Prognostication and Risk-Adapted Therapy of Hodgkin's Lymphoma Using Positron Emission Tomography

The use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for response assessment in lymphoma is now widespread. Prognostic information obtained from PET performed after two to three cycles of chemotherapy may guide more individualized, risk-adapted therapeutic strategies. Progress in the risk stratification of Hodgkin's lymphoma through midtreatment PET is reviewed, with a focus on management implications in newly diagnosed and relapsed disease. How to tailor treatment on the basis of the interim PET result is not yet defined but is the subject of ongoing trials

Prognostication and Risk-Adapted Therapy of Hodgkin's Lymphoma Using Positron Emission Tomography

The use of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) for response assessment in lymphoma is now widespread. Prognostic information obtained from PET performed after two to three cycles of chemotherapy may guide more individualized, risk-adapted therapeutic strategies. Progress in the risk stratification of Hodgkin's lymphoma through midtreatment PET is reviewed, with a focus on management implications in newly diagnosed and relapsed disease. How to tailor treatment on the basis of the interim PET result is not yet defined but is the subject of ongoing trials

Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide

Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post-transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini-haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies

High-dose therapy and blood or marrow transplantation for non-Hodgkin lymphoma with central nervous system involvement

AbstractThe role of autologous or allogeneic blood or marrow transplantation (BMT) remains undefined in patients with central nervous system (CNS) involvement by lymphoma. The records of all adult and pediatric non-Hodgkin lymphoma patients receiving BMT at Johns Hopkins from 1980 to 2003 were reviewed, and 37 patients were identified who had CNS involvement that was treated into remission by the time of BMT. The chief histologies were diffuse large B-cell lymphoma and T-cell lymphoblastic lymphoma/leukemia. Twenty-four percent received intrathecal chemotherapy alone, and 70% received intrathecal chemotherapy and CNS irradiation before BMT. The main preparative regimens were cyclophosphamide/total body irradiation and busulfan/cyclophosphamide. Forty-one percent received an allogeneic transplant. Lymphoma relapsed after BMT in 14 patients (38%), and at least 5 had documented or suspected CNS relapse. In multivariate models, age ≥18 years at diagnosis, resistant systemic disease, busulfan/cyclophosphamide conditioning, and lack of intrathecal consolidation after BMT were statistically significant predictors of inferior survival. The 5-year actuarial event-free survival was 36%, and overall survival was 39%. After BMT, long-term survival is thus achievable in a subset of patients with a history of treated CNS involvement by non-Hodgkin lymphoma. The survival rates are not dissimilar to those typically seen in other high-risk lymphoma patients undergoing BMT. These data suggest that patients with lymphomatous involvement of the CNS who achieve CNS remission should be offered BMT if it is otherwise indicated

Initial Experience with Tositumomab and I-131-Labeled Tositumomab for Treatment of Relapsed/Refractory Hodgkin Lymphoma.

PurposeTo determine the maximum tolerated dose (MTD) of [131I]tositumomab in patients with refractory/recurrent Hodgkin lymphoma (HL) and to preliminarily determine if [131I]tositumomab has activity against HL and if positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) performed 6 weeks post-therapy predicted 12-week response.ProceduresSeparate dose-finding studies were performed for patients with and without prior transplant. A single therapeutic total body radiation dose (TBD) of [131I]tositumomab was administered. TBD was escalated/de-escalated based on dose-limiting hematologic toxicity (DLT) using a modified continual reassessment method. [18F]DG-PET/CT scans were performed at baseline and 6 and 12 weeks post therapy.ResultsTwelve patients (nine classical HL, three lymphocyte-predominant [LP] HL) completed two dosing levels (n = 3 each) in the post-transplant (55 cGy, 79 cGy) and no transplant (75 cGy, 87 cGy) groups. Hematologic toxicities were common and transient. Twelve weeks after [131I]tositumomab, 10 patients progressed and two with LPHL achieved complete response. [18F]DG-PET/CT at 6 weeks post therapy appeared more predictive than CT at 6 weeks of a response at 12 weeks.ConclusionsTositumomab and [131I]tositumomab was well-tolerated in patients with relapsed/refractory HL. Complete responses in LPHL support a therapeutic effect in this subtype. Early metabolic response assessments by [18F]DG-PET in HL after radioimmunotherapy appear to be more predictive than purely anatomic assessments