The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis

To determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve event-free survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60 years and older were randomized to receive 2 induction cycles of daunorubicin and cytarabine with or without PSC-833. Patients in complete remission were then given 1 consolidation cycle without PSC-833. Neither complete response (CR) rate (54% versus 48%; P = .22), 5-year EFS (7% versus 8%; P = .53), disease-free survival (DFS; 13% versus 17%; P = .06) nor overall survival (OS; 10% in both arms; P = .52) were significantly improved in the PSC-833 arm. An integrated P-gp score (IPS) was determined based on P-gp function and P-gp expression in AML cells obtained prior to treatment. A higher IPS was associated with a significantly lower CR rate and worse EFS and OS. There was no significant interaction between IPS and treatment arm with respect to CR rate and survival, indicating also a lack of benefit of PSC-833 in P-gp-positive patients. The role of strategies aimed at inhibitory P-gp and other drug-resistance mechanisms continues to be defined in the treatment of patients with AML

Primary mediastinal DLBCL: evolving biologic understanding and therapeutic strategies.

Primary mediastinal diffuse large B-cell lymphoma is a quite rare clinicopathologic entity. Molecular analysis shows it to be distinct from other types of diffuse large B-cell lymphoma, and some retrospective analyses suggests that it may respond better to third-generation chemotherapy regimens than to the more commonly used CHOP. The addition of rituximab could reduce these differences; the role of consolidation with local radiotherapy, which is often used to treat residual mediastinal masses, remains. The real role of FDG-PET scanning requires prospective studies, and it is hoped that this may allow the de-escalation of radiation therapy accordingly to yield reliable prognostic information

The development of more than one histologic type of lymphoma in the same patient is frequent and confers a worse prognosis

Abstract BACKGROUND AND OBJECTIVES: Distinct types of lymphoma may develop in the same patient either simultaneously or sequentially. The frequency and clinical significance of this phenomenon are still only partially known. DESIGN AND METHODS: We conducted a retrospective analysis of all cases of lymphomas of different histology occurring in the same patient, denoting these cases as multiple histology lymphoma (MHL). The clinicopathologic characteristics of these cases were compared with those of cases with a single histology (SHL). The histologic classifications were made according to the REAL classification by the same pathologists throughout the study period. RESULTS: MHL were identified in 46 of 347 (13%) consecutive cases of lymphoma diagnosed at a single institution. They presented more frequently in stage III-IV (p=0.008), but the age, sex, and IPI score of patients with MHL did not differ from those of patients with SHL. Small lymphocytic/lymphoplasmacytic subtype was more frequent (16.1% vs 3%, p<0.0001) and Hodgkin's lymphoma (4% vs 16%; p=0.004) less frequent in MHL. Response rates to treatment were similar (85% vs 77.5%), whereas 5-year overall survival was significantly lower for MHL than for SHL (31% vs 67%; p=0.015). Among MHL, 14 cases were diagnosed simultaneously and 32 sequentially, after a median of 18 months. The two subgroups with simultaneous and sequential presentation did not differ in their demographic, clinicopathologic or prognostic characteristics. INTERPRETATION AND CONCLUSIONS: Lymphomas of different histology develop frequently in the same patient, either simultaneously or sequentially. Patients with MHL form a subgroup with few peculiar presenting clinicopathologic features but a markedly worse prognosis, thus warranting prospective biological and clinical studies