Relapsed and Refractory Hodgkin Lymphoma: Transplantation Strategies and Novel Therapeutic Options

Abstract

Many patients with Hodgkin lymphoma are cured with initial therapy, although a portion of patients will experience primary induction failure or disease relapse. Pathologic confirmation of refractory or relapsed Hodgkin lymphoma is important. Following two to four cycles of non-cross-resistant salvage chemotherapy, the standard of care is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), which is associated with long-term event-free survival rates of 45-68%. Of note, survival rates for studies integrating total lymphoid irradiation into the autologous HSCT-conditioning regimen are among the highest reported for relapsed/refractory Hodgkin lymphoma. Further treatment options are available for patients not fit to proceed to HSCT, for relapsed disease after autologous HSCT, and for 'high-risk' Hodgkin lymphoma including chemotherapy-resistant disease. Allogeneic HSCT is a valid treatment option, as a graft-vs.-Hodgkin-lymphoma effect has been demonstrated. In addition, novel targeted treatments are being investigated such as receptor-specific antibodies, radiolabeled antibodies, antiapoptotic agents including inhibitors of the nuclear factor-kappaB complex or X-linked inhibitor of apoptosis proteins, transcription pathway modulators such as histone deacetylase and mTOR inhibitors, and Epstein-Barr virus-directed therapy. Continued translational and collaborative prospective clinical research efforts are needed in order to continue to increase the survival rates for Hodgkin lymphoma and to lessen the toxicities associated with lymphoma-related therapy.

Refined Prognostic Role of CD68-Positive Tumor Macrophages in the Context of the Cellular Micromilieu of Classical Hodgkin Lymphoma

“…With risk-and response-adapted multimodal therapy, over 85% of cHL patients achieve a long-lasting and complete remission [2] . Nevertheless, about 3% of stage I and II and about 7% of stage III and IV cases present with refractory disease, and another 10-15% relapse, requiring more intensive treatments [3] . A drawback of the impressive achievements in cHL treatment is the increasing late toxicity, particularly the high incidence of secondary malignancies, such as therapy-related myeloid neoplasms, breast and lung cancer and car-diovascular diseases [4] .…”

Autologous Hematopoietic Stem Cell Transplantation for Patients with Lymphoma-Associated Hemophagocytic lymphohistiocytosis

“…Autologous HSCT has become a standard treatment for patients with relapsed and refractory Hodgkin lymphoma. Also, for relapsed or refractory (R/R) NHL patients, use of high dose chemotherapy (HDT) consolidation with autologous stem cell transplant (ASCT) can be curative 18 – 20 . The main mechanism is to eradicate disease activity by high-dose chemotherapy prior to PBSCT, and then supporting by stem cells infusion 21 .…”

Classical Hodgkin lymphoma: Differential diagnosis and tumour microenvironment

“…These therapeutic improvements have transformed CHL into a curable disease in more than 85% of cases. However, a considerable percentage of patients still fail to respond to current standard therapies requiring more intensive treatments 14 . Identifying subgroups of patients with poor prognostic parameters has become the main objective of clinical and biological research.…”