Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.

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.

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.


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.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5072-5072
Author(s):  
Michele Spina ◽  
Ulrich Jaeger ◽  
Joseph A Sparano ◽  
Renato Talamini ◽  
Giuseppe Rossi ◽  
...  

Abstract Abstract 5072 Background: The combination of Rituximab plus chemotherapy (CT) is more effective than CT alone in the treatment of high grade NHL. Objective: To report the long-term follow-up of CDE plus Rituximab in HIV-NHL. Methods: In June 1998, we started a phase II study using infusional CDE (Cyclophosphamide 187.5 mg/m2/day, Doxorubicin 12.5 mg/m2/day and Etoposide 60 mg/m2/day) administered by continuous intravenous infusion for 4 days every 4 weeks and Rituximab 375 mg/m2 i.v. on day 1. HAART was given concomitantly with CT. Results: Seventy-four patients (pts) have been enrolled. The median CD4+ cell count was 161 (range 3–691) and the median Performance Status was 1 (range 0–3). Diffuse large B-cell NHL was diagnosed in 72% of pts and Burkitt in 28%. Seventy per cent of pts had advanced stage (III-IV) disease and 57% of pts had an age-adjusted international prognostic index >2. Fifty-two out of 74 pts (70%) achieved a complete remission (CR), 4/74 (5%) had a partial remission and 18 pts progressed. With a median follow-up of 61 months, only 17% of CRs have relapsed and 41/74 pts are alive. The overall survival, disease free survival and time to treatment failure (TTF) at 5 years were 56%, 81% and 52%, respectively. Four cases of secondary tumors have been observed. No case of late pulmonary or cardiac toxicity has been reported. Conclusions: The combination of Rituximab and CDE in HIV-NHL treated concomitantly with HAART is very active. CR rate (70%) and TTF at 5 years (52%) are comparable to those observed in high grade NHL of the general population. Our data confirm that in HAART era a high proportion of HIV-NHL can be cured. Disclosures: No relevant conflicts of interest to declare.


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

Abstract 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.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1467-1467
Author(s):  
Michele Spina ◽  
Cecilia Simonelli ◽  
Emanuela Vaccher ◽  
Ulrich Jaeger ◽  
Joseph Sparano ◽  
...  

Abstract Background: The combination of Rituximab plus chemotherapy (CT) is more effective than CT alone in the treatment of high grade NHL. Objective: To report the long-term follow-up of CDE plus Rituximab in HIV-NHL. Methods: In June 1998, we started a phase II study using infusional CDE (Cyclophosphamide 187.5 mg/m2/day, Doxorubicin 12.5 mg/m2/day and Etoposide 60 mg/m2/day) administered by continuous intravenous infusion for 4 days every 4 weeks and Rituximab 375 mg/m2 i.v. on day 1. HAART was given concomitantly with CT. Results: Seventy-four patients (pts) have been enrolled. The median CD4+ cell count was 161 (range 3–691) and the median Performance Status was 1 (range 0–3). Diffuse large B-cell NHL was diagnosed in 72% of pts and Burkitt in 28%. Seventy per cent of pts had advanced stage (III–IV) disease and 57% of pts had an age-adjusted international prognostic index ³2. Fifty-two out of 74 pts (70%) achieved a complete remission (cr), 4/74 (5%) had a partial remission and 18 pts progressed. With a median follow-up of 61 months, only 17% of CRs have relapsed and 41/74 pts are alive. The overall survival, disease free survival and time to treatment failure (TTF) at 5 years were 56%, 81% and 52%, respectively. Only one secondary tumor (acute leukemia) has been observed. No case of late pulmonary or cardiac toxicity has been reported. Conclusions: The combination of Rituximab and CDE in HIV-NHL treated concomitantly with HAART is very active. CR rate (70%) and TTF at 5 years (52%) are comparable to those observed in high grade NHL of the general population. Our data confirm that in HAART era a high proportion of HIV-NHL can be cured. This study was supported by ISS grants.


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.


1991 ◽  
Vol 9 (3) ◽  
pp. 423-431 ◽  
Author(s):  
O W Press ◽  
R Livingston ◽  
J Mortimer ◽  
C Collins ◽  
F Appelbaum

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.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Belisty Temesgen ◽  
Getiye Dejenu Kibret ◽  
Nakachew Mekonnen Alamirew ◽  
Mamaru Wubale Melkamu ◽  
Yitbarek Tenaw Hibstie ◽  
...  

Abstract Background Tuberculosis is the leading cause of morbidity and mortality among people living with human immunodeficiency virus. Almost one-third of deaths among people living with human immunodeficiency virus are attributed to tuberculosis. Despite this evidence, in Ethiopia, there is a scarcity of information regarding the incidence and predictors of tuberculosis among people living with HIV. Thus, this study assessed the incidence and predictors of tuberculosis among HIV-positive adults on antiretroviral therapy. Methods This study was a retrospective record review including 544 HIV-positive adults on antiretroviral therapy at Debre Markos Referral Hospital between January 1, 2012 and December 31, 2017. The study participants were selected using a simple random sampling technique. The data extraction format was adapted from antiretroviral intake and follow-up forms. Cox-proportional hazards regression model was fitted and Cox-Snell residual test was used to assess the goodness of fit. Tuberculosis free survival time was estimated using the Kaplan-Meier survival curve. Both the bi-variable and multivariable Cox-proportional hazard regression models were used to identify predictors of tuberculosis. Results In the final analysis, a total of 492 HIV-positive adults were included, of whom, 83 (16.9%) developed tuberculosis at the time of follow-up. This study found that the incidence of tuberculosis was 6.5 (95% CI: 5.2, 8.0) per 100-person-years (PY) of observation. Advanced World Health Organization clinical disease stage (III and IV) (AHR: 2.1, 95% CI: 1.2, 3.2), being ambulatory and bedridden (AHR: 1.8, 95% CI: 1.1, 3.1), baseline opportunistic infections (AHR: 2.8, 95% CI: 1.7, 4.4), low hemoglobin level (AHR: 3.5, 95% CI: 2.1, 5.8), and not taking Isonized Preventive Therapy (AHR: 3.9, 95% CI: 1.9, 7.6) were found to be the predictors of tuberculosis. Conclusion The study found that there was a high rate of tuberculosis occurrence as compared to previous studies. Baseline opportunistic infections, being ambulatory and bedridden, advanced disease stage, low hemoglobin level, and not taking Isonized Preventive Therapy were found to be the predictors of tuberculosis. Therefore, early detection and treatment of opportunistic infections like tuberculosis should get a special attention.


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