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Blood, 1 February 2001, Vol. 97, No. 3, pp. 616-623
CLINICAL OBSERVATONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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
Craig H. Moskowitz,
Stephen
D. Nimer,
Andrew D. Zelenetz,
Tania Trippett,
Eric E. Hedrick,
Daniel A. Filippa,
Diane Louie,
Maria Gonzales,
Janine Walits,
Nancy Coady-Lyons,
Jing Qin,
Richard Frank,
Joseph R. Bertino,
Andre Goy,
Ariela Noy,
James P. O'Brien,
David Straus,
Carol S. Portlock, and
Joachim Yahalom
From the Lymphoma and Hematology Disease Management
Teams, Departments of Medicine, Radiation Oncology, Pathology,
Biostatistics, and Pediatrics, Division of Hematologic Oncology,
Memorial Sloan-Kettering Cancer Center, New York, NY.
Salvage of patients with relapsed and refractory Hodgkin disease
(HD) with high-dose 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 dose-dense 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 < .001). These results compare favorably with other
series and document the feasibility and efficacy of giving uniform
dose-dense and dose-intense cytoreductive chemotherapy and integrating
accelerated fractionation radiotherapy into an ASCT treatment program.
This prognostic model provides a basis for risk-adapted HDT.
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