Jill M. Vanak

Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma.

To identify prognostic factors for patients transplanted for relapsed or refractory Hodgkin lymphoma we carried out a combined analysis of patients followed prospectively on 3 consecutive protocols at Memorial Sloan-Kettering Cancer Center. One hundred fifty-three patients with chemosensitive disease after ICE (ifosfamide, carboplatin, and etoposide)-based salvage therapy (ST) proceeded to high-dose chemoradiotherapy followed by autologous stem cell transplantation (ASCT). Patients were evaluated with computed tomography and functional imaging (gallium or fluorodeoxyglucose-positron emission tomography) prior to ST and again before ASCT. Functional imaging status before ASCT was the only factor significant for event-free survival (EFS) and overall survival by multivariate analysis and clearly identifies poor risk patients (5-year EFS 31% and 75% for FI-positive and negative patients respectively). Administration of involved-field radiotherapy with ASCT was marginally significant for EFS (P = .055). Studies evaluating novel STs, conditioning regimens, post-ASCT maintenance, or allogeneic stem cell transplantation are warranted for patients who fail to normalize pre-ASCT functional imaging.

Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma.

Most patients with Hodgkin lymphoma (HL) are cured with first and second‐line treatment; however, the outcome is unknown for those who fail high dose chemoradiotherapy with autologous stem cell transplant (HDT‐ASCT). This report is an analysis of patients with relapsed and primary refractory HL who were treated with HDT‐ASCT and failed due to progression of disease (POD). Two hundred and two patients received HDT‐ASCT at Memorial Sloan Kettering Cancer Center for relapsed or refractory HL between December 1994 and 2005 and 71 failed due to POD. The median survival following HDT‐ASCT failure was 25 months. Only 16 (23%) of the 71 patients are currently alive, nine of whom are in remission. Multivariate analysis revealed two factors associated with poor outcome: relapse within 6 months of HDT‐ASCT and primary refractory disease. The only factor associated with improved survival was the ability to receive a second transplant, in particular, reduced intensity allogeneic transplant (RIT). Novel therapies are needed for patients who fail HDT‐ASCT, particularly those with primary refractory disease and those who relapse within 6 months of HDT‐ASCT. Future studies should focus on prospectively evaluating RIT following HDT‐ASCT failure in patients with remission duration from HDT‐ASCT of >6 months.

High‐dose chemo‐radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre‐transplant functional imaging

We previously reported that three risk factors (RF): initial remission duration <1 year, active B symptoms, and extranodal disease predict outcome in relapsed or refractory Hodgkin lymphoma (HL). Our goal was to improve event‐free survival (EFS) for patients with multiple RF and to determine if response to salvage therapy impacted outcome. We conducted a phase II intent‐to‐treat study of tailored salvage treatment: patients with zero or one RF received standard‐dose ifosfamide, carboplatin, and etoposide (ICE); patients with two RF received augmented ICE; patients with three RF received high‐dose ICE with stem cell support. This was followed by evaluation with both computed tomography and functional imaging (FI); those with chemosensitive disease underwent high‐dose chemoradiotherapy and autologous stem cell transplantation (ASCT). There was no treatment‐related mortality. Compared to historical controls this therapy eliminated the difference in EFS between the three prognostic groups. Pre‐ASCT FI predicted outcome; 4‐year EFS rates was 33% vs. 77% for patients transplanted with positive versus negative FI respectively, P = 0·00004, hazard ratio 4·61. Risk‐adapted augmentation of salvage treatment in patients with HL is feasible and improves EFS in poorer‐risk patients. Our data suggest that normalisation of FI pre‐ASCT predicts outcome, and should be the goal of salvage treatment.

Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres

Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan‐Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event‐free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post‐transplant maintenance strategies.

Pertussis Immunity and Response to Tetanus-Reduced Diphtheria-Reduced Pertussis Vaccine (Tdap) after Autologous Peripheral Blood Stem Cell Transplantation

Pertussis is a highly contagious respiratory infection characterized by prolonged cough and inspiratory whoop. Despite widespread vaccination of children aged<7 years, its incidence is steadily increasing in adolescents and adults, because of the known decrease in immunity following childhood immunization. In an effort to reduce pertussis in adolescents and adults, 2 vaccines containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) (BOOSTRIX and Adacel) were licensed in 2005 for use in adolescents, 1 of which (Adacel) contains less pertussis toxoid (PT) for use in adults. This study assessed pertussis titers in 57 adult survivors of an autologous peripheral blood stem cell transplantation (PBSCT; median age, 37.5 years), 28 of whom were subsequently vaccinated with Tdap containing 2.5microg of PT (Adacel). The median time to Tdap administration was 3 years posttransplantation. Before vaccination, 87% of the patients lacked pertussis immunity. Only 2 of the 28 patients developed a >2-fold response to PT following vaccination with Tdap. These data suggest that autologous transplantation recipients are highly susceptible to pertussis and that immunization with 2.5microg of PT induces an inadequate response. Prospective trials evaluating BOOSTRIX, containing 8microg/dose of PT (approved for adults in December 2008) are warranted in this vulnerable population undergoing transplantation.

Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma

Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan‐Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event‐free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post‐transplant maintenance strategies.

Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres: Early Relapsed/Refractory Hodgkin Lymphoma

Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan‐Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event‐free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post‐transplant maintenance strategies.