Treatment of refractory and relapsed Hodgkin's lymphoma: Facts and perspectives

The most effective salvage strategy for patients with Hodgkin's lymphoma relapsed or refractory to front-line therapy has yet to be conclusively defined. This problem has evolved in the last years and it is time to reconsider its dimension and to comment on mature data, new facts and perspective

The Risk of Therapy-Related Myelodysplasia/Acute Myeloid Leukemia in Hodgkin Lymphoma has Substantially Decreased in the ABVD Era Abolishing Mechlorethamine and Procarbazine and Limiting Volumes and Doses of Radiotherapy

Patients with Hodgkin lymphoma treated with DNA-breaking alkylating agents such as mechlorethamine and procarbazine in the MOPP regimen and with topoisomerase II inhibitors, such as etoposide did show a long-term risk of developing therapy-related myelodysplasia and acute myelogenous leukaemia (MDS/AML). With the introduction of the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regimen, this risk has substantially been reduced. In this review, different experiences are discussed to determine whether and how modifications of treatment in different cohorts of patients have reduced the overall risk of secondary MDS/AML. These data are drawn from large cohorts of patients treated over time with different therapies with an adequate follow-up

Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up

Abstract Purpose: To report on long-term events after short doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy and adjuvant radiotherapy in favorable early-stage Hodgkin's lymphoma. Experimental Design: We monitored late events and causes of death over 15 years (median follow-up, 120 months) in 120 patients with nonbulky stage IA-IIA Hodgkin's lymphoma, treated with four cycles of ABVD and limited radiotherapy. Pulmonary and cardiac function tests were done throughout the follow-up. Outcome measures included cause-specific mortality, standardized mortality ratio, and standardized incidence ratio for secondary neoplasia. Results: Projected 15-year event-free and overall survival were 78% and 86%, and tumor mortality was 3%. Standardized mortality ratio was significantly higher than 1 for both males (2.8; P = 0.029) and females (9.4; P = 0.003). The risk of cardiovascular events at 5 and 12 years was 5.5% and 14%, with a median latent time of 67 months (range: 23-179 months) from the end of radiotherapy. Pulmonary toxicity developed in 8% of patients; all had received mediastinal irradiation and the median time from radiotherapy to pulmonary sequelae was 76 weeks (range: 50-123 weeks). The risk of secondary neoplasia at 5 and 12 years was 4% and 8%, respectively, with no cases of leukemia. Fertility was preserved. Conclusions: Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia. A proportion of patients died from causes unrelated to disease progression and the excess mortality risk was mostly due to the occurrence of secondary neoplasms and cardiovascular diseases. A moderate dose reduction of radiotherapy from 40-44 Gy to 30-36 Gy did not decrease the risk of late complications; abolishing radiotherapy in nonbulky early-stage Hodgkin's lymphoma is being evaluated

Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients

Background Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia. Design and Methods We studied 605 patients with essential thrombocythemia (follow-up 4596 person-years) with the aim of defining prognostic factors for thrombosis, myelofibrosis, and leukemia during follow-up. Results Sixty-six patients (11%) developed thrombosis with a 10-year risk of 14%. Age >60 years ( p 60 years ( p =0.02) was significantly correlated with the development of leukemia. Cytotoxic treatment did not imply a higher risk of leukemia. At the time of the analysis, 64 of the 605 patients (10.6%) had died. The 10-year probability of survival was 88%, with a median survival of 22.3 years. Age >60 years ( p <0.001) and history of thrombosis ( p =0.001) were independent risk factors for survival. Conclusions The findings from this study on a large series of patients treated according to current clinical practice provide reassurance that essential thrombocythemia is an indolent disorder and affected patients have a long survival. The main risk is thrombosis, while myelofibrosis and leukemia are rare and late complications

Brentuximab vedotin in relapsed/refractory Hodgkin's lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials

Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin's lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression-free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10-19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions

First-line therapy of CD20+ diffuse large B-cell lymphoma: facts and open questions

CHOP chemotherapy, administered every 21 days, has been for years the standard therapy for advanced diffuse large B-cell lymphoma, with a long-term overall survival rate of about 40%. In this perspective article, Dr. Brusamolino discusses the recent advances in the treatment of this condition. See related paper on page 1250