Haema 2013; 4(3):238-252
by Theodoros P. Vassilakopoulos, Maria Moschogiannis, Maria K Angelopoulou
Department of Haematology and Bone Marrow Transplantation, National and Kapodistrian University of Athens Medical School, Laikon General Hospital, Athens, Greece
Abstract
Hodgkin lymphoma (HL) and diffuse large B-cell lymphomas (DLBCL) are curable with 1st line therapy in 75% and 65% of the patients, while the corresponding figures for primary mediastinal large B-cell lymphoma (PMLBCL) and primary CNS lymphoma (PCNSL) are 75-80% and 50%. Patients who fail 1st line treatment are candidates for high-dose therapy with autologous stem cell transplantation (HDT/ASCT), if permitted by age, performance status and comorbidities. HL: Although a minority of patients can be cured by conventional salvage therapy, salvage chemotherapy, stem cell collection and HDT/ASCT is the treatment of choice for most patients. HDT/ASCT is not indicated as consolidation of the 1st complete remission. On the contrary, the superiority of HDT/ASCT over convention- al chemotherapy was demonstrated in 2 randomized trials for chemosensitive patients with relapsed/ refractory disease. HDT/ASCT results in cure rates of 40-60% in this group. Major prognostic factors for the outcome of HDT/ASCT are the duration of the 1st remission, extranodal or advanced-stage dis- ease at relapse/progression and chemosensitivity to salvage chemotherapy. Patients with a positive PET- scan prior to HDT/ASCT still have a considerable chance of cure, but their outcome is inferior to that of PET-negative patients. DLBCL: Approximately 50% of the patients are <65 years old, and are there- fore eligible for HDT/ASCT in case of development of relapsed/refractory disease. Practically, HDT/ ASCT is their only chance of cure, given the disappointing results of conventional salvage therapy. In- dependent prognostic factors in this setting include early relapse/progression (within 12 months from diagnosis), high aaIPI (2-3) at relapse/progression and prior exposure to rituximab. Several randomized trials had demonstrated the benefit of HDT/ASCT consolidation of 1st remission prior to the introduction of rituximab in patients with high-intermediate or high-risk IPI. This strategy was abandoned due to the improvement achieved by the introduction of R-CHOP, but is currently forming again the scientific question of several randomized trials. The persistence of PET positivity prior to HDT/ASCT is an independent adverse prognostic factor, but does not preclude a successful outcome in chemosensitive patients. PMLBCL: As in DLBCL, HDT/ASCT is the treatment of choice for primary refractory and re- lapsed disease. In the era of immunochemotherapy, HDT/ASCT is not indicated as consolidation of the 1st complete remission. PCNSL: Salvage therapy followed by HDT/ASCT may cure almost 50% of re- lapsed/refractory patients, although neurotoxicity and transplant-related mortality are not negligible. At present, consolidation of 1st remission with HDT/ASCT is not indicated as routine practice. Conditioning regimens containing 3 alkylators are preferable (busulfan, thiotepa, cyclophosphamide), in order to ensure effective drug concentrations in the CNS. In conclusion, the improvement in the outcome of the above disease entities achieved by HDT/ASCT has now reached its upper limits. Further progress will probably result from the incorporation of novel targeted therapies, based on the origin and properties of the neoplastic cells and the understanding of important signaling pathways.