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Biomedical subjects

W Hiddemann

Publications and source records attributed to W Hiddemann.

At least 73 records · Page 4Linked to original sources
PubMed2002

Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases.

For the diagnosis of CML and for monitoring of treatment response the detection of the t(9;22)(q34;q11) or the BCR-ABL rearrangement is necessary. Chromosome banding analysis (CA) is still the gold standard but other techniques like Southern blot, fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are available. We analyzed 350 CML patients at different stages of disease in parallel with CA, interphase-FISH (IP-FISH), hypermetaphase-FISH (HM-FISH) and RT-PCR. In 20 cases with no Ph(+) metaphases in CA, HM-FISH detected 0.2 to 10% BCR-ABL(+)metaphases. After IP-FISH 107 samples were judged as negative. However, in 17 of these samples HM-FISH detected BCR-ABL(+) metaphases (0.3-11%), and in eight cases CA detected Ph(+) metaphases (2.5-25%). A comparison of IP-FISH performed on uncultivated cells vs cells cultivated for 48 h in 70 cases revealed a higher proportion of BCR-ABL+ cells in the cultivated samples. If nested PCR was negative, all other methods were negative in all cases too. In addition, 94 cases were evaluated using real-time PCR (LightCycler technology). The BCR-ABL/cABL ratio measured showed a high correlation with all other methods. Interestingly, a wide range in the BCR-ABL/ABL ratio was observed especially in patients who showed 100% Ph-positive metaphases in CA. In conclusion, CA, IP-FISH, HM-FISH and real-time PCR give reliable results but differences due to measurement of different target structures have to be kept in mind when using these data for definition of remission status.

B-Lymphocytes↗
PubMed2002

Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy.

The instability of the karyotype may play a role in the development of refractoriness of acute myeloid leukemia (AML) to anti-leukemic therapy. Therefore, in the current study cytogenetic analyses were performed in 117 patients with AML both at diagnosis and at relapse. Changes in karyotype were observed in 38% (36% of initially normal karyotypes, 39% of initially aberrant karyotypes). An evolution of karyotype, ie the acquisition of further aberrations in addition to those present at diagnosis, occurred more frequently in patients with unfavorable karyotypes at diagnosis as compared to all others (60% vs 32%, P = 0.0095). The duration from initial diagnosis to relapse was significantly shorter in cases with an evolution of the aberrant karyotype as compared to cases with no changes in the aberrant karyotype between diagnosis and relapse or with solely regression of aberrations at relapse (9.2 +/- 4.4 vs14.0 +/- 8.5 months, P = 0.0081). In an additional analysis, another cohort of 120 patients with refractory and relapsed AML who were treated uniformly within the respective trial of the German AML Cooperative Group was analyzed cytogenetically at diagnosis and at relapse to further prove the prognostic impact of karyotype aberrations at relapse. Karyotypes were prognostically favorable, intermediate, unfavorable and not available in 8%, 50%, 17% and 25% at diagnosis and in 8%, 49%, 21% and 22% at relapse, respectively. Karyotype aberrations at diagnosis had no impact on response to therapy (P = 0.32) but influenced survival and event-free survival significantly (P = 0.03 and P = 0.02). In contrast, karyotype aberrations at relapse strongly influenced response to therapy (P = 0.05), survival (P = 0.01), and event-free survival (P = 0.002). These data suggest that the instability of the karyotype between diagnosis and relapse and thus karyotype aberrations at relapse in particular contribute to the refractoriness of AML to anti-leukemic therapy.

Acute Disease↗
PubMed2001

[Allogeneic transplantation in malignant lymphoma].

INTRODUCTION: Allogeneic transplantation of bone marrow and peripheral blood stem cells is a frequently discussed therapeutic option in the treatment of malignant lymphoma. By analysing the results of our own transplant program in patients with advanced lymphoma we tried to evaluate indications for allogeneic transplantations. METHODS: Data from lymphoma patients treated at the Klinikum Grosshadern between 1985 and 2001 were analysed retrospectively. RESULTS: 56 patients were included. 24 patients had low grade Non-Hogdkin's lymphoma (NHL) (follicular lymphoma: n = 8, mantle cell lymphoma: n = 6) or chronic lymphocytic leukemia (CLL: n = 10), 16 patients had high grade NHL (immunoblastic/lymphoblastic: n = 5; large cell/diffuse: n = 5) and 8 patients suffered from Hodgkins's disease. Median age was 41 years, 34 patients were transplanted from an HLA-identical sibling, 19 from an HLA-id. unrelated donor and three from an HLA-mismatched related donor. 30 patients received bone marrow and 26 peripheral blood stem cells. 22 pat. were treated with an intensive 12 Gy TBI containing conditioning regimen, whereas 34 patients were treated with a dose-intensity reduced conditioning procedere. 25 patients are alive between 2 month and 15 years after transplantation. Overall survival after 2 years is 48 % for patients with low grade NHL (incl. CLL), 9.3 % for patients with high grade lymphoma and 25 % for patients with Hodgkin's disease. 1-year-transplant-related mortality (TRM) was 33.9 % in all patients. Dose-intensity-reduced conditioning was not able to reduce TRM. CONCLUSIONS: Allogeneic bone marrow or stem cell transplantation is able to induce long lasting complete remissions in patients with heavily pretreated malignant lymphoma. Results of allogeneic transplantation are encouraging in patients with follicular and other low grade lymphoma. However transplant-related toxicity is high. At present the impact of reducing the intensity of conditioning is not yet clear.

Adolescent↗
PubMed2001

Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92.

PURPOSE: The study was initiated to obtain epidemiologic data and information on anatomic and histologic distribution, clinical features, and treatment results in patients with primary gastrointestinal non-Hodgkin's lymphomas (PGI NHL). PATIENTS AND METHODS: Between October 1992 and November 1996, 371 PGI NHL patients were eligible to evaluate clinical features. Radiotherapy and chemotherapy were stratified according to histologic grading, stage, and whether surgery had been carried out or not. RESULTS: A total of 74.8% patients had gastric NHL (PGL). Within the intestine, the small bowel and the ileocecal region were involved in 8.6% and 7.0% of the cases, respectively. Multiple GI involvement (MGI) was 6.5%. Approximately 90% of the GI NHL were in stages IE/IIE. Aggressive NHL accounted for the majority, with a distinguishable pattern in several sites. Forty percent of PGL were of low-grade mucosa-associated lymphatic tissue type. One third of large-cell lymphomas had low-grade components. Most intestinal NHL were germinal-center lymphomas. The site of origin was prognostic. In gastric and ileocecal lymphoma, event-free (EFS) and overall survival (OS) were significantly higher as compared with the small intestine or MGI (median time of observation, 51 months). In PGL, localized disease was prognostic for EFS and OS. Histologic grade influenced only EFS significantly. Numbers in intestinal lymphomas were too small for subanalyses. CONCLUSION: PGI NHL are heterogeneous diseases. The number of localized PGL allowed for detailed analyses. Larger studies are needed for stages III and IV and for intestinal NHL. A uniform reporting system for PGI NHL, in terms of definitions and histologic and staging classifications, is needed to facilitate comparison of treatment results.

Adolescent↗
PubMed2001

Primary gastrointestinal non-Hodgkin's lymphoma: II. Combined surgical and conservative or conservative management only in localized gastric lymphoma--results of the prospective German Multicenter Study GIT NHL 01/92.

PURPOSE: The aim of the study was to obtain data on anatomic and histologic distribution, clinical features, and treatment results of patients with primary gastrointestinal non-Hodgkin's lymphomas, particularly combined surgical and conservative treatment (CSCT) versus conservative treatment (CT) alone for primary gastric lymphoma (PGL) in localized stages. PATIENTS AND METHODS: Whether the treatment included surgery was left to the discretion of each participating center. Radiotherapy (Rx) and chemotherapy were stratified according to histologic grading, stage, and the inclusion or omission of surgery as follows: patients with low-grade PGL were treated with extended-field (EF) Rx (30 Gy). In case of residual tumor after surgery or in case of CT only (in stage IIE after six cycles of cyclophosphamide, vincristine, and prednisone), an additional boost of 10 Gy was given. All patients with high-grade PGL were treated with four (stage IE) or six (stage IIE) cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by EF Rx (stage IE) or involved-field (IF) Rx (stage IIE). Rx dosage corresponded to low-grade NHL. RESULTS: Between October 1992 and November 1996, 106 patients had CT only. The survival rate (SR) after 5 years was 84.4% and was influenced neither by patients' characteristics nor by stage or histologic grade. Seventy-nine patients had CSCT. Their SR was 82.0%. Complete resection of the tumor (R0) was prognostic for the overall survival (P =.0165) as compared with incomplete resection. CONCLUSION: Although the study was not randomized, a stomach-conserving approach may be favored.

Aged↗
PubMed2001

The impact of chemotherapy on Leydig cell function in long term survivors of germ cell tumors.

BACKGROUND: Because patients with germ cell tumors expect an additional life span of around 50 years after successful treatment, attention is now focused on potential long term toxicity. Limited data are available on Leydig cell function in long term survivors. METHODS: The authors measured testosterone, sex hormone binding-globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in 244 patients with germ cell tumors. Patients were divided into three groups: Group 1 had received no chemotherapy (n = 58 patients), Group 2 had received cumulative doses of cisplatin < or = 400 mg/m(2) (n = 117 patients), and Group 3 had received cumulative doses of cisplatin > 400 mg/m(2) (n = 69 patients). The median times from chemotherapy were 74 months and 75 months in Groups 2 and 3, respectively. RESULTS: Subnormal testosterone levels (< 10 nmol/L) were found in 5%, 11%, and 20% in Groups 1, 2, and 3, respectively (Group 1 vs. Group 3; P = 0.02). The mean testosterone level and the testosterone/SHBG ratio did not differ significantly between Groups 1 and 2; however, they did differ between Groups 1 and 3 (testosterone: 17.0 nmol/L vs. 14.9 nmol/L, respectively; P = 0.02; testosterone/SHBG ratio: 0.70 vs. 0.59; P < 0.05). There was a significant inverse correlation between the testosterone/SHBG ratio and LH (correlation coefficient [r] = -0.25; P = 0.0002). A significant positive correlation was found for LH and FSH (r = 0.78; P < 0.0001), indicating a strong association between Leydig cell dysfunction and germinal epithelial damage. CONCLUSIONS: Standard doses of cisplatin-based chemotherapy do not lead to a significant deterioration of Leydig cell function in long term survivors of germ cell tumors. In contrast, high cumulative doses of chemotherapy cause a significant and persistent impairment of Leydig cell function. More data are needed regarding the clinical relevance of moderate testosterone deficiency. Further research is necessary to determine whether some patients may benefit from testosterone replacement.

Adolescent↗
PubMed2001

Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): an Eastern Cooperative Oncology Group Study.

A Phase II study of GM-CSF with intermediate-dose cytarabine and mitoxantrone was conducted in patients with high-risk myelodysplastic syndrome. It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy. In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an "S" phase increase of 2.55x at 48 hr. Unexpected hepatotoxicity was noted. This regimen cannot be recommended for this elderly population of patients.

Aged↗