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Biomedical subjects

H Gadner

Publications and source records attributed to H Gadner.

At least 307 records · Page 17Linked to original sources
PubMed1977

[The west-berlin therapy study of acute lymphoblastic leukemia in childhood--report after 6 years (author's transl)].

During the last 6 years 73 previously untreated children and adolescents with acute lymphoblastic leukemia were enrolled on a non-randomized therapy protocol. In this longitudinal sutdy the specific accent was put on the intensified induction treatment of 8 weeks' duration which was thought to achieve a higher remission quality. In this phase 8 effective drugs were applied up to the patient's tolerance limits; in addition prophylactic irradiation to the central nervous system was given in two modifications. After 4 weeks all patients were in complete remission. During the first 4 months 6 children died due to complications for which therapy must be at least partially responsible. 17 out of 67 patients relapsed between 4 and 59 months after diagnosis, which corresponds to a remission rate according to the life table analysis of 62% (50 out of 67 patients in first remission). The majority of patients with relapse is characterized at diagnosis by a specific pattern of clinical findings. 2 therapy groups, differently treated in respect to central nervous system irradaiation and duration of continuation therapy, do not at present statistically differ from each other. According to statistics 8 more children may be expected to suffer from relapse. The improved results are due to a lower incidence of bone marrow relapses; it seems that there is a direct relation between intensity of treatment during the induction phase and the occurrence of bone marrow relapses. The specific problems of the presented study take place during the induction phase, which, due to toxicity, regularly results in a number of side effects and severe complications. In order to realize the induction therapy, the use of prophylactic and supportive procedures is of utmost importance. Profound knowledge of possible side effects and complications is most essential as well as the knowledge of how to cope with these problems. It is the authors' opinion that the induction phase can only be performed in specialized institutions, because only at these places enough information may be obtained from an adequate number of patients and only there pediatric oncologists may share in the decisions and responsibilities. Only by using every kind of medical service this method of therapy may be justified at present, according to the results of this study, for the benefit of children with leukemia.

Adolescent↗
PubMedDate not supplied

Treatment of multisystem Langerhans cell histiocytosis. Results of the DAL-HX 83 and DAL-HX 90 studies. DAL-HX Study Group.

BACKGROUND: The prognosis of children with multisystem Langerhans cell histiocytosis (LCH) has improved with the application of chemotherapy. However, treatment strategies used varied from conservative approach with treatment only during disease exacerbation to intensive chemotherapy starting immediately after diagnosis. No single drug or regimen has been proven to be superior to the others. Thus, optimal treatment of multisystem LCH remains still an unsolved problem. PATIENTS: Three hundred and twenty-four patients enrolled in the DAL-HX 83 and DAL-HX 90 studies were retrospectively re-evaluated by using the current definition for disease extent. Sixty-three patients fulfilling the criteria for multisystem LCH (involvement of > or = 2 organ systems) were object of the present study. These were 33 males and 30 females, median age at diagnosis 11.5 months (range, birth-13 years 2 months). The median observation time was 7 years 6 months (4 years-11 years 8 months). METHODS: All patients had morphologically confirmed diagnosis, which was additionally verified through demonstration of CD1a antigen, presence of Birbeck granules or central pathologic review. Uniform evaluation including a complete medical history and physical examination, laboratory tests (complete blood count, liver function tests, coagulation profile) and radiographic survey (skeletal survey and/or radionuclide bone scan) was performed in all patients. Additional investigations (bone marrow tap, CT, MRI etc.) were performed upon specific indications. The 63 patients with multisystem LCH were evaluated with respect to response to therapy, clinical course, outcome and development of permanent disabilities. The results of the DAL-HX studies were compared with the results of the first randomized international clinical trial on multisystem LCH (LCH-I). RESULTS: Response to 6 weeks of initial therapy showed a clear discrimination between responders and non-responders, with only 6% of the patients having intermediate response. When correlated to survival response to initial therapy appears to be a powerful prognosticator in multisystem LCH. There were some typical patterns of clinical course. Complete disease resolution at some point of the clinical course was documented in 50 (79%) patients. Thirty-five of them remained disease free, while 15 experienced one or more episodes of disease reactivation. Chronic reactivating course without complete disease resolution was observed in one patient. Deteriorating disease with fatal outcome was shown in 12 (19%) patients. The overall survival after 5 years of observation was 81%. One or more disease-related permanent disabilities were documented in 24 patients, in 4 of them these were shown at diagnosis and in 20 patients these developed after therapy had been commenced. Despite more intensive chemotherapy, the overall survival in DAL-HX 83/90 cohort was comparable with that in LCH-I studies. However, LCH-I compares unfavorably to DAL-HX 83/90 in some very important aspects. With respect to reactivation rate, reactivation free interval and development of permanent disabilities better results were achieved with the more intensive initial and prolonged continuation therapy concept of the DAL-HX studies. Even after extended analysis it remains unclear whether the superiority of the DAL-HX studies has to be attributed to the administration of continuous steroids, to the combination of vinblastine and etoposide, or to the prolonged continuation therapy including mercaptopurine. Answers to these questions are expected from the ongoing international clinical trial LCH-II.

Adolescent↗
PubMedDate not supplied

[Improved treatment results in children with AML: Results of study AML-BFM 93].

BACKGROUND: In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was randomly applied in all patients during induction in combination with cytarabine and etoposide. After induction all patients were stratified to the standard or high risk group. To improve outcome in high risk patients high dose cytarabine and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or 3rd therapy block was randomized to evaluate the efficacy and toxicity accordingly. PATIENTS AND METHODS: 471 children with de novo AML entered the trial AML-BFM 93 (161 standard risk, 310 high risk). RESULTS: Overall, 387 of 471 (82 %) patients achieved remission, 5-year survival, event free survival (EFS), and disease free survival were 60 % SE 3 %, 51 % SE 2 % and 62 % SE 3 %, respectively. Idarubicin-based induction resulted in a significantly better blast cell reduction in the bone marrow on day 15 (25 of 144=17 % patients with > 5 % blasts compared to 46 of 149=31 % patients after daunorubicin, pchi(2)=0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19 % vs. 38 %, pchi(2)=0.007). Cardiotoxicity, WHO grade 1 - 3 shortening fraction reduction after induction occurred in 6 % patients in both arms. In the total group of patients probabilities of five years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin. However, in patients presenting with more than 5 % blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (p logrank 0.06). Outcome in high risk patients was superior in study 93 compared to study 87 (remission rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78 % vs. 68 %, p=0.007, and 44 % vs. 31 %, p logrank=0.01). The placing of HAM as the 2nd or 3rd therapy block was of minor importance. However, patients who received the daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Compared to study AML-BFM 87 treatment results in study AML 93 improved significantly in high risk patients. This can partly be contributed to the better response on day 15 after idarubicin induction but is mainly due to the introduction of HAM.

Acute Disease↗
PubMedDate not supplied

Effects of dose-reduced Medac L-asparaginase on coagulation in trial ALL-BFM 2000.

BACKGROUND: Glucocorticoids and L-asparaginase (L-ASP) are essential elements of contemporary chemotherapy of childhood acute lymphoblastic leukemia (ALL). Both cytotoxic drugs are well-known to induce significant alterations in hemostasis, especially affecting the inhibitors of coagulation including antithrombin III (AT III), protein C and protein S. PATIENTS AND METHODS: The objectives of the present prospective study were to analyze the course and degree of the changes of several coagulation proteins during induction therapy of 16 patients treated according to the Berlin-Frankfurt-Münster (BFM) ALL protocol 2000. The induction protocol included a 7-day mono-therapy with glucocorticoids followed by 4 weeks with additional vincristine, daunorubicin and E. coli L-ASP (Medac) which was administered at a dosage of 5000 IU/m (2) 8-times at 3-day intervals. RESULTS AND CONCLUSIONS: This analysis is the first to show that 5000 IU/m (2) of the Medac L-ASP leads to a less pronounced decrease of the plasma AT III and fibrinogen concentrations during induction therapy (after the 5 (th) L-ASP dose), as compared to previous BFM protocols which used the Medac L-ASP in a dosage of 10 000 IU/m (2). Our results confirmed that following a mono-therapy with glucocorticoids the AT III, protein C and protein S levels increased while the fibrinogen level decreased. As the D-Dimers remained within the normal range during the 3 weeks of L-ASP combination chemotherapy and none of the patients suffered a thromboembolic event, we also concluded that despite of the significant decrease of anticoagulant proteins, there might be a balance between coagulation and fibrinolysis; thus the D-Dimers may eventually serve as a helpful indicator for therapeutic interventions.

Adolescent↗
PubMedDate not supplied

Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95.

Large progress has been made in the treatment of acute lymphoblastic leukemia (ALL) of childhood and adolescence over the past 30 years. Eighty percent of the patients can be cured, but clinical subgroups with a dismal outcome can still be identified. In this study, we investigated the association of age with prognosis in 5 181 patients with ALL under 18 years (y) of age enrolled in the three consecutive treatment trials ALL-BFM 86, 90 and 95 in more than 80 centers. Event-free survival (pEFS) of the total group was significantly associated with age. The most unfavorable outcome was found in infancy and the best results were achieved at toddler and pre-school age. Beyond 5 y of age, survival probability decreased (pEFS at 8 y: < 1 y = 0.45; 1-5 y = 0.82; 6-9 y = 0.75; 10-14 y = 0.63; > or = 15 y = 0.59). The proportion of T-ALL as compared to precursor B-cell ALL (pB-ALL) was lower in younger children, due to an incidence peak of pB-ALL in toddlers and at pre-school age compared to a constant incidence of T-ALL. Within the T-ALL group, no correlation of age with sex, initial white blood cell count, CNS disease, or early treatment response was found. Children under 10 y of age had a slightly lower relapse rate compared to older patients. Within pB-ALL patients, the proportion as well as the absolute incidence of TEL/AML1 rearrangement and DNA index of > or = 1.16 was higher in the younger children. A lower proportion of BCR/ABL-positive ALL was observed in the age group of < 6 y when compared to patients aged > or = 6 y, but the absolute incidence was constant across the age groups after the first year of life. More than half of the infants had a CD10-negative pB-ALL. The incidence was constant after a peak in the first year of life, yet the percentage of CD10 negativity increased with rising age in this subgroup. Adolescents with pB-ALL had a significantly higher proportion of prednisone poor-responders. Accordingly, outcome was worse in older patients. This pattern was also evident in the biologically heterogeneous group of patients with a DNA index of > or = 1.16. In contrast, no significant age-related outcome differences could be shown within TEL/AML1- or BCR/ABL-positive patients, as well as within CD10-negative pB-ALL beyond infant age. Analysis of the pB-ALL group in a Cox's regression model including age and the above-listed biological factors revealed age < 1 year and > or = 10 years as independent risk factors. This is in line with the poorer prognosis of these age groups in the pB-ALL subgroup without specific biological characteristics. This subgroup also had an incidence peak at toddler age, presumably containing other favorable biological subsets. An independent prognostic impact of age in pediatric ALL cannot be excluded by this study. However, our analyses show that the age-associated different prognosis in childhood ALL is at least partly related to the different distribution of relevant prognostic subgroups between the age groups.

Adolescent↗
PubMedDate not supplied

[Definition of malignant histiocytosis and large cell anaplastic (Ki-1) lymphoma in children].

Cells belonging to the mononuclear phagocytic system may give rise to a wide variety of proliferative disorders. These neoplastic or reactive diseases of monocytes, histiocytes and macrophages are still poorly understood, both from a biological, clinical and pathological point of view. In 1984 a new type of non-Hodgkin's lymphomas has been described, which recently was termed large cell anaplastic lymphoma (LCAL). Since both "true" malignant histiocytosis (MH) and LCAL display some clinico-pathological similarities, we reevaluated eleven children with the primary diagnosis of MH, who entered the multicentric therapy study DAL-HX 83. On the basis of the typical morphology LCAL and not MH has been diagnosed in all cases. The Ki-1 (CD 30) positive tumor cells of LCAL can display different phenotypes, either T-lymphoid, B-lymphoid, histiocytic or neither of them (O-phenotype). Therefore we investigated the lineage specificity of tumor cells in 15 paediatric patients with LCAL. Tumor cells of histiocytic origin could be demonstrated in only one of them. In 7 patients the neoplastic cells were of T cell and in the remaining 7 cases of non T/non B cell (O) phenotypes, confirming the extreme rarity of MH in children. It is our opinion that MH and LCAL seem to be different diseases not only nosologically but also clinico-pathologically. In the multicentric therapy studies NHL-BFM 81 and NHL-BFM 83 the frequency of LCAL in childhood is compared to all other subentities at 3%.

Adolescent↗
PubMedDate not supplied

[Large cell anaplastic lymphoma in children--clinical experiences with a newly defined histologic entity].

The clinical characteristics of 31 patients (pts.) (17 boys, 14 girls, median age 12 11/12 years) with large cell anaplastic lymphoma (LCAL) have been evaluated. 17 of these pts. had originally been diagnosed as suffering from "malignant histiocytosis" ("MH") and were therefore included in the DAL-Histiocytosis X 83 study. Another 14 pts. with Ki-1 lymphomas were enrolled in the BFM-NHL therapy studies. According to Murphyclassification 24 pts. (77%) had stage III or IV disease and in general presented in a severe condition. The lymphatic system was involved in 28 pts., 8 pts. (26%) had skin infiltration. With regard to lymphoma involvement of lung, bones and bone-marrow were unexpectedly frequent. CNS involvement was seen in just one pt. Despite rather heterogeneous therapy approaches (ALL-schedules, DAL-HX 83 protocol for treatment of "MH", combination of B-NHL-BFM and AML-BFM schedules, CHOP, BFM protocols for B-NHL) 30 out of 31 pts. achieved clinical remission (CR). The only nonresponder died during bone marrow transplantation of septicemia. 4 pts. relapsed during therapy. 3 of them died, 1 during a BMT. 1 pt. achieved 2nd CR with a BFM-B-NHL protocol. 3 pts. experienced a late relapse, 1 died, 1 2nd CR was achieved, the third pt. is still alive after 2 further relapses disease-free for 3 years. 23 pts. (74%, 13 out of 14 of BFM-NHL therapy study, 10 out of 17 of DAL-HX 83 study, 1 pt. after BMT) are in 1st CR with a median observation time of 2 9/12 years (range 5/12 to 17 9/12 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

[Non-testicular germ cell tumors: analysis of the therapy study MAKEI 83/86 anc changes in the protocol for the follow-up study].

205 patients with germ cell tumors were entered into the GPO Cooperative Study MAKEI 83/86 and classified as follows: 97 teratomas, 66 yolk sac tumors, 22 dysgerminomas, 17 embryonal carcinomas and three choriocarcinomas; 20% of all tumors were classified as mixed histology. Predominant primary sites were the ovaries (91 pts), the saccrococcygeal region (74 pts), the mediastinum (12 pts), the peritoneal cavity (10 pts) and other sites (18 pts). The treatment of teratomas was primarily surgery. Localised dysgerminomas received radiotherapy following surgery, in advanced stages (III, IV) four courses of chemotherapy vinblastine 3 mg/m2/day (days 1 + 2), bleomycin 15 mg/m2/day (days 1-3) and cisplatinum 20 mg/m2/day (days 4-8) (VBC) were applied. The other fully malignant tumors received four courses of VBC chemotherapy, in extragonadal primary tumors and advanced stages of all sites additional four courses of VP16 100 mg/m2/day (days 1-3), ifosfamide 1500 mg/m2/day (days 1-5) and cisplatin 20 mg/m2/day (days 1-5) (VPIC) were administered. To avoid mutilating surgery in advanced disease, four courses of VBC chemotherapy were administered prior to resection. The relapse-free survival according to Kaplan-Meier for protocol patients with teratomas is 0.97 +/- 0.01, for dysgerminomas 0.73 +/- 0.09 and for other fully malignant histologic entities 0.81 +/- 0.02 with a median period of observation of 31 months. The toxicity mainly consisted of myelosuppression during VPIC chemotherapy in 39 of 62 pts resulting in twelve incidents of sepsis with lethal outcome in two pts. Impaired renal function was reported in 14 pts, the incidence of neuropathy, ototoxicity and pulmonary toxicity was negligible. For the follow-up study a reduction in chemotherapy seems justified in patients with favourable prognosis. The substitution of VP16 for vinblastine may result in reduced toxicity.

Adolescent↗
PubMedDate not supplied

[Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study].

The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years.

Adolescent↗
PubMedDate not supplied

[The prognostic significance of serum alpha 1-fetoprotein in children and adolescents with malignant extracranial non-testicular germ cell tumors].

The cooperative therapy study MAKEI 83/86 included an examination of the prognostic value of the AFP in children and adolescents with extracranial non-testicular yolk sac tumors. The serum AFP values of 72 protocol- and follow-up-patients were documented at diagnosis and up to the ninth month of treatment. 32 of these patients had saccrococcygeal tumors, 27 had tumors of the ovary and 13 suffered from extragonadal germ cell-tumors. 4 children showed progressive disease under initial chemotherapy and 1 patient died of therapy, 10 of 72 patients relapsed. The AFP measurements were plotted on semilogarithmic charts. They were compared to the measurements of healthy children up to the age of 1 year. According to the development of the patients' AFP values compared to the reference curves the following classifications could be made: 1. Patients with a normal AFP-decrease id est 50% in less than or equal to 6 days during the 1st month of therapy: 48/72 patients 2. Patients with slow AFP-decrease: 17/72 patients 3. Patients with transient AFP-decrease: 5/72 patients 4. Patients with no AFP-decrease: 2/72 patients According to Kaplan-Meier life table analysis, patients with a normal AFP-decrease had an event-free survival of 89% +/- 4%, whereas all other patients showed an event-free survival of 63% +/- 10% (p less than 0.05). Regarding primary therapy id est tumor resection or preoperative chemotherapy an equal distribution of the patients among those with a normal and slow AFP-decrease was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

[Autologous peripheral stem cell transplantation in children].

19 children between 3 and 23 years underwent 79 leukapheres for collection of blood stem cells. In children suffering from acute lymphoblastic leukemia (ALL), Non Hodgkin's Lymphoma (NHL) and Ewing's Sarcoma (ES) we collected 6.87 x 10(4) CFU-GM/kg (range 2,65-21.7), if collections were started with the first platelet rise. In children with peripheral primitive neuroectodermal tumors (PNET) and neuroblastoma (NBL) we gained only 1.20 x 10(4) CFU-GM/kg (range 0.09-2.24). 17 children received high dose chemoradiotherapy and peripheral stem cell +/- bone marrow rescue. 9 suffered from solid tumors, 8 from hematopoietic malignancies. 9 were transfused with peripheral stem cells only, 8 received bone marrow in addition. Time to reach 0.5 x 10(9)/l granulocytes was very short-median 31 days (12-65), in 4 children receiving more than 5 x 10(4) CFU-GM/kg 12 to 13 days, only. On January 31st, 1989 6/17 children are alive in complete remission after a median observation time of 14.5 months (3-26) after autologous stem cell transfusion, one child is alive in "no remission", 7 died with relapse, 3 died because of infections (2 x aspergillosis, 1 x pseudomonas septicemia). The collection of blood derived stem cells by leukaphereses was well tolerated even in very small children and easily repeatable. With optimal timing high stem cell numbers were obtainable, resulting in a very short duration of posttransplant granulocytopenia.

Adolescent↗