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Theodoros P Vassilakopoulos

Publications and source records attributed to Theodoros P Vassilakopoulos.

At least 19 recordsLinked to original sources
PubMed2006

Very high levels of soluble CD30 recognize the patients with classical Hodgkin's lymphoma retaining a very poor prognosis.

OBJECTIVES: To evaluate the prognostic role of pretreatment serum levels of soluble CD30 (sCD30) in patients with advanced stage classical Hodgkin's lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine or equivalent regimens. METHODS: We identified 321 previously untreated patients with cHL who presented to the participating centers between 1985 and 2002, and had serum samples available for the determination of sCD30 levels. RESULTS: With a median follow-up of 72 months, the actuarial 5-year overall survival was 82%, and failure-free survival (FFS) was 71%. The median serum level of sCD30 was 65 U/mL (range: 1-2230), and was significantly higher (P < 0.0001) when compared with a group of 113 healthy controls (4 U/mL, range: 0-20). Increasing level of sCD30 was associated with a continuous worsening of FFS and OS, and patients with sCD30 >or=200 U/mL had a 5-year FFS of 39%. With multivariate analysis, sCD30, Ann Arbor stage, and lactic acid dehydrogenase were significant independent factors in terms of FFS. The association of the above-mentioned three independent prognostic variables could discriminate 22% of patients with 5-year FFS of 40%. CONCLUSIONS: Our data confirm the independent prognostic role of sCD30 in identifying the patients with high risk of treatment failure, and show that its association with other variables can recognize patients with FFS considerably lower than 50%.

Adult↗
PubMed2006

Favorable outcome of primary cutaneous marginal zone lymphoma treated with intralesional rituximab.

Primary cutaneous marginal zone lymphoma (PCMZL) is an indolent disease. Treatment options include excision, local irradiation, interferon-alpha or chemotherapy. We present two patients with PCMZL and multiple skin lesions successfully treated with intralesional administration of the anti-CD20 monoclonal antibody rituximab. The first presented with four red skin lesions and the second with two. Biopsy of the largest lesion revealed marginal zone B-cell lymphoma in both patients. There was no evidence of systemic involvement in either patient. Both patients were treated with intralesional rituximab for 18 consecutive weeks. Skin lesions gradually regressed. Apart from mild local pain during the injection, no other adverse effects were observed. In conclusion, rituximab can be safely administered intralesionally in patients with PCMZL and can produce disease remission.

Aged↗
PubMed2006

Immunotherapeutic and immunoregulatory drugs in haematologic malignancies.

A better understanding of the biology and pathogenesis of hematological malignancies has led to the development of immunotherapeutic and immunoregulatory drugs. Many of these agents have revolutionized the current treatment modalities, while others are under investigation. Rituximab (anti-CD20 antibody) has been established as the gold standard of treatment for aggressive B-cell lymphomas in combination with CHOP and has shown significant activity as monotherapy in the treatment of indolent B-cell lymphomas. In follicular lymphomas the combination of Rituximab with chemotherapy improves the outcome compared to chemotherapy alone. CD 20-based radioimmunotherapy, with the advantage of the bystander effect, represents an additional therapeutic alternative in B-cell lymphomas and may produce tumor regression in Rituximab resistant patients. The anti-CD52 monoclonal antibody, alemtuzumab, further expands the armamentarium against lymphoid malignancies producing high response rates in these entities. Antibody-targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33 antibody combined to calicheamicin, has shown efficacy in the treatment of refractory acute myeloid leukemia; exact indications, timing and dosing schedule for optimized efficacy remain to be determined. Interferons have proven significant activity in cutaneous lymphomas, hairy cell leukemia and chronic myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic cells microenvironment and lead to disease control in multiple myeloma as well as in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor, displays significant anti-tumor activity, especially in multiple myeloma and lymphoproliferative disorders. The addition of these agents in therapeutic regimens has improved considerably the treatment of hematological malignancies.

Animals↗
PubMed2006

Pure infradiaphragmatic Hodgkin's lymphoma. Clinical features, prognostic factor and comparison with supradiaphragmatic disease.

BACKGROUND AND OBJECTIVES: Pure infradiaphragmatic Hodgkin's lymphoma (HL) is a rare disease. The prognostic impact of a purely infradiaphragmatic localization of this lymphoma is controversial. We aimed to evaluate the baseline clinicopathologic features, prognostic factors and outcome of a large series of consecutive patients with pure infradiaphragmatic HL. DESIGN AND METHODS: We analyzed 131 patients with clinical stage I/II infradiaphragmatic HL treated with ABVD or equivalent regimens with or without radiotherapy, and compared 54 of them with 444 patients with pure supradiaphragmatic disease, who were treated at the same center. RESULTS: Older age, clinical stage II (borderline), involvement of > or =3 sites, lymphocyte predominant histology, elevated serum beta2-microglobulin and higher International Prognostic Score were more frequent in patients with infradiaphragmatic disease than in those with supradiaphragmatic disease, while nodular sclerosis was less frequent. The complete remission rate was 100%, 97% and 82% for stages I, IIA and IIB, respectively. Only B-symptoms independently predicted for inferior failure-free survival, while inferior overall survival was independently associated with the involvement of > or =3 sites. At 10 years failure-free survival was 82+/-6% (vs. 85+/-2% for patients with supradiaphragmatic disease, p=0.45), overall survival was 74+/-8% (vs. 91+/-2%, p=0.0006), and disease-specific survival 87+/-5% (vs. 94+/-1%, p=0.04). In multivariate analysis the differences between infradiaphragmatic and supradiaphragmatic disease were obscured by older age and B-symptoms. INTERPRETATION AND CONCLUSIONS: Pure infradiaphragmatic HL presents with distinct clinicopathologic characteristics. The previously reported poorer outcome may be explained by the unfavorable profile of the patients rather than the infradiaphragmatic presentation per se. Patients with stage IIB disease should probably be classified as having advanced HL because of the unacceptable rate of primary refractory disease.

Hodgkin Disease↗
PubMed2005

Reversible dilated cardiomyopathy associated with amphotericin B treatment.

We report two patients, who developed dilated cardiomyopathy and subsequent congestive heart failure after treatment with amphotericin B (AmB). The echocardiographic findings and the symptoms of heart failure resolved after the discontinuation of the drug. The clinical data from our cases and two similar cases reported in the literature suggest that the presence of other factors predisposing to cardiac dysfunction may facilitate the occurrence of this rare side effect.

Adult↗
PubMed2005

Differential diagnosis of Waldenstrom's macroglobulinemia and other B-cell disorders.

Waldenstrom's macroglobulinemia (WM) is characterized by lymphoplasmacytic infiltration of bone marrow and/or other tissues and by the presence of serum monoclonal immunoglobulin M ([IgM], without cutoff limit). Differential diagnosis from other B-cell disorders (BCDs) is usually easy based on clinical, morphologic, histopathologic, immunophenotypic, and genetic features. However, all BCDs potentially produce monoclonal IgM. In this study we reviewed the medical files of 130 patients with IgM-secreting BCDs. Eighty-four patients were diagnosed with WM, 5 with IgM-monoclonal gammopathy of undetermined significance (MGUS), and 41 with other BCDs (9 with B-cell chronic lymphocytic leukemia, 5 with small lymphocytic lymphoma, 14 with marginal zone lymphoma, 5 with mantle-cell lymphoma, 2 with follicular lymphoma, 2 with diffuse large B-cell lymphoma, 2 with cryoglobulinemia, and 2 with low-grade lymphoma not otherwise specified). Median IgM levels were 3215 mg/dL in WM, 840 mg/dL in IgM-MGUS, and 285 mg/dL in other BCDs (5 had IgM levels > 1500 mg/dL). In 10% of non-WM BCDs, monoclonal IgM was found only when more sensitive immunofixation methods were used. Forty-four percent of patients with BCDs (splenic marginal zone lymphoma or small lymphocytic lymphoma) had diagnoses that corresponded to that of WM. Careful diagnosis requires the concomitant evaluation of all parameters of BCDs together. Marginal zone lymphoma is the most frequently overlapping entity. Special attention should be given to mantle cell lymphoma in its atypical forms. Research in this field should continue to further clarify the disease entities that overlap with WM. New technology such as gene-expression profile techniques may contribute to this purpose.

Aged↗
PubMed2004

Development and validation of a clinical prediction rule for bone marrow involvement in patients with Hodgkin lymphoma.

We developed a clinical prediction rule for bone marrow involvement (BMI) in Hodgkin lymphoma based on 826 patients and validated it in 654 additional patients. Independent prognostic factors for BMI were x1, B symptoms; x2, stage III/IV prior to bone marrow biopsy; x3, anemia; x4, leukocytes fewer than 6 x 10(9)/L; x5, age 35 years or older; and x6, iliac/inguinal involvement. Each factor was graded as x(i)=1, if present, or x(i)=0, if absent. A simplified score Zs=8x1+6x2+5x3+5x4+3x5+3x6-8 was assigned to each patient. The sensitivity, specificity, and positive and negative predictive value of this prediction rule was 97.8%, 51.5%, 10.6%, and 99.8%, respectively. In the validation group, they were 98.1%, 40.3%, 12.7%, and 99.6%. According to Zs value, 3 risk groups for BMI were defined: low risk (Zs<0, 44% of patients, 0.3% risk), standard risk (Zs, 0-9; 37% of patients; 4.2% risk), and high risk (Zs>or=10, 20% of patients, 25.5% risk). Patients with low risk (stage IA/IIA without anemia and leukopenia; stage IA/IIA, younger than 35 years, with either anemia or leukopenia but no inguinal/iliac involvement; and stage IIIA/IVA without any of these 4 risk factors) do not need bone marrow (BM) biopsy. Patients with standard risk should be staged with unilateral biopsy, but patients with high risk may benefit from bilateral biopsy.

Bone Marrow Neoplasms↗
PubMed2004

Combination chemotherapy plus low-dose involved-field radiotherapy for early clinical stage Hodgkin's lymphoma.

PURPOSE: To present our long-term experience regarding the use of chemotherapy plus low-dose involved-field radiotherapy (IFRT) for clinical Stage I-IIA Hodgkin's lymphoma. METHODS AND MATERIALS: We analyzed the data of 368 patients. Of these, 66 received mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and 302 received doxorubicin (or epirubicin), bleomycin, vinblastine, and dacarbazine [A(E)BVD]. Patients with complete remission or very good partial remission were scheduled for low-dose IFRT (< or =3200 cGy). RESULTS: The 10-year failure-free survival (FFS) and overall survival (OS) rate was 85% and 86%, respectively. A(E)BVD-treated patients had superior 10-year FFS and OS rates compared with MOPP-treated patients (87% vs. 75%, p = 0.009; and 93% vs. 71%, p = 0.0004, respectively). Only 10 of 41 relapses had any infield (irradiated) component. Of the complete responders/very good partial responders treated with low-dose IFRT, those who received <2800 cGy had inferior FFS but similar OS as those who received 2800-3200 cGy. Adverse prognostic factors for FFS included age > or =45 years, leukocytosis > or =10 x 10(9)/L, and extranodal extension. Secondary acute leukemia developed after MOPP with or without salvage therapy (n = 6) or after ABVD plus salvage therapy (n = 2). None of the nine secondary solid tumors developed within the RT fields. CONCLUSION: IFRT at a dose of 2800-3000 cGy is highly effective in clinical Stage I-IIA HL patients who achieved a complete response or very good partial response with A(E)BVD. The long-term toxicity with respect to secondary malignancies appears to be acceptable.

Adolescent↗
PubMed2004

Serum syndecan-1, basic fibroblast growth factor and osteoprotegerin in myeloma patients at diagnosis and during the course of the disease.

UNLABELLED: Neovascularisation and bone resorption are related to myeloma disease activity. OBJECTIVES: To investigate the possible prognostic importance of serum syndecan-1, basic fibroblast growth factor (bFGF) and osteoprotegerin (OPG) levels, the relationship between them, with parameters of disease activity and the effect of treatment on their levels. PATIENTS AND METHODS: Twenty-seven patients were studied from diagnosis and an additional five from remission, for a median follow-up of 40 months. Twenty-three patients received chemotherapy plus bisphosphonates and nine only bisphosphonates. Sera from 11 healthy individuals (HI) were used as controls. Cytokines were determined by commercially available enzyme-linked immunosorbent assays (ELISA) kits. RESULTS: In HI, median syndecan-1 was 40 ng/mL (28-75), bFGF 8 pg/mL (7-30), OPG 35 pg/mL (4-100). Pretreatment median serum syndecan-1 was 177.5 ng/mL (34-3500), bFGF 11.5 pg/mL (8-65) and OPG 100 pg/mL (4-1000). Pretreatment syndecan-1, bFGF and OPG serum levels were increased in patients compared with HI (P = 0.001, 0.03 and 0.01, respectively). Syndecan-1 and bFGF levels were correlated with stage (P = 0.004 and 0.03, respectively). Both syndecan-1 and OPG levels were correlated with beta2M (P = 0.04 and 0.01, respectively). Patients with elevated syndecan-1 and bFGF serum levels had shorter survival than patients with normal levels (P = 0.01 and 0.05, respectively). After chemotherapy syndecan-1 and OPG levels were found to be decreased in responders and syndecan-1 level was reduced in patients receiving bisphosphonates alone. CONCLUSIONS: Pretreatment syndecan-1, bFGF and OPG levels were found to be increased at diagnosis. Syndecan-1 and OPG fluctuated according to MM activity. Elevated serum syndecan-1 and bFGF levels predicted short survival.

Adult↗
PubMed2004

Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with chemoresistant Ph1+ acute myeloid leukemia.

Imatinib mesylate is a potent, selective inhibitor of the tyrosine kinase activity of bcr-abl,which is now established as the state-of-the-art treatment for chronic, accelerated or even blastic phase of Philadelphia-positive [Ph(1)(+)] chronic myelogenous leukemia. It is also active in Ph(1)(+) acute lymphoblastic leukemia, but its role in Ph(1)(+) acute myeloid leukemia (AML) is less well investigated. We report here a patient with chemoresistant Ph(1)(+) AML, who responded promptly to one cycle of Ida-FLAG second-line chemotherapy by achieving complete morphologic, immunophenotypic, and cytogenetic remission but not a molecular one. The addition of imatinib mesylate led to a molecular remission, which is sustained for 10 months so far.

Adult↗
PubMed2004

Adult T-cell leukemia/lymphoma (ATLL): report of two fully documented Hellenic patients.

ATLL is etiologically associated with HTLV-I retrovirus. A population of 10 to 20 million worldwide is estimated to be infected by the virus, but only 1-4% develop ATLL during a 70-year lifespan. The latency period is more than 30 years. The aim of this study was to report two cases of ATLL in Greek patients with the concomitant study of their family members. A 55-year-old woman and a 59-year-old man presented with leucocytosis and lymphocytosis. Both were asymptomatic and physical examination was unremarkable except for minimal lymphadenopathy in the second patient. In both patients blood smears showed small-to-medium-sized, multilobulated lymphocytes, with different degrees of nuclear irregularity. Immunophenotypic study was as follows: CD2 + (97%), CD3 + (95%), CD5 + (95%), CD3/CD4 + (93%), CD3/CD25 + (84%), CD7 -/CD4 + (89%) CD2 + /HLA-DR + (53%), TCRabeta + (96%) and CD7-(7%). Bone marrow biopsy revealed a normal cellularity with dyserythropoiesis and scattered small lymphocytes (CD4 + on immunostaining) Serum HTLV I and II antibodies were positive. T-cell receptor gamma-chain rearrangement was positive in blood lymphocytes by PCR. Cytogenetic analysis showed complex karyotypic abnormalities. DNA analysis by PCR demonstrated the integration of the HTLV-I DNA in the DNA of the neoplastic T cells. Both patients rapidly developed acute type ATLL. In the first patient multiple subcutaneous nodules on the palmar surface of both hands were also observed. She received deoxycoformycin, which was stopped because of autoimmune hemolytic anemia. Corticosteroid treatment was initiated, with gradual improvement. She suffered from recurrent opportunistic infections. She is currently under interferon and zidovudine therapy with stable blood parameters. Chemotherapy was administered to the other patient with > 50% initial response. Both patients' families were tested for serum anti HTLV-I antibodies and their mates were found to be positive; they also had detectable viral DNA by PCR analysis while asymptomatic, with no abnormal clinical findings and normal white blood cell count and morphology. In conclusion, the two aforementioned patients are the first fully documented ATLL patients described in Greece. Investigation for HTLV-I antibodies should be mandatory in all patients with T-cell lymphoproliferative disorders.

CD4-Positive T-Lymphocytes↗
PubMed2004

Elevated serum levels of IL-10 are associated with inferior progression-free survival in patients with Hodgkin's disease treated with radiotherapy.

Elevated pretreatment serum interleukin-10 (IL-10) is associated with inferior progression-free survival (PFS) in patients with Hodgkin's disease (HD) treated with ABVD or equivalent regimens. Therefore, we explored the association of serum IL-10 with presenting features and PFS in HD patients treated only by radiotherapy (RT) with curative intent. Eligible patients were previously untreated, had biopsy-proven HD, were older than 16 years, HIV-negative, and had unthawed pretreatment serum. Serum IL-10 levels were measured with ELISA and were considered high if > or = 10 pg/ml. We identified 69 patients with median age of 34 years (range 16 - 74), of who 52% were males, and 3% had B-symptoms. Ann Arbor Stage was I in 35%, II in 58%, and III in 7% of the patients. Histology was lymphocyte predominance in 26%, and classical HD in 74% of the patients. Serum IL-10 was elevated in 35% of the patients. After a median follow-up of 67 months for survivors, the 5-year PFS of patients with high vs. normal serum IL-10 was 50% vs. 81% (all patients, P = 0.006), and 43% vs. 77% for the subset with classical HD (P = 0.008). Multivariate analysis revealed that high serum IL-10 and beta2-microglobulin were independently associated with inferior PFS. Patients with none, 1, or 2 adverse features comprised 57%, 36%, and 7% of the population, and their 5-year PFS was 80%, 63%, and 0%, respectively (P < 0.0001). In conclusion, high serum IL-10 is independently associated with inferior PFS in patients with HD treated with RT.

Adolescent↗
PubMed2003

Differential diagnosis of Waldenstrom's macroglobulinemia from other low-grade B-cell lymphoproliferative disorders.

Waldenstrom's macroglobulinemia (WM) is a rare lymphoproliferative disorder (LPD) characterized by lymphoplasmacytic infiltration of the bone marrow (BM) and/or occasionally other tissues and by the presence of a serum monoclonal IgM. The disease belongs to the lymphoplasmacytic lymphoma (LPL) subtype. Whether WM is indeed a separate entity or is merely an IgM-secreting subtype of low-grade B-cell lymphoma is still controversial. In our series of 67 patients, WM has a long median overall survival of 110 months, and the male/female ratio is 1.2/1. Clinical features include a wide spectrum of manifestations, many of which may be common to other LPDs. Differential diagnosis is based on: (1) clinical and laboratory features (anemia, organomegaly, lymphadenopathy, IgM paraproteinemia), (2) cell morphology (lymphocytes, lymphoplasmacytes, few plasma cells), (3) histopathology of bone marrow or lymph node, (4) immunophenotype (CD5 expression and the intensity of CD5, CD20, and CD79b antigens may help in discrimination from other LPDs and atypical CLL), and (5) characteristic genetic features (present in other LPDs). Based on the former, diagnosis is usually easy. It may be harder in LPL cases not secreting IgM. We consider that WM should be, for the time being, handled as a separate entity. Further studies are necessary.

Diagnosis, Differential↗
PubMed2003

A randomized trial comparing intensified CNOP vs. CHOP in patients with aggressive non-Hodgkin's lymphoma.

The standard CHOP regimen may cure 30-40% of patients with advanced aggressive non-Hodgkin's lymphoma (ANHL). Mitoxantrone is an anthracenedione, which is active in NHL and its toxicity profile may be more favorable than doxorubicin with respect to alopecia, mucositis and cardiotoxicity. This study was designed to compare the effectiveness of an escalated dose of mitoxantrone with that of standard doxorubicin, used in the CHOP regimen in patients with ANHL. One hundred and forty three eligible patients with ANHL were randomized to receive 6 cycles of either CHOP (n = 71) or intensified CNOP (iCNOP) (n = 72), with mitoxantrone 20 mg/m2, i.v., d.1 instead of doxorubicin. Complete responders (CR) were again randomized either to receive interferon-alpha (IFN-alpha) maintenance (3 MU t.i.w., s.c.) or not. The CR rate was 70 vs. 76% for iCNOP and CHOP (p = 0.45), and the overall response rate was 81 vs. 83%, respectively (p = 0.71). The 5-year failure free survival (FFS) was 48 and 50% in the iCNOP and CHOP arm, respectively (p = 0.45), and the 5-year overall survival (OS) was 61 vs. 64% (p = 0.56). IFN-alpha did not prolong relapse free survival (p = 0.91). iCNOP produced less alopecia (p = 0.001) but more febrile episodes (p = 0.04) than CHOP, while requiring more frequent G-CSF support (p = 0.01). Two cases of acute myelogenous leukemia (AML) were recorded, both in the iCNOP arm (p = 0.14). In conclusion, iCNOP was equally effective to CHOP in patients with ANHL, producing more leukopenia and febrile episodes, but less alopecia. The development of two cases of secondary AML in th e iCNOP arm is of concern.

Aged↗