Abstract

Background: While autologous stem cell transplantation (ASCT) for patients with relapsed/refractory Hodgkin lymphoma (HL) appears to offer a survival advantage over conventional therapy, only approximately 25–35% of patients with primary progressive or poor risk recurrent Hodgkin Lymphoma achieve durable remission after ASCT with disease progression after transplant accounted for most of the treatment failures. We (a collaboration between City of Hope Comprehensive Cancer Center and Loyola University Medical Center) conducted a pilot study to evaluate the toxicities and efficacy of a tandem transplant approach in this subgroup of patients.

Methods: Between 4/98 and 3/00, 46 patients (median age: 37 [range 17–65]) were enrolled in the study.

Eligibility criteria: primary progressive (n=28) or recurrent HL (n=18) with at least one of the following poor prognostic factors: first CR < 12 months (n=15) or extra-nodal disease (n=4) or B symptoms at relapse (n=4). The 1st cycle consisted of melphalan (150mg/m2) alone. The 2nd cycle consisted of Fractionated total body irradiation (1200cGy) or BCNU (450mg/m2) in combination with etoposide (60mg/kg) and cytoxan (100mg/kg). A minimum of 2 x 106 CD 34/kg autologous stem cells were re-infused after each cycle of therapy.

Results: Of the 46 pts, 41 (89%) patients completed the planned tandem transplants. Five (11%) did not receive the planned tandem transplants because of inadequate stem cells collection for 2nd ASCT. After a median of 64 days (25–105), 41 patients received the 2 transplants. With a median follow up of 5 years (1.6–6.4), 24 patients are alive and progression-free at last follow up. Of the 41 patients who received both cycles of high dose therapy, 21 are alive and disease-free; 17 developed disease progression at a median of 4 months (range 1–61) post-ASCT. There were 2 early deaths secondary to regimen related toxicities. Both of them died of interstitial pneumonitis. The Day100 mortality was 4%. One patient developed secondary MDS 28 months post-ASCT after receiving further chemotherapy for relapsed disease. Using an intent-to-treat analysis for all 46 patients included in the study, the 5-year K-M estimate of overall survival, progression free survival and event free survival were 73% (95%CI 60,87), 61% (95% CI 46, 76) and 50% (95% CI 35, 64) respectively.

Conclusion: Our mature results from this study suggest that in patients with primary progressive or poor risk recurrent Hodgkin Lymphoma, this tandem ASCT program is effective and well tolerated and compares favorably with the conventional single transplant without increase in transplant related toxicities.

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