Treatment Of Aggressive non-Hodgkin Lymphoma Research Articles

Phase II Study of Cyclophosphamide, Epirubicin, Vincristine, Prednisone, and Etoposide (CEOP-E) for Aggressive Non-Hodgkin's Lymphoma

The main objectives of the current study were to evaluate the efficacy and safety of a CEOP-E regimen for patients with aggressive non-Hodgkin's lymphoma (NHL). Fifty-one consecutive patients with newly diagnosed aggressive NHL were enrolled in the study. Median age of patients was 57 (range, 18-75) yr old, and male to female ratio was 1.32:1. Diffuse large B cell lymphoma (68.8%) was the most common histological subtype. Thirty patients (58.8%) had Ann Arbor stage III or IV diseases at diagnosis. One course of chemotherapy consisted of an intravenous combination of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, vincristine 2 mg, etoposide 80 mg/m2 on day 1 and oral administration of 100 mg prednisone on days 1 to 5 (CEOP-E). A complete response or unconfirmed complete response was achieved in 31 (63.3%) out of 49 evaluated patients. With a median follow-up of 16.3 months, 26 events including relapse and death were observed. The estimated 2-yr survival rate for all patients and disease free survival rate for patients achieving complete re-sponse was 58.9% and 57.1%, respectively. Episodes of febrile neutropenia occurred in 5 (10.2%) patients. Transient episodes of ECG abnormality (1st degree AV block) were observed in 2 patients. Accordingly, the CEOP-E regimen produced comparable results to those of other regimens, including CHOP, in terms of the response rate and overall survival. The current regimen seemed to minimize the cardiac toxicity due to an accumulated dose of anthracycline in the treatment of aggressive NHL.

Effectiveness of Interferon-Alfa and Mid-Cycle Chemotherapy Added to an Anthracycline-Based Regimen in the Treatment of Aggressive Non-Hodgkin's Lymphoma

Interferon-alfa in combination with cytotoxic chemotherapy has been shown to be effective in treating certain types of non-Hodgkin's lymphoma (NHL) (1). However, there is no published data on upfront induction treatment of aggressive NHL with IFN-alfa containing regimens. Studies have also shown that one can overcome regrowth resistance by administering mid-cycle agents which slow tumor proliferation between courses of cytotoxic therapy (2). Based on this, we treated 32 consecutive patients between 1/93 and 9/96 with a regimen containing cyclophosphamide 750 mg/m2, mitoxantrone 12 mg/m2, and teniposide 60 mg/m2 IV on day 1 with prednisone 100 mg PO given on days 1–5. On day 15, patients received vincristine 1.4 mg/m2 (2 mg max.) and bleomycin 10 units/ m2 IV. Interferon-alfa-2b 5×l06 units/m2 SQ was administered on days 22–26. The median age was 55 (range 26–83), M:F ratio was 2.5:1, and the median International Prognostic Index was 2. 38% of patients had stages I-II and 62% had stages III-IV disease. Fifty-nine percent of the patients achieved a complete response, 22% a partial response, and 19% had progressive disease. The overall survival (OS) was 81% and the progression free survival (PFS) was 56% at 4.3 years. There were no severe (grade IV) hematologic, flu-like, GI and infectious toxicities from IFN-α. Leukopenia was the main severe toxicity related to the chemotherapy regimen (days 1–15), but not IFN-α. Severe infection secondary to the chemotherapy regimen occurred in one patient. Interferon-alfa-2b and mid-cycle chemotherapy added to an anthracycline based regimen is effective induction treatment for patients with aggressive NHL. The OS and PFS using this regimen, based on regrowth resistance, appears to be at least as or more effective than CHOP therapy for this group of patients. Severe toxicities were rare.

18-FDG-PET as a Prognostic Indicator in the Treatment of Aggressive Non-Hodgkin's Lymphoma-Comparison with CT

Less than 50%, of newly diagnosed patients with aggressive histology Non-Hodgkin's Lymphoma (NHL) are cured with standard treatment. The ability to accurately monitor response to treatment is crucial in order to select out patients who need more intensive or salvage treatment. This study assesses the accuracy of FDG-PET as compared to CT in remission assessment following treatment of aggressive NHL, and its value in estimating relapse-free survival. It also evaluates the prognostic value of early interim PET scan in prediction of treatment outcome. Forty-nine adult patients with biopsy-proven aggressive NHL between September 1993 and December 1997 were included. All patients had pre-treatment FDG-PET demonstrating increased uptake in sites of disease. Forty-five patients had a post-treatment PET to assess remission status and 4 had an interim but not a post-treatment PET. Thirty-three of these patients also had a pre- and a post-treatment CT scan. Twenty-three of the 49 patients had an interim PET during chemotherapy to assess early response. PET and CT scan results were correlated with relapse data to examine their accuracy in remission assessment and prediction of prognosis. The median follow-up duration is 30 months.Overall the result of post-treatment PET scan appears to predict diseasc outcome, with relapse rates of 100% (919) and 17% (6/36) for positive and negative PET respectively [p<0.001]. In a subgroup of 33 patients, direct comparison of post-treatment PET and CT shows that PET was more accurate than CT in assessing remission status following treatment. Relapse rate was 100% for positive PET and only 18% for negative PET (p<0.001). compared to 41% and 25%. for patients with positive and negative CT respectively (p<0.1). PET was particularly useful in assessment of residual masses seen on CT scan. The interim PET provided valuable information regarding early assessment of response and long-term prognosis, with no relapses in patients with no or minimal residual uptake compared to 87.5% relapse rate in patients with persistent PET activity (p<0.001). FDG-PET is an accurate method of assessing remission and estimating prognosis following treatment of aggressive NHL, with positive and negative predictive accuracies of 100% and 82% respectively. PET is more accurate than CT in assessing remission and prediction of relapse-free survival. An interim PET scan after 2-3 cycles of chemotherapy predicts the long-term outcome early-on and has a high negative predictive value (100%). This may assist to separate at an early stage good-prognosis patients who are likely to be cured with standard chemotherapy from those patients with poorer prognosis who require alternative treatment.

Current guidelines for the management of aggressive non-Hodgkin's lymphoma.

The prognosis of aggressive non-Hodgkin's lymphoma (NHL) has improved greatly during recent years with the use of combination chemotherapy. Planning the treatment must take into consideration the patient's age, performance status, histological subtype and disease extent and severity. Recently, a 4-part International Prognostic Index (IPI), based on 5 prognostic factors, has permitted the allocation of patients with NHL in 2 well defined prognostic groups: good prognosis (low and low-intermediate risk) and poor prognosis (intermediate-high and high risk). Conventional chemotherapy with CHOP (a chemotherapeutic regimen consisting of a combination of cyclophosphamide, doxorubicin, vincristine and prednisone) or other equivalent third-generation regimens may be considered the standard treatment for the good prognosis group. In the poor prognosis group the probability of long term survival is less than 40% with conventional chemotherapy. Therefore, an early intensification with high dose therapy following peripheral stem cell transplantation (PSCT) should be considered in the setting of randomised trials. Localised stage disease, defined as stages I-IE and II-IIE without adverse prognostic factors, has a very good prognosis with a long term survival exceeding 80% using brief conventional chemotherapy regimens plus involved field radiotherapy. Refractory or relapsing patients after the drugs of first choice are given who subsequently respond to salvage chemotherapy should be enrolled for a course of high dose consolidation chemotherapy followed by PSCT. Elderly patients without severe organ dysfunction can take advantage from specifically devised chemotherapy regimens, with a response rate similar to that of younger patients. However, despite major advances in the treatment of aggressive NHL, additional clinical trials are required to enable the clinician to define the best therapeutic programmes to treat patients with this disorder.