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 ◽  
...  

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.

1996 ◽  
Vol 14 (3) ◽  
pp. 955-962 ◽  
Author(s):  
P L Zinzani ◽  
M Bendandi ◽  
M Martelli ◽  
B Falini ◽  
E Sabattini ◽  
...  

PURPOSE During the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkin's-like/Hodgkin's-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkin's disease (HD). PATIENTS AND METHODS From September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkin's lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively. RESULTS Complete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms. CONCLUSION The data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.


2020 ◽  
pp. 000313482095000
Author(s):  
Nam Young Choi ◽  
Byung-Sik Kim ◽  
Sung Tae Oh ◽  
Jeong Hwan Yook ◽  
Beom Su Kim

Background Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. Methods This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. Results DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN ( P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN ( P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN ( P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs ( P < .05 each). Conclusion DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.


1990 ◽  
Vol 8 (1) ◽  
pp. 94-102 ◽  
Author(s):  
A M Schneider ◽  
D J Straus ◽  
A E Schluger ◽  
D A Lowenthal ◽  
B Koziner ◽  
...  

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.


1995 ◽  
Vol 13 (8) ◽  
pp. 2005-2011 ◽  
Author(s):  
G P Canellos ◽  
G R Petroni ◽  
M Barcos ◽  
D B Duggan ◽  
B A Peterson

PURPOSE To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). PATIENTS AND METHODS Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. RESULTS Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. CONCLUSION EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7042-7042 ◽  
Author(s):  
A. W. Blackstock ◽  
M. A. Socinski ◽  
J. Bogart ◽  
L. Gu ◽  
X. Wang ◽  
...  

7042 Background: Combined chemoradiotherapy is the standard of care in stage III NSCLC. At standard TRT doses, local failures remain problematic and strategies exploiting the dose-response aspect of TRT are warranted. 3-D TRT allows escalation of TRT dose with acceptable toxicity (Socinski et al, J Clin Oncol 22:4341, 2004) and may enhance survival by improving loco-regional control. Methods: This is a two-arm randomized phase II trial evaluating 74 Gy with Con chemotherapy: Arm A- 2 cycles of Ind carboplatin (C) (AUC 6) and paclitaxel (P) (225 mg/m2) followed by weekly Con C (AUC 2/wk) and P (45 mg/m2) and 74 Gy; Arm B- 2 cycles of Ind C (AUC 5) and gemcitabine (G) (1000 mg/m2 d1,8) followed by Con G (35 mg/m2 twice weekly) and 74 Gy. The primary endpoint was a survival rate of ≥50% at 18 months after treatment initiation or med survival time (MST) of ≥18 mos. Results: 69 pts were entered (43 Arm A, 26 Arm B)- med age 61 yrs (39–77), 77% male, PS 0:1 42%:58%, stage IIIA:B 52%:48%. Ind therapy on both arms was well tolerated with no pts experiencing disease progression. ARM A- Overall response rate (RR) to all therapy was 61.9%. Gr 3–4 toxicities during Con therapy were anemia (15%), neutropenia (26%), esophagitis (9%), fatigue (9%), neuropathy (3%) and pulmonary (12%). There was 1 (3%) Gr 5 cardiac event. With med follow-up of 16.4 mos, the med progression-free survival (PFS) is 15.2 mos. The MST is not mature enough to estimate as only 15 deaths have occurred. ARM B- Closed early due to 3 (13%) Gr 5 pulmonary events. Overall RR to all therapy was 66.6%. Gr 3–4 toxicities during Con therapy were anemia (13%), fatigue (35%), esophagitis (35%), hemoptysis (4%), pulmonary (26% plus the 3 Gr 5 events). With med follow-up of 22 mos, the med PFS is 7.7 mos and the MST is 13.9 mos. There was a correlation between Gr 3–5 pulmonary toxicity and V20 ≥ 38% (p<0.05). Conclusions: 1) High dose 3-D TRT is feasible within CALGB, 2) the details of TRT (V20) are important with regard to toxicity, 3) the survival of pts on Arm A appears promising. [Table: see text]


1987 ◽  
Vol 73 (2) ◽  
pp. 121-126 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Filippo Gherlinzoni ◽  
Francesco Lauria ◽  
Patrizio Mazza ◽  
Enza Barbieri ◽  
...  

Between February 1982 and June 1984, 36 previously untreated patients with high-grade non-Hodgkin's lymphomas (NHL) according to the Kiel classification were treated with an intensive therapeutic regimen including cyclophosphamide, vincristine, doxorubicin, prednisone, cytarabin, VM 26 and local radiotherapy on bulky disease. Twenty-three patients (64 %) achieved a complete remission and 11 patients (30 %) had a partial response. Over a median follow-up from the diagnosis of 32.5 months, the overall survival was 55 %; relapse-free survival for complete responders was 56.5 %. Toxicity was irrelevant. This regimen was effective in the treatment of high-grade NHL, but probably needs intensification and rotation of different drugs.


2006 ◽  
Vol 9 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Patrick J. Leavey ◽  
Charles Timmons ◽  
William Frawley ◽  
Donald Lombardi ◽  
Raheela Ashfaq

Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n = 30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.


2019 ◽  
Vol 180 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S Asioli ◽  
A Righi ◽  
M Iommi ◽  
C Baldovini ◽  
F Ambrosi ◽  
...  

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.


Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 498-504 ◽  
Author(s):  
D Emilie ◽  
J Coumbaras ◽  
M Raphael ◽  
O Devergne ◽  
HJ Delecluse ◽  
...  

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.


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