Combined modality therapy for advanced, diffuse lymphocytic and histiocytic lymphomas

Sixty-five patients with Stages III and IV diffuse histiocytic lymphoma (DHL) were treated with two different and successive combination chemotherapy protocols. Twenty-seven patients were treated with the cyclophosphamide (CTX) L2 protocol, which included maintenance chemotherapy for three years. Thirty-eight patients received the NHL-3 program. Both protocols included radiotherapy (1350--4000 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system prophylaxis with intrathecal methotrexate or cytosine arabinoside in patients with bone marrow involvement. Two-year survival rates were 44 and 56%, respectively, for the CTX-L2 and NHL-3 protocols. Of the 65 patients, 59 were evaluable for response to therapy. The CTX-L2 produced a 58% total response (TR) rate, 39% complete (CR), and 19% partial (PR). The patients on NHL-3 achieved a TR rate of 82%, 33% CR, and 48% PR. The difference in TR was significant (P = 0.05), but in CR was not. Prior chemotherapy (P = 0.077) and serum lactic dehydrogenase (LDH) level above 500 U/liter (P = 0.01) significantly lessened the chances for achievement of a CR. However, sex, age, the presence of systemic symptoms, stage (III vs. IV), and prior RT were not found to be significantly related to CR rate. This analysis suggests that a high level of serum LDH characterizes a subgroup of patients with particularly aggressive DHL that requires a more intensive modality of treatment.

Section: Analysis Of the Factors Predicting Response To Therapy And Smentioning

confidence: 99%

Treatment of advanced diffuse histiocytic lymphoma: An analysis of prognostic variables

Koziner¹,

Little²,

Passe

et al. 1982

Treatment of diffuse poorly differentiated lymphocytic lymphoma an analysis of prognostic variables

Al‐Katib

Koziner

Kurland

et al. 1984

Forty patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL) Stages II‐IV were treated with three different and successive combination chemotherapy protocols. Seventeen patients were treated with the cyclophosphamide (CTX) L2 protocol which included maintenance chemotherapy for 3 years. Only three patients were treated with the NHL‐3 (non‐Hodgkin's lymphoma) protocol, and 20 patients received the NHL‐5 program. All protocols included radiotherapy (1500–4800 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system (CNS) prophylaxis with intrathecal methotrexate in patients with bone marrow involvement. Seventy‐eight percent of local recurrences occurred in previously irradiated areas. Two‐year survival rates were 55% and 70% for the CTX‐L2 and NHL‐5 protocols, respectively. Median disease‐free survival for 24 complete response (CR) patients was 16.5 months. of the 40 patients, 37 were evaluable for response to therapy. The CTX‐L2 produced an 80% total response (TR) rate, a 60% CR, and a 20% partial response (PR). The patients on the NHL‐5 achieved a TR rate of 95%, 74% CR, and 21% PR. Differences in TR and CR between the two protocols were not significant. Only 1 of 3 patients on the NHL‐3 protocol achieved a CR. There was a trend for age >50 years to lessen the chances of CR (P = 0.091); however, sex, symptoms, stage of disease, and LDH level were not significantly related to CR rate. Response to treatment (CR versus PR versus failure) was the most important factor influencing survival (P <0.001); age (>50 years) was also significant (P = 0.008). Lactate dehydrogenase (LDH) was of borderline significance (P = 0.06). Cox regression model showed age (>50 versus <50 years, P = 0.001), LDH (>500 versus≦500 U/L, P = 0.019) and symptoms (A or B) to be the best predictors of survival.

NHL-3 protocol six-drug combination chemotherapy for non-hodgkin's lymphoma

Koziner

Sklaroff

Little

et al. 1984

Combination chemotherapy and radiotherapy (RT) were administered to 73 adults with non‐Hodgkin's lymphoma (NHL). Ten cycles of the following drugs were given: intravenous Adriamycin (doxorubicin) (25 mg/m2), cyclophosphamide (700 mg/m2) and vincristine (1.5 mg/m2) on day 1; arabinosylcytosine (100 mg/m2) and methotrexate (10 mg/m2) on days 3 to 5; and oral prednisone (60 mg/m2) on days 1 to 5. Radiotherapy was given to resistant or initially bulky disease (2000 rad). Patients were also randomized to receive pseudomonas vaccine or no immunotherapy. of 61 evaluable patients, 33 (54%) achieved a complete response (CR) and 18 (30%) a partial response (PR). Among 44 evaluable patients with diffuse histiocytic lymphoma (DHL), 22 (50%) had a CR, and 15 (34%) a PR. for 17 evaluable patients with nodular (4) and diffuse (11) mixed and poorly differentiated lymphocytic and diffuse “undifferentiated” (2) lymphomas, CR and PR rates were 65% and 18%, respectively. No statistically significant differences in response rate or duration and survival have been observed between the patients randomized to receive pseudomonas vaccine or no immunotherapy. Median follow‐up time from start of treatment was 47.5 months. Median survival for all 73 patients (including inevaluables) and for 52 DHL patients was 30.7 months. Poor prognostic features influencing survival included: female sex (P = 0.003), poor response to therapy (CR versus PR; P = 0.001), prior chemotherapy, (P = 0.01) and high levels of lactic dehydrogenase (P = 0.001). It can be concluded that this combination of cycle and phase‐active agents is of similar efficacy to other reported regimens in inducing major responses and that it has the potential to prolong disease‐free survival. The analysis of prognostic factors has been used to dissect poor prognostic categories that might require different modalities of treatment.