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H Gadner

Publications and source records attributed to H Gadner.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

[Treatment of acute lymphoblastic leukemia in childhood and adolescence: results of the multicenter therapy study ALL-BFM 81].

In therapy study ALL-BFM 81 633 previously untreated patients with acute lymphoblastic leukemia (ALL) less than 18 years of age have been recruited from April 1, 1981 to September 30, 1983 and treated in 37 institutions throughout West-Germany and Austria. Here only therapy results of 611 patients with non-B-ALL are presented. Patients with ALL of B-type are described elsewhere. In this fourth consecutive trial of the BFM study group three major questions have been asked: 1. Is it possible to assess the individual risk for relapse more accurately by the use of a risk factor rather than by the risk score which was the discriminator in studies ALL-BFM 76 and ALL-BFM 79? Does this risk factor discriminate more precisely patients at the highest risk for relapse? Offers more intensive risk-adapted therapy to this patient group a better chance for disease-free survival? 2. In patients at a standard risk for relapse with a risk factor below 1.2--approximately 60% of patients with non-B-ALL--can radiotherapy for prevention of CNS disease effectively be replaced by chemotherapy (intermediate dose Methotrexate)? 3. It is possible to reduce duration of maintenance therapy by 6 months to a total duration of 18 months with no unfavorable effect? To assess the radiation problem in standard risk patients and to evaluate the importance of duration of maintenance therapy two randomisations have been utilized. After a median duration of study ALL-BFM 81 of 4 1/2 years and 3 1/4 years after the study had been closed (date of evaluation January 1, 87) the answers are as follows: 1. For the majority of patients risk-adapted therapy had a curative effect. The probability for event-free survival (EFS) in standard risk patients in slightly above 70%, in medium risk patients 67%. In high-risk patients risk-adapted therapy did not improve prognosis, the EFS being still in the order of 50%. A good assessment of the individual risk for relapse is possible by the newly introduced risk factor. This principle is superior to the risk score used in former studies ALL-BFM 76 and ALL-BFM 79 because a low risk group (risk factor below 0.8) could be identified including approximately 25% of all patients with non-B ALL. Selection, quality, and timing of therapy elements remain the decisive prognostic factors, however. 2. Standard risk patients with a risk factor below 0.8 can effectively be protected for CNS relapse by treatment with intermediate dose Methotrexate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMedDate not supplied

[Langerhans cell histiocytosis in childhood--results of the DAL-HX 83 study].

Owing to the unclear and mostly unknown etiology of Langerhans' cell Histiocytosis (LCH) and the unsatisfactory results in treating disseminated LCH a prospective multicentric study DAL-HX 83 was commenced, including 45 different clinics of West-Germany, Austria and Netherlands. From June 1st, 1983 to October 31st, 1986, 97 patients (pts) were involved in this study. 35 pts (9 females, 26 males, medium age 6 2/12 years, age range 0/12-14 2/12 years) suffering from localized disease (28x unifocal bone, 6x isolated skin, 1x isolated lymphnode involvement) were treated by surgery and/or radiation or were just kept in observation. 2 children (1 pt with primary localized bone lesion, 1 child with isolated skin rash) developed a new bone lesion after 1/2 year and 1 1/2 years respectively. 62 pts (33 females, 29 males, medium age 2 years, range 0/12-17 1/2 years) with previously untreated disseminated disease were assigned to 3 different risk groups (A, B and C) and were treated according to a standardized induction and risk adapted maintenance protocol. The whole treatment period was limited to 1 year. 19 pts with multifocal bone involvement (group A, medium age 6 1/2 years) were allocated to regimen A, 30 pts with bone and soft tissue involvement or soft tissue involvement alone (group B, medium age 1 8/12 years) to regimen B and 13 pts with dysfunction of the liver, lungs and/or haematopoietic system (group C, medium age 1 year) to regimen C. So far, 1 pt of group A (19 available pts) developed a new bone lesion after 10 months, another pt a suspicious bone involvement 16 months after diagnosis. A 4 months old girl of group B (27 available pts) died 11 months after diagnosis with progressive organ dysfunction, 2 pts are still alive with recurrent multifocal bone lesions and 1 pt achieved stable 2nd clinical remission after a local relapse (mediastinum). 4 pts of group C (11 available pts) died because of progressive disease between 5 days and 3 years after diagnosis, 3 pts are in partial remission after persistent and recurrent disease episodes. All the others are in clinical remission. The medium observation time of the whole group of pts with disseminated LCH is 1 9/12 years (range 0/12-3 5/12 years). The worst prognostic criteria were found to be the presence of organ dysfunction at diagnosis or its development during the course of disease and the age under two years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMedDate not supplied

[Wiedemann-Beckwith syndrome: clinical characteristics, constitutional chromosome abnormalities and tumor incidence].

The observation of constitutional chromosome abnormalities in a one and half year old boy with Wiedemann-Beckwith syndrome (WBS) and hepatoblastoma prompted us to review the currently available literature dealing with this subject. In approximately 500 published cases with complete and incomplete forms of WBS, 42 malignant and 9 benign neoplasms have been described. Malignant tumors, in particular, mainly consisted of nephroblastomas and adrenocortical carcinomas. The patient presented in this paper is the fourth with a hepatoblastoma. The constitutional karyotype was analysed in 84 cases; in 68 of them with banding techniques. Abnormalities have only been detected in 11 patients. A 47;XXY karyotype, an inversion of chromosome 2, a partial duplication of the long arm of chromosome 8 and reciprocal translocations t(11;22) and t(X;1), respectively, have been observed in one case each. Individually differing changes in the remaining six cases led to a common triplication of the region 11p15. This triplication has also been the only abnormality, which has so far been reported in one out of six investigated WBS patients with a tumor. Cytogenetic analysis in our case revealed an interstitial deletion of the short arm of chromosome 11 and a complete pericentric inversion of the chromosome 9 heterochromatin block. The breakpoints of the deletion, del(11) (p11.1p11.2), are located proximal of those (11p15) reported in anomalies of other WBS patients, as well as proximal of those involved in patients with the aniridia/Wilm's tumor complex (11p13-11p14). Inversion of the heterochromatin of chromosome 9 has been recognized as a normal variant, which generally remains without phenotypic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗
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[Combined treatment strategy in over 200 children with Hodgkin's disease: graduated chemotherapy, involved field irradiation with low dosage and selective splenectomy. A report of the cooperative therapy study DAL-HD-82].

UNLABELLED: It was the aim of the cooperative therapy study HD-82 for children with Hodgkin's disease to reduce chemo- and radiotherapy and to investigate of a strategy for selective splenectomy previously developed in the Hodgkin study HD-78. Between December 1981 and December 1984 207 patients (131 boys and 76 girls) below 16 years of age were enrolled in this study. In 174 out of 207 patients (84.1%) the criteria for selective splenectomy were applied i.e. the spleen was only removed when the splenic surface was nodular or when the lymphnodes at the splenic hilus and/or the pancreatic tail were enlarged. 69 out of 174 patients (39.7%) had a splenectomy. 50 of the removed 69 spleens (72%) showed histological evidence of Hodgkin's disease. These results were comparable to the 36% and 73% predicted from the retrospective analysis in the HD-78 study. According to the stage of Hodgkin's disease three different treatment groups with 2, 4 and 6 cycles of OPPA/COPP were formed (stage I/IIA, IIB/IIIA and IIIB/IV). Radiation therapy was given as involved field irradiation with a total dose of 35, 30 and 25 Gy depending on the extent of the chemotherapy. 203 patients were treated according to the protocol. Until the 30th of November 1985 3 patients died from intercurrent disease during a follow-up period of 11 to 47 months (median 29 months). 5 patients relapsed. The probability for disease-free survival after 3 1/2 years is 96% for the total group and 99%, 96% and 87% for the three treatment groups including 100, 53 and 50 patients in each group respectively. CONCLUSIONS: 1. The OPPA/COPP chemotherapy eliminates reliably occult microfoci. 2. The radiation doses in combination with the chemotherapy are sufficient to prevent local recurrences. 3. The decisional model for selective splenectomy has proved to be extremely valuable prospectively.

Adolescent↗
PubMedDate not supplied

[Guidelines for therapy of idiopathic thrombocytopenic purpura (ITP) in childhood].

The term "idiopathic thrombocytopenic purpura (ITP)" comprises a rather heterogeneous group of diseases with different etiology and pathogenesis. 80% of the cases are acute forms following viral infections. Within the first 6 months the spontaneous remission rate is higher than 80%. The remaining patients develop an intermittent or chronic form of the disease. Lethal complications, commonly cerebral hemorrhage, are rare (less than 2%). Following a review of the established and the recent experimental therapeutic approaches, the authors try to give comprehensive therapeutical guide-lines for the management of the various clinical forms of the disease. If there is only a minor bleeding diathesis, it is recommended to withhold therapy for 2 to 3 weeks, irrespective of the platelet count. If no spontaneous remission occurs, we suggest therapy with corticosteroids. In case of failure of this therapy, infusions of high-dose immunoglobulins are advisable. Short-lasting successes may even be prolonged with further infusions (once a week or at longer intervals)--thus postponing splenectomy. In addition, a combination of high-dose immunoglobulins and corticosteroids may be effective. Following pneumococcal vaccination and penicillin prophylaxis, splenectomy should be performed not earlier than one year after diagnosis of ITP and only in children older than 5 years. If splenectomy does not lead to recovery of the platelet count, immunoglobulin infusions--possibly combined with corticosteroids--may be repeated. Finally, if all the above proposed therapeutic actions have failed, immunosuppressive drugs (azathioprime or vincristine) may be necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
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ITP in childhood: difficulties in the individual treatment.

To date, immunoglobulin preparations and corticosteroids are the most important therapeutic principles in idiopathic thrombocytopenic purpura (ITP). Initial treatment with high-dose immunoglobulins (HD-IgG) as well as the following prednisone therapy, however, were only of short lasting success in three children with newly diagnosed ITP. Recurrent bleeding tendency tempted to combine both drugs. A desired longterm elevation of platelet counts, however, was not achieved. Administration of Anti-Rho (D) to two of the patients was also disappointing. Splenectomy which could not be postponed any longer has already led to 17 and 21 months lasting remissions in 2 patients, respectively. The third patient who required monthly single doses of HD-IgG for 6 months after surgery, is in a partial remission since 27 months now. All types of drug administration--alone, consecutive or even combined--must be considered to defer splenectomy. As experienced in our patients, however, splenectomy still seems to be justified in case even such individually adapted therapeutic approaches fail.

Adolescent↗
PubMedDate not supplied

[Unexpected regeneration of a congenital unilateral hypoplastic- dysplastic kidney after a contralateral nephrectomy for Wilms tumor].

The congenital hypoplastic-dysplastic kidney is characterized by a significant reduction of renal mass, an abnormal parenchymal differentiation and is associated with anomalies of the whole urinary tract. Not much is known about the ability for regeneration in such a kidney. We report on a 2 year 11 months old boy with an anaplastic Wilms tumor of the left kidney, in whom after tumor-nephrectomy an unexpected functional and sonographically documented morphological regeneration of the contralateral hypoplastic-dysplastic kidney occurred. The regeneration of this kidney is especially notable, because it occurred during nephrotoxic chemotherapy and radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group.

Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.

Adolescent↗
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Prevention of CNS recurrence in childhood ALL: results with reduced radiotherapy combined with CNS-directed chemotherapy in four consecutive ALL-BFM trials.

BACKGROUND: The introduction of cranial radiotherapy (CRT) has provided efficient control of overt or subclinical meningeosis in acute lymphoblastic leukemia (ALL). Especially due to the long-term toxicity of CRT, reduction or elimination of radiotherapy appeared mandatory after cure rates of more than 70% had been achieved in ALL. The Berlin-Frankfurt-Münster (BFM) Study Group initiated several attempts in certain ALL subgroups to omit or reduce CRT while using more CNS-directed chemotherapy but without extended intrathecal treatment during maintenance therapy. This analysis summarizes the essential results that are in particular relevant because irradiation of the central nervous system (CNS) has been further reduced in the most recent trial ALL-BFM 95. PATIENTS AND METHODS: More than 4000 patients enrolled between 1981 and 1995 in one of the last four ALL-BFM trials have been analyzed to demonstrate the efficiency of intensive systemic and intrathecal chemotherapy with or without reduced CRT in the prevention of CNS relapses. RESULTS: In trial ALL-BFM81, it was shown that only in low-risk (LR) patients preventive radiotherapy can be replaced safely by intermediate dose (0.5 g/m2) methotrexate (MHD-MTX). In intermediate risk (IR) patients this attempt failed: IR pts had 8 times more CNS relapses if treated by MHD-MTX without CRT. In the subsequent trial ALL-BFM 83, all pts received MHD-MTX. IR pts were randomly treated with 12 or 18 Gy of preventive CRT which did not result in a significantly different outcome. The results from the subsequent trial ALL-BFM 86, using a more intensive consolidation with high-dose methotrexate (HD-MTX), demonstrated that the elimination of CRT in low-risk ALL, the reduced CRT of 12 Gy for IR, 18 Gy for medium (MR), and the reduced CRT with 18 Gy for high risk (HR) ALL, respectively, was justified: the incidence of relapses with CNS involvement was reduced to less than 5% (Reiter et al. 1994, Blood 84: 3122). When even less intensive preventive CRT (12 Gy for all medium and high risk patients) was used in trial ALL-BFM 90, the rate of CNS-related relapses was again below 5%. HR patients now treated with more CNS-directed chemotherapy had the lowest rate of CNS-related relapses observed so far in the BFM trials, even though CRT was also reduced to 12 Gy. Patients with T-cell ALL were shown to be protected from CNS recurrence by the combination of CRT (12 Gy) and HD-MTX more effectively than by HD-MTX in consolidation and TIT therapy during maintenance, especially if they presented with high WBC as shown in a joint AIEOP/BFM analysis (Conter et al. 1997, JCO 15: 2786). Patients with overt meningeosis which are characterized by a high leukemic cell load at diagnosis had a rate of recurrences that was comparable to that of patients with high WBC but no CNS disease. CONCLUSION: Low-risk ALL patients can be efficiently prevented from CNS relapse by intensive systemic and intrathecal chemotherapy without CRT. Patients with intermediate or medium risk ALL, including T-cell ALL, did not suffer from more CNS or systemic relapses when CRT was reduced to only 12 Gy. Patients with inadequate response to therapy are at particularly high risk for relapse with CNS involvement. Therefore, more CNS-directed systemic and intrathecal chemotherapy was applied in trial ALL-BFM 90, combined with only 12 Gy cranial irradiation, and improved the control of CNS recurrence. It seems likely that larger subsets of B-precursor ALL can be protected from CNS-related relapse by intensive chemotherapy without extended IT treatment and without CRT. This is being investigated in the ongoing trial ALL-BFM 95.

Adolescent↗
PubMedDate not supplied

[Use of corticosteroids and immunoglobulins in acute and chronic immune thrombocytopenia in childhood. A clinically oriented treatment concept].

In 80% of children suffering from immune thrombocytopenic purpura, the disease is a self-limited process. Established therapeutic measures are commonly used to effect symptomatic relief. The foremost of these is the administration of immunoglobulins and corticosteroids. A total of 113 children and adolescents with immune thrombocytopenic purpura were examined retrospectively in this study. Of these, 48%, did not require any therapy, 37% were treated with high-dose immunoglobulin, and 15% with prednisolone as first-line treatment of extensive purpura of the skin and the mucous membrane. The time until the thrombocyte count reached 100 G/l was shorter in the treated group than in the one that was not treated (4.5 and 6.0 versus 21 days). 71% of all patients achieved remission in six month. In 29% the disease took a chronic course. Of 33 children with chronic therapy-dependent disease, 7 were splenectomised successfully. Seven further patients continue to live with thrombocyte counts below 20 G/l, of which 4 suffer from recurrent bleeding episodes. In patients with acute and chronic immune thrombocytopenic purpura, the aim of treatment is to prevent potentially fatal bleeding. Patients with thrombocyte counts below 20 G/l are high-risk patients. Nevertheless, even in this group, the therapy should be decided clinically according to bleeding tendency. Ideally, the therapy should result in a quick increase of thrombocyte counts whilst causing minimum side effects. Of the various established treatment modalities, high-dose immunoglobulin and high-dose prednisolone best fulfil these requirements.

Adolescent↗
PubMedDate not supplied

[Long-term monitoring of therapy-induced computerized tomographic cranial changes in children with acute lymphoblastic leukemia].

PURPOSE: Long-term follow-up of cranial CT scans of children with acute lymphoblastic leukemia and evaluation of the influence of chemo- and radiotherapy on the CCT changes. PATIENTS AND METHODS: CCT scans of 68 children with non-B-ALL were analyzed retrospectively for signs of atrophy and changes in density. Patients were treated between 1981 and 1990 at the St. Anna Childrens Hospital Vienna according to the ALL-BFM protocols. Children were examined with CCT in defined periods from diagnosis until 3 years after cessation of treatment. As a control group served 69 patients with solid tumors who had not received corticoids or cranial irradiation. RESULTS: At the initial examination 56% of the ALL-patients showed CCT changes, 85% of these patients had already received corticoids. In the control group only 20% of the CCTs were found abnormal (p = 0.005). In both groups an age-dependence was found: 64% of the ALL-patients under five years of age and 22% of the patients above 5 years had initial CCT changes (p = 0.001). In the control group 39% of the patients under five years of age and 7% of the older patients showed CCT changes at the beginning of treatment (p = 0.003). The highest incidence of abnormal CCT scans (68%) was seen during intensive chemo- and radiotherapy. Until the end of therapy the incidence of abnormal CCTs decreased to 32%. After cessation of antileukemic therapy 35% of the patients whose CNS-prophylaxis included cranial irradiation, and 12% of the non-irradiated patients had abnormal CCT scans. CONCLUSION: Corticoids can cause reversible signs of cerebral atrophy. In the assessment of CCTs a physiological age-dependence of the volume of the CSF compartment has to be taken into consideration. The main reason for non-reversible CCT changes is the CNS- prophylaxis, above all the cranial irradiation, whereby younger children seem to be particular vulnerable.

Age Factors↗
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A single centre experience with allogeneic stem cell transplantation for severe aplastic anaemia in childhood.

BACKGROUND: Severe aplastic anaemia (SAA) is a rare disorder which has a fatal course when allogeneic stem cell transplantation (SCT) or an immunosuppressive regimen is not applied. Stem cell replacement is the only curative approach for these patients but it is limited by the availability of a compatible donor. PATIENTS: Between 1982 and 1993, 18 children (15 boys, 3 girls) with SAA and HLA identical, MLC negative donors underwent SCT in our institution. SAA was preceded by viral infection in 8 patients (3x hepatitis, 1x measles, 1x herpes simplex infection and 3x viral upper respiratory tract infections). It was drug-associated in one and idiopathic in the 9 others. The median age at diagnosis was 9.7 years (range, 2 months to 16 years). Pretreatments included corticosteroids in 11/18 patients, androgens in 4 patients in addition, two had received cyclosporin A (CSA). One patient progressing from Diamond- Blackfan anaemia to SAA had multiple immunosuppressive treatment courses over 7 years before his grand-uncle was identified as donor while 4 patients had no treatment prior to SCT. METHODS: Early SCT (within 90 days after diagnosis) was performed in 9/18 patients and the median interval between diagnosis and SCT was 2.6 months (range, 0.5 to 7 years). The stem cell source was the bone marrow (BM) of a syngeneic twin in 2 patients, the BM (13 patients) or the cord blood (1 patient) of a sibling whilst it was BM from a HLA-phenotypical family donor (1 father, 1 grand-uncle) in two patients. Cyclophosphamide 50 mg/kg on 4 consecutive days was given as preparative regimen to 16 patients but not to the two syngeneic twins. Rejection prophylaxis included total lymphoid irradiation in 5/16 patients while in the other 11 patients donor buffy coat cells were given on days +1 to +4. The syngeneic twins had no need for either approach. Patients received a median number of 3.7 x 10(8)/kg nucleated cells (range, 2.6 to 6.7). Prophylaxis of graft versus host disease (GVHD) was carried out with MTX alone (n = 12), with CSA alone (n = 2) or with both (n = 4). All patients received standard supportive care. RESULTS: The overall survival is 89% at the median observation time of 100 months. The median time to reach 500 granulocytes was 24 days (range, 15 to 40). Median time to become transfusion independent after BMT was 30 days for platelets (range, 2 to 111) and was 28 days for packed red blood cells (range, 6 to 128). Acute GVHD was observed in 10/18 patients and involved only skin in 6 patients, skin and liver or gut in two patients and all 3 organs in another two patients. Seven of 10 patients had grade 1 to 2 a GVHD toxicity, whereas 3 patients experienced grade 3 to 4 acute GVHD. Chronic GVHD developed in 5 patients. Acute transplant related mortality was 5.5%. Cause of death was persisting non engraftment till day +180 after 2 transplant procedures in a boy with previous platelet transfusions from his mother. Late mortality occurred in 2 patients: one chronic GVHD associated haemorrhage 20 months after SCT and one chronic GVHD associated septicaemia 10 years after SCT. CONCLUSION: Although this report reflects patients data accumulated over 15 years, results compare favourably with more recent survival data. Acute and late transplant related toxicity was low in patients undergoing early transplantation with adequate prior supportive care. This data confirms that SCT still should be the first treatment choice if an HLA identical sibling is available.

Anemia, Aplastic↗
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The influence of maximum supportive care on dose compliance and survival. Single-center analysis of childhood acute lymphoblastic leukemia and non-Hodgkin's-lymphoma treated within 1984-1993.

BACKGROUND: The administration of intensive, risk-adapted multiagent chemotherapy has markedly improved the event-free survival in childhood acute lymphoblastic leukemia and Non-Hodgkin's lymphoma. Current treatment protocols may achieve complete remission rates of more than 95% and event-free survival rates of approximately 70% in non-B-acute lymphoblastic leukemia/non-B-Non-Hodgkin's lymphoma patients. Due to a higher proliferation rate and aggressiveness of B-cells treatment of B-acute lymphoblastic leukemia/B-Non-Hodgkin's lymphoma must be more intensive, but can be shorter to attain similar event-free survival rates. METHODS: Between 1984 and 1993 79 primarily admitted patients up to 18 years of age (range 0.6-17.9 years) received therapy according to the treatment protocols ALL A 84, ALL 86, NHL 86, ALL 90 and NHL 90 of the Berlin-Frankfurt-Münster Study Group. Intensive phases of treatment were given on an inpatient basis with maximum supportive care in order to achieve the prescribed doses. RESULTS: Median follow-up time from diagnosis is now 8 years (range 40 to 157 months) with a probability of event-free survival of 92% for the entire group. CONCLUSION: Multiagent chemotherapy tailored to the individual risk profile of each patient but given in the prescribed dose is currently the mainstay to achieve high complete remission rates with the aim to cure most acute lymphoblastic leukemia/Non-Hodgkin's lymphoma patients. The administration of intensive supportive care is important for the achievement of complete drug dosage and for the reduction of therapy-related toxicity.

Adolescent↗
PubMedDate not supplied

[Value of prognostic factors in the Austrian A-NB87 Neuroblastoma Study].

AIMS: A multivariate analysis was performed to evaluate the impact of various prospectively evaluated risk factors. PATIENTS AND METHODS: From January 1987 to December 1993, 120 patients were registered in the study. 108/120 patients were eligible. There were 49 girls and 59 boys with a median age at diagnosis of 14 months (range, 0 to 224 months). Patients were classified according to the Evans classification system. LDH, NSE, Ferritin, N-myc amplification, 1p-deletion and ploidy were evaluated at diagnosis. Treatment intensity was based on the results of primary surgery: surgery only for 22 (20%) stage I and IIA patients (macroscopic residue without lymph node involvement), the 9 IIB patients (8,5%) (macroscopic residue with lymph node involvement) had mild chemotherapy in addition (6 x VCR/CYC) and elective radiation (Rx). Stage III patients were divided into 2 groups: IIIA patients (n = 17/16%) had to have ferritin levels under 300 micrograms/ml, NSE lower than 100 ng/ml and age below 2 years at diagnosis and received 6 alternating cycles of DAMO/ MVDOC. If one of these three criteria was not fulfilled, patients were assigned to the more intensive treatment arm stage IIIB (n = 12/11%), i.e. 9 alternating cycles of DAMO/MVDOC/IPE. Stage IV pts (n = 35/32.5%) received 8 MVDOC/IPE cycles and 20 patients received megatherapy followed by stem cell reinfusion in addition. 13 stage IVs patients (12%) were registered and had elective VCR/CYC and/or liver radiation in case of poor clinical condition. The median observation time is 4.2 years (range, 1 to 7.5). RESULTS: The survival rate at 3 years was excellent for localized disease and stage IVs with survival rates of 100% for stage I/IIA and 92% for stage IVs. Stage IIIA patients had an EFS rate of 81% whereas stage IIB patients achieved only 69%. Stage IV patients reached 51%, however outcome was especially poor for stage IIIB patients (20%) due to treatment related toxicities. The toxic death rate in the study was 13% (2 surgical deaths, 8 infections, 4 multiple organ failures). Univariate analysis demonstrated the following significant unfavorable risk factors: age over 1 year at diagnosis (58/108 pts, p = 0.006), NSE > 100 ng/ml (26/95 pts, p < 0.0001), Ferritin > 300 ng/ml (19/98 pts, p = 0.007), LDH > 300 (400) U/L, 51/87 pts, p = 0.004), presence of N-myc amplification (17/59 pts, p = 0.001), deletion of the short arm of chromosome 1 (19/74 pts, p < 0.0001) and di/tetraploidy (32/72 pts, p = 0.008). The power of these factors was even stronger in patients with localized disease whereas no significant prediction was observed for stage IV patients. Furthermore a significant correlation of the serological (NSE, ferritin, LDH) and biological factors (N-myc, deletion 1p, di/tetraploidy) was detected in this study. Only NSE was identified as an independent prognostic factor (p = 0.018) whereas no independent factor could be identified within the 3 biological parameters due to their high correlations (Kendall's tau for N-myc and deletion 1p:0.7). However, N-myc (p = 0.005) as well as deletion 1p (p = 0.01) were found significantly more important than di/tetraploidy. CONCLUSIONS: Biological classification of neuroblastomas should be mandatory and be the prerequisite for any risk adapted treatment. One serological and 2 biological factors could be a good standard evaluation to identify neuroblastoma patients at risk.

Adolescent↗
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[Treatment of chronic myeloid leukemia in children and adolescents--concept of the multicenter pilot study CML-ped].

CML is a rare malignancy in childhood not yet being treated by an established protocol of the Society of Pediatric Oncology and Hematology (GPOH). Up to now only allogeneic bone marrow transplantation (BMT) offers a curative treatment option. After being enrolled into the study "CML-päd" patients with a matched sibling donor should undergo BMT within six months after diagnosis and within one year if an unrelated donor can be identified. Progress in palliative therapy results from the experience in adult patients: Hydroxyurea in combination with interferon alpha (IFN) is the treatment of choice. One aim of the study is to monitor quantitatively in bone marrow aspirates the activity of the disease in all patients on treatment every three months by performing cytogenetics and molecular analysis. As a pilot protocol intensification of treatment by idarubicine and cytarabine is scheduled one year after diagnosis for those patients not undergoing BMT and exhibiting after IFN treatment less than partial response. After progress to the accelerated phase of the disease a decision has to be made on an individual basis whether the patient should undergo new experimental treatment approaches.

Adolescent↗
PubMedDate not supplied

[Phenotypic differences between CD34 positive cells in various transplantation tissues].

Transplantations to restore the hematopoietic system were originally performed with cells from the bone marrow (BM) (20) which was considered the only cell source comprising repopulating progenitor cells. The discovery that chemotherapy induced the mobilization of CD34+ cells into the peripheral blood (PB) (14) gave rise to the successful autologous transplantation of PBSC (1, 13). Also cord blood (CB) was found to contain considerable numbers of "stem cells", and to date at least 42 allogeneic transplantations have been performed with this cell source (22, J. Wagner, personal communication). Further investigations led to the successful autologous transplantation of positively selected CD34+ cells from BM and PB (18), and the latest results indicate that it is promising to transplant purified CD34+ cells obtained from cytokine-stimulated donors (4, 10, 15-16). Despite such achievements it remains unclear how many "stem cells" are required per kg of the recipient and how they are phenotypically characterized. In this communication we give examples of typical differences observed by flow cytometry and clonogenic assay between the CD34+ cells contained in the different cell sources. They may explain why it is not sufficient only to analyze the CD34+ cell populations which may represent progenitors of different lineages as well as of various states of differentiation. CB CD34+ cells are early myeloid progenitor cells with the highest incidence of CFU-mix among the three cell sources. They have a high proliferative potential in vitro. They hardly coexpress B cell antigens and they are partially negative for CD38.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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[Cytogenetic aspects of pediatric germ cell tumors].

We have performed in situ hybridization (ISH) studies predominantly on paraffin sections and on isolated nuclei of 22 pediatric germ cell tumors (GCTs) from 18 patients including 4 recurrences from three patients. In addition, we performed conventional cytogenetic analyses in three tumor samples. Because reports on cytogenetic studies in pediatric GCTs are scarce we focused our studies on those chromosome abnormalities frequently observed in adult GCTs. These included numeric and structural abnormalities of chromosomes 1 and 12 (e.g. isochromosome 12p) and numeric deviations of chromosomes 8, 10, X and Y. The histological subsets of the tumors investigated included two dysgerminomas (DGE), one seminoma (SE), one combined seminoma, two embryonal carcinomas (EC), two recurrent ECs, six pure yolk sac tumors (YST), five combined teratomas, one immature teratoma (IT) and two recurrences of IT, and three differentiated teratomas (TD). Similar to the GCTs in adults, additional copies of chromosome 12 were the most frequently observed numeric abnormalities. The analysis of two paraffin-embedded tumors suggested that changes in the size of the pericentromeric hybridization signals of chromosome 12 may be attributed to the presence of i(12)(p10). This was confirmed following the karyotype analysis of one EC which unequivocally revealed the presence of two i(12)(p10). Interestingly, using these probes, no chromosomal abnormalities were found in the pure TD or in the TD cells of mixed tumors containing a YST component. In the YST portion, however, the 1p deletions and/or numeric chromosome changes were present. Surprisingly, deletions at the short arm of chromosome 1, del(1)(p36.3), were frequently observed in malignant pediatric GCTs and were the sole abnormality detected in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗