scholarly journals Treatment of Refractory Hodgkin's Disease With an Anti-CD16/CD30 Bispecific Antibody

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2042-2047 ◽  
Author(s):  
Frank Hartmann ◽  
Christoph Renner ◽  
Wolfram Jung ◽  
Christina Deisting ◽  
Marietta Juwana ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Lymphocyte Subsets ◽  
Nk Cell ◽  
Hodgkin’S Disease ◽  
Maximum Tolerated Dose ◽  
Clear Cut ◽  
Bispecific Monoclonal Antibody ◽  
Mixed Response ◽  
Cd30 Antigen ◽  
Cd16 Antigen

Abstract Fifteen patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural killer (NK)-cell–activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fcγ-receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen, respectively. Median counts of NK cells and of all lymphocyte subsets were considerably decreased in the patients before therapy. HRS-3/A9 was administered 4 times every 3 to 4 days, starting with 1 mg/m2. The treatment was well tolerated, and the maximum tolerated dose was not reached at 64 mg/m2, the highest dose administered because of the limited amounts of HRS-3/A9 available. Side effects were rare and consisted of fever, pain in involved lymph nodes, and a maculopapulous rash. A total of 9 patients developed human antimouse Ig antibodies, and 4 patients developed an allergic reaction after attempted retreatment. A total of 1 complete and 1 partial remission (lasting 16 and 3 months, respectively), 3 minor responses (1 to 11+ months), and 1 mixed response were achieved. There was no clear-cut dose-side effect or dose-response correlation. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the murine bispecific antibodies.

scholarly journals The difference in NK-cell activity between patients with non-Hodgkin's lymphomas and Hodgkin's disease

1999 ◽  
Vol 104 (1) ◽  
pp. 144-151 ◽  
Author(s):  
Gordana Konjević ◽  
Vladimir Jurišić ◽  
Božidar Banićević ◽  
Ivan Spužić
Keyword(s):  
Hodgkin's Disease ◽  
Nk Cell ◽  
Hodgkin’S Disease ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
The Difference ◽  
Hodgkin's Lymphomas

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

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1983-1988
Author(s):  
A Gause ◽  
C Pohl ◽  
A Tschiersch ◽  
L Da Costa ◽  
W Jung ◽  
...  
Keyword(s):  
Complete Remission ◽  
Hodgkin's Disease ◽  
Hodgkin’S Lymphoma ◽  
Progressive Disease ◽  
Hodgkin’S Disease ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Soluble Form ◽  
Soluble Cd30 ◽  
Cd30 Antigen

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.

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

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1983-1988 ◽  
Author(s):  
A Gause ◽  
C Pohl ◽  
A Tschiersch ◽  
L Da Costa ◽  
W Jung ◽  
...  
Keyword(s):  
Complete Remission ◽  
Hodgkin's Disease ◽  
Hodgkin’S Lymphoma ◽  
Progressive Disease ◽  
Hodgkin’S Disease ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Soluble Form ◽  
Soluble Cd30 ◽  
Cd30 Antigen

Abstract 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.

Severe Pulmonary Toxicity in Patients With Advanced-Stage Hodgkin's Disease Treated With a Modified Bleomycin, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone, and Gemcitabine (BEACOPP) Regimen Is Probably Related to the Combination of Gemcitabine and Bleomycin: A Report of the German Hodgkin's Lymphoma Study Group

2004 ◽  
Vol 22 (12) ◽  
pp. 2424-2429 ◽  
Author(s):  
Henning Bredenfeld ◽  
Jeremy Franklin ◽  
Lucia Nogova ◽  
Andreas Josting ◽  
S. Fries ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Pulmonary Toxicity ◽  
Hodgkin’S Disease ◽  
Maximum Tolerated Dose ◽  
Multicenter Trial ◽  
Advanced Stage ◽  
Dose Escalation Study ◽  
Starting Dose ◽  
Lymphoma Study Group

Purpose To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin's disease (HD). Patients and Methods Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m2 on days 1 and 4 of each cycle. Results Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. Conclusion The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin.

scholarly journals A killing defect of natural killer cells with the absence of natural killer cytotoxic factors in a child with Hodgkin's disease

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1686-1690
Author(s):  
A Komiyama ◽  
H Kawai ◽  
S Yamada ◽  
M Kato ◽  
M Yanagisawa ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Hodgkin's Disease ◽  
Nk Cell ◽  
Hodgkin’S Disease ◽  
Cell Activity ◽  
K562 Cells ◽  
Normal Numbers ◽  
Nk Cell Activity ◽  
Cell Defect

A killing defect of natural killer (NK) cells in the absence of NK cytotoxic factors (NKCF) was first demonstrated in a child with Hodgkin's disease. The patient lacked detectable NK cell activity in every phase of the disease as measured by a four-hour 51Cr-release assay using K562 cells as a target. The percent lysis at a 40:1 effector:target ratio by the patient's lymphocytes was persistently below 0.3% as compared with the normal lymphocyte value of 46.2% +/- 5.8% (mean +/- SD). NK cell activity was not detectable at effector:target ratios of 10:1 to 80:1 and by prolongation of the incubation time, and the NK cell defect was not restored or improved by lymphocyte stimulation with polyinosinic-polycytidilic acid, interferon (IFN)-alpha, or interleukin 2 (IL 2). The numbers of Leu-7+ cells and Leu-11+ cells were normal as counted by flow cytometry. A single cell- in-agarose assay demonstrated normal numbers of target binding cells (TBCs), and they showed the morphology of “large granular lymphocytes.” However, there were no TBCs with dead targets. These results indicated that the patient's lymphocytes contained normal numbers of NK cells that were capable of recognizing and binding to a target but were incapable of killing the bound target cell. The patient's lymphocytes were then studied for their release of NKCF upon interaction with K562 cells. The patient's cells did not release NKCF, and the NK cell defect was not restored or improved by stimulation of the cells with IFN or IL 2. It is suggested that the deficient release of NKCF may have been related to the killing defect of the NK cells in this patient.

scholarly journals The Effects of Two Alkaloids Derived from Vinca Rosea on the Malignant Cells of Hodgkin’s Disease, Lymphosarcoma and Acute Leukemia in Vivo

Blood ◽  
1967 ◽  
Vol 29 (1) ◽  
pp. 1-21 ◽  
Author(s):  
ALBERTO M. MARMONT ◽  
EUGENIO E. DAMASIO
Keyword(s):  
Acute Leukemia ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Growth Fraction ◽  
Malignant Cells ◽  
Proliferating Cells ◽  
Acute Leukemias ◽  
Clear Cut ◽  
Vinca Rosea

Abstract Hodgkin’s disease, lymphosarcoma, and acute leukemia have been studied after treatment with the Vinca rosea alkaloids (vinblastine and vincristine), in order to demonstrate and evaluate the mitosis-arresting effects of the two drugs on the malignant cells. Histologic sections, lymph node and bone marrow aspirations were performed immediately before and 24 hours after the intravenous administration of the drugs in 15 cases of Hodgkin’s disease, 12 of lymphoblastic lymphosarcoma, and 12 of acute leukemia, besides other miscellaneous cases. In Hodgkin’s disease aspirates and sections showed a clear-cut metaphase arrest in the post-VLB specimens, chiefly affecting the pre-Sternberg or Hodgkin cells. This effect, besides corroborating the fundamentally stathmokinetic mechanism of VLB in Hodgkin’s disease, was considered an additional factor in confirming the widely proposed conception that these cells represent the fundamentally proliferating and malignant tissue of this disease. In the acute leukemias and lymphoblastosarcomas, cytomorphologic and quantitative studies demonstrated that the oncolytic effects correlated well with the magnitude of metaphasic blockade. It is postulated that only actively proliferating cells—the so-called "growth fraction"—are the target for these alkaloids.

scholarly journals A killing defect of natural killer cells with the absence of natural killer cytotoxic factors in a child with Hodgkin's disease

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1686-1690 ◽  
Author(s):  
A Komiyama ◽  
H Kawai ◽  
S Yamada ◽  
M Kato ◽  
M Yanagisawa ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Hodgkin's Disease ◽  
Nk Cell ◽  
Hodgkin’S Disease ◽  
Cell Activity ◽  
K562 Cells ◽  
Normal Numbers ◽  
Nk Cell Activity ◽  
Cell Defect

Abstract A killing defect of natural killer (NK) cells in the absence of NK cytotoxic factors (NKCF) was first demonstrated in a child with Hodgkin's disease. The patient lacked detectable NK cell activity in every phase of the disease as measured by a four-hour 51Cr-release assay using K562 cells as a target. The percent lysis at a 40:1 effector:target ratio by the patient's lymphocytes was persistently below 0.3% as compared with the normal lymphocyte value of 46.2% +/- 5.8% (mean +/- SD). NK cell activity was not detectable at effector:target ratios of 10:1 to 80:1 and by prolongation of the incubation time, and the NK cell defect was not restored or improved by lymphocyte stimulation with polyinosinic-polycytidilic acid, interferon (IFN)-alpha, or interleukin 2 (IL 2). The numbers of Leu-7+ cells and Leu-11+ cells were normal as counted by flow cytometry. A single cell- in-agarose assay demonstrated normal numbers of target binding cells (TBCs), and they showed the morphology of “large granular lymphocytes.” However, there were no TBCs with dead targets. These results indicated that the patient's lymphocytes contained normal numbers of NK cells that were capable of recognizing and binding to a target but were incapable of killing the bound target cell. The patient's lymphocytes were then studied for their release of NKCF upon interaction with K562 cells. The patient's cells did not release NKCF, and the NK cell defect was not restored or improved by stimulation of the cells with IFN or IL 2. It is suggested that the deficient release of NKCF may have been related to the killing defect of the NK cells in this patient.

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