Ilidia Moreira

Minimal Residual Disease Tests Provide an Independent Predictor of Clinical Outcome in Adult Acute Lymphoblastic Leukemia

PURPOSE Investigation of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) using molecular markers has proven superior to other standard criteria (age, sex, and WBC) in distinguishing patients at high, intermediate, and low risk of relapse. The aim of our study was to determine whether MRD investigation is valuable in predicting outcome in Philadelphia-negative adult patients with ALL. PATIENTS AND METHODS MRD was assessed in 85 adult patients with B-lineage ALL by semiquantitative immunoglobulin H gene analysis on bone marrow samples collected during four time bands in the first 24 months of treatment. Fifty patients received chemotherapy only and 35 patients received allogeneic (n = 19) or autologous (n = 16) bone marrow transplantation (BMT) in first clinical remission. The relationship between MRD status and clinical outcome was investigated and compared with age, sex, immunophenotype, and presenting WBC count. RESULTS Fishers exact test established a statistically significant concordance between MRD results and clinical outcome at all times. Disease-free survival (DFS) rates for MRD-positive and -negative patients and log-rank testing established that MRD positivity was associated with increased relapse rates at all times (P <.05) but was most significant at 3 to 5 months after induction and beyond. MRD status after allogeneic BMT rather than before was found to be an important predictor of outcome in 19 adult patients with ALL tested. In patients receiving autologous BMT (n = 16), the MRD status before BMT was more significant (P =.005). CONCLUSION The association of MRD test results and DFS was independent of and greater than other standard predictors of outcome and is therefore important in determining treatment for individual patients.

Genetic and clinical characterization of 45 acute leukemia patients with MLL gene rearrangements from a single institution

Chromosomal rearrangements affecting the MLL gene are associated with high‐risk pediatric, adult and therapy‐associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL‐related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL–AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL–MLLT3 (27%), a MLL–MLLT1 (20%), or MLL–MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL–MLLT3 fusion (42%), followed by MLL–MLLT10 (23%), MLL–MLLT1 (8%), MLL–ELL (8%), MLL–MLLT4 (4%), and MLL–MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL–MLLT4 fusion variant.

Treatment Outcomes of Patients with Primary Mediastinal Diffuse Large B-CellLymphoma: A Single-Center Experience

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity from diffuse large B-cell lymphoma. The optimal first-line therapy for PMBCL is subject of ongoing debate with no accepted standard of care. Patients and Methods: We searched retrospectively for adult patients with newly diagnosed PMBCL treated at our department between 2002 and 2014. Clinical, management and follow-up data were collected. Staging and response assessment of patients included PET and/or CT scan. Results: Twenty-nine patients with PMBCL (17 female and 12 male) were included. The median age at diagnosis was 36 years (18-79 years). Eighteen (62.1%) and 20 (69%) patients had limited-stage and bulky disease, respectively. All patients were treated with rituximab-based combination chemotherapy; 21 patients underwent consolidation radiotherapy. Seven patients (24.1%) were transplanted (six in first remission and the remaining in second remission). At the end of frontline therapy, 28 patients had responded (27 complete response and 1 partial response) and one patient showed progressive disease. Febrile neutropenia was the most frequent acute adverse event and three patients developed late toxicity. The median follow-up was 51,5 months. The 5-year overall progression-free survival was 83.8%. Four patients died, half of which died within the first year after diagnosis. Conclusion: Our study shows favorable prognosis of patients with PMBCL treated with rituximab-based chemotherapy and consolidation radiotherapy or autologous stem-cell transplant. While consolidation therapy continues to be commonly used, its role has become increasingly controversial.