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1.  Early lenalidomide treatment for low and intermediate‐1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence 
Cancer Medicine  2015;4(12):1789-1797.
Abstract
Lenalidomide is approved for the treatment of transfusion‐dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion‐independent (TI) del(5q) MDS. In the first, observational, part of this 2‐part study, we assessed the impact of transfusion dependence on overall survival (OS) and non‐leukemic death in untreated del(5q) MDS patients who were TD (n = 136), TI with hemoglobin (Hb) ≥10 mg/dL (n = 88), or TI with Hb <10 mg/dL (n = 96). In the second, interventional, part we assessed the quality‐of‐life (QoL) benefits and clinical efficacy of lenalidomide (10 mg/day) in 12 patients with TI del(5q) MDS and Hb <10 mg/dL. In the untreated population, OS was significantly longer in TI than in TD patients (TI [Hb ≥10 g/dL], 108 months; TI [Hb <10 g/dL], 77 months; TD, 44 months). Transfusion dependence also negatively impacted non‐leukemic death rates. In the interventional part of the study, baseline Hb levels were found to correlate significantly with physical (R = 0.666, P = 0.035) and fatigue (R = 0.604, P = 0.049) QoL scores. Median physical QoL scores improved significantly after 12 weeks' treatment with lenalidomide (+12.5; P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide.
doi:10.1002/cam4.523
PMCID: PMC5123712  PMID: 26376955
5q deletion syndrome; anemia; lenalidomide; myelodysplastic syndromes; quality of life
2.  Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia 
The Journal of Clinical Investigation  2015;125(5):1857-1872.
Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in genes encoding epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable, with few means to predict which patients will benefit. Here, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients who were responsive or resistant to decitabine (DAC) in order to develop a molecular means of predicting response at diagnosis. While somatic mutations did not differentiate responders from nonresponders, we identified 167 differentially methylated regions (DMRs) of DNA at baseline that distinguished responders from nonresponders using next-generation sequencing. These DMRs were primarily localized to nonpromoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. Transcriptional analysis revealed differences in gene expression at diagnosis between responders and nonresponders. In responders, the upregulated genes included those that are associated with the cell cycle, potentially contributing to effective DAC incorporation. Treatment with CXCL4 and CXCL7, which were overexpressed in nonresponders, blocked DAC effects in isolated normal CD34+ and primary CMML cells, suggesting that their upregulation contributes to primary DAC resistance.
doi:10.1172/JCI78752
PMCID: PMC4611703  PMID: 25822018
Genetics; Hematology; Immunology; Oncology; Therapeutics
3.  Valproic acid for the treatment of low-risk myelodysplastic syndromes: A case report and a review of the literature 
Leukemia Research Reports  2013;2(2):44-46.
Myelodysplastic syndromes are heterogeneous myeloid neoplasms ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukemia. Here we report a 51-year-old woman with depression and severe obesity who was diagnosed with an International Prognostic Scoring System low-risk myelodysplastic syndrome, presenting mainly with thrombocytopenia, treated with escalating dose of valproic acid as a single agent. After two years of treatment her platelet count is almost normal and the tolerance to therapy is good. It is already known that valproic acid could be used in high-risk myelodysplastic syndromes and acute myeloid leukemia, mainly in association with other drugs, but its role in low-risk myelodysplastic syndrome is not well established yet.
doi:10.1016/j.lrr.2013.03.003
PMCID: PMC3850370  PMID: 24371778
Low-risk myelodysplastic syndromes; Valproic acid
4.  Tailored Therapy in an Unselected Population of 91 Elderly Patients with DLBCL Prospectively Evaluated Using a Simplified CGA 
The Oncologist  2012;17(5):663-672.
Ninety-one elderly patients with diffuse large B-cell lymphoma were given tailored treatment based on the results of a comprehensive geriatric assessment. Treatment was feasible with encouraging outcomes.
Learning Objectives:
After completing this course, the reader will be able to: Demonstrate the proper use of a simplified comprehensive geriatric analysis, including activities of daily living (ADL), Mini-Mental State Evaluation (MMSE), Cumulative Illness Rating Scale–Geriatrics (CIRS-G), and geriatric syndromes (multidimensional geriatric assessment [MGA]).Maintaining a tailored anthracycline-based therapy, describe alternative treatment in elderly diffuse large B-cell lymphoma (DLBCL) patients unfit for the standard chemotherapy.
This article is available for continuing medical education credit at CME.TheOncologist.com
Background.
Elderly patients with diffuse large B-cell lymphoma (DLBCL) are a heterogeneous population; clinical trials have evaluated a minority of these patients.
Patients and Methods.
Ninety-one elderly patients with DLBCL received tailored treatment based on a comprehensive geriatric assessment (CGA). Three groups were identified: I, fit patients; II, patients with comorbidities; III, frail patients. Group I received 21-day cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21), group II received R-CHOP-21 with liposomal doxorubicin, and group III received 21-day cycles of reduced-dose CHOP. Fifty-four patients (59%) were allocated to group I, 22 (25%) were allocated to group II, and 15 (16%) were allocated to group III.
Results.
The complete response (CR) rates were 81.5% in group I, 64% in group II, and 60% in group III. With a median follow-up of 57 months, 42 patients are alive, with 41 in continuous CR: 31 patients (57%) in group I, seven patients (32%) in group II, and four patients (20%) in group III. The 5-year overall survival, event-free survival, and disease-free survival rates in all patients were 46%, 31%, and 41%, respectively. Multivariate analysis selected group I assignment as the main significant prognostic factor for outcome.
Conclusions.
This approach in an unselected population of elderly DLBCL patients shows that treatment tailored according to a CGA allows the evaluation of elderly patients who are currently excluded from clinical trials.
doi:10.1634/theoncologist.2011-0355
PMCID: PMC3360906  PMID: 22531362
Elderly patients; DLBCL; CGA; R-CHOP
5.  Quality of life and physicians' perception in myelodysplastic syndromes 
To detect factors associated with quality of life (QOL) of patients with myelodysplastic syndrome (MDS) and to compare the MDS patients’ self-assessed QOL with that perceived by their physicians. In an observational, non-interventional, prospective, multicentre study, QOL was evaluated in 148 patients with newly diagnosed low- and intermediate-risk IPSS MDS. QOL measures (QOL-E v.2, LASA and EQ-5D) and patient-related candidate determinants of QOL were assessed for up to 18 months. Patients' QOL scores were compared with those obtained by appointed hematologists’ assessment and with ECOG performance status (PS). Fatigue was not prevalent at diagnosis, though physical QOL and energy levels were low. Transfusion-dependent patients had worse QOL scores. In multivariate analysis, Hb levels and comorbidities were a major determinant of QOL. Physicians’ perception of patients’ well-being correlated with patients’ QOL. Physicians underestimated the impact of disturbances on patients’ QOL, mainly in the MDS-specific components. ECOG PS did not discriminate patients according to QOL status. In conclusion, the association of anemia with QOL is confirmed, while co-morbidities emerge as an independent predictor of QOL in MDS. Fatigue is not a major concern. ECOG PS is not a valuable surrogate of patient’s QOL, thus highlighting that physician’s judgment of patient’s well-being must not substitute patient-reported outcomes. Appropriate questionnaires should be used to assess MDS patients’ QOL in order to improve communication and therapeutic choice.
PMCID: PMC3384400  PMID: 22762033
Myelodysplastic syndromes; quality of life; comorbidities; anemia; transfusion-dependence; patient-reported outcomes

Results 1-5 (5)