Gemcitabine in the Treatment of Refractory Hodgkin’s Disease: Results of a Multicenter Phase II Study

2000 ◽  
Vol 18 (13) ◽  
pp. 2615-2619 ◽  
Author(s):  
A. Santoro ◽  
H. Bredenfeld ◽  
L. Devizzi ◽  
H. Tesch ◽  
V. Bonfante ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Response Rate ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow ◽  
Disease Status ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy Analysis ◽  
Duration Of Response ◽  
Heavily Pretreated

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin’s disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m2, was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1,250 mg/m2 to 1,500 mg/m2. RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients’ main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin’s disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.

Recombinant human granulocyte colony-stimulating factor hastens granulocyte recovery after high-dose chemotherapy and autologous bone marrow transplantation in Hodgkin's disease.

1989 ◽  
Vol 7 (12) ◽  
pp. 1791-1799 ◽  
Author(s):  
K M Taylor ◽  
S Jagannath ◽  
G Spitzer ◽  
J A Spinolo ◽  
S L Tucker ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Autologous Bone ◽  
Stimulating Factor ◽  
Historical Controls

To determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate granulocyte recovery after high-dose combination chemotherapy with autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease, we performed a nonrandomized phase II study using historical controls as a comparison. Eighteen relapsed/refractory Hodgkin's disease patients who received cyclophosphamide at 1.5 g/m2/day (days -6 to -3), carmustine (BCNU) at 300 mg/m2 (day -6), and etoposide (VP-16) at 125 mg/m2 every 12 hours (days -6 to -4), followed by ABMT (day 0) were treated with rhG-CSF at 60 micrograms/kg/day for a maximum of 28 days beginning on day 1. rhG-CSF dosage was gradually diminished and stopped once an adequate granulocyte count was maintained. rhG-CSF significantly accelerated absolute granulocyte count (AGC) compared with historical controls recovery to the 100/microL level (median, 9 days v 13 days; P = .103 x 10(-4), 500/microL level (median, 13 days v 22 days; P = 0.189 x 10(-2), and 1000/microL level (median, 16 days v 30 days levels; P = .125 x 10(-5). Platelet recovery to 50,000/microL was not significantly altered (P = .370). rhG-CSF was well tolerated, bone pain and myalgia being the only side effects noted. rhG-CSF hastens granulocyte recovery after high-dose chemotherapy with ABMT in patients with relapsed/refractory Hodgkin's disease without significant toxicity.

High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.

1993 ◽  
Vol 11 (4) ◽  
pp. 704-711 ◽  
Author(s):  
M Crump ◽  
A M Smith ◽  
J Brandwein ◽  
F Couture ◽  
H Sherret ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Intensive Therapy ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Disease Status ◽  
High Dose ◽  
Bulky Disease ◽  
Therapy Regimen ◽  
Advanced Hodgkin’S Disease

PURPOSE To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm). RESULTS Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor. CONCLUSION Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.

scholarly journals The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1137-1145 ◽  
Author(s):  
R Chopra ◽  
AK McMillan ◽  
DC Linch ◽  
S Yuklea ◽  
G Taghipour ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
First Relapse ◽  
Autologous Bone

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

Recombinant Human Granulocyte Colony-Stimulating Factor Hastens Granulocyte Recovery After High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in Hodgkin's Disease

1990 ◽  
Vol 8 (3) ◽  
pp. 567-567 ◽  
Author(s):  
Kerry McD. Taylor ◽  
Sundar Jagannath ◽  
Gary Spitzer ◽  
Jorge A. Spinolo ◽  
Susan L. Tucker ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Autologous Bone ◽  
Running Head ◽  
Stimulating Factor

The running head of the report by Taylor et al published in the December 1989 issue (J Clin Oncol 7:1791–1799, 1989) was incorrect. It should have read: "G-CSF AND ABMT IN HODGKIN'S DISEASE."

scholarly journals The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1137-1145 ◽  
Author(s):  
R Chopra ◽  
AK McMillan ◽  
DC Linch ◽  
S Yuklea ◽  
G Taghipour ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
First Relapse ◽  
Autologous Bone

Abstract Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

Allogeneic Stem Cell Transplantation for Hodgkin's Disease From Sibling and Unrelated Donors: The German Cooperative Transplantation Study Group Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2293-2293
Author(s):  
Christof Scheid ◽  
Peter Dreger ◽  
Dietrich W. Beelen ◽  
Martin Bornhäuser ◽  
Matthias Stelljes ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Disease Status ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Unrelated Donor ◽  
Free Survival ◽  
Unrelated Donors

Abstract Abstract 2293 Poster Board II-270 Introduction: Although modern chemotherapy regimens achieve a high cure rate in primary Hodgkin's disease and relapsed patients can be salvaged by high dose chemotherapy with autologous stem cell transplantation there remains a subgroup of patients with early relapse despite high dose chemotherapy. The prognosis of these patients is dismal with further chemotherapy. Allogeneic transplantation has the potential to exert an alloimmune response against lymphoma cells and has therefor been offered to patients with relapsed or refractory Hodgkin's disease, in particular when a matched sibling donor was available. However only limited information on the feasability of allogeneic transplantion from an unrelated donor is available. Methods: We performed a retrospective analysis of allogeneic transplants for Hodgkins disease within the German Cooperative Transplantation Study Group. 18 centres have provided data on patient and donor characteristics, transplant procedure and outcome. Survival data were analysed by Kaplan-Meier and tested for differences by log rank test. Cumulative incidences for relapse, non-relapse mortality and graft-versus-host-disease were calculated in a competing risk model. Results: 79 patients with a median age of 30 years (range 14-59) were included. 65 (82%) patients had failed a previous autologous transplantation 582 days (median) before allotransplantation. Disease status at transplantation was CR in 17.6%, PR in 54.0%, stable disease in 9.5%, PD in 12.2%, and untreated relapse in 6.8%. Donors were matched related in 33%, mismatched related in 5%, matched unrelated in 42% and mismatched unrelated in 20%. With a median follow up of 19 months for surviving patients the median overall survival (OS) after allotransplant was 42 months with a 2 year survival of 51%. Non-relapse mortality was 21.1% after 12 and 24 months. The median progression-free survival was 14.6 months with a 2 year PFS of 42.0%. Patients relapsing after an autologous transplantation had a significantly better OS (median 53.7 vs 8.4 months, p=0.029) and PFS (22.0 vs 7.5 months, p=0.039) than patients without a prior autograft. No significant difference was seen for OS or PFS regarding the use of related or unrelated donors or disease status at transplant. Conclusions: Allogenic transplantation is a feasible option for high-risk patients with relapsed or refractory Hodgkins disease in particular after failing an autograft. Non-relapse mortality appears to be acceptable in view of the intensive prior treatment. Probabilities for overall survival and progression-free survival were similar after transplantation from a related or unrelated donor. Further optimisation strategies have to focus on on efforts to reduce the high relapse-rate after transplantation, thereby potentially increasing overall and progression free survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Idiopathic pneumonia syndrome after high-dose chemotherapy for relapsed Hodgkin's disease

1997 ◽  
Vol 75 (7) ◽  
pp. 1044-1048 ◽  
Author(s):  
C Rubio ◽  
ME Hill ◽  
S Milan ◽  
MER O'Brien ◽  
D Cunningham
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Idiopathic Pneumonia Syndrome
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