Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with a high-dose doxorubicin-containing regimen.

1990 ◽  
Vol 8 (2) ◽  
pp. 248-256 ◽  
Author(s):  
K S Zuckerman ◽  
A F LoBuglio ◽  
J A Reeves
Keyword(s):  
Survival Rates ◽  
Stage Iv ◽  
Large Cell ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
High Grade ◽  
Term Survival ◽  
Short Period ◽  
Hodgkin's Lymphomas

Forty-seven previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with four courses of a regimen that consisted of high-dose (120 mg/m2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine (2 mg), cytarabine (3 gm/m2), and dexamethasone (50 mg intravenously [IV] on day 1 and 20 mg/day orally on days 2 to 5) (AVAD), which was administered every 3 to 4 weeks. The median age of the patients was 58 years; 72% were Ann Arbor stage IV, 49% had "B" symptoms, 62% had masses larger than 7 cm, 40% had masses at least 10 cm in diameter, and 49% had serum lactate dehydrogenase (LDH) greater than 250 U/L. Overall, 72% of the patients (89% of diffuse large-cell lymphoma [DLCL] patients) attained complete (CR) or probable complete responses (PCR), and relapses occurred in 32%. There were no episodes of clinical congestive heart failure, but one patient developed recurrent ventricular arrhythmias. Fever during neutropenia occurred with 65% of treatment courses. Three deaths were attributed primarily to complications of therapy. The lymphoma-free survival of all entered patients is 51% (24 of 47), with a follow-up of 30 to 67 months (median, 58 months). These results confirm that high CR/PCR and long-term survival rates can be achieved in patients with aggressive histologies of non-Hodgkin's lymphomas, even in groups with poor prognostic factors, using high-dose anthracycline-containing chemotherapy regimens delivered over a short period of time. However, the apparently higher relapse rate in comparison to our previous study leads us to speculate that consolidation with noncross-resistant agents may be helpful in increasing even further the cure rate in this group of patients.

scholarly journals Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an intensive epirubicin-containing regimen

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3564-3573 ◽  
Author(s):  
KS Zuckerman ◽  
DC Jr Case ◽  
RA Gams ◽  
EF Prasthofer
Keyword(s):  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Severe Neutropenia ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
High Grade ◽  
Free Survival ◽  
Study Results ◽  
Hodgkin's Lymphomas

Abstract An intensive chemotherapy regimen (EVDAC), including high-dose epirubicin, vincristine, and dexamethasone followed by cyclophosphamide and high-dose cytarabine, was administered to 54 untreated adults with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 59, 61% were Ann Arbor Stage IV, 57% had “B” symptoms, 50% had serum lactate dehydrogenase greater than 250 U/L, and 48% had masses greater than 7 cm (33% > 10 cm) in diameter. Seventy-six percent of patients attained complete or probable complete remissions. The Kaplan- Meier actuarial failure-free survival at 7 years is 50%, and 59% (32 of 54) of all patients started on therapy remain alive and in first remission at a median of 62+ (range, 49+ to 76+) months from completion of therapy. Nearly all patients developed severe neutropenia. Febrile episodes requiring hospitalization during neutropenia occurred after 56% of courses of epirubicin, vincristine, and dexamethasone and after 9% of courses of cyclophosphamide and cytarabine; 80% of patients were hospitalized at least once. Platelet count nadirs of less than 20,000/microL occurred after only 1 of 146 evaluable courses of epirubicin and after none of the cyclophosphamide/cytarabine courses. Although 8 patients had decreases of at least 0.12 in their left ventricular ejection fractions (5 to below normal levels), none have developed clinically evident congestive heart failure. Clinically significant mucositis occurred after only 8% of courses of high-dose epirubicin. Three deaths from infections and one from hyperkalemia with cardiac arrest occurred during therapy. These results confirm that high remission and sustained, failure-free survival rates can be achieved in patients with aggressive NHL, using high-dose anthracycline-containing chemotherapy regimens. Epirubicin appears to have an advantage over doxorubicin at high doses because of decreased toxicity at a therapeutically equivalent dose. These phase II study results need to be validated in a randomized phase III trial, and growth factors should be used to attempt to reduce the neutropenia-associated complications.

Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation.

1991 ◽  
Vol 9 (3) ◽  
pp. 423-431 ◽  
Author(s):  
O W Press ◽  
R Livingston ◽  
J Mortimer ◽  
C Collins ◽  
F Appelbaum
Keyword(s):  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Large Cell ◽  
High Dose ◽  
Primary Therapy ◽  
Bulky Disease ◽  
Free Survival ◽  
Hodgkin's Lymphomas ◽  
Disease Free

Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease. We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated with a median of three previous chemotherapy regimens. Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria. Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months. Myelosuppression was the major toxicity, but there were no treatment-related deaths. To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%. We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor.

scholarly journals Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an intensive epirubicin-containing regimen

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3564-3573
Author(s):  
KS Zuckerman ◽  
DC Jr Case ◽  
RA Gams ◽  
EF Prasthofer
Keyword(s):  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Severe Neutropenia ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
High Grade ◽  
Free Survival ◽  
Study Results ◽  
Hodgkin's Lymphomas

An intensive chemotherapy regimen (EVDAC), including high-dose epirubicin, vincristine, and dexamethasone followed by cyclophosphamide and high-dose cytarabine, was administered to 54 untreated adults with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 59, 61% were Ann Arbor Stage IV, 57% had “B” symptoms, 50% had serum lactate dehydrogenase greater than 250 U/L, and 48% had masses greater than 7 cm (33% > 10 cm) in diameter. Seventy-six percent of patients attained complete or probable complete remissions. The Kaplan- Meier actuarial failure-free survival at 7 years is 50%, and 59% (32 of 54) of all patients started on therapy remain alive and in first remission at a median of 62+ (range, 49+ to 76+) months from completion of therapy. Nearly all patients developed severe neutropenia. Febrile episodes requiring hospitalization during neutropenia occurred after 56% of courses of epirubicin, vincristine, and dexamethasone and after 9% of courses of cyclophosphamide and cytarabine; 80% of patients were hospitalized at least once. Platelet count nadirs of less than 20,000/microL occurred after only 1 of 146 evaluable courses of epirubicin and after none of the cyclophosphamide/cytarabine courses. Although 8 patients had decreases of at least 0.12 in their left ventricular ejection fractions (5 to below normal levels), none have developed clinically evident congestive heart failure. Clinically significant mucositis occurred after only 8% of courses of high-dose epirubicin. Three deaths from infections and one from hyperkalemia with cardiac arrest occurred during therapy. These results confirm that high remission and sustained, failure-free survival rates can be achieved in patients with aggressive NHL, using high-dose anthracycline-containing chemotherapy regimens. Epirubicin appears to have an advantage over doxorubicin at high doses because of decreased toxicity at a therapeutically equivalent dose. These phase II study results need to be validated in a randomized phase III trial, and growth factors should be used to attempt to reduce the neutropenia-associated complications.

Treatment of lymphoblastic lymphoma in adults.

1986 ◽  
Vol 4 (11) ◽  
pp. 1628-1637 ◽  
Author(s):  
C N Coleman ◽  
V J Picozzi ◽  
R S Cox ◽  
K McWhirter ◽  
L M Weiss ◽  
...  
Keyword(s):  
High Risk ◽  
Stage Iv ◽  
Risk Groups ◽  
Cranial Irradiation ◽  
Serum Lactate ◽  
Lymphoblastic Lymphoma ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Risk Patients

Forty-four adult patients with lymphoblastic lymphoma (LBL) were treated according to one of two protocols. Both included (1) induction with cyclophosphamide, doxorubicin, vincristine, prednisone, and L-asparaginase; (2) CNS prophylaxis; and (3) maintenance therapy with methotrexate (MTX) and 6-mercaptopurine. In the second protocol, CNS prophylaxis began earlier than in the first protocol and included cranial irradiation and intrathecal (IT) MTX rather than simultaneous high-dose systemic and IT MTX. The overall response rate was 100% (95% complete). With a 26-month median follow-up, the 1-and 3-year actuarial freedom from relapse (FFR) for the composite patient group was 70% and 56%, respectively. The incidence of CNS relapse was reduced from 31% in the first protocol to 3% in the second protocol (P = .04, Gehan). Patients can be assigned retrospectively to low (n = 19) and high (n = 25) risk prognostic groups, as indicated by a multivariate analysis of pretreatment prognostic factors. High-risk is defined by Ann Arbor stage IV disease with bone marrow or CNS involvement or initial serum lactate dehydrogenase (LDH) concentration of greater than 300 IU/L (normal, less than 200). FFR of low- and high-risk groups at 5 years are 94% and 19%, respectively (P = .0006). Low-risk patients are highly curable using this approach to adult LBL. More intensive treatment for high-risk patients is warranted.

scholarly journals Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites

2021 ◽  
Vol 10 (2) ◽  
pp. 294
Author(s):  
Atsushi Hosui ◽  
Takafumi Tanimoto ◽  
Toru Okahara ◽  
Munehiro Ashida ◽  
Kohsaku Ohnishi ◽  
...  
Keyword(s):  
Conventional Therapy ◽  
Low Dose ◽  
Therapy Group ◽  
Survival Rates ◽  
Refractory Ascites ◽  
High Dose ◽  
Term Survival ◽  
Conventional Therapy Group ◽  
One Year ◽  
The One

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.

scholarly journals Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Wilfred Delacruz ◽  
Robert Setlik ◽  
Arash Hassantoufighi ◽  
Shyam Daya ◽  
Susannah Cooper ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Unmet Need ◽  
Case Series ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Hematologic Malignancies ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
First Line

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted.

scholarly journals Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 498-504 ◽  
Author(s):  
D Emilie ◽  
J Coumbaras ◽  
M Raphael ◽  
O Devergne ◽  
HJ Delecluse ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Interleukin 6 ◽  
Large Cell ◽  
Malignant Cell ◽  
High Grade ◽  
Follicular Hyperplasia ◽  
Immunodeficiency Virus ◽  
Hodgkin's Lymphomas

The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large- cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study.

1993 ◽  
Vol 11 (2) ◽  
pp. 248-254 ◽  
Author(s):  
B A Parker ◽  
M Santarelli ◽  
M R Green ◽  
J R Anderson ◽  
M R Cooper ◽  
...  
Keyword(s):  
Large Cell ◽  
High Grade ◽  
Intermediate Grade ◽  
Free Survival ◽  
Major Toxicity ◽  
Central Pathology ◽  
Group B ◽  
Hodgkin's Lymphomas ◽  
Leukemia Group

PURPOSE In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas. PATIENTS AND METHODS Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms. RESULTS Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred. CONCLUSION We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.

Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.

1993 ◽  
Vol 11 (9) ◽  
pp. 1770-1779 ◽  
Author(s):  
A Garaventa ◽  
B De Bernardi ◽  
C Pianca ◽  
A Donfrancesco ◽  
L Cordero di Montezemolo ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Standard Dose ◽  
Serum Lactate ◽  
Response To Therapy ◽  
Serum Lactate Dehydrogenase ◽  
Risk Category ◽  
High Dose ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Response To Chemotherapy

PURPOSE To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.

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