Early chemotherapy intensification with BEACOPP in advanced-stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses

Interim 2-[18F]Fluoro-2-deoxy-D-glucose Positron Emission Tomography performed after two chemotherapy cycles (PET-2) is the most reliable predictor of treatment outcome in ABVD-treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET-2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET-2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score (Meignan, 2009). After a median follow up of 34 months (12-52) the 2-year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET-2 positive and 92% for PET-2 negative patients. For 154 patients in which treatment was correctly given according to PET-2 review, the 2-year FFS was 91%: 62% for PET-2 positive and 95% for PET-2 negative patients. CONCLUSIONS: this strategy, with BEACOPP intensification only in PET-2 positive patients, showed better results than ABVD-treated historic controls, sparing BEACOPP toxicity to the majority of patients.     

Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome

The appropriate therapy for limited-stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is unclear. In contrast to classical Hodgkin lymphoma (CHL), chemotherapy is often omitted; however, it is unknown whether this impacts the risk of relapse. Herein, we compared the outcome of patients with limited-stage NLPHL treated in an era in which ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy was routinely incorporated into the primary therapy to an earlier era in which radiotherapy (RT) was used as a single modality. Using the British Columbia Cancer Agency Lymphoid Cancer Database, 88 patients with limited-stage NLPHL (stage 1A/1B or 2A, nonbulky disease < 10 cm) were identified. Treatment followed era-specific guidelines: before 1993, (n = 32) RT alone; and 1993 to present (n = 56), ABVD-like chemotherapy for 2 cycles followed by RT with the exception of 14 patients who received ABVD chemotherapy alone. Most patients were male (75%) with stage I disease (61%). In an era-to-era comparison, the 10-year time to progression (98% vs 76% P = .0074), progression-free survival (91% vs 65% P = .0024), and OS (93% vs 84%, P = .074) favored the ABVD treatment era compared with the RT alone era. Treating limited-stage NLPHL similarly to CHL may improve outcome compared with the use of radiation alone.     

A single institution experience on 314 newly diagnosed advanced Hodgkin lymphoma patients: the role of ABVD in daily practice

Based on the results of clinical trials, there is no global consensus on the optimal first‐line therapy for patients with advanced Hodgkin lymphoma (HL) with both ABVD and BEACOPP currently being used. However, the results of clinical trials are usually better than those in daily practice. We thus describe here our experience on 314 advanced classical HL patients treated with ABVD at the Clinical Center of Serbia and associated centers between 1997 and 2008. The median follow‐up for all patients was 91 months; the estimated 5‐yr event‐free survival was 62% and the 5‐yr overall survival (OS) 76%. Multivariate Cox regression analysis revealed that patients with IPS ≥ 3 and extranodal disease involving more than one site have a poorer outcome. The data presented here show on overall improvement in outcome as compared to more previous data and illustrate the problems of treating advanced stage HL outside the setting of a clinical trial.     

ABVD vs BEACOPP escalated in advanced-stage Hodgkin’s lymphoma: Results from a multicenter European study

The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more intensive chemotherapy regimens, escalated BEACOPP (BEACOPPesc) is superior to ABVD for initial disease control and prolonged time-to-relapse. However, this advantage is associated with higher rate of early and late toxicities. As most of these data have been accumulated from clinical trials, a retrospective analysis was conducted in a large database of patients treated outside clinical trials to investigate the advantages and disadvantages of these regimes in a real-world setting. From October 2009 to October 2018, 397 advanced-stage HL patients treated with either ABVD or BEACOPPesc were retrospectively assessed in 7 European cancer centers (2 Austrian and 5 Italian centers). Complete metabolic remission (CMR) by PET was achieved in 76% and 85% of patients in the ABVD and BEACOPPesc groups, respectively (p = .01). Severe adverse events occurred more frequently with BEACOPPesc than ABVD. At a median follow-up of 8 years, 9% of the patients who achieved CMR after BEACOPPesc relapsed compared to 16.6% in the ABVD group (p = .043). No statistical difference in progression free survival (PFS) was observed between the two cohorts overall (p = .11), but there was a trend towards a superior PFS in high-risk patients treated with BEACOPPesc (p = .074). Nevertheless, overall survival was similar between the two groups (p = .94). In conclusion, we confirm that ABVD is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control, the long-term outcome remains similar between the two regimens.     

Successful treatment of Hodgkin lymphoma in second trimester of pregnancy: feasibility of ABVD regimen

A 34-year-old woman at 18 weeks of gestation during her third pregnancy was diagnosed with Hodgkin lymphoma stage IVA. She was treated with standard ABVD and showed good response. After three-and-a-half courses of ABVD, she spontaneously delivered a healthy baby girl at 41 weeks of gestation. She continued chemotherapy after delivery. A total of six courses of ABVD were given. Complete remission was obtained and has continued for 6 months post chemotherapy. Neither mother nor child developed any infections during the observation period. The child has also shown no physiological or developmental abnormalities. Here, we describe the feasibility and safety of the ABVD regimen for the treatment of Hodgkin lymphoma, and discuss the optimal treatment strategy.     

Combined ifosfamide, etoposide and oxalipatin chemotherapy, a low-toxicity regimen for first-relapsed or refractory Hodgkin lymphoma after ABVD/EBVP: a prospective monocentre study on 34 patients

Around 20% of Hodgkin lymphoma (HL) patients are refractory to first‐line therapy with ABVD (adriamycin–bleomycin–vinblastine–dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose‐reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide–etoposide–oxaliplatin) salvage regimen in terms of response rate, toxicity and stem‐cell mobilization. Thirty‐four patients with relapsed/refractory HL after anthracycline‐containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m² days 1–3), etoposide (150 mg/m² days 1–3) and oxaliplatin (130 mg/m² day 1). Patients <65 years old received high‐dose therapy followed by autologous stem‐cell transplantation (HDT–ASCT). Response was assessed by computed and positron‐emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose‐reductions. Twenty‐six patients underwent HDT–ASCT. With median follow‐up at 5 years, the 5‐year overall and event‐free survival rates were 74% and 63%, respectively. IVOx is a well‐tolerated outpatient regimen for relapsed HL, that does not hamper stem‐cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens.     

Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma

In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m(2) weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHL was 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial.     

Unrelated cord blood transplantation for patients with adult T-cell leukemia/lymphoma: experience at a single institute

We report the results of unrelated cord blood transplantation (UCBT) for patients with adult T-cell leukemia/lymphoma (ATLL) conducted in our single institute. Ten patients with ATLL (nine acute and one lymphoma-type) received UCBT during the period from August 2003 to July 2011. The median age at the time of diagnosis of ATLL was 51?years (range 37?C64). The median period from diagnosis of ATLL to UCBT was 130?days (range 94?C344). Conditioning regimens were myeloablative for six and reduced intensity for four. The median number of infused nucleated cells and CD34 positive cells were 2.52?×?10⁷/kg and 1.04?×?10⁵/kg, respectively. There was no engraftment failure. Three patients developed grade II acute graft versus host disease, and four developed grade III. The estimated 2-year overall survival was 40?% (95?% CI 12?C67?%). Four of six chemosensitive patients prior to UCBT survived for 1035, 793, 712, and 531?days post-UCBT, respectively. There were no survivors among the four chemorefractory patients prior to UCBT. Our data indicates that UCBT is feasible and provides long-term survival in patients with chemosensitive ATLL.     

No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy

When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.     

Hodgkin lymphoma

Hodgkin lymphoma (HL) is a curable malignancy which shows a bimodal curve in incidence in economically developed countries; there is a putative association with Epstein–Barr virus. The WHO 2008 classification schema recognises two histological types of HL: the nodular lymphocyte predominant and the “classic” HL. The latter encompasses four entities: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich. Most patients with HL present with asymptomatic superficial lymphadenopathy. The commonest sites of disease are the cervical, supraclavicular and mediastinal lymph nodes, while sub-diaphragmatic presentations and bone marrow and hepatic involvement are less common. Splenic involvement is usually concomitant with hepatic disease and systemic symptoms; extranodal presentations are quite rare. Systemic symptoms are present in ～35% of cases. The stage of disease is defined according to the Ann Arbor staging system or its Cotswolds variant, and staging work-up includes physical examination, chest X-rays, chest and abdominal CT scan, and bone marrow biopsy. ¹⁸FDG-PET (¹⁸fluordeoxyglucose positron emission tomography) plays a central role in staging, response assessment and prognosis definition.Classic HL usually spreads by contiguity within the lymphatic tissue network, with a late extension to adjacent and distant viscera. Mortality from HL has been progressively decreasing, as confirmed by the most recent 5-year survival figure of 81%. The list of putative prognostic factors in HL has been increasing, but most factors still require prospective validation. Some of these variables are used to stratify early-stage disease into “favourable” and “unfavourable” categories, with “unfavourable early-stage” being intermediate between “favourable early-stage” and “advanced-stage”.ABVD (adriamycin(doxorubicin), bleomycin, vinblastine, dacarbazine) combination chemotherapy followed by involved-field irradiation is the standard treatment for patients with early-stage HL, with a 5-year OS >95%. Several trials assessing less intensive approaches for patients with favourable early-stage HL are ongoing. More intensified combinations, such as the BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone) regimen, are being investigated, usually in patients with unfavourable early-stage HL and interim PET+. ABVD is the standard chemotherapy treatment also for patients with advanced disease. Although some evidence suggests that more intensive combinations provide better disease control, the inevitable increased risk of relevant late toxicity worries investigators. Consequently, there has been a shift towards investigating the innovative strategy of a more aggressive schedule for patients with ¹⁸FDG-PET positive results after the first 2 courses of ABVD. High-dose chemotherapy supported by ASCT (autologous stem cell transplantation) is considered the standard of care in patients with HL which has relapsed after, or is refractory to conventional chemoradiotherapy, while allogeneic transplant is a suitable tool for patients with chemorefractory disease and patients failed after ASCT.