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Biomedical subjects

G Dölken

Publications and source records attributed to G Dölken.

At least 19 recordsLinked to original sources
PubMed2006

Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

BACKGROUND: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. PATIENTS AND METHODS: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. RESULTS: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. CONCLUSION: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.

Adolescent↗
PubMed2006

The modification of high-dose therapy shortens the duration of neutropaenia by delay of leucocyte nadir.

Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.

Adolescent↗
PubMed2006

[Therapy-resistant cutaneous infiltrates in chronic lymphocytic leukemia].

Chronic lymphocytic leukemia (CLL) is a low-grade B-cell non-Hodgkin lymphoma. Skin involvement is observed in up to 25% of patients. A 70-year-old men with presented with prominent erythematous facial infiltrates. After the diagnosis of CLL was established, he showed a good hematologic response to the monoclonal antibody rituximab, but the skin infiltrates were therapy-resistant.

Aged↗
PubMed2005

[Minimal residual disease in follicular and mantle cell lymphoma. Detection using quantitative molecular monitoring of circulating lymphoma cells].

BACKGROUND AND OBJECTIVE: In patients with follicular lymphoma and mantle cell lymphoma circulating lymphoma cells can be detected by quantitative real-time PCR with a high sensitivity and reproducibility. With this study we wanted to ascertain whether a continuous molecular remission achieved in patients with mantle cell lymphoma and follicular lymphoma has an impact on survival of these patients. PATIENT AND METHODS: We conducted these investigations in 32 patients (24 with follicular lymphoma and 8 with mantle cell lymphoma) who were treated in a randomized trial with chemotherapy plus/minus rituximab (MCP, R-MCP). A further ten patients had follicular lymphoma (stage I and II) in long-term complete remission after radiation therapy. RESULTS: Up to 18 years after initial diagnoses of a stage I or II follicular lymphoma circulating t(14;18) positive cells could be detected in the peripheral blood. In advanced stage follicular lymphoma patients molecular remissions could only be achieved when they were treated with combined chemo-immunotherapy (MCP+R). A significantly higher relapse-free survival correlates with sustained molecular remission. In contrast, the frustrating clinical results obtained from the treatment of patients with mantle cell lymphoma corresponded to an achievement of only short molecular remissions in very few patients. CONCLUSIONS: The consequent application of quantitative real-time PCR will further improve current treatment strategies in lymphoma patients. Especially, individual treatment options can be developed for patients who do not respond to a standard chemotherapy or progression of disease is recognized, if results of molecular monitoring will be confirmed in large prospective studies.

Humans↗
PubMed2005

Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is associated with chromosomal aberrations characterized by juxtaposition of proto-oncogenes to T-cell receptor gene loci (TCR), resulting in the deregulated transcription of these proto-oncogenes. Here, we describe the molecular characterization of a novel chromosomal aberration, inv(14)(q11.2q32.31), in a T-ALL sample, involving the recently described BCL11B gene and the TCRD locus. The inversion joined the 5' part of BCL11B, including exons 1-3, to the TRDD3 gene segment of the TCRD locus, whereas the reciprocal breakpoint fused the TRDV1 gene segment to the fourth exon of BCL11B. The TRDV1-BCL11B joining region was 1344 bp long and contained fragments derived from 20q11.22, 3p21.33 and from 11p12, indicating the complex character of this aberration. A strong expression of in-frame transcripts with truncated BCL11B and TCRD constant region (TRDC) were observed, but in contrast to normal T cells and other T-ALL samples, no wild-type BCL11B transcripts were detected in the T-ALL sample. Screening of 37 other T-ALLs revealed one additional case with expression of the BCL11B-TRDC fusion transcript. As BCL11B appears to play a key role in T-cell differentiation, BCL11B disruption and disturbed expression may contribute to the development of T-cell malignancies in man.

Base Sequence↗
PubMed2004

[Malignant melanoma of the anorectal mucosa].

HISTORY: A 62-year-old man was admitted to hospital because of rectal bleeding of unknown cause. INVESTIGATIONS: Coloscopy showed a rectal tumour as cause of the bleeding and concomitant hypochromic microcytic anaemia. Histological examination established the diagnosis of anorectal malignant melanoma. Further staging examinations did not reveal metastatic disease. TREATMENT AND COURSE: An radical abdominoperineal rectal resection amputation was performed. The postsurgical course was uneventful. However, multiple lung metastases were detected 6 weeks later. CONCLUSION: Anorectal malignant melanoma is a rare cause in the differential diagnosis of anorectal tumours. Surgery remains the therapy of choice. Chemotherapy and immunotherapy are principally used in a palliative setting. Despite advances in therapy, the prognosis of this tumour entity remains unfavourable.

Anemia, Hypochromic↗
PubMed2004

[Thoracic neuroblastoma in a young adult].

HISTORY AND CLINICAL FINDINGS: A 21-year-old patient was admitted to the hospital because of massively enlarged cervical lymph nodes. Additionally, a left-sided facial and brachial edema was visible. Auscultation of the left lung was remarkable for diminished breath sounds. EXAMINATIONS: Diagnostic imaging showed an extensive thoracic tumor and enlarged mediastinal and cervical lymph nodes. The diagnosis of neuroblastoma was established by biopsy. TREATMENT AND CLINICAL COURSE: The patient was treated with a polychemotherapy protocol according to the pediatric neuroblastoma study NB97. Subsequently, the patient underwent partial tumor resection, received two further chemotherapy courses and irradiation of the remaining tumor. Because of residual vital tumor cells, a second surgical tumour reduction followed by high-dose chemotherapy with autologous stem-cell support was performed. Two cycles of high-dose retinoic acid followed. Six months after the end of therapy, the patient is in a good condition despite of the presence of residual tumor. CONCLUSION: Neuroblastoma is a very rare tumor in adult patients. Therapy is multimodal and should follow pediatric guidelines for neuroblastoma treatment.

Adult↗
PubMed2002

Early tandem high-dose ifosfamide, carboplatin, etoposide therapy with stem cell rescue for small-cell lung cancer: brief report on the results of a phase-I/II trial.

OBJECTIVE: High-dose therapy (HDT) for small-cell lung cancer is experimental. Late intensification HDT for chemosensitive disease can increase the number and quality of remissions and prolong relapse-free survival, but has not yet shown impact on overall survival. This is possibly due to resistant residual disease. To overcome the development of resistance, we have tested early intensification tandem HDT. METHODS: We performed a phase-I/II trial using 1 conventional cycle of ifosfamide, carboplatin, etoposide (ICE) plus granulocyte colony-stimulating factor for stem cell recruitment followed by 2 cycles of high-dose ICE with rescue by CD34+ cell-enriched peripheral blood mononuclear cells. Dose escalation was performed for the 2 high-dose ICE cycles. Radiotherapy for limited disease was according to standard protocols. RESULTS: 17 patients were entered: 2 female patients; 15 male patients; median age 53 (range 36-65) years; 2 patients with limited disease, and 15 patients with extensive disease. We treated 4 patients at dose level 1, 11 patients at level 2, and 2 patients at level 3. The maximum tolerable dose was at level 2 with neuropathy being dose-limiting. Overall, toxicity was < or = grade 2 for all patients up to dose level 2 with hematotoxicity being grade 4 for all patients. There were 15 partial remissions (88%), 1 no change (6%), and 1 progressive disease (6%). Median time to progression was 7.9 months. Overall survival was 12.9 months (median). CONCLUSIONS: Early intensification with this protocol is feasible. Although a comparatively good response rate and median time to progression have been observed in this group dominated by patients with extensive disease, overall survival is short and no substantial long-term survival was found.

Adult↗
PubMed2001

Low frequency of BCL-2/J(H) translocation in peripheral blood lymphocytes of healthy Japanese individuals.

The incidence of follicular lymphoma differs significantly between white and Japanese individuals. Translocation between the BCL-2 and immunoglobulin heavy chain genes is detected in 85% to 90% of all follicular lymphomas in whites. Recently, BCL-2/J(H) translocation was detected in peripheral blood lymphocytes from more than 50% of healthy white individuals. To clarify the reason for the difference in incidence of follicular lymphoma between whites and Japanese, the frequency of BCL-2/J(H) translocation in peripheral blood lymphocytes of healthy Japanese individuals was compared with that of German individuals. The prevalence of BCL-2/J(H) translocation in Japanese adults appeared to be significantly lower than that in German adults. The present data suggest that the low frequency of BCL-2/J(H) translocation in the Japanese general population may be one of the major reasons for the difference in incidence of follicular lymphoma between whites and Japanese.

Adult↗
PubMed2001

Detection of minimal residual disease.

A high percentage of patients with leukemia, lymphoma, and solid tumors achieve a complete clinical remission after initial treatment, but the majority of these patients will finally relapse from residual tumor cells detectable in clinical remission only by the most sensitive methods. The in vitro amplification of tumor-specific DNA or RNA sequences by polymerase chain reaction (PCR) allows identification of a few neoplastic cells in 10(4) to 10(6) normal cells. Depending on the underlying malignant disease and therapeutic treatment, the presence of residual tumor cells in an individual patient may herald relapse, but a long-term stable situation or slowly vanishing tumor cells are also possible. Molecular monitoring of residual leukemia and lymphoma cells by quantitative PCR techniques has provided important information about the effectiveness of treatment and the risk of recurrent disease as shown by minimal residual disease (MRD) analysis in patients with various malignant diseases. Such diseases include childhood acute lymphoblastic leukemia, after induction therapy; acute promyelocytic leukemia, during and after chemotherapy; and chronic myelogenous leukemia, during treatment with alpha-interferon and after allogeneic bone marrow transplantation. Evaluation of the predictive value of the detection of MRD has to take into account its evolution and course, the pathogenesis, biology, and natural course of the underlying malignant disease, the molecular genetic lesion, and finally, the type of treatment. Quantification of minimal residual cells by the recently developed real-time quantitative PCR technique will surely have a major impact on our therapeutic strategies for patients with leukemia, lymphomas, and solid tumors. Based on quantitative PCR data, the terms molecular remission and molecular relapse have to be exactly defined and validated in prospective clinical trials to assess the biological and clinical significance of MRD in various types of malignancies.

Antigens, CD↗
PubMed2001

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

Adolescent↗
PubMed2000

Quantitative detection of t(14;18)-positive cells in patients with follicular lymphoma before and after autologous bone marrow transplantation.

The aim of this study was to evaluate whether a quantitative analysis of circulating t(14;18)-positive cells is of prognostic significance in patients with follicular lymphoma (FL) after myelo-ablative therapy supported by ABMT. We tested DNA from primary lymphoma tissue as well as PBMC before and after ABMT from 15 patients for the presence of the t(14;18) translocation. Nine patients showed a t(14;18) translocation, six patients were t(14;18)-negative. Circulating t(14;18)-positive cells of seven patients were quantitatively determined by limiting dilution assays combined with a two-step PCR and by real-time quantitative PCR. The results of both methods correlate very well. The number of circulating t(14;18)-positive cells decreased significantly in all patients after myeloablative therapy and ABMT, t(14;18)-negative blood samples were found in five of seven patients. In all patients circulating t(14;18)-positive cells reappeared within 2 years after ABMT showing two different patterns. During continuous CR the numbers of circulating t(14;18)-positive cells were found to be stable within one order of magnitude. In contrast, in one patient the relapse was accompanied by a logarithmic increase of t(14;18)-positive cells. In a second patient the enlargement of lymph nodes developing over a period of 12 months was accompanied by very slowly increasing numbers of t(14;18)-positive cells. In all cases where diagnostic lymph node tissue was available, the same t(14;18) translocation was found at first diagnosis and after ABMT as shown by nucleotide sequence analysis. We conclude that the quantitative detection of circulating t(14;18)-positive cells during follow-up of patients with FL after ABMT reflects the clinical course of the disease. Relapses are associated with increasing numbers of circulating t(14;18)-positive cells and continuous complete remissions with stable cell counts.

Adult↗
PubMed2000

Multicenter phase II study of oral idarubicin in treated and untreated patients with B-chronic lymphocytic leukemia.

Idarubicin is the first anthracycline that can be administered orally facilitating antineoplastic chemotherapy at an improved quality of life. In different studies idarubicin has proved clinical effectiveness in patients with advanced low grade non Hodgkin's lymphoma. We performed a phase II study in 19 patients with untreated and pretreated B-CLL of Binet stage A-C. Idarubucin was administered orally at a dose of 15 mg/m2 over 3 days every 4 weeks. Of 19 evaluable patients (m:f, 16:3, median age 64 years, range 41-80 years) 7 were previously untreated while 12 patients had received prior therapy with fludarabine, chlorambucil or similar non-anthracycline containing regimens. 12 pts had Binet stage C, 5 Binet stage B and 2 Binet stage A. Five patients achieved a partial remission (26%), 5 patients had stable disease (26%) and 9 patients showed progressive disease (47%), resulting in an overall response of 26% (5/19). There was no correlation of response rate with Binet stages or previous treatment regimens. Treatment associated side effects consisted predominantly of mild nausea and vomiting (26%) as well as minor infections (21%) and diarrhoea (16%). These data demonstrate that oral idarubicin as a single agent is well tolerated but of limited effectiveness in B-CLL. Further studies are needed to assess different doses and schedules of oral idarubucin and to test it in combination with other chemotherapeutic agents.

Administration, Oral↗
PubMed1998

Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.

Adolescent↗