A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model

Abstract

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with highdose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dosedense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P < .

Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma

“…Features that are considered important survival determinants include first response duration, age, anemia, presence of extranodal disease, B-symptoms at recurrence, stage, and chemosensitivity before ASCT. 5,[10][11][12] Chemosensitivity and response to treatment are assessed using clinical, radiologic, and pathologic criteria. Computed tomography (CT) remains the standard for lymph node disease evaluation.…”

The relationship between absolute lymphocyte count with PFS in patients with Hodgkin's lymphoma undergoing autologous hematopoietic cell transplant

“…5,8 Like others, 3,[15][16][17] we have shown that patients with chemotherapy-sensitive disease have an improved PFS compared to patients who have SD. B symptoms at relapse have been shown to be associated with PFS in several studies, 3,18,19 however we and others 20,21 did not find a strong association between B symptoms at relapse and PFS. We also did not find any association between time to relapse or refractory disease and PFS, and the significance of these factors has also been variably reported in the literature.…”

“…We also did not find any association between time to relapse or refractory disease and PFS, and the significance of these factors has also been variably reported in the literature. 2,[18][19][20][21][22] Immune reconstitution post-AHCT is a complex process whereby cells of the immune system recover at different rates, both in number, function and antigenetic spectrum that may influence tumor surveillance. 23 Our study that noted an association between pre-apheresis ALC and PFS does provide some support that overall immune recovery may be important in survival and that the ALC may represent a crude marker for immune reconstitution.…”

Intermediate dose gemcitabine–cisplatin combination chemotherapy without treatment delay for cytopenia followed by autografting—a new standard of care in relapsed or refractory Hodgkin lymphoma?

“…Many regimens have been reported, often containing a platinum-based agent, but no single regimen has emerged as the accepted standard. Table 2 provides a summary of commonly used salvage regimens [3,[13][14][15][16][17][18]. All of these have inferior or comparable response rates to those reported here and where data is given the haematological toxicity is generally comparable or higher.…”