No abstract

No abstract

Background: The prognostic score for Hodgkin’s lymphoma was defined as the number of adverse prognostic factors presented at diagnosis. Seven factors had similar independent prognostic effects. This model was validated retrospectively in advanced disease using different therapeutic approaches (D Hasenclever et al N Eng J Med339:1506–14, 1998). Methods: From December 1996 up to October 2005, the GATLA completed a risk-adapted therapy with ABVD and IFRT. Patients with stages I-IIIA without bulky disease, who achieved complete remission (CR) after three cycles of ABVD, favorable group (FG) received only IFRT 25 GY to areas of >2 cm at diagnosis. Patients with FG not in CR after three cycles of ABVD, slow responders (FGSR), all stages IIIB-IV and all bulky disease, unfavorable group (UG) received six cycles of ABVD and IFRT 30 GY at remaining areas after 3 cycles of ABVD. A total of 584 patients, completed therapy; of them 513 were evaluated with the IPS. Patients were divided in three groups according to the number of adverse prognostic factors 0–1, 2–3, and ≥ 4. Results: The number of patients, complete remission (CR) rate, event-free survival (EFS) and overall survival (OSV) at 5 years according to prognostic factors in the 513 patients were as follows: IPS # patients (%) # CR (%) % EFS % OSV 0–1 224 (44) 217 (97) 86 95 2–3 241 (47) 213 (88) 73 90 ≥4 48 (9) 40 (83) 65 72 P< 0.020 0.001 0.001 A total of 200 patients with FG had a 5 years EFS and OSV of 89% and 98% while 53 patients with FGSR had an EFS and OSV of 66% and 88% respectively (P<0.001). The IPS in FG and FGSR was 0–1 of 61% versus 49%, 2–3 of 38.5% versus 43% and ≥4 of 0.5% versus 8% respectively (p=0.003). In UG with an EFS and OSV of 72% and 87%, the incidence of IPS 0–1 was 29%, 2–3 was 54% and ≥4 was 17%. Conclusion: The IPS is an excellent tool to predict outcome. Patients with stages I-IIIA without bulky tumour who did not achieve CR after three cycles of ABVD (FGSR) had poorer IPS than FG. In spite of receiving six cycles of ABVD, those with FGSR instead of three of those with FG had statistically a poor outcome. In the PET-TC era, patients who remain positive after three cycles of ABVD will need an intensified therapy with the purpose of improving the bad prognosis.

Background: ABVD (Doxorrubicin, Bleomycin, Vinblastine, Dacarbazine) can be considered as first line treatment for Hodgkin Lymphoma (HL). Our cooperative group has an experience of 584 patients treated with 3 or 6 cycles plus involved field radiotherapy (IFRT) with a complete remission (CR) of 91% and an event free survival and overall survival at 60 months of 79% and 95%. The new recommendations by B. Cheson define CR for HL as the lack of signs and symptoms of lymphoma with a negative PET-CT. (B Cheson et al, JCO: 25-579-586, 2007). A negative PET-CT either early during treatment of ABVD or after completion of it, has also shown to be a powerful prognostic tool (Hutchings: Blood 2006, Gallamini: Haematologica 2006). In an attempt to maintain high rate of CR and to reduce toxicity due to chemotherapy and radiotherapy we have conducted a trial with PET–CT adapted therapy. Aims: Test the feasibility and efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of patients who have a negative PET scan after three cycles of ABVD and receive no further treatment. Offer more intense therapy to patients who have persistent hypermetabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 123 newly diagnosed patients with HL have been included in a prospective multicenter trial. One hundred and two have already finished treatment. Initially all patients received 3 cycles of ABVD. After the third cycle, patients were evaluated with a PET-CT. Those patients who achieved CR with a negative PET-CT received no further treatment. Patients with partial response (PR) completed 6 cycles of ABVD and IFRT on PET-CT positive areas. Those patients with less than PR after 3 cycles received high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were reevaluated at the end of treatment. The median age at diagnosis was 33 years. Eighty-two patients (80%) had localized stage at diagnosis (I–II) and 20 (20%) presented with advanced stage (III–IV). Fifty-one (55%) patients had IPI 0–1, 37 (40%) had IPI 2–3 and 5 (5%) patients had IPI 4–5. Sixteen (16%) patients had bulky disease at diagnosis. Results. All patients completed treatment as planned. Eighty-seven (85%) achieved CR with negative PET-TC after the first 3 cycles of ABVD. Fifteen were PET positive, one with PD who achieved CR after ESHAP and ASCT. The other 14 patients completed 6 cycles of ABVD + RT. Twelve achieved CR and 2 PR. One died of progressive disease and the other one is in CR after third line treatment. Six patients relapsed, 4 are in second CR, and 2 are currently under treatment. Five of these 6 patients had achieved CR after 3 cycles of ABVD and 1 had progressive disease in PET–TC after the third cycle of treatment and received ESHAP and ASCT. With a median follow up of 17 months, 95 (93%) are in first CR, 4 (4%) in second CR and 2 in treatment. The event free survival and overall survival at 18 months are 92% and 100%. Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding potential long-term toxicity due to more aggressive chemotherapy and radiotherapy. Three courses of ABVD without radiation are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT, it is possible to intensify therapy improving the otherwise bad prognosis. These results need to be confirmed by a larger group of patients and a longer follow-up.

Introduction: The present goal standard for the treatment of HL is ABVD plus low doses of IFRT. With the purpose of maintaining a high response rate, event-free survival (EFS) and overall survival (OSV) with minimal toxicity we adapted the number of cycles of ABVD and doses of IFRT to the risk at diagnosis and early response. Methods: From December 1996, up to October 2005 a total of 527 patients, 15 to 75 years old (median 28) previously untreated entered the study. Patients with clinical stage I, II, IIIA without bulky tumor (< 10 cm mass or < 1/3 thoraxic diameter) (low-risk) received 3 cycles of ABVD followed by IFRT 25 Gy to all node areas of more than 2 cm at diagnosis. A total of 55 out of 267 patients (21%) with low-risk who failed to achieve complete remission (CR) after 3 cycles of ABVD were included as high-risk completing 6 cycles of ABVD. Patients with clinical stage IIIB and IV or all other stages with bulky disease or persistance lymph nodes areas after 3rd cycle of ABVD (high risk) received 6 cycles of ABVD followed by IFRT 30 Gy to bulky areas at diagnosis or those areas remaining > 2cm after 3 cycles. The dose of ABVD was the standard; Adriamycin 25 mg/m2, Bleomycin 10 IU/m2, Vinblastine 6 mg/m2 and Dacarbacine 375 mg/m2 all IV on day 1 and 15 of each 28 days cycles. Patients who achieved partial remission (PR) were salvage with other regimen mainly ESHAP × 3 cycles followed by high dose therapy with autograft rescue. Results: A total of 211 (99%) out of 212 patients with low-risk achieved CR. One 74 year old patient died of pneumonia after the third ABVD. A total of 277 (87%) of 315 patients with high-risk achieved CR, 28 PR, 9 failed to respond (FR), and 1 died of sepsis (P<0,001). The estimate EFS at 60 months was 91% and 72% (P< 0.001), while the OSV was 99% and 89% (P=0.001) for low and high risk respectively. Of the 28 patients with PR, all received second line therapy followed in 17 by an autograft, 13 patients are in CR, 3 are in PR, 1 alive in progressive disease (PD) and 11 died of PD. Of the 9 who FR, five received an autograft, five are alive (CR 3, PR 2) and four died of PD. One patient developed a MDS/AML after relapsing from an autograft and 8 months after having been rescued with BEACOPP. Eight other second cancer (2 NHL, and 6 solid tumours) appeared after treatment, three died and 6 remain alive, 2 in CR of their HL. Using the IPI HL 205 patients (45%) have scored 0–1, 206 (46%) scored 2–3, and 39 (9%) scored ≥ 4 out of 450 patients. The rate of CR was 97%, 90%, and 87% respectively (P<0.020). The estimated EFS at 60 months was 87%, 76% and 61% respectively (P=0.001). The OSV was 97%, 91% and 78% (P=0.004). Conclusion: This risk-oriented therapy based in cycles of ABVD and doses of IFRT in 527 patients with HL without previous treatment, produced an overall CR rate of 93%, EFS of 80% and OSV of 93% at 60 months.