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Biomedical subjects

U Creutzig

Publications and source records attributed to U Creutzig.

At least 73 records · Page 4Linked to original sources
PubMed1995

12q13, a new recurrent breakpoint in acute non-lymphoblastic leukemia.

The karyotypes of 312 successfully analyzed samples of children with acute non-lymphoblastic leukemia (ANLL), which were sent to us by 72 German hospitals, were examined in order to find new recurrent chromosome abnormalities of possible clinical relevance. Whereas most of the patients had one of the specific aberrations of ANLL or a normal karyotype, random numerical or structural changes were found in 61 children (20%). Four of them showed an abnormality involving band 12q13: t(12;17)(q13;q21), t(12;21)(q13;q21), t(2;12)(p13;q13), and t(5;12)(p11;q13). Despite the fact that FAB subtypes were different (M0, M1 M6, AHL), the blasts of all patients were characterized by immaturity and were difficult to classify. The breakpoint 12q13 might be of clinical importance in ANLL, because the four patients in our study, as well as the 21 patients with this aberration found in the literature, had a very poor prognosis.

Child↗
PubMed1995

Clinical, morphologic, cytogenetic and prognostic implications of CD34 expression in childhood and adult de novo AML.

Expression of CD34 by leukemic blasts was analyzed in 230 pediatric and 251 adult patients with de novo AML enrolled in two large multicenter trials (AML-BFM-87 and AMLCG respectively). The association between CD34 positivity and morphological classification according to FAB criteria, cytogenetic aberrations, immunophenotypic features and clinical characteristics was investigated. CD34 was expressed (> or = 20%) by leukemic cells from 45% of childhood and 43% of adult AML patients. CD34+ AML was often associated with M1/M2 morphology as well as the coexpression of CD7 and TdT. Translocation t(8;21), inv(16) and chromosome 5 and 7 aberrations were more frequently observed in CD34+ AML. There was a low frequency of CD34 expression in infant AML but no age dependency was evident in adult patients. CD34 expression exerted no influence on the rate of complete remissions (CR) after intensive multidrug induction therapy. In adults, 56% of the CD34-positive and 64% of CD34-negative cases achieved CR (P = 0.29), and the childhood trial even revealed a slight advantage for CD34+ AML with a CR rate of 80% vs. 71% for CD34-negative cases (P = 0.068). Long-term follow-up disclosed no significant differences in remission duration or event-free survival between the CD34-positive and CD34-negative groups. In conclusion, CD34+ AML patients comprise a heterogeneous group with good as well as poor risk factors. Though characterized by some distinct features, CD34 lacks prognostic significance in de novo AML patients submitted to intensive polychemotherapy.

Adolescent↗
PubMed1995

In vitro chemosensitivity assessed with the MTT assay in childhood acute non-lymphoblastic leukemia.

Cellular drug resistance is supposed to play a major role in chemotherapy failures which frequently occur in childhood acute non-lymphoblastic leukemia (ANLL). Therefore, we determined in vitro chemosensitivity to daunorubicin, doxorubicin, mitoxantrone, 6-thioguanine, etoposide, and cytosine arabinoside (Ara-C) in childhood ANLL using the colorimetric MTT assay. The 4-day MTT assay was successfully performed in 62/73 samples obtained from 53 children with ANLL. We obtained comparable results from bone marrow or peripheral blood samples, and from fresh or cryopreserved samples. In vitro chemosensitivity was not related to clinical features such as sex, age, white blood cell count, or FAB-types. The group of poor responders to chemotherapy was median 3-fold more resistant to Ara-C than the group of good responders, but identification of a threshold for Ara-C sensitivity predictive for individual responses was limited due to the great overlap of in vitro chemosensitivities between both groups. Children with relapsed ANLL were in vitro median 3-fold more resistant to Ara-C than the initial ANLL group. No significant differences for the other drugs were observed with respect to clinical response or disease status. These results suggest that in vitro resistance to Ara-C plays an important role in chemotherapy failures in childhood ANLL, but larger studies are necessary to establish the predictive value of Ara-C sensitivity assessed with the MTT assay.

Antineoplastic Agents↗
PubMed1993

Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87.

PURPOSE: One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS: Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS: In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION: These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.

Adolescent↗
PubMed1992

Acute myelogenous leukaemia in children under 2 years--experiences of the West German AML studies BFM-78, -83 and -87. AML-BFM Study Group.

Clinical, morphological, immunological, cytogenetical and prognostic features of 84 children under 2 years of age with AML in studies AML-BFM-78, -83 and -87 were retrospectively analysed. There was a high incidence of acute monoblastic leukaemia (FAB M5) (41 patients--49%) and acute megakaryoblastic leukaemia (FAB M7) (study AML-BFM-87: five patients--13%) in this age group. Acute monoblastic leukaemia was associated with hepatosplenomegaly, extramedullary organ manifestations and chromosomal abnormalities involving 11q23. The probability of an 11-year event-free survival of all patients under 2 years of the three studies combined was 39% (SD 6%). While the event-free survival rates of patients aged 2 years and older could be improved in studies AML-BFM-83 and -87 compared with study AML-BFM-78, overall prognosis in children under 2 years in the three consecutive studies remained unchanged. The event-free survival rate of children with acute monoblastic leukaemia in both age groups was comparable (7 yr-EFS (AML-BFM-83 and -87): much less than 2 years--43% (SD 9%), =/much greater than 2 years--33% (SD 9%); P much greater than 0.5). This also applied to other risk groups. In conclusion, taking the high incidence of acute monoblastic and megakaryoblastic leukaemia in children under 2 years into account, no significant differences between children under 2 years or older children concerning response to therapy and overall prognosis could be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Treatment results of three consecutive German childhood AML trials: BFM-78, -83, and -87. AML-BFM-Group.

Acute myelogenous leukemia (AML) represents a heterogenous group of leukemias in adults as well as in children. The BFM group initiated 3 consecutive studies on the treatment of this disease. Between December 1978 and April 1991, 543 children under the age of 17 years entered the 3 consecutive multicenter studies, AML-BFM-78 (n = 151), AML-BFM-83 (n = 182), and the still ongoing study AML-BFM-87 (n = 210). The treatment strategy of BFM-78 consisted of an eight week induction/-consolidation regimen employing 7 different drugs together with cranial irradiation, followed by continuous maintenance for two years. The main alteration in the second study BFM-83 was the addition of an intensive 8-day ADE induction course (cytosine arabinoside, daunorubicin, etoposide). In the ongoing trial BFM-87 two courses of HD-ARA-C and etoposide are given after consolidation. CR rates were 80% in trials I and II, and 78% in trial III. The probability of a 4.5-year event-free survival was 35%, SD 4% in study I; 49%, SD 4% in study II, and 45%, SD 4% in study III. The probability of a 4.5-year event-free interval (EFI) was increased from 45%, SD 5% in study I to 61%, SD 4% in study II, it is in the same range in study III (58%, SD 5%). Seven of 10 children which underwent bone marrow transplantation (BMT) in 1. CR are still in first CR after a maximum follow-up time of 3.5 yrs. In summary, the addition of HD-ARA-C together with etoposide given after induction/consolidation treatment did not further reduce the incidence of relapses in childhood AML. So far, the results of study BFM-87 are in the same range than those of study BFM-83.

Adolescent↗
PubMed1990

Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group.

The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE (cytosine arabinoside, daunorubicin, etoposide) induction treatment in the second study. Due to this intensification, the relapse rate, but not the rate of induction failures, was reduced. The probability of a 6-year event-free survival increased from 38%, SD 4%, in study AML-BFM-78 to 49%, SD 4%, in study AML-BFM-83, P = .08. The improvement of the 6-year event-free interval (EFI) was significant in the second study (61%, SD 4%, versus 47%, SD 5%, P less than .05); it was restricted to the FAB types M1 through M4 (EFI: 67%, SD 5%, versus 45%, SD 5%, P less than .01). The difference in EFI seen in FAB M5 was not statistically significant (EFI: 40%, SD 10%, versus 63%, SD 11%, NS). According to the results of the second study, two different risk groups (low and high) could be identified by combinations of predominantly pretherapeutic parameters. The low risk group, comprising 37% of the patients who achieved complete remission, included the FAB types with granulocytic differentiation and specific additional features: FAB M1 with Auer rods, FAB M2 with white blood cell count of less than 20,000/microL, FAB M3 all patients, and FAB M4 with eosinophilia. The 6-year Kaplan-Meier estimation of EFI is 91%, SD 4%, compared with 42%, SD 6% in the high risk group. In future studies based on the AML-BFM-83 treatment, bone marrow transplantation in first remission should be mandatory only for children of the high risk group.

Adolescent↗
PubMed1990

Bone marrow transplantation in comparison with conventional therapy in children with adult type chronic myelogenous leukemia.

From 1983 to 1988 14 patients under 16 years of age with adult type chronic myelogenous leukemia (CML) in chronic or blastic phase were treated by allogeneic bone marrow transplantation (BMT) in our center. These comprise 54% of all patients under 16 years of age grafted for this disease in FRG. These BMT patients were compared with 24 similar patients treated conventionally with busulfan and/or hydroxyurea in various centers. The probability of an event-free survival 5 1/2 years after BMT was 0.61 (SD 0.16); the estimated probability of survival for 3-8 years after diagnosis in the group treated by GMT was 0.78 (SD 0.14) vs 0.55 (SD 0.12) for the non-BMT group. The difference is not significant. In the BMT group only two patients died of transplant-related complications. The non-BMT patient with the longest survival period died recently 10 years after diagnosis. For children with adult type CML, BMT is a safe and effective treatment, and should be recommended if there is an HLA compatible sibling donor or even a fully compatible unrelated donor. However, for a more conclusive comparison between bone marrow transplantation and conventional treatment a longer observation period and larger patient numbers are necessary.

Adolescent↗
PubMed1989

Prognostic significance of Auer rods in childhood acute myelogenous leukemia: results of the studies AML-BFM-78 and -83.

The prognostic significance of Auer rods in predicting response rate and remission duration was investigated in 257 patients of the two West German acute myelogenous leukemia (AML) studies BFM-78 and -83. Auer rods were found in 129 children (50%) in the initial bone marrow smear. The incidence was higher in myeloid subtypes M1 (63%) and M2 (78%) compared with subtypes M4 (47%) and M5 (5%) with monocytic differentiation. In both studies, the remission rate was significantly higher in patients with Auer rods (P = 0.01), and in the study AML-BFM-83 a significantly longer remission duration was evaluated for Auer rod-positive patients (P = 0.007). In the M1 type, Auer rods were of high prognostic significance regarding both the induction success (P = 0.003) and the remission duration (P = 0.004), whereas no significant differences between Auer rod-positive and -negative patients in other subtypes were found. Occurrence of Auer rods was independent of hyperleukocytosis, the most powerful prognostic parameter in the studies AML-BFM-78 and -83, whereas absence of Auer rods was associated with the AML risk group M5. In the M1 type, Auer rod-negative leukemias appears to represent cases of poorly differentiated AML. Auer rods were therefore useful in differentiating between patients with a poor and a more favorable prognosis, particularly in the M1 type.

Adolescent↗
PubMed1989

Phenotypic and genotypic heterogeneity in infant acute leukemia. II. Acute nonlymphoblastic leukemia.

We have studied the immunophenotypic and genotypic characteristic of acute nonlymphoblastic leukemias (ANLL) in infants aged less than one year. Sixty-four percent of cases (16/25) showed a myeloid or myelomonocytic differentiation pattern and 10 of these were classified as FAB M5 (7 M5a, 3 M5b). Only seven of the latter cases expressed the CD14 antigen. Acute megakaryocytic leukemia with a high number of glycoprotein IIb/IIIa or IIIa positive blasts were identified in five patients. Erythroleukemia with a high percentage of rather mature glycophorin A positive erythroblasts were diagnosed in two infants. Cytogenetic studies were successfully performed in all 20 cases investigated. Abnormalities involving chromosome 11 were present in 10 of 17 patients with an abnormal karyotype including five cases with a t(9;11)(p21;q23). Immunoglobulin (Ig) and T cell receptor (TCR) gene analyses were performed in 20 patients. A rearrangement of Ig heavy chain sequences was detected in five cases (20%), one of whom exhibited multiple rearranged fragments. Three of these patients showed additional TCR delta-chain gene rearrangements, while Ig kappa, TCR beta- as well as TCR gamma-chain genes showed a germline configuration in all cases analyzed. Our study confirms the high incidence of myelomonocytic and monoblastic subtypes in infants with ANLL, which are particularly closely associated with chromosome 11 abnormalities. However, we also observed an unexpected high frequency of megakaryoblastic leukemias as well as erythroleukemias. As previously reported for ALL in infants, ANLL of infancy shows a similar heterogeneity regarding phenotypic and genotypic features.

Antigens, Differentiation↗
PubMed1987

Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia. Associations with hyperleukocytosis and acute monocytic leukemia.

There were 294 children with acute myelogenous leukemia (AML) entered into the German AML Berlin, Frankfurt, and Münster hospitals (BFM) 78 and 83 studies. Thirty (10%) died as a result of hemorrhage and/or leukostasis prior to or in the first 12 days of therapy. The risk of early death due to hemorrhage and/or leukostasis is significantly greater when certain features are initially present: acute monocytic leukemia (French-American-British [FAB] M5), hyperleukocytosis (greater than or equal to 100,000/microliter), and extramedullary organ involvement (P less than 0.001). The risk increases sharply when these factors exist in combination: 72% mortality with FAB M5 and hyperleukocytosis, and 43% with FAB M5 and extramedullary organ involvement. In 11 patients leukostasis alone or in combination with hemorrhage was probably the cause of death during the first 3 days after diagnosis. All 11 children presented with hyperleukocytosis and were classified as monocytic subtype FAB M4 or M5. After induction, a close temporal association between rapid blast reduction and occurrence of fatal hemorrhage was established in five patients. Thrombocytopenic hemorrhages were controllable and, therefore, responsible for death only in exceptional cases. It is difficult to avoid these early fatal complications with current therapeutic measures. Early exchange transfusion together with special supportive care may be useful.

Adolescent↗