The influence of histologic subtype on toxicity and response to chemotherapy in non‐Hodgkin‐s lymphoma an eastern cooperative oncology group study utilizing the BCVP regimen

The authors analyzed the results of treatment in 164 patients with non‐Hodgkin‐s lymphoma who received combination chemotherapy with BCNU, cyclophosphamide, vincristine and prednisone (BCVP). The data, derived from three consecutive Eastern Cooperative Oncology Group (ECOG) protocols, demonstrate a statistically significant influence of histologic subtype on toxicity and on response to therapy. For this study all nodular lymphomas and diffuse well differentiated lymphocytic lymphoma (DLWD) were defined as prognostically favorable histologic subtypes while all other diffuse lymphomas were considered unfavorable histology. Patients with favorable histologic subtypes experienced a 24% incidence of severe myelotoxicity (leukocyte count < 2000/μl or platelet count < 50,000/μl) compared with a 48% incidence for patients with unfavorable histologic subtypes (P < 0.005). This difference in toxicity was not related to prior radiotherapy or to bone marrow involvement with lymphoma. In patients with unfavorable histologic subtypes, severe myelotoxicity was associated with a complete response (CR) rate of only 16% while patients with similar histology but milder toxicity had a CR rate of 49% (P < 0.01). Patients with favorable histologic subtypes, however, demonstrated no correlation between myelotoxicity and response to BCVP. Furthermore, the 97 patients with favorable histologic subtypes had a higher CR rate (64%) than did patients with unfavorable histologic subtypes (33%) (P < 0.001). Survival rates were also strongly influenced by histology. The two‐year survival for patients with unfavorable histologic subtypes was 28% while survival for the favorable histologic subtypes was 72% at two years and a projected 62% at five years (P < 0.001). This study demonstrates that patients treated with BCVP for unfavorable histologic subtypes of non‐Hodgkin‐s lymphoma have greater myelotoxicity, a poorer response rate and a correlation between severe myelotoxicity and failure to achieve CR that is not observed in patients with favorable histology. While BCVP is an effective chemotherapy with an acceptable level of acute toxicity for patients with favorable histologic subtypes, it yields a poor CR rate with unacceptable toxicity and short survival in patients with unfavorable histologic subtypes.