Biomedical subjects

D Hasenclever

Publications and source records attributed to D Hasenclever.

43 records · Page 3Linked to original sources

PubMed1992

The Second International Symposium on Hodgkin's Disease. Workshop III: Recommendations for future clinical trials.

In the opinion of the participants of the workshop, the following problems should be addressed with high priority: 1st, a clear definition of the 10%-15% of patients who should receive radiotherapy only; 2nd, reduction of toxicity of combined modality approaches for patients in localized stages with risk factors; and 3rd, definition of a poor-prognosis subgroup of patients in stages IIIB/IV for whom more efficient treatment programs must be developed. Dose intensification in the form of ABMT as the prominent example of high dose intensity should be tested in these patients. If this approach proves its efficacy, the concept of dose intensification could be extended to other patients with advanced disease. Results of recent trials in Hodgkin's disease suggest that the cure rates which increased considerably between 1960 and 1980 have reached a plateau. Further improvements that can be realistically expected will be small and studies to prove such progress need large numbers of patients ('megatrials') to avoid 'false negative' results. Such megatrials could be performed as large international or even intercontinental trials. To some extent, overviews could substitute for megatrials, if sufficient high-quality randomized studies addressing a specific question are available for a meta-analysis. The installation of an international steering committee was recommended, which should stimulate and coordinate world-wide efforts for the solution of the remaining problems in the treatment of Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Clinical significance of soluble CD30 antigen in the sera of patients with untreated Hodgkin's disease.

The soluble form of the CD30 antigen (sCD30), an 88-kd glycoprotein that is released by Hodgkin's-derived cell lines in vitro, can be detected in patients with Hodgkin's lymphoma, adult (HTLV-1+) T-cell leukemia, rare cases of non-Hodgkin's lymphoma, and acute infectious mononucleosis (anti-EBV-IgM+). In a prospective study of 90 consecutive untreated patients with newly diagnosed Hodgkin's disease who were treated according to the protocols of the German Hodgkin Study group, 22% had detectable levels of sCD30 in their serum. sCD30 was only detected in patients with B symptoms (20 of 44 or 45%), and maximum sCD30 levels (88 U/mL) were found in stage IVB. Of 87 patients evaluable for response, sCD30+ patients had significantly lower rates of complete remission (9 of 20 or 45% v 60 of 67 or 90%; P less than .001) and higher rates of progressive disease (9 of 20 or 45% v 6 of 67 or 9%; P less than .001) than CD30+ patients. Similarly, freedom from treatment failure curves were significantly worse for CD30+ patients (P = .0003). sCD30 disappeared after successful treatment, but increased in patients with progressive disease. It was never detected in patients in complete remission or in healthy controls. We conclude that sCD30 is a valuable marker for disease activity and has prognostic significance in Hodgkin's disease.

Adolescent↗

PubMed1991

Low serum interleukin-2 receptor levels correlate with a good prognosis in patients with Hodgkin's lymphoma.

In order to evaluate the clinical significance of soluble interleukin-2 receptor (sIL-2R) levels in the serum of patients with Hodgkin's disease (HD), we tested the pretreatment sera of 82 patients. The HD patients had significantly higher sIL-2R levels than normal controls (4787 U/ml versus 290 U/ml; P less than 0.001). In patients presenting with B-symptoms, the median sIL-2R levels were significantly higher than in patients without B-symptoms (7978 versus 2128 U/ml; P less than 0.01). Patients in stage IVB had the highest sIL-2R levels (10,450 U/ml). Of 77 patients evaluable for response, all patients with sIL-2R levels less than 1000 U/ml achieved complete remission and no relapses occurred in this group after a median of 20 months. The fact that sIL-2R levels dropped after therapy, even in patients who suffered from progressive disease, suggests that Hodgkin and Reed-Sternberg cells are only a minor source of sIL-2R in HD. Therefore sIL-2R levels are of limited value as a marker of disease activity. However, pretreatment sIL-2R levels less than 1000 U/ml define a subgroup of adult HD patients with an excellent prognosis, and this fact might be helpful for the design of more custom-tailored therapy programs.

Adolescent↗

PubMed1991

The clinical significance of serum CD8 antigen levels in adult patients with Hodgkin's disease.

Increased suppressor T-cell activity has been observed in patients with Hodgkin's disease. In order to evaluate the clinical significance of soluble CD8 antigen (sCD8), which is released from CD8+ suppressor/cytotoxic T-lymphocytes, we determined sCD8 levels in the sera of 82 consecutive patients with newly diagnosed untreated Hodgkin's lymphoma who were entered into prospective trials of the German Hodgkin's Disease Study Group. sCD8 levels were significantly higher (p less than 0.01) in stage IV (781 U/ml, n = 19) than in stages I-IIIB (443 U/ml; n = 63). Patients with B-symptoms (n = 36) had slightly higher levels (611 U/ml) than patients without (n = 46) systemic symptoms (447 U/ml; p = 0.08). In 77 patients evaluable for response, the complete remission (CR) rate of patients with sCD8 less than 750 U/ml was higher (54/60 or 90%) than that of patients with sCD8 greater than 750 U/ml 11/17 or 65%; p = 0.01). The time to treatment failure was significantly longer in patients with sCD8 less than 750 U/ml (p = 0.008), even among the group with stages IIIB/IV only (p = 0.04). Our data suggest that the pretreatment levels of sCD8 in adult patients with Hodgkin's lymphoma have prognostic relevance, and that they should be determined especially in patients with advanced disease. Increased understanding of the role of sCD8 may shed light on the pathogenesis of Hodgkin's disease.

Adolescent↗

PubMed1988

Prognostic risk factors in advanced Hodgkin's lymphoma. Report of the German Hodgkin Study Group.

In a national multicentre trial in the FRG patients with Hodgkin's lymphoma in stages CS/PS III B/IV were entered into the HD 3 protocol and received induction chemotherapy with 3 x (COPP + ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or chemotherapy (COPP + ABVD). Patients not in CR received salvage therapy (40 Gy in case of persisting nodal disease, else 4 x CEVD chemotherapy). Between July 1983 and May 1987 230 untreated patients aged 15 to 60 qualified for this HD 3 protocol. This analysis is based on the first 137 patients evaluable for response. Of these, 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. Univariate and multivariate prognostic risk factor analyses were performed using freedom from treatment failure (FFTF) as endpoint. Sex, age, splenectomy, bone marrow, liver and bone involvement had no prognostic impact nor had stage according to the Ann Arbor classification. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml appeared as significant risk factors (p less than 0.01, relative risk 2.3). The two parameters were not independent. Comparing a group A (ESR less than or equal to 80 and AP less than or equal to 230) versus a pooled group B (ESR greater than 80 and/or AP greater than 230) increased the difference (p less than 0.001, relative risk of 2.8) which was also significant for survival (p less than 0.04).

Adolescent↗

PubMedDate not supplied

Increased levels of circulating interleukin-6 in patients with Hodgkin's disease.

Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow-up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6.

Adolescent↗

PubMedDate not supplied

The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies.

Today it is possible to cure more than 90 % of children and adolescents with Hodgkin's disease with a combination of radiotherapy and chemotherapy. Since the DAL-HD 82 study, the main scientific focus has been on avoiding late effects such as the OPSI syndrome, late complications involving the heart, lungs, thyroid and/or gonads particularly sterility in men and premature onset of menopause in women, and the prevention of secondary malignancies. The GPOH-HD 2003 study will introduce FDG-PET to the initial diagnostic program and the assessment of response to therapy in order to evaluate further possibilities for reducing therapy. In this context, the central review of all clinical and radiological findings, systematically done since the DAL-HD 90 study, will be increasingly relevant in maintaining standardised stage classification and therapy group assignment which was established by the preceding studies. Continuing in the direction of the earlier studies, the indications for radiotherapy will be restricted even further. In the early stages (treatment group 1) patients with CR or a negative FDG-PET at the end of chemotherapy will receive no radiotherapy in order to reduce the risk of a secondary malignancy. In a randomized comparison, procarbazine will be replaced by dacarbazine in the COPP cycles to determine whether sterility in men and premature onset of menopause in women can be avoided by elimination of procarbazine while retaining the same clinical efficacy. Finally, relapse therapy is to be tailored according to the time of relapse, the initial therapy group, and the patient's response to the relapse therapy with more patients receiving autologous transplantation in order to further improve the results of relapse treatment.

Antineoplastic Combined Chemotherapy Protocols↗