Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine.

The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.

Standardization of 18F-FDG-PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma.

PURPOSE: 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS: Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS: At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively). CONCLUSION: FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.

Expression of the glucocorticoid receptor and its isoforms in relation to glucocorticoid resistance in childhood acute lymphocytic leukemia.

In vitro prednisolone resistance is a poor prognostic factor in the treatment of childhood acute lymphoblastic leukemia (ALL). In a cohort of 54 children with ALL, a lower expression of the glucocorticoid receptor (GR), but not the relative expression levels of the GR-alpha, GR-beta and GR-P isoforms, was associated with in vitro prednisolone resistance.

Disease control in patients with relapsed and/or refractory multiple myeloma: what is the optimal duration of therapy?

Novel agents such as thalidomide, bortezomib, and lenalidomide have improved outcomes and extended survival in patients with relapsed and/or refractory multiple myeloma (RRMM). These agents appear to be most effective when used at first relapse rather than later in the treatment sequence; however, the optimal duration of therapy has not been defined. Continuous therapy from relapse to disease progression may be able to maintain suppression of residual disease, thereby extending overall survival. This article reviews the currently available data on treatments, including novel agents for patients with RRMM, focusing on the duration of therapy required to improve clinical outcomes.

Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma.

The prompt response to bortezomib observed in a 63-year-old woman with multiple myeloma was associated with a significant increase in alkaline phosphatase (ALP). After similar elevations were noted in patients responding to bortezomib, thalidomide, dexamethasone combination, ALP levels were analysed in two large bortezomib trials. A statistically significant elevation of ALP from baseline was observed in responding patients (complete and partial responders) within three cycles of therapy. The rise in ALP after bortezomib in three patients was explained by a parallel increase in bone-specific ALP and parathyroid hormone, suggesting that response to bortezomib in myeloma is closely associated with osteoblastic activation.