Decisional early interim (18)F-fluoro-2-deoxy-D-glucose positron emission tomography after two cycles of chemotherapy in de novo Hodgkin lymphoma.

BACKGROUND/AIMS: An early evaluation with positron emission tomography (FDG-PET) has been demonstrated to be a valuable tool in the prediction of Hodgkin lymphoma's outcome. Herein we report a retrospective study on the outcome of Hodgkin lymphoma treated in accordance with interim FDG-PET results. METHODS: 48 patients with de novo Hodgkin lymphoma were treated with 2 cycles of chemotherapy. According to the interim FDG-PET (PET2) evaluation, pre-established treatment was continued if PET2 was considered negative. Patients with a positive PET2 result underwent a salvage therapy. Progression-free survival (PFS) and overall survival (OS) were chosen as end points. RESULTS: PET2 scan results were negative for 37 patients and positive for 11 patients. After salvage therapy, 7/11 patients were in complete remission and 4 patients had stable disease and were considered for third-line therapy. After a median follow-up of 5.2 years, 46 patients were still alive. The 4-year PFS were 84.5 and 45.4% for PET2-negative and PET2-positive patients, respectively (p = 0.007). In multivariate analysis, PET2 scan and extranodal disease remained relevant on PFS (p = 0.001 and 0.009, respectively). No difference was seen in OS. CONCLUSION: Our retrospective study suggests that salvage therapy for non-responder Hodgkin lymphoma using interim FDG-PET could improve the PFS of this group of patients.

Alteration Analysis of Bone Marrow Mesenchymal Stromal Cells from De Novo Acute Myeloid Leukemia Patients at Diagnosis.

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) frequently display alterations in several hematologic disorders, such as acute lymphoid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndromes. In acute leukemias, it is not clear whether MSC alterations contribute to the development of the malignant clone or whether they are simply the effect of tumor expansion on the microenvironment. We extensively investigated the characteristics of MSCs isolated from the BM of patients with de novo AML at diagnosis (L-MSCs) in terms of phenotype (gene and protein expression, apoptosis and senescence levels, DNA double-strand break formation) and functions (proliferation and clonogenic potentials, normal and leukemic hematopoiesis-supporting activity). We found that L-MSCs show reduced proliferation capacity and increased apoptosis levels compared with MSCs from healthy controls. Longer population doubling time in L-MSCs was not related to the AML characteristics at diagnosis (French-American-British type, cytogenetics, or tumor burden), but was related to patient age and independently associated with poorer patient outcome, as was cytogenetic prognostic feature. Analyzing, among others, the expression of 93 genes, we found that proliferative deficiency of L-MSCs was associated with a perivascular feature at the expense of the osteo-chondroblastic lineage with lower expression of several niche factors, such as KITLG, THPO, and ANGPT1 genes, the cell adhesion molecule VCAM1, and the developmental/embryonic genes, BMI1 and DICER1. L-MSC proliferative capacity was correlated positively with CXCL12, THPO, and ANGPT1 expression and negatively with JAG1 expression. Anyway, these changes did not affect their in vitro capacity to support normal hematopoiesis and to modify leukemic cell behavior (protection from apoptosis and quiescence induction). Our findings indicate that BM-derived MSCs from patients with newly diagnosed AML display phenotypic and functional alterations such as proliferative deficiency that could be attributed to tumor progression, but does not seem to play a special role in the leukemic process.