Athens Medical Center Psychikon Branch

Athens, Greece

Athens Medical Center Psychikon Branch

Athens, Greece
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Siakantaris M.P.,National and Kapodistrian University of Athens | Argyropoulos K.V.,National and Kapodistrian University of Athens | Ioannou S.,National and Kapodistrian University of Athens | Papadopoulou V.,National and Kapodistrian University of Athens | And 6 more authors.
Neurologist | Year: 2015

The efficacy and safety of rituximab against B-cell lymphomas is well established. However, there has been an increased incidence of infectious complications after rituximab treatment, mostly hepatitis B reactivation and progressive multifocal leukoencephalopathy. This is the case of a 67-year-old patient with primary central nervous system lymphoma, who developed cytomegalovirus meningoencephalitis after receiving high-dose chemotherapy and rituximab. As there was no evidence of lymphoma relapse or additional immunosuppression, besides his previous treatment, an association between rituximab and cytomegalovirus meningoencephalitis cannot be ruled out. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Xochelli A.,G Papanicolaou Hospital | Kalpadakis C.,University of Crete | Gardiner A.,Royal Bournemouth Hospital | Baliakas P.,G Papanicolaou Hospital | And 21 more authors.
Blood | Year: 2014

The biological and clinical significance of a clonal B-cell lymphocytosis with an immunophenotype consistent with marginal-zone origin (CBL-MZ) is poorly understood. We retrospectively evaluated 102 such cases with no clinical evidence to suggest a concurrent MZ lymphoma. Immunophenotyping revealed a clonal B-cell population with Matutes score ≤2 in all cases; 19/102 were weakly CD5 positive and all 35 cases tested expressed CD49d. Bone marrow biopsy exhibited mostly mixed patterns of small B-lymphocytic infiltration. A total of 48/66 (72.7%) cases had an abnormal karyotype. Immunogenetics revealed overusage of the IGHV4-34 gene and somatic hypermutation in 71/79 (89.8%) IGHV-IGHD-IGHJ gene rearrangements. With a median follow-up of 5 years, 85 cases remain stable (group A), whereas 17 cases (group B) progressed, of whom 15 developed splenomegaly. The clonal B-cell count, degree of marrow infiltration, immunophenotypic, or immunogenetic findings at diagnosis did not distinguish between the 2 groups. However, deletions of chromosome 7q were confined to group A and complex karyotypes were more frequent in group B. Although CBL-MZ may antedate SMZL/SLLU, most cases remain stable over time. These cases, not readily classifiable within the World Heath Organization classification, raise the possibility that CBL-MZ should be considered as a new provisional entity within the spectrum of clonal MZ disorders. © 2014 by The American Society of Hematology.


Kalpadakis C.,University of Crete | Pangalis G.A.,University of Crete | Pangalis G.A.,National and Kapodistrian University of Athens | Angelopoulou M.K.,University of Crete | And 15 more authors.
Oncologist | Year: 2013

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. Fiftyeight received rituximab at a dose of 375 mg/m2 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 firstline treatment of choice for patients with SMZL. © AlphaMed Press 2013.


Kalpadakis C.,University of Crete | Pangalis G.A.,Athens Medical Center Psychikon Branch | Angelopoulou M.K.,National and Kapodistrian University of Athens | Sachanas S.,Athens Medical Center Psychikon Branch | Vassilakopoulos T.P.,National and Kapodistrian University of Athens
Expert Opinion on Orphan Drugs | Year: 2016

Introduction: Splenic marginal zone lymphoma (SMZL) represents a distinct entity within the spectrum of marginal zone lymphomas (MZL). Due to its rarity, treatment is not standardized. Areas covered: Currently two therapeutic options have been associated with the best outcome: splenectomy and rituximab. Splenectomy is associated with high response rates (~90%) with a median PFS>5 years. However, responses are not complete and it is associated with increased surgical risk as well as increased risk of septic episodes. Rituximab has shown significant efficacy with minimal toxicity in SMZL. The ORR is > 90%, with half of these responses being complete with a long duration of response. For the small proportion of SMZL with more aggressive clinical behavior, not responding or relapsing shortly after rituximab, novel agents are required. Several new drugs have shown significant activity in other low grade lymphomas. However, there is currently no trial testing the role of these agents specifically in SMZL. Expert opinion: Rituximab monotherapy currently represents the best choice for first line treatment for SMZL. Randomized studies are required in order to improve the outcome, especially for the small proportion of cases with the more aggressive clinical behavior. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Kalpadakis C.,University of Crete | Pangalis G.A.,Athens Medical Center Psychikon Branch | Vassilakopoulos T.P.,National and Kapodistrian University of Athens | Sachanas S.,Athens Medical Center Psychikon Branch | Angelopoulou M.K.,National and Kapodistrian University of Athens
Leukemia and Lymphoma | Year: 2014

Splenic marginal zone lymphoma (SMZL) is a rare chronic B-cell lymphoproliferative disorder recognized as a distinct entity in the World Health Organization (WHO) classification. SMZL usually runs an indolent clinical course with a median survival of more than 10 years. However, in a proportion of patients (10-20%) SMZL behaves more aggressively, with a median survival of less than 4 years. Many efforts are ongoing to establish commonly accepted prognostic factors as a guide to therapy for this disorder. Data on the treatment of SMZL come from reported retrospective series including relatively limited numbers of patients. Despite these limitations, much progress has recently been made in the management of patients with SMZL. The oldest and most commonly used first-line therapeutic modality is splenectomy, which offers rapid alleviation of splenomegaly-related symptoms along with an improvement of cytopenias in the majority of patients, with a median PFS of 5 years. However, SMZL is a systemic disease, and splenectomy is not carried out with eradicative intent. Furthermore, splenectomy is a major surgical procedure with significant morbidity or even mortality, especially in older patients. Chemotherapy has only moderate activity in this form of MZL. Recent data suggest that rituximab is a very effective therapy with minimal toxicity and could replace splenectomy as first-line treatment. The overall response rate is > 90%, with almost half of responses being complete, while the 5-year progression-free survival is approximately 70%. The combination of rituximab with chemotherapy requires further evaluation. Based on the current data, splenectomy could be abandoned as first-line treatment for patients with SMZL. © 2014 Informa UK, Ltd.


PubMed | University of Crete, 401 Military Hospital, National and Kapodistrian University of Athens and Athens Medical Center Psychikon Branch
Type: | Journal: BioMed research international | Year: 2014

Monoclonal B-cell lymphocytosis (MBL) is a premalignant condition characterized by the presence of less than 5000/L circulating clonal B cells in otherwise healthy individuals. Three subcategories have been identified according to the immunophenotypic features: CLL-like, CD5(+) atypical, and CD5(-) MBL. CLL-like MBL is by far the most frequent and best studied category and further divided in low-count [LC] and high-count [HC] MBL, based on a cutoff value of 500/L clonal B cells. LC-MBL typically remains stable and probably does not represent a truly premalignant condition, but rather an age-related immune senescence. On the other hand, HC-MBL is closely related to CLL-Rai0, bearing similar immunogenetic profile, and is associated with an annual risk of progression to CLL requiring therapy at a rate of 1.1%. Currently there are no reproducible factors for evaluating the risk of progression to CLL. CD5(-) MBL is characterized by an immunophenotype consistent with marginal zone origin and displays many similarities with marginal zone lymphomas (MZL), mainly the splenic MZL. The cutoff value of 5000/L clonal B cells cannot probably be applied in CD5(-) MBL, requiring a new definition to describe those cases.


PubMed | University of Crete, Evangelismos Hospital of Athens, National and Kapodistrian University of Athens and Athens Medical Center Psychikon Branch
Type: | Journal: Hematological oncology | Year: 2016

Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P<.0001). In addition, mutated cases displayed more frequently CD38 and CD25 positivity (P=.002 and P=.005, respectively). Moreover, cases without paraproteinemia presented more frequently with lymphocytosis, irrespective of the presence of the MYD-88 mutation (P=.02). The present study demonstrates that MYD-88 L265P mutation may represent the only sensitive marker for the differentiation of CBL-MZ from probable WM. However, further studies are warranted to better define the biological significance of MYD-88 L265P mutation and to clarify whether the presence of the mutation establishes WM diagnosis or that it can also be present in borderline cases associated with paraproteinemia.


Sachanas S.,Athens Medical Center Psychikon Branch andersen | Pangalis G.A.,Athens Medical Center Psychikon Branch andersen | Karouzakis P.,Athens Medical Center Psychikon Branch | Koulieris E.,Athens Medical Center Psychikon Branch andersen | And 4 more authors.
Anticancer Research | Year: 2016

Malakoplakia, a rare granulomatous disease of infectious etiology, is commonly observed in immuno-compromised patients. Chronic lymphocytic leukemia (CLL) is characterized by profound immune dysregulation resulting in significant infection-related morbidity and mortality, and several drugs used in CLL treatment have a severe immunosuppressive effect. Ibrutinib, has become a new standard-of-care in patients with CLL, especially for those harboring unfavorable genetic characteristics such as 17 p deletion, with however, unknown long-term immunological consequences. Here we report a case of a patient with CLL with 17 p deletion diagnosed with malakoplakia of the urinary bladder under ibrutinib therapy who developed severe hypogammaglobulinemia during treatment administration. Presumably, ibrutinib might contribute to the development of malakoplakia on the grounds of induced immunosuppression. This case report highlights the need for regular assessment of immunogammaglobulin adequacy during treatment with ibrutinib, considering that it should be given on a permanent basis.


PubMed | University of Crete, Evangelismos General Hospital and Athens Medical Center Psychikon Branch
Type: Journal Article | Journal: Anticancer research | Year: 2016

Malakoplakia, a rare granulomatous disease of infectious etiology, is commonly observed in immunocompromised patients. Chronic lymphocytic leukemia (CLL) is characterized by profound immune dysregulation resulting in significant infection-related morbidity and mortality, and several drugs used in CLL treatment have a severe immunosuppressive effect. Ibrutinib, has become a new standard-of-care in patients with CLL, especially for those harboring unfavorable genetic characteristics such as 17 p deletion, with however, unknown long-term immunological consequences. Here we report a case of a patient with CLL with 17 p deletion diagnosed with malakoplakia of the urinary bladder under ibrutinib therapy who developed severe hypogammaglobulinemia during treatment administration. Presumably, ibrutinib might contribute to the development of malakoplakia on the grounds of induced immunosuppression. This case report highlights the need for regular assessment of immunogammaglobulin adequacy during treatment with ibrutinib, considering that it should be given on a permanent basis.


Kansal R.,Cedars Sinai Medical Center | Kansal R.,University of California at Los Angeles | Nathwani B.N.,Cedars Sinai Medical Center | Nathwani B.N.,City of Hope National Medical Center | And 5 more authors.
Human Pathology | Year: 2015

We report a 13-year-old adolescent girl, the youngest thus far, with "an indolent T-lymphoblastic" proliferation (~10%) that uniquely presented within recurrent, large inguinal lymph node masses in a predominating (90%) background of Castleman disease. These nodal masses were resected thrice; the patient is well 5 years after diagnosis without further treatment. Histologically, the features of Castleman disease, hyaline vascular type, were present. Importantly, the interfollicular T-lymphoblastic component occurred as multiple clusters and islands of variable shapes and sizes composed of small "lymphoblasts" indistinguishable from normal cortical thymocytes but without thymic epithelial cells. Immunohistochemically, these lymphoblasts were consistent with the intermediate stage of T-cell differentiation (TdT+CD34-CD99+CD1a+CD2+CD3+CD4+CD8+CD5+CD7+CD10+ [subset]), with 80% Ki-67. Molecularly, the T cells were nonclonal. Our case provides evidence for the benign nature of this highly unusual and poorly understood entity; because the current terminology can be readily misinterpreted as an indolent lymphoblastic lymphoma, we suggest a new term accurately reflecting this entity. © 2015 Elsevier Inc.

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