Liposome-Encapsulated Doxorubicin in Combination With Standard Agents (cyclophosphamide, vincristine, prednisone) in Patients With Newly Diagnosed AIDS-Related Non-Hodgkin's Lymphoma: Results of Therapy and Correlates of Response

2004 ◽  
Vol 22 (13) ◽  
pp. 2662-2670 ◽  
Author(s):  
Alexandra M. Levine ◽  
Anil Tulpule ◽  
Byron Espina ◽  
Andy Sherrod ◽  
William D. Boswell ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Liposomal Doxorubicin ◽  
International Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Newly Diagnosed ◽  
Viral Control ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact ◽  
Mdr 1

Purpose To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. Patients and Methods Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. Results Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm3 (range, 19/mm3 to 791/mm3). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P = .027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. Conclusion Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.

scholarly journals Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Randy D. Gascoyne ◽  
Sheryle A. Adomat ◽  
Stanislaw Krajewski ◽  
Maryla Krajewska ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hodgkin’S Lymphoma ◽  
Gene Rearrangement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

Abstract The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.

Prospective Study of Survival Outcomes in Non-Hodgkin's Lymphoma Patients With Rheumatoid Arthritis

2006 ◽  
Vol 24 (10) ◽  
pp. 1597-1602 ◽  
Author(s):  
Ted R. Mikuls ◽  
Justin O. Endo ◽  
Susan E. Puumala ◽  
Patricia A. Aoun ◽  
Natalie A. Black ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prospective Study ◽  
Lower Risk ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Risk Of Death ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

Purpose Although preliminary studies suggest that non-Hodgkin's lymphoma (NHL) complicating rheumatoid arthritis (RA) may be a clinically distinct entity compared with that occurring in the general population, studies examining the impact of antecedent RA on survival are limited. In this prospective study, we examined the association of RA with survival in patients with NHL. Patients and Methods Using two large lymphoma registries, we identified patients with evidence of RA preceding NHL. Survival in RA patients was compared with that of controls using proportional hazards regression, adjusting for the effects of age, sex, lymphoma diagnosis-to-treatment lag time, calendar year, International Prognostic Index score, and NHL grade. Results The frequency of NHL subtypes was similar in RA patients (n = 65) and controls (n = 1,530). Compared with controls, RA patients with NHL had similar overall survival (hazard ratio [HR] = 0.95; 95% CI, 0.70 to 1.30) but were at lower risk of lymphoma progression or relapse (HR = 0.41; 95% CI, 0.25 to 0.68) or death related to lymphoma or its treatment (HR = 0.60; 95% CI, 0.37 to 0.98), but were more than twice as likely to die from causes unrelated to lymphoma (HR = 2.16; 95% CI, 1.33 to 3.50). Conclusion RA is associated with improved NHL-related outcomes, including a 40% reduced risk of death occurring as a result of lymphoma or its treatment and approximately a 60% lower risk of lymphoma relapse or progression compared with non-RA controls. However, the survival advantage gained in RA from the acquisition of lymphomas with favorable prognoses is negated through an increased mortality from other comorbid conditions.

scholarly journals Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Randy D. Gascoyne ◽  
Sheryle A. Adomat ◽  
Stanislaw Krajewski ◽  
Maryla Krajewska ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hodgkin’S Lymphoma ◽  
Gene Rearrangement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.

scholarly journals International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1460-1463 ◽  
Author(s):  
J Hermans ◽  
AD Krol ◽  
K van Groningen ◽  
PM Kluin ◽  
JC Kluin-Nelemans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Population Based ◽  
Hodgkin's Lymphoma ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years.

1997 ◽  
Vol 15 (8) ◽  
pp. 2945-2953 ◽  
Author(s):  
Y Bastion ◽  
J Y Blay ◽  
M Divine ◽  
P Brice ◽  
D Bordessoule ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Parameters ◽  
Aggressive Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma. PATIENTS AND METHODS Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks. RESULTS The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death. CONCLUSION Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.

Results of Multicentre Phase IV Study of Rituximab in Combination with CHOP Chemotherapy in Patients with Previously Untreated Non-Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4624-4624
Author(s):  
Ti Shen ◽  
Zhongzhen Guan ◽  
Zhixiang Shen ◽  
Yuankai She ◽  
Jun Zhu
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Response Rate ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Phase Iv

Abstract Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody that was the first antibody approved by the FDA in the United States of America and SDA in China for the treatment of B-cell non-Hodgkin’s Lymphoma (NHL). It has shown significant efficacy and good tolerability in refractory and relapsed NHL. We have conducted a multicenter phase IV trial to evaluate the efficacy and safety of rituximab combined with standard CHOP chemotherapy in patients with newly diagnosed B-NHL. Methods: Patients with newly diagnosed, histologically proven CD20-positive NHL were eligible for the study. All patients received 4–6 infusions of rituximab (375mg/m2 per dose) in combination with CHOP chemotherapy, either concurrently (rituximab administered on the first day of each 21-day CHOP cycle) or sequentially (4–6 once-weekly infusions of rituximab followed by six 21-day cycles of CHOP). Each CHOP cycle consisted of cyclophosphamide 750 mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2.0mg/dose) given intravenously on day 1, and prednisone 100mg/day orally on days 1-5. Tumor responses were assessed at the end of treatment. Results: A total of 347 patients were recruited between February 2002 and December 2003. Of these 235 (68%) were male and 94 (27%) aged >60. The main lymphoma subtypes were diffuse large B-cell 196 (56%), follicular 41(12%), small lymphocytic/chronic lymphocytic leukemia 13(4%) and MALT 11(3%). Ann Arbor staging was as follows: stage I, 52 (15%); stage II, 80 (23%); stage III, 90(26%); stage IV, 105(30%); twenty patients (6%) could not be assessed. Of the 347 patients enrolled, 314 were evaluable for response. An objective response was observed in 94% of evaluable patients with a complete response (CR) in 56%, stable disease in 3.8% and progressive disease in 2.5%. The complete response rate was 63% for patients receiving 6 cycles of rituximab and 54% for those receiving four cycles of rituximab. No difference in response rate was observed between the sequential and concurrent groups. The most common adverse events were leucopenia in 122 patients (35%), nausea and vomiting 66 (19%), fever 39 (11%), rash 15 (4%) and asthma 4 (1%). Conclusion: The combination of rituximab and CHOP chemotherapy is an effective and well-tolerated treatment for patients with newly-diagnosed CD20-positive NHL. The safety and efficacy achieved in this study suggests that more than four doses of rituximab may be required for optimal efficacy.

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