Biomedical subjects

Maria N Dimopoulou

Publications and source records attributed to Maria N Dimopoulou.

14 recordsLinked to original sources

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

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↗

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↗

PubMed2002

B-chronic lymphocytic leukemia: practical aspects.

B-CLL is the most common adult leukemia in the Western world. It is a neoplasia of mature looking B-monoclonal lymphocytes co-expressing the CD5 antigen (involving the blood, the bone marrow, the lymph nodes and related organs). Much new information about the nature of the neoplastic cells, including chromosomal and molecular changes as well as mechanisms participating in the survival of the leukemic clone have been published recently, in an attempt to elucidate the biology of the disease and identify prognostic subgroups. For the time being, clinical stage based on Rai and Binet staging systems remains the strongest predictor of prognosis and patients' survival, and therefore it affects treatment decisions. In the early stages treatment may be delayed until progression. When treatment is necessary according to well-established criteria, there are nowadays many different options. Chlorambucil has been the standard regimen for many years. During the last decade novel modalities have been tried with the emphasis on fludarabine and 2-chlorodeoxyadenosine and their combinations with other drugs. Such an approach offers greater probability of a durable complete remission but no effect on overall survival has been clearly proven so far. Other modalities, included in the therapeutic armamentarium, are monoclonal antibodies, stem cell transplantation (autologous or allogeneic) and new experimental drugs. Supportive care is an important part of patient management and it involves restoring hypogammaglobulinemia and disease-related anemia by polyvalent immunoglobulin administration and erythropoietin respectively.

Adult↗

PubMed2002

The splenic form of mantle cell lymphoma.

OBJECTIVES: To describe the clinical, immunophenotypic and molecular features, as well as the clinical course of patients with unusual presentation of mantle cell lymphoma (MCL) purely located to the spleen. PATIENTS AND METHODS: We describe seven patients presented with splenomegaly and a leukemic picture without lymphadenopathy, fulfilling the diagnostic criteria of MCL. In addition to clinical and pathologic features, patients were studied with respect to surface immunophenotype, including adhesion molecule profile, immunohistochemical expression of cyclin-D1 and bcl-1 rearrangement by polymerase chain reaction. RESULTS: Four patients were male and three female. The median palpable spleen size was 15 cm. A preliminary diagnosis of MCL was made, based on blood cell morphology and immunophenotype. All patients underwent splenectomy for therapeutic purposes. Studies done in blood and splenic lymphocytes revealed the following: 7/7 patients were CD19/CD5, CD20 and CD38 positive; CD10 negative and 6/7 CD23 negative. The adhesion molecule expression pattern was consistent in all patients: L-Selectin and CD11c were negative, CD11alpha and CD18 weakly positive and CD54 strongly positive. The median spleen weight was 1775 g. Histology disclosed a cytologic and architectural pattern consistent with MCL. Cyclin-D1 was positive in 6/6 studied patients. Bcl-1 rearrangement was found in 5/7 patients. Splenectomy was applied as the sole treatment and was beneficial in all patients, with median blood values as following: prior to splenectomy, Ht 29.5%, platelets 110 x 10(9)/l, lymphoma cells 5.0 x 10(9)/L, and at 6 months post-splenectomy, Ht 43%, platelets 311 x 10(9)/l and lymphoma cells 3.0 x 10(9)/L. Of the seven patients, two developed progressive disease 11 and 26 months post-splenectomy. The remaining five are in improving clinical and hematological condition without chemotherapy at a median follow up of 20 months. CONCLUSIONS: We conclude that this presentation represents a separate form of MCL which requires splenectomy. It remains to be seen whether it carries a better prognosis than classical MCL.

Aged↗

PubMed2002

Hodgkin's lymphoma in first relapse following chemotherapy or combined modality therapy: analysis of outcome and prognostic factors after conventional salvage therapy.

OBJECTIVES: To investigate the prognosis of patients with Hodgkin's lymphoma (HL) who relapse following a complete remission (CR) achieved by chemotherapy with or without radiotherapy (CT+/-RT), and to identify prognostic factors for freedom from second progression (FF2P). METHODS: We analyzed the prognostic significance of the initial CT regimen (4 vs. 7-8 drugs), treatment-free interval (TFI), and demographic, clinical, and laboratory factors at the time of relapse and diagnosis, in 113 patients with HL, who relapsed after a CR achieved by CT+/-RT. RESULTS: Conventional salvage CT+/-RT was administered in 107 patients, while six received RT only. The 5-yr FF2P was 24%, while the 10-yr survival after relapse (O2S) was 39% and was not afffected by the initial CT regimen. Multivariate analysis revealed that extranodal disease at relapse (P<0.001), TFI<6 month (P<0.001), > or =5 involved sites at diagnosis (P=0.04) and anemia at relapse (P=0.03) were independent predictors of FF2P. 55% of patients had 0 or 1 of these adverse prognostic factors. The 5-yr FF2P of patients with 0, 1 or 2 adverse factors was 58%, 34% and 5% (P<0.0001). The corresponding rates for 10-yr O2S were 68%, 51% and 25%, respectively (P=0.002). CONCLUSIONS: Our data confirmed the significance of TFI and extranodal relapse and demonstrated a potential role for anemia at relapse and number of involved sites at diagnosis, for the prognosis of patients with HL relapsing after CT+/-RT. The combination of these prognostic factors defines a sizeable subgroup of patients with favorable outcome following conventional salvage therapy.

Adolescent↗

PubMed2002

Downstaging Rai stage III B-chronic lymphocytic leukemia patients with the administration of recombinant human erythropoietin.

BACKGROUND AND OBJECTIVES: To investigate the effectiveness of recombinant human erythropoietin (r-HuEPO) on disease-related anemia in patients with B-chronic lymphocytic leukemia (B-CLL) and to explore whether improvement of anemia could delay the initiation of cytotoxic therapy. DESIGN AND METHODS: Twenty five B-CLL patients (12 males and 13 females; median age 70 years) with disease-related anemia were treated with r-HuEPO. Patients were either on no treatment or on a standard regimen, and had at least Rai stage III disease, with a hematocrit (Hct) <32%. Eleven were newly diagnosed, whereas 14 developed anemia during follow-up. Treatment induction lasted for a maximum of 3 months, during which patients were receiving 150 IU/kg of r-HuEPO s.c. t.i.w. with an escalation to 300 IU/kg t.i.w. if response was slow after one month. Responding patients were placed on maintenance r-HuEPO with 150 IU/kg s.c. once weekly, continuously. Complete response (CR) was defined as an increase of Hct to 38% or more and partial response (PR) as an increase of >6% from pretreatment level. RESULTS: CR was observed in 18/25 (72%) and PR in 2/25 (8%) of the patients. Six patients were downstaged to stage Rai 0, 9 to Rai I and 4 to Rai II. Response was sustained with maintenance therapy. At a median follow-up of 32 months only 4 of the responders required antileukemic treatment. The median survival of responders has not been reached, and 3-year survival is 84%. INTERPRETATION AND CONCLUSIONS: r-HuEPO was efficient in downstaging Rai stage III B-CLL patients, and delayed the initiation of antileukemic therapy. Whether this effect can be translated into better survival rates remains to be clarified in randomized trials.

Aged↗

PubMed2002

The prognostic significance of beta(2)-microglobulin in patients with Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Serum beta(2)-microglobulin (s beta(2)m) is an established prognostic factor for multiple myeloma and non-Hodgkin's lymphoma, but only limited data suggest an adverse prognostic significance for Hodgkin's lymphoma (HL). This study was undertaken to examine the impact of s beta(2)m on the prognosis of patients with HL. DESIGN AND METHODS: s beta(2)m was measured by a radioimmunoassay (upper normal limit 2.4 mg/L), in pretreatment serum samples of 232 patients with HL, who were then treated with ABVD or equivalent regimens with or without radiotherapy. Multivariate survival analysis was based on Cox's proportional hazards model. RESULTS: Main patients' characteristics: median age 30.5 years (14-78); 58% males; 68% nodular sclerosis, 20% mixed cellularity and 12% lymphocyte predominance; 34% B-symptoms; 24% Ann Arbor stage I, 49% II, 18% III and 9% IV. Elevated s beta(2)m levels were detected in 65/232 patients (28%) and correlated with older age (p<0.001), mixed cellularity (p=0.03), B-symptoms (p=0.002), advanced stage (p=0.02), > or = 5 involved sites (p=0.02), inguinal/iliac involvement (p=0.009), lymphocytopenia (p=0.002) and elevated lactate dehydrogenase (p=0.01). The 7-year failure free survival (FFS) was 75% vs. 72% for patients with normal vs. elevated s beta(2)m (p=0.15). The corresponding 7-year overall survival (OS) rates were 86% vs. 52% (p=0.003). In multivariate analysis, elevated s beta(2)m was not predictive of FFS, but was independently associated with inferior OS (p=0.01), along with the number of involved sites (p<0.001). INTERPRETATION AND CONCLUSIONS: s beta(2)m is not a potent prognostic factor for FFS in optimally treated patients with HL. However s beta(2)m may be predictive of OS, probably due to its effect on the timing of treatment failure.

Adolescent↗

PubMedDate not supplied

Serum levels of soluble syndecan-1 in Hodgkin's lymphoma.

BACKGROUND: Syndecan-1 (CD138) is expressed by the Hodgkin-Reed-Sternberg (HRS) cells of classic Hodgkin's lymphoma (cHL), but not in nodular lymphocyte-predominant HL. Syndecan-1 may be involved in the interaction between HRS cells and the cellular and stromal microenvironment typical of nodular sclerosing HL. PATIENTS AND METHODS: Serum levels of soluble syndecan-1 were determined by ELISA in 66 patients with HL and 14 age- and sex-matched healthy individuals. RESULTS: The levels of syndecan-1 were higher in HL patients than controls (100.2 +/- 35.9 ng/ml vs. 67.9 +/- 24.5 ng/ml, p < 0.001). They marginally correlated with advanced age (p = 0.06), male gender (p = 0.07) and consequently high IPS (p = 0.01), but did not correlate with markers of tumor burden and prognosis, including serum interleukin-10 and soluble CD30. At 6 years, failure-free survival was 70 +/- 9% vs. 50 +/- 11% (p = 0.32) for patients with serum soluble syndecan-1 levels above or below the observed median value of 91 ng/ml. CONCLUSION: The serum levels of syndecan-1 were elevated in patients with HL, but were not strongly correlated with other potential prognostic factors. Their effect on prognosis deserves further evaluation.

Adolescent↗