0000000000025678
AUTHOR
Stefano Molica
Differentiation on Biological Basis of Monoclonal B-Cell Lymphocytosis (MBL) From Chronic Lymphocytic Leukemia (CLL): Results of a Prospective GISL (Gruppo Italiano Studio Linfomi) Trial
Abstract Abstract 1360 The arbitrary cut-off of 5000/μL chronic lymphocytic leukemia (CLL)-phenotype cells in peripheral blood is generally used to separate monoclonal B-cell lymphocytosis (MBL) from CLL. However, a major concern is the biological differentiation, if any, between MBL and CLL. We tried to address the issue therefore analyzing 261 Rai stage 0 patients enrolled in a Gruppo Italiano Studio Linfomi (GISL) prospective multicentre trial designed to validate biological parameters in early CLL as well as to assess the impact on clinical outcome of an early versus delayed policy of treatment with subcutaneous alemtuzumab in the high biological risk. In this cohort, biological charact…
High BCR-ABL/GUS(IS) levels at diagnosis of chronic phase CML are associated with unfavorable responses to standard-dose imatinib
Abstract Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses. Experimental Design: We correlated BCR–ABL/GUSIS and BCR–ABL/ABL transcripts at diagnosis with the outcome—defined by the 2013 European LeukemiaNet recommendations—of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR–ABL/GUSIS and BCR–ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transform…
Microenvironment Regulation of IL23R/IL-23 Axis Drives Chronic Lymphocytic Leukemia (CLL) Progression
Abstract Background : CLL displays a considerable degree of clinical heterogeneity, which is in part ascribable to clone-intrinsic biological features and that are also influenced by clone-extrinsic events related to the microenvironment. Among the dynamics-taking place within the CLL microenvironment, those finalized to the induction of an overly inflammatory milieu may significantly impact on the CLL natural history by hijacking the immunological microenvironment at the same time fostering clone fitness. IL-23 acts as a prototypical pro-inflammatory mediator representing a promising therapeutic target. We analyzed the ability of CLL cells to sense IL-23 through the IL-23R complex (consist…
Differences among young adults, adults and elderly chronic myeloid leukemia patients
Abstract BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old)…
Response-guided ABVD chemotherapy plus involved-field radiation therapy for intermediate-stage Hodgkin lymphoma in the pre-positron emission tomography era: a Gruppo Italiano Studio Linfomi (GISL) prospective trial.
Abstract Purpose In the pre—positron emission tomography era, the Gruppo Italiano Studio Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients. Patients and Methods Patients with stage I/II showing at least one adverse prognostic factor and stage IIIA without adverse prognostic factors were recruited. Treatment included a first step of 3 ABVD courses, followed by an early-restaging. Patients in CR/CRu received 1 additional ABVD cycle, patients in PR received 3 more ABVD, and nonresponder patients went off study. Involved-fi…
The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.
AbstractIdentification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated …
The Pro-Inflammatory IL23/IL23R/IL17 Axis Is Active in IL23R-Expressing Circulating CLL Cells in Patients with Poor Prognosis
Abstract Abstract 3889 Inflammatory cytokines play a biological role in the pathogenesis of Chronic lymphocytic leukemia (CLL). IL23 is a pro-inflammatory cytokine involved in T-cell responses and in tissue remodeling. It has been shown that the IL23 receptor (IL23R) is up-regulated in primary acute lymphoblastic leukemia (ALL) cells, and that IL23 inhibits ALL cell growth. Nevertheless, the anti-tumor function of IL23 still remains controversial. The role of the IL23R/IL23 axis in CLL has not been investigated so far. Herein we evaluated the expression pattern of IL23R/IL23 axis and its correlation with progression free survival (PFS) in CLL patients. A total of 233 newly diagnosed Binet s…
Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma
BACKGROUND. The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS. One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EFRT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp sched…
Irinotecan (CPT-11) and Mitomycin-C (MMC) as Second-Line Therapy in Advanced Gastric Cancer
Objective The aim of this study was to evaluate the activity and toxicity of a combination regimen of CPT-11 and mitomycin-c as second-line chemotherapy for pretreated patients with advanced, metastatic, or both, gastric adenocarcinoma. Materials and methods Patients with pretreated metastatic disease or early relapsed after adjuvant chemotherapy were enrolled. Entry criteria included histologic/cytologic diagnosis of gastric adenocarcinoma, age 18 to 75 years, performance status > or =70 (Karnofsky scale), bi-dimensionally measurable disease. Patients received CPT-11 and mitomycin-c at the dosage of 150 mg/m2 on days 1 and 15, and 8 mg/m2 on day 1, respectively, every 4 weeks. The disease …
Flow Cytometric Immunobead Assay for Detection of BCR-ABL1 Fusion Proteins in Chronic Myleoid Leukemia: Comparison with FISH and PCR Techniques
Chronic Myeloid Leukemia (CML) is characterized by a balanced translocation juxtaposing the Abelson (ABL) and breakpoint cluster region (BCR) genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response. Currently, measurement of BCR-ABL1 mRNA transcript levels by real-time quantitative PCR (RQ-PCR) defines critical response endpoints. An antibody-based technique for BCR-ABL1 protein recognition could be an attractive alternative to RQ-PCR. To date, there have been no studies evaluating whether flow-cytometr…