Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis.

TLDR

Diffuse large‑cell lymphoma is highly curable with current therapy, yet treatment failures still occur even with intensive combination chemotherapy regimens. The study aimed to evaluate the prognostic significance of actual dose intensity of chemotherapy in diffuse large‑cell lymphoma. A retrospective analysis of 115 untreated patients treated between 1975 and 1986 with CHOP, BACOD, or MACOP‑B regimens calculated the relative dose intensity (RDI) of each drug standardized to CHOP and examined it alongside clinical prognostic factors. Multivariate tree‑structured survival analysis showed that an Adriamycin relative dose intensity above 75 % was the strongest predictor of survival, and a model incorporating RDI, performance status, LDH, and extranodal disease stratified patients into three groups with 3‑year survival rates of 89 %, 63 %, and 18 %, a pattern that persisted in complete responders, younger patients, and when dose intensity was defined relative to regimen‑specific optimum doses, underscoring the prognostic value of early RDI assessment for treatment planning.

Abstract

While diffuse large-cell lymphoma (DLCL) is considered to be highly curable with current therapy, treatment failures are observed even with intensive combination chemotherapy regimens. In order to study the prognostic significance of actual dose intensity of chemotherapy in DLCL, we retrospectively analyzed 115 previously untreated patients treated as Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclosphosphamide, vincristine, prednisone, and bleomycin (MACOP-B). The actual relative dose intensity (RDI), the amount of drug actually administered to each patient during the first 12 weeks of therapy, was calculated as standardized to CHOP and analyzed in addition to clinical factors prognostic for survival by univariate analysis. Multivariate recursive partitioning (tree-structured) survival analysis identified the actual RDI of Adriamycin greater than 75% as the single most important predictor of survival. A model incorporating the actual RDI of Adriamycin and performance status, in combination with serum lactate dehydrogenase (LDH) and extranodal disease, defined three overall prognostic groups of patients with respective 3-year survival rates of 89%, 63%, and 18%. The three prognostic groups remained distinct, even when restricted to complete responders. This model was also predictive of survival when dose intensity was analyzed relative to the optimum dose defined for each of the three regimens and when applied to a subgroup of patients aged 50 years or younger. We conclude that actual RDI is an important prognostic factor for survival in DLCL and that analysis of RDI early in the course of treatment may allow modification of the treatment plan.