Search PubMed⌕ Search

Biomedical subjects

U Creutzig

Publications and source records attributed to U Creutzig.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

[Transient myeloproliferation and acute myeloid leukemia in infants with Down's syndrome].

Transient neonatal myeloproliferative disorders (TMD's) indistinguishable from acute leukaemia by clinical and morphological criteria have been described in neonates with Down's syndrome. To analyse its clinical significance, 10 infants under 1 year of age presenting with Down's syndrome and the morphological picture of acute myelogenous leukaemia were reviewed. 3 of these children had true AML leading to death after 2, 8 and 11 months. In the other 7 children the diagnosis TMD was suggested as spontaneous or in one case interferon-induced remission occurred within 4 to 25 weeks after diagnosis. The interferon-treated patient died of SIDS at the age of 11 months. Another one of the TMD children developed fatal erythroleukaemia at the age of 2 years. Regarding initial clinical and haematological parameters, TMD was indistinguishable from true congenital leukaemie. In all patients classification according to the FAB criteria was difficult, as mainly undifferentiated or poorly differentiated myeloid blasts were seen, sometimes with erythro- or megakaryocytic features. Because of the difficulties in the differential diagnosis of TMD and true AML it is recommended to delay specific cytostatic therapy in neonates with Down's syndrome, until definite progression of the leukaemic process is observed or cytogenetic analyses suggesting true AML are available.

Antigens, CD↗
PubMedDate not supplied

[Acute myelogenous leukemia in children under 2 years of age: studies and treatment results in 23 children in the AML therapy study BFM-78].

23 out of 151 patients of the childhood AML study BFM-78 were less than two years of age at the time of diagnosis, 10 of them being less than one year old. The incidence of M5-subtype was high in infants with 12/23 (52%) compared with 20/128 (16%) in those 2 to 17 years of age. The percentage of boys was 44% in the young children compared with 56% in the older ones. Initial skin infiltrations were seen in five infants with monoblastic subtypes (M4, M5) and in only three patients more than two years of age. The incidence of liver and spleen enlargement greater than or equal to 5 cm below the costal margin was significantly higher in young children. Due to infectious complications frequent therapy-free intervals and/or reduced drug dosages were necessary in the 8-week induction treatment regimen. The prophylactic cranial irradiation with 12 Gy in the first year of life and 15 Gy in the second year has so far not caused any long-term sequelae. The results were similar to those in older children: 18/23 (78%) of the infants achieved complete remission compared with 101/128 (79%) of those 2 to 17 years old. With a follow-up period of 16 to 49 months the probability of continuous complete remission (disease-free interval) was 52% in children under the age of 2 and 54% in those more than 2 years of age. We conclude that with the improved prognosis an intensive chemotherapy is justified in infants with acute myelogenous leukemia.

Adolescent↗
PubMedDate not supplied

[Myelodysplastic syndrome: a review].

Myelodysplastic syndromes (MDS) are heterogeneous diseases with cytopenia in the peripheral blood, dysplasia of two or three cell lines, and a low leukemic blast count in the bone marrow and peripheral blood. The syndrome is rare in childhood (1%-2% of all acute leukemias). In the advanced subtypes of MDS with 5% to 30% of blasts the risk of progression into acute leukemia is high, especially in childhood. Cytogenetic abnormalities like monosomy 7 are typical for children with MDS, and probably are an unfavourable prognostic factor. The overall prognosis is almost the same as in adults, with a median survival time of 19 months. There are no well-established therapy strategies in MDS. Intensive chemotherapy may be beneficial, at least in children and young adults, but the decision when to start treatment is difficult. At present allogeneic bone marrow transplantation is the only curative therapy available for MDS.

Bone Marrow↗
PubMedDate not supplied

[Biclonal leukemia O-ALL/AMoL) with 11;19 translocation and trisomy X in an 8-month-old girl].

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Current results of cooperative AML therapy studies in children: BFM-78 and 83].

271 children with AML entered the cooperative studies BFM-78 (151 pat.) and BFM-83 (120 pat.) since Dec. 1, 1978. In the second study BFM-83 the 8-10 week intensive induction/consolidation therapy of study BFM-78 was preceded by an 8-day intensive therapy consisting of cytosine arabinoside, daunorubicin and VP-16. 10 children died prior to starting the protocol therapy from hemorrhage and/or leukostasis. 80% of the 261 protocol patients achieved a complete remission. 7% were early deaths by hemorrhage and/or leukostasis 3% died of other complications. 10% were partial or nonresponders. 54 relapses, 11 with CNS involvement have occurred in study BFM-78 after a follow up of 2.10-6.7 years (median 4.10 yrs.). The life table probabilities for event free survival (EFS) and event free interval (EFI) after 6.7 years are 37% (SD 4%) and 47% (SD 5%) respectively. The results of study BFM-83 after a follow up of 0.3-2.8 years (median 1.8 yrs.) are: 23 relapses, EFS 40% (SD 10%) and EFI 48% (SD 12%). So far, the overall results of both studies are nearly identical. The analyses of the prognostic factors show that initial hyperleukocytosis (greater than or equal to 100 X 10(3)/mm3) represents a high risk for early fatal hemorrhage and/or leukostasis, for nonresponse and for the incidence of relapses. Initial deaths caused by hemorrhage and/or leukostasis occur also significantly more often in patients with M5-subtype and extramedullary organ involvement. Additional strategies for achieving a better prognosis in high risk patients are necessary.

Adolescent↗
PubMedDate not supplied

[Therapy realization and complications in the BFM-83 therapy study of acute myelogenous leukemia].

Data on the realization of therapy are available for 159 out of 173 (92%) protocol patients included in the study AML-BFM-83. The induction therapy could be carried out according to protocol in almost 80% of patients, with a dose compliance (= actual dose/prescribed dose) of greater than or equal to 80% for all substances. During the second therapy phase (consolidation) considerable deviations from the recommended therapy occurred in all nonresponders and in 34% of the patients who had achieved remission. The maintenance therapy had to be reduced in one third of the patients, mainly due to thrombopenias. Lethal complications caused by therapy-induced toxicity, occurred in 7 out of 173 cases (4%), and followed severe infections (mycoses), or other complications such as cardiotoxicity. The proportion of severe complications decreased from the induction through the first to the second consolidation phase. They were rare during maintenance therapy, but markedly more frequent in nonresponders and in children with early relapse (within 12 months). In view of the small differences in dose compliance, it is difficult to determine the prognostic significance of the realization to therapy. With the application of the COX regression and special life table analyses the dose compliance decreases in significance after including the known initial prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Adult form of chronic myelogenous leukemia in childhood--a retrospective analysis of 20 patients].

The initial findings and the course of 20 children and adolescents with adult CML from 10 children hospitals were analyzed retrospectively. The Philadelphia chromosome was found in 18 patients. Initial findings, the course and the prognosis were similar to those published from adult patients. 7 of the 11 children who received chemotherapy alone are still alive with a median survival time of 26 months (range: 14 to 68 months). One patient survived the third blast crisis. For 9 children with a bone marrow transplantation during the chronic phase (median time before transplantation 30 months) the follow-up of 7 months is still too short. 4 of these patients died following graft versus host reaction, 5 show no signs of a renewed occurrence of CML so far. Since CML is rare in children, there is little large scale experience. Hence, there is an urgent need for the prospective and cooperative study of these patients.

Adolescent↗
PubMedDate not supplied

[DNA aneuploidy in children with acute leukemia: I. Incidence and clinical significance within the scope of the BFM studies].

Analyses of the cellular DNA content were carried out in 226 patients with acute lymphoblastic leukemia (ALL) and in 61 children with acute myeloid leukemia (AML) to assess the incidence and clinical significance of DNA aneuploidies. All children were treated within the BFM studies ALL 79/81 and 81/83 as well as AML 78 und 83. DNA aneuploidies were identified in ALL in 39,8% and in AML in 36,1% of cases. Within the ALL group a significantly higher rate of aneuploid DNA stemlines was observed for non-T/non-B ALL with 44,1% as compared to T-ALL with 14,3% (p less than 0,01). In AML the morphologic subgroups M 1/2 revealed a lower frequency of 21,7% DNA aneuploidies than M 4/5 leukemias with 44,4%. The rates of complete remissions were not different between patients with and without DNA aneuploidy neither in ALL nor in AML. In the study ALL 79/81, however, a tendency towards longer remissions for patients with DNA aneuploidy was found (p = 0.053) which could not be confirmed at present by the study ALL 81/83. In both ALL trials patients with the lowest pretherapeutic risk-score revealed the highest rate of aneuploid DNA stemlines.

Aneuploidy↗
PubMedDate not supplied

[Acute myelogenous leukemia in children: results of the cooperative BFM-78 therapy study after 3 3/4 years].

Between December, 1978, and October, 1982, 151 children with acute myelogenous leukemia from 30 pediatric clinics entered the cooperative study. The treatment consisted of a 10-week intensive induction therapy and a subsequent maintenance therapy, which is terminated for children in complete continuous remission after 2 years. The induction treatment during the first 4 weeks consisted of a combination of prednisone, 6-thioguanine (TG), vincristine, adriamycin (ADR) and cytosine-arabinoside (ARA-C). In the following 4 weeks i.v. cyclophosphamide, i.th. methotrexate and prophylactic cranial irradiation were administered in addition to TG, ARA-C and ADR. 119 of the 151 patients (79%) achieved complete remission. 13 children (9%) died of early hemorrhages, 2 of them before onset of therapy. 5 patients died initially of other complications, another 6 after remission has been achieved. 13 children did not respond or responded poorly to the induction therapy. So far, 40 relapses occurred, mainly in the bone marrow. In 6 relapses the central nervous system was involved. The probability for a continuous complete remission for the total group is 0.41 +/- 0.05 (life table analysis) and for the total group 0.56 +/- 0.06 after 45 months. The corresponding probability for survival after 46 months are 0.43 +/- 0.06 for the remission group. The risk for occurrence of early fatal hemorrhages was higher in children with acute monocytic leukemia than in the other morphological subtypes. An initial leukocyte count of more than 100,000/microliters was found significantly more often in patients who did not achieve remission (early deaths and nonresponders) than in children of the remission group. So far, no factors could be identified which influence the risk for relapse. The present results of the study allow the conclusion, that with the applied treatment strategy it is possible to achieve not only in a high portion of children with AML remission but also to improve the chances for long-time remission and perhaps cure.

Adolescent↗
PubMedDate not supplied

[Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood: a special risk group?].

The Philadelphia chromosome is rarely observed in acute myelogenous and acute lymphoblastic leukemias. There are only a few case reports about pediatric patients, the prognosis of whom seems to be extremely poor. Reviewing the case of a girl aged 18 months with Philadelphia chromosome positive acute lymphoblastic leukemia, the differences between this entity and blast crisis of chronic myelogenous leukemia are described. This subgroup of Philadelphia chromosome positive acute lymphoblastic leukemia may represent a new risk group.

Chromosomes, Human, 21-22 and Y↗
PubMedDate not supplied

[Computer-assisted documentation and therapy planning in pediatric oncology--introduction of a nationwide solution].

In Pediatric Oncology in Germany, 90% of the patients are treated according to multicenter clinical trials, which means an enormous effort for documentation in the participating clinics. In order to enable multiple use of data for patient records as well as for clinical trials a computer-based documentation system for pediatric oncology (DOSPO) is being developed, which can be used nationwide. DOSPO currently comprises a minimum basic data set, which represents the common core of all multicenter trials and which has been approved by the German Society for Pediatric Oncology and Hematology (GPOH). It is intended to enhance the documentation by specific items of each clinical trial. Functions for computer-aided chemotherapy planning and medical report writing have already been implemented in the documentation system. Various centers in Germany are currently validating the system in routine use.

Child↗
PubMedDate not supplied

Cellular drug resistance in acute myeloid leukemia: literature review and preliminary analysis of an ongoing collaborative study.

Cellular drug resistance is one of the main causes of the frequent ultimate failure of chemotherapy in childhood acute myeloid leukemia (AML). We here summarize the results of a literature review on in vitro drug resistance in childhood AML, focusing on studies using so-called cell culture assays. We also briefly describe some results of an ongoing collaborative study between the Research Laboratory of Pediatric Oncology in Amsterdam (University Hospital Vrije Universiteit) and the German BFM-AML Group. In general, the literature and our preliminary data on in vitro cellular drug resistance in AML are promising in terms of clinical relevance. Cell biological features and clinical response to chemotherapy are related to in vitro drug resistance. However, a large study including multivariate analysis is required to more firmly establish the clinical value of cellular drug resistance testing in childhood AML, and the collaborative study will therefore be continued. Possible applications of cell culture assays include risk-group stratification, rational improvements of current treatment protocols for subgroups of patients based on specific drug resistance profiles, individualised tailored therapy, the study of cross-resistance patterns between drugs, the study of possibilities to modulate or circumvent drug resistance, the study of drug interactions, selection of patients for clinical phase II studies and drug screening.

Acute Disease↗
PubMedDate not supplied

[Primary isolated myeolosarcoma in childhood].

Isolated myelosarcomas are rare first manifestations of acute myeloid leukemia (AML), preceding bone marrow involvement by weeks to months. Seventeen of 654 children observed during the studies AML-BFM 87 and 93 were diagnosed as extramedullar myelosarcomas (2.6%). The predominantly myelomonocytic or monoblastic tumor cells (M4 or M5 according to FAB classification) mainly infiltrated skin (n = 8). Additional tumors were located in mucosa (n = 2), central nervous system (n = 2), orbita (n = 2), bone (n = 1), glandulae parotis (n = 1) and lymph nodes. Due to the initial mild and variable symptoms in some children the diagnostic measurements were delayed and treatment was inadequate. This might be responsible for the high rate of relapse (79%) and the poor outcome. Ten of 17 patients died from disease (estimated survival 0.27 +/- 0.13 compared to AML-BFM 87/93 0.51 +/- 0.03). Suspect skin lesions or tumors should be considered as isolated myelosarcoma of a primary manifestation of AML. An intensive AML-specific chemotherapy is recommended.

Child↗
PubMedDate not supplied

[Prognosis, treatment completion, and complications in nonresponders in the study AML-BFM87].

BACKGROUND: Nonresponders (NR) are patients (pts.) with no or insufficient response to initial treatment, which may be caused by either initial risk factors or poor therapy realization. In study AML-BFM 87, 49 NR of 307 patients (16%) did not achieve remission until the end of intensive chemotherapy and were analysed to assess the specific contribution of prognostic factors, therapy realization and complications of therapy. THERAPY AND METHODS: Therapy started with an 8-day induction therapy followed by a 6-week consolidation and two 5-day intensification blocks with high-dose cytosine-arabinoside and VP-16. Maintenance therapy was given for a total duration of 1.5 years. To evaluate the impact of treatment intensity in NR, we compared the dose compliance (DC = dose given/intended dose), the dose intensity (DI = dose per time given), the treatment results, and toxicity of the individual therapy phases in responders (CR) and NR. RESULTS: In 19 of 49 NR therapy was stopped before starting intensification blocks. Twenty-six NR received at least one block of intensification, and seven patients between three and six intensification blocks. Six children entered maintenance therapy. Twelve patients received a bone marrow transplant (9 allogeneic, 3 autologous). Six (5 after bone marrow transplantation) of 49 NR are still alive for 64 to 108 months. In nearly all patients induction therapy could be applied according to protocol (mean DC: 98%, range 85%-100%), whereas therapy realization was more difficult in the 2nd phase of therapy (mean DC: 92%, range 12%-113%). Deviations from the protocol in the treatment blocks (changes of dose and/or schedule) were mainly attributable to persistence of blasts (n = 33) and septic complications (n = 24). The mean relative DI of 1.01 was according to protocol. Bleeding and infectious complications in the individual therapy phases varied from 7% to 61%. NR compared to CR patients suffered significantly more often from bleeding during the first and second part of consolidation and from infections during the second part of consolidation. Withdrawal from protocol in NR was mainly due to persistence of blasts (n = 16), followed by bone marrow transplantation or other therapies (n = 13), and sepsis (n = 11). CONCLUSIONS: It is difficult to discriminate between nonresponse associated with blast persistence followed by complications and subsequent discontinuation of therapy and nonresponse due to insufficient therapy in patients with complications. Our analyses revealed that therapy with 2 intensifications according to protocol was feasible in 13 NR. Patients' condition permitting, therapy should not be stopped prematurely, in order to sustain the option of BMT after blast cell reduction.

Acute Disease↗
PubMedDate not supplied

[Antiinfectious prophylaxis in pediatric oncology. Work group "Quality Assurance" of Society for Pediatric Oncology and Hematology (GPOH)].

Infections in disease- and/or chemotherapy-related neutropenia are major, often emergency-type problems in the treatment of pediatric oncology patients and explain the ongoing discussion about antiinfectious prophylaxis. The different aspects of prophylaxis and an overview on the literature are presented. Antiinfectious prophylaxis in pediatric oncology includes the following issues: 1. General aspects such as information for patients and parents on neutropenia and risk of infectious diseases and indication and management of reverse isolation and barrier isolation; 2. antibacterial prophylaxis with oral non-absorbable and oral absorbable antibiotics; 3. Pneumocystis carinii (Pc) prophylaxis; 4. antifungal prophylaxis to prevent disseminated candidiasis and aspergillosis; 5. antiviral prophylaxis, especially varicella-zoster-virus (VZV) post-exposure prophylaxis and cytomegalovirus (CMV) prophylaxis; 6. immunoglobulins and hematopoietic growth-factors (HGF); 7. active immunization. An evaluation of those measures leads to the following conclusions: A major controversy exists regarding antibacterial and antifungal prophylaxis. Probably not effective are the use of reverse isolation and of oral, non-absorbable antibiotics. Oral absorbable antibiotics, antifungal prophylaxis using fluconazole and amphotericin B and the use of hematopoietic growth factors are likely to be effective. Clearly effective are strict hand-washing procedures, Pc and CMV prophylaxis and passive vaccination against VZV in case of VZV exposure of a seronegative patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Prognosis of children with acute myelocytic leukemia after first relapse].

UNLABELLED: Nearly 40% of children treated within the AML BFM studies experience recurrence of their disease after having achieved remission. In our retrospective analysis we tried to estimate prognosis after relapse in children treated with intensive relapse regimens and studied the impact of prognostic factors for second remission and survival. PATIENTS: 102 patients suffering from first relapse were treated intensively according to the relapse protocols BFM REZ91 and REZ93 or intensive salvage therapy consisting of double induction with high dose Ara-C, mitoxantrone and VP-16. Once in CR, patients continued to receive a 6-week consolidation and either allogeneic or autologous bone marrow transplantation (BMT). RESULTS: Time to relapse was in median 1.1 years, range 0-8 years. Fifty-two of 102 pts. (51%) achieved 2nd remission (CR), 10 (10%) partial remission, 37 (36%) were nonresponders, and 3(3%) died early during salvage therapy. Twenty-seven were still in CR, median 2.5 years, range 0.4-7.0 years, with an overall survival of 21%, SE 5% after 5 years. The response and survival rate was similar in all treatment groups. Fifty patients were transplanted, 43 being in 2nd CR, and 7 with residual blasts. Twenty-seven patients received an allograft: Twenty-one from a matched sibling (MSD), 1 from a haploid and 5 from a matched unrelated donor (MUD); 23 received an autograft. None of the patients transplanted in partial remission survived. Whereas 7 of 16 patients were alive after MSD in 2nd CR, 1 after haploid BMT. Four of 5 patients died after MUD BMT. Multivariate risk factor analysis revealed duration until relapse to be the most important factor for survival after relapse. The maximum risk-ratio was obtained at a threshold value of 1.5 years after diagnosis resulting in a 5-year survival of 10%, SE 5% for early relapse, and 40%, SE 10% for late relapse, p logrank 0.0001. CONCLUSION: Intensive relapse regimens can induce a 2nd CR in half of the patients. Children with late relapse (> 1.5 years after diagnosis) have a realistic chance for longtime survival.

Antineoplastic Combined Chemotherapy Protocols↗