Paola Finsinger

MDS-specific comorbidity index is useful to identify myelodysplastic patients who can have better outcome with 5-azacitidine

Recently Della Porta and colleagues[1][1] reported on the importance of evaluation of comorbidities at baseline in myelodysplastic syndrome patients (MDS) in order to better tailor treatment strategies according to WPSS stratification. They proposed a prognostic score, the so-called MDS-CI, which

Clinical features and prognostic factors in solitary plasmacytoma

This study aimed to review the clinical features and outcome of 53 patients with solitary plasmacytoma managed at our Institution between 1976 and 2012. Thirty‐five patients had bone solitary plasmacytoma and 18 extramedullary solitary plasmacytoma. Tumour sizes were larger in patients with bone involvement (P = 0·003). Treatment consisted of local radiotherapy (n = 26), radiotherapy + chemotherapy (n = 15), surgery (n = 4) and chemotherapy (n = 8); the local control rate was 94·3%. Progression to multiple myeloma was recorded in 20/35 (57·1%) patients with bone involvement and in 1/18 (5·5%) patients with extramedullary disease (P = 0·0003). The 5‐year overall survival (OS) rate was 78·4%; bone solitary plasmacytoma patients had a significantly worse OS (71·9% vs. 88·2%, respectively; P = 0·029) and 5‐year progression‐free survival (PFS; 53·0% vs. 88·5%; P = 0·0003) compared to extramedullary solitary plasmacytoma patients. On univariate analysis, bone disease and size (≥5 cm) impacted negatively on PFS (P = 0·0027 and P = 0·04, respectively). Bone disease also affected OS (P = 0·04). In multivariate analysis bone location was the only independent prognostic factor for PFS (P = 0·0041) and OS (P = 0·021). Patients with bone solitary plasmacytoma have a significantly worse prognosis than extramedullary solitary plasmacytoma cases.

Subcutaneous bortezomib for multiple myeloma treatment: patients’ benefits

The use of novel agents such as thalidomide, lenalidomide, and bortezomib has considerably improved the outcome of multiple myeloma patients. Besides greater biological activity, these drugs unfortunately have also been associated with greater toxicity. To evaluate the positive effect on the quality of life of patients, driven by both the tolerability and antimyeloma activity of bortezomib, we analyzed data that have been published concerning different strategies used to improve its tolerability as once weekly and/or subcutaneous administration.

Prognostic features of patients with myelodysplastic syndromes aged < 50 years: update of a single-institution experience

Abstract Fewer than 10% of patients with myelodysplastic syndromes (MDS) are younger than 50 years. A series of 91 younger patients (median age 44 years with female prevalence) are reported and compared with elderly patients. Frequent karyotypic changes were trisomy 8 (9.8%) and monosomy 7 (5%). Twenty-three patients had occupational exposure to potential mutagens (benzene and solvents), with a male predominance, higher frequency of refractory cytopenia with multilineage dysplasia (RCMD) (52%) and higher frequency of monosomy 7 (21.7%). At a median follow-up of 72 months, 22 patients (24%) evolved to acute leukemia, with higher frequency being observed among the exposed cohort (39% vs. 19% non-exposed). Unfavorable factors for overall survival were: age > 40 years, > 5% of blasts, trilinear bone marrow involvement and intermediate–high World Health Organization Prognostic Scoring System (WPSS) risk. The present results suggest that younger MDS could be identified as a distinct subset. For patients belonging to the low/intermediate-I risk group, due to a low transformation rate, aggressive approaches should rarely be recommended.

Complete Clearance of Ph+ Metaphases after 3 Months Is a Very Early Indicator of Good Response to Imatinib as Front-Line Treatment in Chronic Myelogenous Leukemia

Aim: To address the incidence and the prognostic role of a very early standard complete cytogenetic response (CCyR) or all Ph– metaphases (MET–, when <20 cells were evaluable). Methods: We revised 182 chronic phase chronic myelogenous leukemia patients treated with frontline imatinib (IM) at two institutions from June 2002 to June 2011. Results: After 3 months of treatment, 138 patients (75.8%) achieved CCyR/MET– while 44 patients (24.2%) still presented Ph+ metaphases (MET+) (<33%, 24 patients; ≥33%, 20 patients). On univariate analysis, palpable spleen enlargement (p < 0.001), WBC count >100.0 × 109/l at onset (p < 0.001), and male gender (p = 0.019) had a negative impact on achievement of CCyR/MET– at 3 months. Among patients with CCyR/MET– after 3 months, there were 15 failures (10.8%) compared to 21 (47.7%) among patients with MET+ (p < 0.001). The 5-year overall survival was 97.0% in patients CCyR/MET– at 3 months and 91.8% in patients MET+ at 3 months (p = 0.277); the 5-year progression-free survival was 88.2% in patients CCyR/MET– at 3 months and 48.4% in patients MET+ at 3 months (p < 0.001). Conclusions: The achievement of CCyR/MET– at 3 months seems to have prognostic relevance and could be a very early and useful indicator of an excellent response to IM beyond European LeukemiaNet guidelines.

Lenalidomide for myelodysplastic syndromes with del(5q): how long should it last?

Lenalidomide induces in patients with myelodysplastic syndrome (MDS) and del(5q) erythroid and cytogenetic response rates as high as 75% and 50%, respectively. It is still unclear, however, how long lenalidomide treatment should be continued and whether or not the drug could be interrupted. To assess the feasibility of lenalidomide discontinuation, we revised a cohort of 16 low‐risk MDS patients with del(5q) treated at our institute in a phase II multicentric Italian study. Among the 12 responding patients, four discontinued lenalidomide while in complete response. All four patients needed during treatment a permanent lenalidomide reduction from 10 to 5 mg/day because of haematological toxicity (three patients) or grade 3 muscular and bone pain (one patient). At lenalidomide discontinuation after 16, 20, 27 and 20 months from the start, respectively, all four patients were in complete hematologic response and three forth in complete cytogenetic response. Three patients are still in response after 36, 30 and 20 months from lenalidomide discontinuation, respectively: The remaining patient relapsed after 20 months, and she is now receiving a new course of lenalidomide. In conclusion, long‐lasting remissions are achievable in MDS patients with del(5q) in complete response after lenalidomide discontinuation. Copyright

Incidence of persistent/late chronic anemia in newly diagnosed patients with chronic myeloid leukemia responsive to imatinib

In patients with chronic myeloid leukemia (CML) responsive to imatinib, it is still unknown whether the long‐lasting treatment could induce the appearance of a persistent/late chronic anemia. To highlight this issue, we revised 128 patients with CML (M/F 64/64, median age at diagnosis 56.9 years, interquartile range 43.0–69.3) treated at our Institution with 1st line imatinib for at least 36 months and in stable complete cytogenetic response. At the 36th month of imatinib, a chronic anemia (Hb < 12 g/dl for > 6 months) was present in 38/128 patients (29.6%): the anemia was moderate (Hb > 8 ≤ 10 g/dl) in 12 patients (9.3%) and mild (Hb > 10 < 12 g/dl) in 26 patients (20.3%). All patients with persistent/late chronic anemia had a low reticulocyte count and 8/38 a condition of iron deficiency without clinical and instrumental signs of chronic blood loss. Four out of 38 patients (10.5%) needed red cell transfusions during the follow‐up. At a landmark analysis from the 36th month of imatinib treatment, cumulative 4‐year overall survival (OS) for patients with chronic anemia was 94.4% (CI 95% 83.8–100) compared to 93.5% (CI 95% 87.2–99.8) for patients without chronic anemia (P = 0.617). In conclusion, the occurrence of a late chronic anemia during long‐lasting treatment with imatinib has been observed in about 30% of our responsive patients: its occurrence does not seem to affect OS, but its real impact should be evaluated on a larger cohort of patients. Am. J. Hematol. 90:105–108, 2015.

The degree of anemia has an impact on survival in myelodysplastic syndrome patients classified with WPSS

Recently, Malcovati and colleagues[1][1] integrated the degree of anemia into WPSS stratification and found that this refined model (rWPSS) is able to identify five risk groups of myelodysplastic syndrome (MDS) patients with different overall survival (OS). The new score was tested in a German

Bendamustine and dexamethasone are an effective salvage regimen for patients with advanced multiple myeloma in a Home Care Unit program

Increasing evidence from clinical studies demonstrates the efficacy of bendamustine as first-line treatment of multiple myeloma (MM) patients [1], as well as in heavily pre-treated relapsed/refractory patients. The combination of bendamustine with novel agents [bortezomib, immunomodulatory drugs (IMiDs)] has been investigated in patients who have exhausted other treatment options, showing an anti-tumoral efficacy and a favorable toxicity profile [2–6]. The unique mechanism of action of bendamustine, a bifunctional molecule with alkylator and antimetabolite properties which lacks cross-reactivity with many other cancer drugs, may constitute the basis for the efficacy of this drug in the setting of resistance to other alkylators, including melphalan [7]. Data are scarcer regarding the use of bendamustine in patients exposed to novel agents. A dose of 60 mg/m of bendamustine was employed in a British compassionate program in combination with thalidomide and dexamethasone to treat a cohort of high risk relapsed/ refractory MM patients with prior exposure to bortezomib and lenalidomide, obtaining a clinical benefit (stable disease or better) in 61% of patients. Overall, grade 3/4 hematological toxicity was observed in 39% of cases and seven patients (30%) required hospitalization for infection [8]. A Home Care Unit program, including a team composed of hematologists, nurses, psychologists and social workers, was instituted in 1993 at our Department of Cellular Biotechnologies and Hematology, ‘‘Sapienza’’ University of Rome (Italy), to provide adequate care and ensure quality of life to patients with advanced hematological malignancies in a domiciliary setting [9]. In this single arm study, we assessed the activity and safety of bendamustine and dexamethasone in a cohort of heavily pre-treated relapsed/refractory MM patients in the context of our Home Care Unit program. The study had the prior approval of our Ethics Committee. Between May 2012 and March 2013, eight relapsed/ refractory frail MM patients were treated with bendamustine (60 mg/m; days 1, 8, 15) and dexamethasone (20 mg; days 1, 8, 15, 22) for up to nine 28-day cycles. Based on the frailty of our patients’ population, we chose to employ the schedule described by Grey-Davies and colleagues [8] avoiding the use of thalidomide. All patients were followed by our Home Care Unit in view of the advanced stage of the disease and of the patients’ inability to attend our day hospital unit. Patients had received a median of 4 (range 2–6) previous lines of therapy including alkylating and new drugs. Twenty-five percent of patients had been previously treated with thalidomide, all of them had prior exposure to lenalidomide and bortezomib. One patient received an autologous stem cell transplant (ASCT) as first line treatment, followed by a second ASCT as salvage treatment and a sibling allogenic transplantation. None of the other patients underwent transplantation, because of their advanced age. Six patients (75%) were refractory to bortezomib and five (62.5%) to lenalidomide, four (50%) were double refractory. The patients’ demographics and disease characteristics are summarized in Table I. Main pre-treatment characteristics were: median age 76 years (range 53–83), median time from diagnosis 82.1 months (range 14.2– 255.6), Eastern Cooperative Oncology Group (ECOG) performance status 2–3. All patients had bone lytic

Erythropoietin treatment in patients with myelodysplastic syndromes and type 2 diabetes 促红细胞生成素治疗骨髓增生异常综合征合并2型糖尿病的患者

The aim of the present study was to assess the role of a concomitant type 2 diabetes as a potentially negative factor in the management of low‐risk myelodysplastic syndrome (MDS) patients treated with high‐dose (40 000 UI s.c. 2 times/week) recombinant human erythropoietin (EPO) alpha (rHuEPO alpha).