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Publications (10)56.06 Total impact

  • Blood 01/2013; 122. · 9.78 Impact Factor
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    ABSTRACT: Background: The International Prognostic Index (IPS), based on the analysis of 5023 patients treated before 1992, remains the most widely accepted prognostic system for advanced Hodgkin lymphoma. Nevertheless, IPS needs to be verified in independent patient series homogeneously treated with anthracycline-based chemotherapy (mostly ABVD) with or without radiotherapy. Few validation studies have been published so far with conflicting results.Aims: To assess the applicability of IPS in a relatively large series of patients with advanced HL under treatment with ABVD or equivalent regimens.Methods: In this retrospective study, we analyzed an homogeneous series of 510 patients with advanced Hodgkin lymphoma (stage IIB / III / IV) who were diagnosed and treated with anthracycline-containing therapy in 3 participating hospitals. Complete data for all parameters of IPS were available in 416 patients (82%), while at least half of the remaining patients were suitable for pooled analysis of the IPS (<3 versus ≥ 3 or <2 versus ≥ 2). Endpoints of the study were freedom from progression (FFP) and overall survival (OS). Results: Among 510 patients, 149 (29%) had stage IIB, 212 (42%) stage III, and 149 (29%) stage IV. The frequency of adverse IPS factors were: age ≥ 45 years 30%, male gender 57%, stage IV 30%, Hb <10.5g/dl 26%, leukocytosis ≥15x109/L 24%, severe lymphocytopenia 16% and albumin <4g/dl 65%. Only 23/416 patients (6%) had ≥5 risk factors. At a median follow up time of 81 months (6-308), 153 patients had refractory disease or relapsed and 107 had died. The 5-year FFP was 70% and the 10-year OS 73%. Among individual IPS factors, only stage IV was significantly correlated with FFP (p=0.0001), while the significance of hypoalbuminemia was marginal (0.05<0.0001 and p=0.02, respectively). Overall, the IPS was a statistically significant predictor of OS (p=0.01) but not FFP (p=0.11), as shown in the table. Instead, the discriminating ability of IPS was significantly improved for both OS (p<0.0001) and FFP (p<0.0001), when 306 patients with stage IIA were incorporated in the analysis. Summary/Conclusions: In an adequately sized series of patients with truly advanced stage HL, the IPS predicted OS and -less satisfactorily- FFP, without identifying subgroups of patients with very good or very unfavorable prognosis. Other conventional, biological or functional imaging-related factors need to be co-evaluated in order to identify sizeable subgroups of patients with sufficiently poor or favorable outcomes, suitable for treatment intensification or de-escalation respectively.
    Haematologica 06/2012; 97(s1-97 (s1)):87. · 5.94 Impact Factor
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    ABSTRACT: Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.
    Leukemia & lymphoma 01/2012; 53(8):1481-7. · 2.61 Impact Factor
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    ABSTRACT: BACKGROUND Essential thrombocythaemia (ET) is the most frequent myeloproliferative disorder characterized by a long natural history. The identification of JAK2V617F mutation facilitates the diagnosis and probably defines two distinct disease subgroups. AIM Aim of the present study is to report the clinical and laboratory findings, the outcome, potential prognostic factors as well as the clinical importance of JAK2V617F mutation in patients with ET. METHODS 181 patients diagnosed with ET in a single center were retrospectively studied from 1998 to 2011.RESULTS The median age of our patients was 64 years (16-91), 72 were males and 109 females. At diagnosis 75% were asymptomatic, 17% presented either a thrombotic or a bleeding episode and 11% had splenomegaly. The JAK2V617F mutation was detected in 64/95 patients (67%). The median values of Ht, Hb, WBC and PLT were 42.6% (30.8-54.7), 13.9g/dL (9.5-17.3), 8.48 x 109/L (4.44-27.4) and 781 x 109/L (468-2288) respectively. LDH levels were elevated in 25%, while the median serum erythropoietin level was 10.2IU/mL. Bone marrow biopsy revealed the presence of typical megakaryocytes in clusters in 75%, while reticulin fibrosis was found in 29% with 8 cases showing grade 2 fibrosis. An abnormal karyotype was evident in 9%. The comparison between JAK2V617F(+) and JAK2V617F(-) patients showed that JAK2V617F(+) patients presented more frequently a major event at diagnosis (p=0.05), had statistically significantly higher values of Ht (median: 44.9% vs 39.9% p<0.001), Hb (median: 14.5g/dL vs 13.1g/dL p<0.001), lower platelet counts (median: 698x109/L vs 892x109/L and lower MCV (median: 84.5fl vs 88.2fl). Antiplatelet treatment was administrated in 78%. Cytotoxic therapy was given in 80%, while the remaining patients were put under observation. The median interval from diagnosis to the initiation of cytotoxic therapy was 0.8 months (0-115). First line treatment was hydroxyurea in 86%, anagrelide in 12% and interferon-a in 1%. Complete and partial response was achieved in 68% and 26% of the patients respectively, at a median time of 1.64 months. Change of treatment was required in 11%. At a median follow up of 40 months (1.1 – 207), 94% of the patients are alive with a 5- and 10-year overall survival (OS) of 96% and 87% respectively. Events were observed in 13 patients: 6 experienced a thrombotic episode, 5 progressed to myelofibrosis and 2 developed a second malignancy. Prognostic factor analysis revealed male gender (p=0.001) and WBC counts ≥10X109/L (p=0.001) as adverse factors for OS. Bone marrow fibrosis and the presence of an event at diagnosis were of marginal significance (p=0.09). Furthermore, Hb<12g/dl and PLT<600X109/L at diagnosis correlated with a statistically significantly increased risk for the development of a thrombotic event (p=0.002 καιp=0.006, respectively), while increased LDH at diagnosis correlated with increased risk for progression to myelofibrosis (p=0.04).CONCLUSION E.T is characterized by an extremely favorable prognosis. Patients with lower hemoglobin levels and lower platelet counts present thrombotic events more frequently, while males and patients with leukocytosis are characterized by an inferior overall survival. Finally JAK2V617F(+) patients differ from JAK2V617F(-) ones regarding their hematological profile and mimic polycythaemia vera patients.
    Haematologica 01/2012; 97(s1):633. · 5.94 Impact Factor
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    ABSTRACT: BACKGROUND Polycythaemia vera (PV) belongs to the bcr-abl negative group of myeloproliferative disorders. The introduction of the JAK2V617F mutation, has led to a clearer description of this entity. AIM Aim of the present study is to report the clinical and laboratory findings and the outcome of PV patients from a single center, as well as to evaluate the application of the new diagnostic criteria in everyday clinical practice. METHODS The WHO 2008 diagnostic criteria for PV were retrospectively applied in 61 patients diagnosed with PV between 1998 and 2011. Patients were distributed into 3 groups: Group I included patients who fulfilled both major criteria (increased Hb values for gender: Hb≥16.5g/dL in women and Hb≥18.5g/dL in men, or increased red cell mass and the presence of JAK2V617F mutation), group II included those who fulfilled the 1st major and two minor criteria (low/low-normal EPO levels and bone marrow biopsy consistent with PV). In this group JAK2V617F mutation was either unavailable or negative. Group III consisted of JAK2V617F(+) patients, who were diagnosed and treated as PV, but did not strictly fulfill the WHO 2008 criteria. RESULTS The median age of our patients was 64 years (29-91), 31 were males and 30 females. At diagnosis, 52% were asymptomatic, 21% had splenomegaly and 16% hepatomegaly. A major thrombotic or bleeding episode was reported at 30% with the most frequent being an arterial thrombosis/ischemia. JAK2V617F mutation was found in 36/38 patients (95%), median values of Ht, Hb, MCV, WBC and PLT were 53.8%, 17.3g/dL, 81.8fl, 9.050x109/L and 575x109/L respectively. LDH levels were elevated in 34%, while median serum erythropoietin levels were 6.65 IU/mL (0-28.4). Bone marrow biopsy revealed panmyelosis in 55%, fibrosis in 33% with grade 2 fibrosis in 3%, while 12% had an abnormal karyotype. First line treatment was hydroxyurea in 73%, while 24% were treated with phlebotomy only. Median time to the initiation of cytotoxic treatment was 0.9 months (0-77). Antiplatelet and anticoagulation treatment was administrated in 77% and 7% respectively. The overall response rate to cytotoxic therapy was 95% with 63% complete and 32% partial remission. Median time to response was 2.4 months. At a median follow up time of 38 months (0.9-162) 5 deaths were recorded, with a 5- and 10-year overall survival (OS) of 92% and 77% respectively. Age >65 years (p=0.029), increased LDH (p=0.026) and the presence of a thrombotic/bleeding event (p=0.048) at diagnosis were adverse prognostic factors for OS. The comparison of the 3 subgroups revealed statistically significant differences depicted in the table: Subgroup III consists of cases that cannot be objectively classified as PV or essential thrombocythaemia (ET) and might represent the pre-polycythaemic phase of PV. CONCLUSIONS Although the new diagnostic criteria of PV make the differential diagnosis between true PV and secondary erythrocytosis clear-cut, they cause difficulty in classifying patients between PV, ET and the pre-polycythaemic phase of PV. The biology of this disease subgroup is not known, while its clinical importance needs to be further elucidated.
    Haematologica 01/2012; 97(s1):639. · 5.94 Impact Factor
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    ABSTRACT: Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin's lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 HL patients diagnosed between 1990 and 2010, 2 cases of AIHA (0.19%) and 3 of AITP (0.29%) were identified at presentation of the disease. These patients were significantly older, had more frequently features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, 7 (0.7%) patients developed autoimmune cytopenias (3 AITP, 3 AIHA, 1 autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40% respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and diseaserelated profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not
    Leukemia and Lymphoma. 01/2012;
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    ABSTRACT: Background: Patients with HL who remain PET/CT(+) after ABVD combination chemotherapy have a relatively unfavorable prognosis. Prognostic factors for the outcome of PET/CT(+) patients, especially after additional radiotherapy, have not been systematically studied. However, such factors may have a role in decision making between additional RT vs. salvage chemotherapy and autologous stem cell transplantation (ASCT).Aims: We aimed to identify predictive factors for the outcome of HL patients who remain PET/CT(+) after ABVD chemotherapy and are planned to receive additional RT.Methods: 311 patients with HL were treated with 4-8 cycles of ABVD from December 2004 to early 2011: 245 responders (CR, CRu, PR) underwent PET/CT after ABVD; 38 responders did not due to technical reasons. There were missing data for 6 patients, 3 died prematurely and 19 rapidly developed progressive disease prior to PET/CT assessment. Among 245 responders, 52 (21%) were PET/CT(+) and were retrospectively analyzed in terms of disease progression.Results: Characteristics of the 52 PET/CT(+) patients were as follows: median age 31.5 years (15-73), 58% males, 77% nodular sclerosis, 27% stage III/IV, 19% B-symptoms, 10% ≥5 involved sites, 31% anemia, 18% significant leukocytosis, 10% severe lymphocytopenia, 56% ESR ≥50 mm/h, 31% elevated LDH, 39% albumin <4g/dL, 23% IPS≥3. The median SUVmax was 5.2 (IQR 3.7-8.5) without any correlation with the above parameters. The majority of patients were irradiated (42/52 or 81%; median dose 3620 cGy; range 2880-4600). Ten (10) patients were not irradiated (too extensive disease 2, rapid progression 1, medical decision 1, refusal 1, findings judged borderline by treating physician 5). After a median follow-up of 29 months (2-67), 22/52 patients have experienced disease progression. The median SUVmax was 6.7 versus 4.1 for patients with and without disease progression respectively (p=0.02). Progression free survival (PFS) was 73%, 63%, 51% and 46% at 1, 2, 3 and 4-5 years after PET/CT respectively. The 3-year PFS was 59% vs. 24% for patients with SUVmax < and ≥9 respectively (p=0.0005). Among other factors, only anemia significantly affected PFS in univariate analysis (p=0.01). In multivariate analysis, SUVmax ≥9 was the only independent prognostic factor for PFS (hazard ratio 3.1; 95% CI: 1.1-9.2; p=0.037) obscuring the significance of anemia (p=0.17). The significance of SUVmax ≥9 was maintained, if the analysis was restricted to the 42 irradiated patients (3-year PFS 69% vs. 30%, p=0.004). In 14 of the irradiated patients, a repeated PET/CT scan converted to negative: only 2/14 have relapsed for a 3-year PFS of 83%.Summary/Conclusions: Despite additional radiotherapy, patients with HL who remain PET/CT(+) after ABVD have a 50-60% risk of relapse over the next 4 years. Patients with lower SUVmax (optimal cut-off to be determined) may benefit more from additional radiotherapy, while more intense uptake was associated with an even higher risk of disease progression. These findings may facilitate the selection of optimal treatment in this patient subgroup with uncertain prognosis. The potential contribution of conventional prognostic parameters needs further investigation. Patients rendered PET/CT(-) after RT appear to be at lower risk of relapse.
    Haematologica 01/2012; 97(s1):562. · 5.94 Impact Factor
  • Blood 01/2012; 120. · 9.78 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2011; 26(4):824-6. · 10.16 Impact Factor
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    ABSTRACT: Background. Serum CRP levels are elevated in the majority of patients with HL at diagnosis; reflecting tumor burden and aggressive biologic behavior. Despite being an easily and frequently measured marker, data on its potential prognostic significance are extremely limited. Aim. To analyze the correlation between baseline CRP levels and clinical-labora¬tory findings and outcome of patients with HL treated with anthracy-cline-based chemotherapy with or without radiotherapy (RT). Patients and Methods. Baseline CRP levels were recorded in 496 patients with HL7 who were treated with anthracycline-based chemotherapy with or without radiotherapy (RT) in 2 Centers. Baseline CRP levels were cor¬related with other baseline clinical-laboratory features (Spearman corre¬lation coefficient or Mann-Whitney test), Failure Free Survival (FFS) and Overall Survival (OS) (Kaplan-Meier curves, log-rank comparison). Mul-tivariate FFS analysis was based on Cox's proportional hazards model. CRP levels s>5 mg/L were considered elevated. Results. The median value of CRP levels in the 496 evaluable patients was 21.10 mg/L; 27% and 73% had normal and elevated CRP levels respectively. Baseline CRP levels correlated with virtually all other parameters reflecting tumor burden or disease aggressiveness: There were strong correlations with advanced stages and B-symptoms (p<0.001) as well as specific extran-odal sites (bone marrow, lung, liver). Baseline CRP presented a very strong correlation with ESR (Spearman's rho 0.74, p<0.001), strong cor¬relations with haemoglobin (inverse), platelet counts and albumin (in¬verse) (S-rho 0.40-0.60, p<0.001) and looser correlations with white blood cell counts, serum LDH; and absolute lymphocyte counts (in¬verse) (S-rho <0.35, p<0.001). A trend towards a dose-response effect with FFS was observed: 5-year FFS for patients with CRP levels <5, 5-21.09, 21.1-69.99 and s=70 mg/L (roughly the CRP quartiles) was 81%, 78%, 68% and 66% (p=0.02). The difference was more pronounced for patients with normal versus elevated CRP levels (81% versus 71%, p=0.006). Differences in OS were not significant (p>0.10). The prog¬nostic impact of CRP on FFS was borderline in early stage patients (IA,IIA: 5-year FFS 83% versus 75% for normal versus elevated levels, p=0.09), but no difference was detected in advanced disease (68% versus 66%, p=0.48). CRP was an independent adverse prognostic factor for FFS, when adjusted for stage (III/IV versus I/II), B-symptoms and IPS factors (except of lymphocytopenia). However, baseline CRP was not analyzed along with ESR in the same model, because of their very strong correlation, raising issues of collinearity. Conclusions. CRP levels are elevated in -70% of HL patients at diagnosis and correlated with FFS independently from other established prognostic factors in¬cluded in the IPS. The very strong correlation between baseline CRP and ESR probably suggests that only one of them should be included in a given prognostic model. Even larger patient series should be analyzed in order to draw definite conclusions, but the final selection might be re¬lied on specific biologic and technical advantages of either marker.
    Haematologica 96(s2), 318, 2011. 01/2011; 96:318.