNS leukemia symptoms. Therefore the value of a craniospinal irradiation to prevent a CNS and systemic relapse is discussed.