Excellent therapeutic results achieved in chronic myeloid leukemia patients with front-line imatinib and early treatment modifications in suboptimal responders: a retrospective study on 91 unselected patients.

Second generation tyrosine kinase-inhibitors (TKI) have been claimed to represent now the first-choice therapy for chronic myeloid leukemia (CML). Indeed, they generally induce faster and deeper molecular responses compared to imatinib that, however, is equally effective in at least 50% of patients. Moreover, some recent reports have questioned the long term safety of dasatinib and nilotinib. Therefore, upfront imatinib with early shift to second generation TKI for patients with slow/incomplete response might be as effective as front-line second generation TKI, with a possibly better safety profile. We retrospectively evaluated 91 chronic phase CML patients (median follow-up 57 months, median age 61 years), treated front-line with standard-dose imatinib and early therapy modifications (at 3-12 months) in case of unsatisfactory response or intolerance. Thirty-three patients (24 with unsatisfactory response, 9 intolerant) changed therapy, either by increasing imatinib dose (11/91) or by switching to second generation TKI (22 directly, 4 after high-dose imatinib). Globally, our strategy led to complete cytogenetic response (CCyR) in 98% of the patients, major molecular response (MMR) in 88% and molecular response 4 logs (MR(4.0) ) in 62%. Three patients in CCyR (3%), 2 of them in MMR too, suddenly progressed to blastic phase. At the last follow-up nine patients had died, seven of CML-unrelated causes and two only of CML progression. These results suggest that our strategy could be as effective as front line second generation TKI, with most of patients still receiving imatinib, a drug of better known long-term side effects and lower cost.

Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL).

We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma (DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.

Derivative (1)t(1;16)(p11;p11.1) in myelodysplastic syndrome: a case report and review of the literature.

We report on the occurrence of an unbalanced translocation between chromosomes 1 and 16 as a single abnormality in an 81-year-old patient with myelodysplastic syndrome (MDS) diagnosed as refractory cytopenia with multilineage dysplasia. The derivative chromosome, causing trisomy 1q and monosomy 16q, was described on the basis of fluorescent in situ hybridization results as der(1)t(1;16)(p11;p11.1). Review of the literature showed that the der(1)t(1;16) is a rare but nonrandom abnormality in MDS, being reported to date in an additional seven MDS cases. Notably, all MDS patients carrying t(1;16) described to date are men, suggesting a putative association of this translocation with male gender in the context of MDS. The unbalanced nature of the t(1;16)(p11;p11.1) indicates that gain of 1q and/or loss of 16q might be relevant for neoplastic transformation in a subset of MDS patients.

Beta-2-microglobulin is an independent predictor of progression in asymptomatic multiple myeloma.

BACKGROUND: Although serum beta-2 microglobulin (B2M) represents a key variable for symptomatic multiple myeloma (MM) prognostication, its role in predicting the risk of progression of asymptomatic MM to symptomatic disease has not been explored. METHODS: This study was bases on a consecutive series of 148 patients with asymptomatic MM and explored the cumulative probability of progression to symptomatic MM as the primary endpoint. RESULTS: In univariate analysis, a serum B2M level >2.5 mg/L was associated with an increased probability of disease progression (5-year risk, 64.5%; P < .001) along with serum monoclonal component (sMC) (P < .001), urinary monoclonal component (uMC) (P < .001), and bone marrow plasma cells (BMPCs) (P < .001). In multivariate analysis, serum B2M was selected as an independent predictor of progression (hazard ratio, 3.30; P = .002). Serum B2M was combined with sMC, uMC, and BMPC to create a risk-stratification model based on 4 groups with different risk of progression: very low (5-year risk, 0%), low-intermediate (5-year risk, 19.6%), high-intermediate (5-year risk, 60.7%), and high (5-year risk, 80.7%). The model that included serum B2M along with sMC, uMC, and BMPC was able to predict disease progression better than the model that was based on sMC, uMC, and BMPC without serum B2M (C statistics, 0.760 vs 0.726). CONCLUSIONS: The current results indicated that 1) serum B2M is an independent predictor of asymptomatic MM progression, and 2) serum B2M adds prognostic information when combined with the most widely used prognosticators of asymptomatic MM progression.