High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy

Abstract

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16–213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow- up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.

Hodgkin lymphoma: 2016 update on diagnosis, risk‐stratification, and management

“…An analysis of treatment outcome in primary progressive patients showed that the 5‐year freedom from failure and overall survival for all patients were 17% and 26%, respectively, compared to 31% and 43% for those treated with HDCT and an ASCT . Other studies have further confirmed that patients receiving HDCT followed by ASCT have a better outcome than patients treated with chemotherapy . However, a majority of these patients still relapse following HDCT and ASCT.…”

What is the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy and adjuvant radiation therapy?

“…Numerous centers throughout North America and Europe currently administer adjuvant RT to their patients undergoing HDCT and stem cell rescue (SCR) . The rationale underlying this approach is that patients treated with HDCT alone have a high rate of failure in sites of prior and/or persistent disease [5,7,8,13,17,27,28]. We [28] and others [24][25][26] have demonstrated that adjuvant RT significantly decreases the risk of relapse in these sites and, in select patients, may improve survival.…”

“…Controversy exists, however, over the radiation treatment volume in these patients. We [28] and others [3][4][5][6][7][8][9][10][11][13][14][15][16][17][20][21][22][23][24][25][26] have used localized volumes encompassing solely sites of prior and/or persistent disease (involved-field RT, IFRT). In contrast, Yahalom and co-workers at the Memorial Sloan Kettering Cancer Center (MSKCC) have advocated more comprehensive treatment volumes, i.e., total lymphoid irradiation (TLI), to decrease relapse in new nodal sites [1,19,29].…”

Hodgkin lymphoma: 2014 update on diagnosis, risk‐stratification, and management

“…An analysis of treatment outcome in primary progressive patients showed that the 5‐year freedom from failure and OS for all patients were 17 and 26%, respectively, compared to 31 and 43% for those treated with HDCT and an ASCT . Other studies have further confirmed that patients receiving HDCT followed by ASCT have a better outcome than patients treated with chemotherapy . However, a majority of these patients still relapse following HDCT and ASCT.…”