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Publications (18)62.27 Total impact

  • Leukemia & lymphoma 02/2014; · 2.61 Impact Factor
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    ABSTRACT: A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in ∼40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereasIL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients.
    BioMed Research International 01/2014; 2014:251479. · 2.88 Impact Factor
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    ABSTRACT: ABSTRACT We have analyzed the immunohistochemical expression of a wide range of molecules, along with the proliferation rate separately in the proliferation centers (PCs) and in the rest of tumor area on lymph node or spleen sections of CLL patients. Fas, FasL and c-FLIP were observed both within and outside the PCs in all cases. However only the difference in FasL expression between the PCs and the non-PC areas attained statistical significance. Median survivin expression in the PCs was higher compared to the non-PC areas. Cleaved-caspase 3 was expressed in very low levels both within and outside PCs while the BCL-2 protein was expressed in high levels in all cases in both tumor compartments. Multivariate analysis demonstrated that concurrent overexpression of Fas/FasL/c-FLIP in the PCs was correlated with worse outcome for progression free survival as well as for overall survival.
    Leukemia & lymphoma 05/2013; · 2.61 Impact Factor
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    ABSTRACT: Background. Treatment of splenic marginal zone lymphoma (SMZL) patients is not standardized. Recent data suggest that rituximab is highly effective and could be considered as initial therapy.Aim. To assess the efficacy of rituximab monotherapy in a large series of patients with SMZL and compare these results with splenectomy results.Methods. The studied population included 85 patients. Fifty-eight received rituximab at a dose of 375 mg/m(2) per week for 6 weeks as induction followed by maintenance at the same dose every 2 months for 1-2 years, whereas 27 patients were treated using splenectomy only.Results. The overall response rate to rituximab 2 months after the end of induction was 95% (complete response [CR], 45%; unconfirmed CR, 26%; partial response, 24%). The median times to hematologic and clinical response were 2 weeks and 3 weeks, respectively. Forty-three of 55 patients already completed the maintenance phase: 28 sustained their initial response, 14 improved their response, and one progressed. Eighty-five percent of splenectomized patients responded, and two were treated with rituximab as consolidation after splenectomy and achieved a CR. The 5-year overall and progression-free survival (PFS) rates for rituximab-treated and splenectomized patients were 92% and 77% (p = .09) and 73% and 58% (p = .06), respectively. Furthermore, maintenance therapy with rituximab resulted in a longer duration of response (at 5 years, PFS was 84% for patients receiving maintenance and 36% for patients without maintenance, p <.0001).Conclusions. Rituximab is a very effective and well-tolerated therapy and may be substituted for splenectomy as the first-line treatment of choice for patients with SMZL.
    The Oncologist 01/2013; · 4.10 Impact Factor
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    ABSTRACT: Data concerning angiogenesis in chronic lymphocytic leukaemia (CLL) indicate that CLL patients are characterized by various abnormalities in the angiogenic profile including increased microvessel density in lymph nodes and in bone marrow and increased levels of certain pro-angiogenic vascular growth factors. Vascular endothelial growth factor (VEGF) and its receptors, basic fibrobast growth factor (bFGF) and matrix metalloproteinases(MMPs) were found to be highly expressed in CLL patients while there was no difference in angiogenin expression between CLL patients and healthy individuals. VEGF is implicated in CLL pathogenesis through various mechanisms. Enhanced angiogenesis in CLL has been associated in several reports with disease characteristics and patients’ survival. Various anti-angiogenic agents targeting angiogenesis related pathways such as immunomodulatory drugs and receptor tyrosine kinase inhibitors have already been entered in clinical trials. Among them lenalidomide is the most promising antiangiogenic drug showing a significant efficacy in relapsed/refractory CLL patients.
    Current Angiogenesis. 01/2013; 2(2).
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    ABSTRACT: Background: Chemosensitivity prior to ASCT is a powerful prognostic factor for outcome in HL. The prognostic significance of PET/CT in the ASCT setting has not been firmly established yet. Patients/Methods: CT and PET/CT were performed pre- and 3 months post-ASCT. Pts with residual FDG-avid lesions and SUVmax<4 were considered as minimal residual uptake positive (MRUp). Results: Among 68 evaluable pts, 47% were treated for primary refractory disease, 41% at and 12% beyond first relapse; 75% had chemosensitive disease prior to ASCT. A PET/CT was available pre-ASCT in 55 pts, post-ASCT in 62 and at both time points in 53. Pre-ASCT PET/CT was positive/MRUp in 24/45 chemosensitive vs 10/10 chemoresistant pts (p=0.02). At a median follow-up of 30 mo, 2-year failure free survival (FFS) was 85% vs. 48% (p=0.005) in 21 pre-ASCT PET/CT-neg and 34 PET/CT-pos/MRUp pts. Chemosensitivity remained significant (2-year FFS 71% vs. 24%, p=0.0001) and could further stratify pre-ASCT PET-pos patients: 2-year FFS was 85% for chemosensitive PET-neg vs. 56% for chemosensitive PET-pos and 30% for chemoresistant PET-pos pts (p=0.002). Post-ASCT PET scan had the strongest predictive value for outcome: 2-y FFS was 91% for post-ASCT PET-neg/MRUp vs. 12% for PET-pos pts (p< 0.0001). Patients renderd PET-neg/MRUp post ASCT had excellent outcomes irrespectively of pre-ASCT PET/CT results (2-year FFS 86-93%). Conclusions: Pre-ASCT PET/CT positivity does not preclude a favorable outcome in relapsed/refractory HL pts undergoing HDT/ASCT. Particularly pts who ultimately achieve PET-negativity post-ASCT have an excellent outcome. Conventional Chemosensitivity is still a major determinant of the outcome.
    4th International Workshop on PET in Lymphoma, Menton 2012; 10/2012
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    ABSTRACT: Introduction: Although baseline PET/CT (bPET/CT) is recommended, it is not considered mandatory for the initial staging of HL. Furthermore, the role of bPET/CT on first-line treatment decisions is not clear. Patients/Methods: 67 HL pts, selected solely based on the availability of bPET/CT, were evaluated by conventional and PET-based methods. Results: Pts' characteristics: median age 33 yrs; 60% males; 8,25,17 and 17 pts with clinical stage (CS) I,II,III,IV; median number of involved sites (NIS) 1, 2(1-5), 5(2-14), 7(4-11) for CS I,II,III,IV. Based on PET/CT, the corresponding figures were 2(1-5), 3(2-9), 7(2-14) and 11(5-14). CS or PET/CT-based NIS were highly correlated (Spearman's rho 0.80). PET/CT resulted to stage shift in 20 pts (30%; 17 upstaged and 3 downstaged). Similarly, PET/CT revealed higher NIS than CS in 50 pts (67%). Among 20 pts with potential stage shift, major treatment modifications could have been justified in 16 (24% of the total). However, in only 7/16 a different therapeutic strategy was actually applied due to PET/CT findings. Among 33 CSI/II pts, 21 (64%) actually received wider RT field, based on PET/CT-identification of more involved sites. Regarding bone marrow (BM) findings, 43 pts had no evidence of bone/BM uptake (all had negative BM biopsies), 11 had diffuse BM uptake (2 or 18% had positive BM biopsy), and 13 had multifocal bone/BM uptake (5 or 38% had positive BM biopsy). Conclusions: PET/CT can identify a higher NIS in the majority of HL pts, with a 30% stage shift rate. The variable use of PET/CT for the initial HL staging and its heterogenous effect on treatment decisions may render comparisons of retrospective series difficult.
    4th International Workshop on PET in Lymphoma, Menton 2012; 10/2012
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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: Background: Patients with HL who become PET/CT(-) after ABVD chemotherapy are expected to have a very favorable prognosis. Nevertheless, it is known that relapse risk persists for prolonged time periods. Prognostic factors determining the outcome of PET/CT(-) patients have not been adequately studied, although they may be very important for patient monitoring and counseling. Aims: The aim of this study was to identify relevant prognostic factors in this specific subgroup of HL patients. Methods: 341 patients with HL were treated with 4-8 ABVD cycles from December 2004 to mid 2011. 268 responders (CR, CRu, PR) underwent PET/CT after ABVD, while 40 did not due to technical reasons. There were missing data for 8 patients, 4 died prematurely and 21 rapidly developed progressive disease before PET/CT. Among the 268 responders who were evaluated by PET/CT, 212 patients became PET/CT(-) after ABVD, forming the patient population of the present study. Results: The median age of 212 PET/CT(-) patients was 29.5 years (15-78), 51% were males, 98% had classical HL, 26% had stage III/IV, 30% had B-symptoms, 21% had ≥5 involved sites, 37% had anemia, 15% significant leukocytosis, 9% severe lymphocytopenia, 48% had ESR ≥50 mm/h, 54% albumin <4g/dL, 20% elevated LDH and 25% high IPS (≥3). Eleven patients relapsed and 1 died in 1st CR. The median follow-up (after PET/CT) for the remaining 201 patients was 34 months (1-80). 96% of stage I/II patients received additional radiotherapy (median 3000 cGy). In contrast, 88% of advanced stage patients were not irradiated. Relapse free survival (RFS) was 98%, 96%, 94% and 92% at 1, 2, 3 and 4-6 years after the negative PET/CT scan respectively. Among the above potential predictive factors, univariate analysis demonstrated that an inferior RFS was predicted by advanced stage (3-year RFS 98% vs. 83% for stages I/II vs. III/IV, p=0.0002) and involvement of ≥5 sites (97% vs. 84%, p=0.02). Especially for the 19 stage IV PET/CT(-) patients, the 3-year RFS was only 72% vs. 89% for the 35 stage III patients. In multivariate analysis only stage III/IV was an independent prognostic factor for RFS (hazard ratio 8.8, p=0.006). At least 2/3 relapses in stages I/II and 1/8 in stages III/IV were detectable by clinical examination only; 1/8 advanced stage patients relapsed in a previously bulky site, which could have been irradiated. Summary/Conclusions: Patients with HL achieving a negative PET/CT after ABVD, have an approximately 8% cumulative risk of relapse during the subsequent 5 years. A negative PET/CT after 4-6 cycles of ABVD predicts an excellent short/mid-term outcome in patients with stages I/II, who are typically irradiated. On the contrary, stage III/IV patients rendered PET/CT(-) after 6-8 cycles of ABVD, who are not usually irradiated, still remain in a considerable risk of relapse approaching 20% within the initial 3 years. Therefore, although stage III/IV PET/CT(-) patients may require regular monitoring with imaging studies, this can probably be avoided in stage I/II PET/CT(-) patients who have received radiotherapy, in order to minimize further exposure to radiation and save health care costs.
    Haematologica 01/2012; 97(s1):87-88. · 5.94 Impact Factor
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    ABSTRACT: Background: ASCT is the standard approach for relapsed/refractory HL patients. Chemosensitivity prior to ASCT is a powerful prognostic factor for outcome; the predictive significance of PET scan in the ASCT setting has not been firmly established yet. Aim: To further update our previous results (presented in EBMT 2010) with respect to the prognostic significance of PET scan before and after HDT/ASCT in a series of 68 patients with relapsed/refractory HL from a single Transplant Unit.Methods: Computed tomography and PET scan were performed just prior to ASCT and at 3 months post transplant. Findings were correlated with failure free survival (FFS). PET scan was considered negative, when no uptake was present, positive, when any lesion was FDG-avid with SUV ≥4 and minimal residual uptake positive (MRUp), when any lesion showed abnormal uptake with SUV<4. MRUp cases were analyzed as positive pre-ASCT and as negative post-ASCT. Patients achieving a complete or partial remission prior to ASCT as assessed by conventional methods were considered chemosensitive. Results: Among 68 patients included in the study, 47% were treated for primary refractory disease, 41% at first relapse and 12% beyond first relapse. All patients received salvage chemotherapy and 75% had chemosensitive disease prior to ASCT. A PET-scan was available pre-ASCT in 55 patients, post ASCT in 62 and at both time points in 53. Pre-ASCT PET scan was positive or MRUp in 24/45 chemosensitive patients vs 10/10 chemoresistant ones (p=0.02). There was no chemoresistant patient with a negative PET-scan. Pre-ASCT PET-scan was of prognostic significance for outcome: 3/21 patients with a negative pre-ASCT scan relapsed vs 17/34 with a positive or MRUp one, resulting in a 2-year FFS of 85% and 48% respectively (p=0.005), Thus almost 50% of pre-ASCT PET(+) patients did not relapse at a median follow-up of 30 months (4-93), while a plateau was reached at 15 months post-transplant. Chemosensitivity remained significant as expected: 2-year FFS was 71% and 24% for chemosensitive and chemoresistant patients respectively (p=0.0001) Chemosensitivity could further stratify pre-ASCT PET(+) patients: Chemosensitive PET(-) patients had a 2-year FFS of 85%, vs 56% for chemosensitive PET(+) and 30% for chemoresistant PET(+) ones (p=0.002). Post-ASCT PET scan had the strongest predictive value for outcome: 2-y FFS was 87% for post ASCT PET(-) or MRUp cases vs 19% for PET(+) ones (p< 0.0001). When we further compared the results for the 53 patients who had a PET-scan available both pre- and post-ASCT, we found that patients who became PET(-) post ASCT had an excellent outcome irrespectively of pre-ASCT PET-scan findings, whereas almost all PET(+) ones relapsed, as shown in the table. Conclusions: Pre-ASCT PET scan positivity does not preclude a favorable outcome for patients with relapsed/refractory HL undergoing HDT/ASCT, since half of them remain relapse free. Chemosensitivity prior to ASCT can further discriminate the outcome of PET(+) patients. Patients who become PET(-) after ASCT have an excellent outcome in contrast to PET(+) ones whose prognosis is dismal.
    Haematologica 01/2012; 97(s1):178-179. · 5.94 Impact Factor
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    ABSTRACT: Background: Peripheral T-cell Non Hodgkin lymphomas (PTCL) are rare diseases in the Western World. Among them, the most common entities are the nodal PTCL. Due to their rarity and difficulties in their diagnosis and classification, reports from large series are scarce in the literature. Aims: To record and analyze nodal PTCL patients’ characteristics, outcome and prognostic factors. Methods: We retrospectively studied 120 consecutive patients with nodal PTCL diagnosed and treated in 2 University Hematology Units between1991-2011.Results: Median age at diagnosis was 57 years (13-91) with 40% being >60 years, 63% were male, 65% had clinical stage III-IV, 53% B-symptoms,19% PS≥2, 54% abnormal LDH, 54% extranodal disease (27% in ≥2 sites), 26% bone marrow and 25% splenic involvement. Histology was as follows: 34% anaplastic large cell lymphoma (ALCL, 11% ALK+, 13% ALK-, 10% unknown), 31% angioimmunoblastic lymphoma (AITL) and 32% peripheral T-cell not otherwise specified lymphoma (PTCL-NOS). Table 1 presents patients’ characteristics. Initial treatment was CHOP/CHOEP/CNOP in 81%. At a median follow-up of 51 months the 5-year progression free survival (PFS) and overall survival (OS) were 39% and 54% respectively. 65 events of relapse/progression were recorded: 10 proceeded to autologous stem cell transplantation with 8/10 being cured, whereas 6/65 achieved long-term remission following 2nd line conventional chemotherapy. Only 5/65 patients who progressed or relapsed, did so after 2 years from diagnosis. Univariate analysis revealed that advanced stage (p=0.02), elevated LDH (p=0.02), ≥2 extranodal sites (p=0.004) and non-anaplastic histology (p=0.02) were statistically significant adverse prognostic factors for PFS. The aforementioned factors in addition to age>60 correlated with an adverse OS, as well (p=0.04, 0.02, 0.045, 0.02 and 0.0004 respectively). Although both IPI and PIT had prognostic significance for PFS (p=0.02 and 0.03) and OS (both p=0.02), they were particularly effective in separating the good prognosis patients but not those with a worse outcome. Multivariate analysis indicated that involvement of ≥2 extranodal sites (p=0.02) was the sole significant prognostic factor for PFS, whereas age>60 years(p=0.003) was the only significant parameter for OS. In addition ≥2 extranodal sites, and high LDH proved of marginal independent prognostic significance for OS(p=0.06 and 0.08 respectively). Conclusion: Nodal peripheral T- cell lymphomas are associated with poor prognosis. ALCL and AITL are characterized by distinct clinical and biological features. Disease can be successfully controlled in 40% of the patients with a low probability of relapse after the first two years. Extranodal involvement in ≥2 sites is a strong prognostic indicator, whereas IPI and PIT have a limited prognostic value.
    Haematologica 01/2012; 97(s1):656-657. · 5.94 Impact Factor
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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
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    ABSTRACT: Background: PET/CT is crucial in the post-treatment evaluation of patients with HL, while several studies support the implication of interim PET/CT in the design of treatment strategy. Although baseline PET/CT is recommended, it is not considered mandatory for the initial staging of HL. Furthermore, the effect of baseline PET/CT on the choice of the first-line treatment has not been systematically studied so far. Aim: To compare the results of conventional clinical staging (CS) and PET-based staging (PET-S) in patients with previously untreated HL.Methods: Sixty-seven patients with HL, who were selected based solely on the availability of baseline PET/CT results, were evaluated by conventional and PET-based methods. Results: The median age of the 67 patients was 33 years; 40/67 were males. Based on CS, 8, 25, 17 and 17 patients had stage I, II, III and IV. The median number of involved anatomic sites was 1, 2 (1-5), 5 (2-14) and 7 (4-11) for patients with CS I, II, III and IV respectively. Based on PET/CT results, the corresponding figures were 2 (1-5), 3 (2-9), 7 (2-14) and 11 (5-14). The number of involved anatomic sites as determined by CS or PET-S were highly correlated (Spearman’s rho 0.80). Compared to CS, PET-S resulted in stage change in 20/67 patients (30%): 17 were upstaged (25%) and 3 were downstaged (5%), as shown in the table. Similarly, PET-S revealed more sites of involvement than CS in 50/67 patients (67%). Among 20 patients with potential stage shift, major treatment modifications could have been justified in 16 (24% of the total) based on PET-S. However, in only 7/16 a different therapeutic strategy was actually applied due to PET/CT findings. Among 33 patients with CS I/II, 21 (64%) actually received wider field irradiation, based on the identification of more involved sites by PET/CT. With respect to bone marrow (BM) findings, 43 patients had no evidence of bone/BM uptake and all of them had negative BM biopsies. A diffuse BM uptake was observed in 11 patients: 2/11 (18%) had histologically proven BM involvement. Multifocal bone/BM uptake was noted in 13 patients: 5/13 (38%) had histologically proven BM involvement. Conclusions: PET-S resulted in the identification of more disease sites in the majority of patients with HL. A stage shift was noted in 30% of patients, with the majority of them being upstaged. In everyday practice only 10% of the patients had their treatment strategy changed due to PET/CT findings, although less radical changes did occur in 2/3 of early stage patients due to the widening of radiotherapy fields. The variable use of PET/CT for the initial staging of HL and its heterogenous effect on treatment decisions may render comparisons of retrospective series difficult. Furthermore, PET/CT-based design of radiotherapy may lead to the use of larger fields, in an era that minimization of radiotherapy is warranted. The optimal use of baseline PET/CT in HL needs to be further evaluated.
    Haematologica 01/2012; 97(s1):88-89. · 5.94 Impact Factor
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    ABSTRACT: The optimal treatment approach for patients with mantle cell lymphoma (MCL) is not well defined. Intensive therapeutic regimens result in high response rates and prolonged progression-free survival but at the expense of significant toxicity. We report here our results of the administration of rituximab plus chlorambucil (R-Chl) as first line treatment in patients with MCL. Twenty consecutively diagnosed patients were treated with this combination in which an induction and a maintenance arm were included. During induction, rituximab was administered at a dose of 375 mg/m(2) on day 1, while chlorambucil was given afterward at a dose of 10 mg/day for 10 consecutive days for eight cycles and then as a single agent for an additional four cycles. Maintenance consisted of rituximab administration every 2 months for 1 year. Most patients had indolent disease features such as a low mantle-cell international prognostic index (MIPI) score. The overall response rate was 95% (90% CR, 5% PR). Among patients in CR, 78% presented a molecular remission. The 3-year progression-free survival was 89%. There were no serious side effects. These results show that the R-Chl combination could be an effective therapeutic option as first line treatment in MCL, especially for patients with indolent disease characteristics.
    Leukemia & lymphoma 03/2011; 52(3):387-93. · 2.61 Impact Factor
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    ABSTRACT: Background. Patients with HL who relapse after HDT/ASCT are con¬sidered incurable. Aims. To evaluate the outcome and prognostic factors of 45 HL patients, who relapsed after HDT/ASCT. Methods. Out of 95 consecutive patients with primary refractory/relapsed HL undergoing HDT/ASCT at a single unit from March 1996 to January 2010, 45 pa¬tients who relapsed after HDT/ASCT were recorded. Thirty-one out of 45 (69%) were males, their median age at ASCT was 28 years (19-54), 18 (40%) underwent HDT/ASCT at first relapse, 5 (10%) for multiple relapses and 23 (50%) for primary refractory disease. Prior to HDT/ASCT; 14 (31%) were in complete remission (CR), 18 (40%) in partial remission (PR) and and 13 (29%) were chemoresistant. Results. Median time between ASCT and the following relapse was 6.3 months (1-54). At relapse after ASCT median hemoglobin was 11.8 g/dL (7.6-14.4), 32%; 18%, 24% mi 26% had clinical stage I, II, III mi IV respec¬tively and 27% had B symptoms. The median number of involved sites was 3 (1-12), 16% had bulky and 41% extranodal disease. The most common involved extranodal sites were lungs, bones and soft tissue. Patients received the following therapies: 47% radiotherapy (RT), 25% chemotherapy containing gemcitabine/vinorelbine +/- liposomal dox-orubicin; and 22% MOPP-like chemotherapy. Furthermore, 5 patients underwent a second ASCT and 2 patients allogenic stem cell transplan¬tation. At a median follow up of 36 months, 3-year freedom from second failure (FF2F) and 3-year overall survival (OS) after relapse was 23% mi 64%, respectively. Thirteen out of 45 patients died of HL; 4 due to secondary myelodysplatic syndrome/acute non lymphoblastic leukemia, 15 are alive with active HL and 13 are alive in CR. Prognostic factor analysis for FF2F disclosed that a short (<12months) interval be¬tween ASCT and relapse (p<0.002); chemoresistance prior to ASCT (p<0.002), anemia (p<0.004) and B symptoms at relapse post ASCT (p<0.02) were of unfavourable prognostic significance. Chemoresis-tance prior to ASCT (p<0.005), anemia (p<0.03) and B symptoms at re¬lapse (p<0.0001) were unfavorable prognostic parameters for OS, as well. In addition, age ^45 (p<0.03) proved as a poor prognostic factor for OS. Despite the limited number of patients, multivariate analysis revealed that chemoresistance prior to ASCT and B symptoms at re¬lapse post ASCT were independent prognostic factors for FF2F and OS. Conclusions. Patients with HLwho relapse after ASCT have a poor prog¬nosis. However, the natural history of the disease remains long, with 2/3 of the patients remaining alive at 3 years after relapse. Chemoresis¬tance prior to ASCT, B symptoms and anemia at relapse post ASCT, as well as, relapse in <12 months after ASCT, are unfavorable prognostic parameters.
    Haematologica 01/2011; 96:323. · 5.94 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.
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    ABSTRACT: The prognostic significance of PET-scan in advanced stage HL patients treated with ABVD as first line treatment is well established. However, the prognostic impact of PET scan in the relapsed setting is not clearly defined, while chemosensitivity before HDT/ASCT - as assessed with conventional imaging - is one of the most important prognostic factors for outcome. Aims. To study the prognostic significance of PET scan before and after HDT/ASCT in pa¬tients with relapsed/primary refractory HL. Methods. Clinical staging with computed tomography (CT) and clinical examination, as well as PET-scan were performed after salvage chemotherapy just prior to ASCT and at 3 months post transplant and findings were correlated with failure free survival (FES). PET scan was considered negative when no uptake was present, positive, when any lesion was FDG avid with SUV> 4 and minimal residual uptake positive (MRUp), when any lesion showed abnormal uptake with SUV<4. Chemosensitive patients were considered those who had achieved complete or partial remis-,sion, whereas chemoresistant those with stable or progressive disease by conventional clinical staging pre-ASCT. Failure-free Survival (FFS) was calculated from ASCT to relapse, progression, death from any cause or last follow-up. Results. Sixty-one patients were retrospectively studied. Eighty % were chemosensitive by CT criteria. PET scan was available in 52 patients before HDT/ASCT, 59 after HDT/ASCT and in 50 at both time points. Pre-ASCT PET scan was positive or MRUp in 23/42 chemosensitive patients, vs 10/10 chemorefractory. The analysis of the prognostic significance of pre-transplant PET scan revealed: three relapses were observed among 19 PET negative patients, vs 17 among 33 MRUp or positive ones, leading to a 2-year FFS of 77% vs 45%, respectively (p=0.02). Post ASCT PET scan had a strong prog¬nostic impact on outcome: 2-year FFS was 87% for PET negative or MRUp patients vs 6% for positive ones, (p< 0.0001). The analysis of the 50 patients who had a PET scan available both pre- and post-trans¬plant disclosed: a. One relapse was recorded for those who were PET scan either positive or MRUp pre-ASCT and became negative or MRUp after ASCT (1/16 patients), b. 15 patients relapsed among 16, who were PET scan positive or MRUp pre-transplant and remained or became positive post-transplant c. 2 relapses were recorded among 16 patients who were negative both pre- and post-ASCT. These differ¬ences we're statistically significant (p<0.0001). Conclusions. PET scan positivity prior to ASCT does not preclude a favorable outcome in pa¬tients with primary refractory/relapsed HL, since approximately 50% remain disease free after ASCT. Patients who remain or become PET scan positive after ASCT have a dismal outcome in contrast to those who become PET negative.
    Haematologica 01/2011; 96:414. · 5.94 Impact Factor
  • HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, GIUSEPPE BELLI 4, 27100 PAVIA, ITALY. FERRATA STORTI FOUNDATION; 06/2008