Dose-Dense(dd) ABVD and Dose-Dense/Dose-Intense(dd-di) ABVD in Newly Diagnosed Patients (pts), Intermediate- and Advanced-Stage with Classical Hodgkin's Lymphoma (cHL): Final Results.

We previously reported interim results (Blood-ASH Annual Meeting Abstracts-2007 110: abstract 2324) of a prospective study evaluating dose-dense and dose-intense variants of ABVD regimen. Seventy pts with a newly diagnosis of cHL were enrolled from 06/04 to 03/08. Pts had intermediate-(INT) or advanced-stage (ADV) according to GHLSG criteria (Tab.1). INT (n=24) were treated with dd ABVD, and ADV (n=46) with dd-di ABVD. Briefly, the strategy concepts of treatment were: 6 cycles of chemotherapy; the inter-cycle period shortened from 28 to 21 days; drugs delivered at day 1 and 11 of each cycle; In the dd-di-ABVD, adriamycin was escalated from 50 to 70 mg/m2 in cycles 1-4; primary G-CSF was given; the therapy was driven by interim-FDG-PET; radiotherapy was planned with very stringent criteria.

On a total of 838 courses of chemo we had 18 events which needed red cell transfusion; 5 of severe thrombocytopenia completely reversed within one week; 25 of severe neutropenia (<500 mmc) at the recycle. In 9 events pts were hospitalized to treat infections. Reversible palmar-plantar erythrodysesthesia was seen in 27 pts.The onset was between the 2^nd and 4^th cycle and disappeared within one month from the end of therapy (Tx). Three reversible events mimicking acute abdominal emergency needed a brief hospitalisation for support therapy. A suspect drug's alveolitis was seen in 3 events. This condition appeared between the 5^th/6^th cycles and was successfully treated with support. In all cases pts continued the Tx with a minimum delay and a moderate dose reduction of bleomycin. One case of sporadic reversible epileptogenic syndrome was seen in a 16-yr old girl. Early(1-yr) and late(4-yr) cardiac toxicity was studied in 70 and 25 pts, respectively: there was no evidence of relevant cardiac dysfunction.

Median duration of chemotherapy (planned 18-wk) was 19.7-wk (range 17.6-21.7). Planned and delivered RDIs of drugs were significantly higher as compared with the most used regimens (Tab.2).

Early-CR (PET_neg > 2 cycles) was obtained in 65/70 pts (95%). No statistical differences was noted between INT and ADV subsets. At the end of 6^thcycle 69/70 pts (98,6%) were in CR. Three out of 69 complete responders (4.3%) had a biopsy-proven relapse: a 33-yr old man ( IV_EA), a 27-yr old girl (IIB) and 29-yr old girl ( IV_XEB). Relapsed occurred at 3, 10 and 14 months from the end of Tx, respectively.

Data with a minimum follow up of 12-mo from the end of Tx were available in all 70 pts. Fig.1 shows the EFS rates of 24 INT-stage (95.8%), and 46 ADV-stage (91.3%) pts, respectively. A comparative analysis (Fig.2) between this series of 70 pts treated with dd ABVD or dd-di ABVD and the last 70 historical INT-stage (n=25) and ADV-stage (N=45) pts treated with baseline ABVD shows a statistically significant increment in EFS rate in pts receiving intensified ABVDs (93.0% vs 73.2% p=0.0041).

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The final results of this study shows that the activity of intensified ABVD is significantly higher than baseline ABVD in terms of response (CR) and survival (EFS) rates, still maintaining a low-toxicity profile. Based on these results a randomised comparison of intensified versus baseline ABVD seems justified.

No relevant conflicts of interest to declare.