Distinctive Patterns of Intraclonal Diversification In IGHV1-2*04 Immunoglobulin Receptors of Patients with Splenic Marginal Zone Lymphoma: A of Ongoing Interactions with Antigen?

Abstract Abstract 2638 We recently demonstrated that over 30% of cases with splenic marginal-zone lymphoma (SMZL) express distinctive immunoglobulin (IG) receptors that utilize a single polymorphic variant of the IGHV1-2 gene (IGHV1-2*04) and also exhibit restricted antigen-binding site motifs and precise targeting of somatic hypermutation (SHM). On these grounds, we proposed the existence of molecular subtypes of SMZL defined by immunogenetic analysis of the IG receptors with implications for selection by specific (super) antigenic element(s) in the development of at least a major subset of SMZL. In order to gain insight as to whether antigen involvement is relevant only prior to the malig…

Splenectomy influences bone marrow infiltration in patients with splenic marginal zone cell lymphoma with or without villous lymphocytes.

BACKGROUND Splenic marginal zone cell lymphoma (SMZL) is a low grade B-cell lymphoma in which patients can have circulating villous lymphocytes and can show a peculiar intrasinusoidal bone marrow (BM) infiltration. Splenectomy is the reported treatment of choice for these patients. The objective of this study was to evaluate the effects of splenectomy on patients with BM lymphomatous infiltration. METHODS BM biopsies of 16 patients with SMZL were studied morphologically and immunohistochemically. In 12 patients, BM biopsies were taken before and after splenectomy. Four patients did not undergo splenectomy, and their BM biopsies were performed with an approximately 1 year interval. RESULTS B…

Over 30% of Patients with Splenic Marginal Zone Lymphoma Express Distinctive Antigen Receptors Utilizing a Single Immunoglogulin Variable Gene: Implications for the Origin and Selection of the Neoplastic Cells

Abstract Abstract 634 We systematically explored the immunoglobulin (IG) gene repertoire in 337 cases with splenic marginal-zone lymphoma (SMZL), by far the largest series yet. To resolve classification uncertainties, we included in the analysis only cases with a diagnosis of SMZL based on spleen histopathological findings or cases fulfilling the 2008 SBLG criteria (Matutes et al. Leukemia 2008). We here report that the IG heavy variable (IGHV) gene repertoire in SMZL is remarkably biased, with only three genes accounting for 45.8% of cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23: 8.1%, respectively), significantly extending previous similar observations. Particularly for the IGHV1-2 gen…

Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report

Increase in the number of blood platelets to over 1 000 000/mm 3 in elderly patients is generally considered secondary to a myeloproliferative or neoplastic disease. To report the case of an elderly woman hospitalized for extreme thrombocytosis associated with severe anaemia, who was found to be suffering from coeliac disease. The patient, aged 83 years, was hospitalized presenting with fatigue. Laboratory tests showed microcytic hypochromic anaemia (haemoglobin 4 g/dl) and extreme thrombocytosis (platelet count 1 400 000/mm 3 ). Physical examination was normal, with the exception of marked thinness. There was no evidence of macroscopic bleeding from the gastrointestinal or genitourinary tr…

Differentiation on Biological Basis of Monoclonal B-Cell Lymphocytosis (MBL) From Chronic Lymphocytic Leukemia (CLL): Results of a Prospective GISL (Gruppo Italiano Studio Linfomi) Trial

Abstract Abstract 1360 The arbitrary cut-off of 5000/μL chronic lymphocytic leukemia (CLL)-phenotype cells in peripheral blood is generally used to separate monoclonal B-cell lymphocytosis (MBL) from CLL. However, a major concern is the biological differentiation, if any, between MBL and CLL. We tried to address the issue therefore analyzing 261 Rai stage 0 patients enrolled in a Gruppo Italiano Studio Linfomi (GISL) prospective multicentre trial designed to validate biological parameters in early CLL as well as to assess the impact on clinical outcome of an early versus delayed policy of treatment with subcutaneous alemtuzumab in the high biological risk. In this cohort, biological charact…

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin’s lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remiss…

Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications.

We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele *04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2*04 peaked at 31%. The IGHV1-2*04 rearrangements carried significantly lo…

T/NK “Nasal Type” Lymphomas: An Italian Cooperative Retrospective Survey.

Abstract T/NK “nasal type” lymphoma is a neoplasm that shows a peculiar geographical distribution. In fact most of the reported cases come from Far Eastern countries such as Hong Kong, and Central America, particularly from Mexico; this kind of lymphoma occurrs rarely in western countries. Between 1997 and 2004, 19 new cases of T/NK nasal type lymphoma were diagnosed in 7 Italian Hematology Division. Patients characteristics were as follows: all caucasian; 14 men and 5 women; median age 53 years (range 20–80). The presentation at the onset was in the nasal cavity or adjacent structures in 15 cases, who presented symptoms like nasal obstruction, dysphagia, orbital edema; in 2 cases, skin les…

Reply to Pich et al.: intrasinusoidal bone marrow infiltration and splenic marginal zone lymphoma: a quantitative study

Assessment of the frequency of additional cancers in patients with splenic marginal zone lymphoma

Abstract: Objectives: Solid second primary cancers (SPC) have become an issue of extensive research. The purpose of the present study was to estimate the standardised incidence ratio (SIR) and the absolute excess risk (AER) of SPC in patients with splenic marginal zone lymphoma (SMZL). Methods: We investigated the incidence of additional cancers in 129 patients consecutively diagnosed with SMZL in three Italian haematological centres, asking the cooperating doctors for additional information on initial and subsequent therapies and on the onset and type of second cancers. Results: Twelve SPC were recorded (9.3%); the 3- and 5-yr cumulative incidence rates were 5.5% and 18.3% respectively, wi…

Immunophenotypic profile and role of adhesion molecules in splenic marginal zone lymphoma with bone marrow involvement

Abstract Splenic Marginal Zone Lymphoma (SMZL), with or without villous lymphocytes (VL+/-), is a low-grade lymphoproliferative disorder with constant involvement of the bone marrow (BM). Different BM infiltration patterns, mainly intra-sinusoidal, interstitial and nodular, have been described. Adhesion molecules (AMs) constitute a heterogeneous group of antigenic receptors playing a major role in leukocyte recruitment, in lymphocyte homing and in cellular-mediated immune response. Evolution and pattern of the BM infiltrate could be influenced by a variable expression of AM on SMZL lymphocytes. The degree and pattern of BM infiltration and the immunohistochemical expression of AM (H-CAM, BL…

RUOLO DELL’INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO

-

Deoxycoformycin (pentostatin) in the treatment of splenic marginal zone lymphoma (SMZL) with or without villous lymphocytes.

: Background: Splenic marginal zone lymphoma (SMZL) is an infrequent B-cell neoplasm that pursues an indolent course. Signs and symptoms, mostly related to hypersplenism, are successfully managed by splenectomy. However, the therapy of patients who are not fit for a surgical procedure or who relapse after splenectomy, is still an unsettled issue. Patients and methods: We report a phase-II study on 16 patients with SMZL, three therapy naive and 13 pretreated, all showing systemic symptoms or progressive worsening of peripheral cytopenia, who were treated with pentostatin at a dose of 4 mg/m2 every other week for 6–10 wk. In relapsed patients, the median interval between diagnosis and treatme…

Hepatitis B Virus Reactivation and Alemtuzumab Therapy.

Abstract Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for haematological malignancies occurs in 21–53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 on lymphoid cells, produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed a full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab. Lam…

Anaplastic large cell lymphoma (CD30+/Ki-1+). Analysis of 35 cases followed at GISL centres

Between January 1988 and June 1992, 35 patients with primary anaplastic large cell lymphoma (ALCL)CD30+ were referred to one of the institutions participating in GISL (Gruppo Italiano per lo Studio dei Linformi). 16 patients were treated with ProMACE-CytaBOM, two with MACOP-B, one with CHOP and one with LSA2-L2. As of November 1990, all newly diagnosed patients were treated with MOPP/EBV/CAD hybrid. 27 (77%) cases of ALCL CD30+ and 8 (23%) cases of Hodgkin's-related (HR) lymphoma CD30+ were diagnosed. Extranodal disease was present in 22 cases (63%), and 8 patients (23%) had primary bone marrow involvement. Twenty-three complete remissions (CR) (66%), six partial remissions (PR) (17%) and s…

Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable?

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. Results: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (a…

Response-guided ABVD chemotherapy plus involved-field radiation therapy for intermediate-stage Hodgkin lymphoma in the pre-positron emission tomography era: a Gruppo Italiano Studio Linfomi (GISL) prospective trial.

Abstract Purpose In the pre—positron emission tomography era, the Gruppo Italiano Studio Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients. Patients and Methods Patients with stage I/II showing at least one adverse prognostic factor and stage IIIA without adverse prognostic factors were recruited. Treatment included a first step of 3 ABVD courses, followed by an early-restaging. Patients in CR/CRu received 1 additional ABVD cycle, patients in PR received 3 more ABVD, and nonresponder patients went off study. Involved-fi…

Splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a specific low-grade small B-cell lymphoma that is incorporated in the World Health Organization classification. Characteristic features are splenomegaly, moderate lymphocytosis with villous morphology, intrasinusoidal pattern of involvement of various organs, especially bone marrow, and relative indolent course. Tumor progression with increase of blastic forms and aggressive behavior are observed in a minority of patients. Molecular and cytogenetic studies have shown heterogeneous results probably because of the lack of standardized diagnostic criteria. To date, no definitive therapy has been established. Therapeutic options include treatment absten…

The clinical value of tumor burden at diagnosis in Hodgkin lymphoma

BACKGROUND The authors investigated the clinical role of tumor burden (TB) in patients with Hodgkin lymphoma, relating this parameter to most of the current clinical and prognostic factors and to the best predictive multifactorial models. METHODS The volume of TB at diagnosis was measured directly from the initial staging computed tomography scans in 351 patients who were treated on standard protocols. The mean patient age was 34.0 years ± 16.4 years. Forty-six patients had clinical Stage I disease, 201 patients had Stage II disease, 64 patients had Stage III disease, and 40 patients had Stage IV disease. There were 146 symptomatic patients. Overall survival (OS), disease-free survival (DFS…

Angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive neoplasm clinically characterized by sudden onset of constitutional symptoms, lymphadenopathy, hepatosplenomegaly, frequent autoimmune phenomena, particularly hemolytic anemia and thrombocytopenia, and polyclonal hypergammaglobulinemia. The lymph node histological picture is also distinctive, constituted by a polymorphic infiltrate, a marked proliferation of high endothelial venules, and a dense meshwork of dentritic cells. The neoplastic CD4+ T-cells represent a minority of the lymph node cell population; its detection is facilitated by the aberrant expression of CD10. Almost all cases arbor an EBV infected B-cell populatio…

Comparison of prognostic models in patients with advanced Hodgkin disease

Several prognostic systems have been elaborated for patients with Hodgkin disease (HD) over the last 12 years, but early identification of a reasonably large group of both low and high risk, advanced stage patients remains unsatisfactory.Seven well known models were applied to 516 patients with advanced HD, with 315 patients used for the study sample and 201 patients used for the test sample. Individual performances as well as joint performances were analyzed univariately and multivariately in relation to overall survival, recurrence free survival, and time to treatment failure by means of a proportional hazards model.None of the models identified a group containing10% of patients from the …

Interim 18f-PDGPET for Aggressive Non-Hodgking's Lymphoma: A Systematic Review and Meta-Analysis

Abstract Abstract 5183 Background: The advantage of using interim 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) scan in the clinical work-up of patients with non-Hodgkin's lymphoma (NLH) is unclear. Data from meta-analyses are inconclusive, mainly because of the low number of patients evaluated and heterogeneity among studies. New clinical investigations, focused on this topic, have been recently published. We conducted an updated systematic review on the role of 18PDG-PET for the interim evaluation in patients with aggressive lymphomas. Materials and Methods: Medline, Embase, Scopus and Databases were searched for relevant studies through March 2011. We included studies t…

Human cytomegalovirus glycoprotein B genotypes in immunocompetent, immunocompromised, and congenitally infected Italian populations

Human cytomegalovirus (HCMV) strains, obtained from immunocompetent and immunocompromised Italian hosts, were typed with glycoprotein B (gB) gene restriction analysis. A predominant circulation of HCMV strains with gB type 2 and 3 was detected in both the immunocompetent host with a primary HCMV infection and the immunocompromised host with or without HCMV disease. No association between gB types and subjects with different risks of developing HCMV disease was found. All four gB genotypes were capable of causing congenital infection in Italian babies, with gB type 1 accounting for 50% of the strains examined in symptomatic infants and a remarkable incidence of gB type 4 viruses.

A rapidly progressive motor neuron disease associated to a natural killer cells leukaemia

une system play a complex role, either protective or toxic, in ALS pathogenesis [1–3]. In particular, compelling evidence indicate that increased blood level of natural killer (NK) and NK-T cells may contribute to the disease development and progression [2,3]. Here, we report on a patient with an aggressive Motor Neuron Disease (MND) associated with NK/NK-T cells leukaemia. 1. Case report A 79-year-old man presented with several months-history of a progressive atrophy and weakness of the upper limbs, which quickly spread to the lower limbs. Onset was subtle and apparently occurred in the month of July (the specific date is not shown for privacy), when the patient noticed a mild weakness in …

Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study

Rituximab ® provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP). Fifty-one patients were eligible for the analysis. The overall response rate was 84%. The 6-year progression-free survival and overall survival were 54% and 72%, respectively. Toxicity was substantial (grade ≥ 3 neutropenia: 26%; grade ≥ 3 infections: 8%).…

Use of intrapleural bortezomib in myelomatous pleural effusion

Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria

Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992, an increasing number of publications have dealt with multiple aspects of SMZL diagnosis, molecular pathogenesis and treatment. This process has identified multiple inconsistencies in the diagnostic criteria and lack of clear guidelines for the staging and treatment. The authors of this review have held several meetings and exchanged series of cases with the objective of agreeing on the main diagnostic, staging and therapeutic guidelines for patients with this condition. Specific working groups were created for diagnostic criteria, immunophenotype, staging and treatment. As results of this work, guidelines are pr…

Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma

BACKGROUND. The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS. One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EFRT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp sched…

No association between human herpesvirus type 8 infection and multiple myeloma.

Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day −1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follo…

Splenic lymphangiomatosis showing rapid growth during lactation: a case report.

Splenic lymphangiomatosis is a very rare condition that, from 1990 to date, has been described only nine times. In the present report, we describe the first case of splenic lymphangiomatosis with rapid growth during lactation in a 35-year-old woman. We also underline the difficultly in making an accurate preoperative diagnosis, despite more modern imaging techniques. Total splenectomy was considered to be the treatment needed, both to make a definitive diagnosis and to exclude the presence of malignancy.

Methodological Issues in the Baffling Relationship Between Hepatitis C Virus and Non Hodgkin’s Lymphomas

The association between Hepatitis C Virus infection and B-cell Non-Hodgkin’s Lymphoma has been the matter of several studies: they showed disagreeing results with a marked regional variability. In this paper we present a review of the literature, highlighting methodological issues and main statistically critical aspects. Review suggests that studies were often not methodologically well approached. Moreover, we present main results from an original case-control study conducted in Italy, in an area of high endemicity of Hepatitis C Virus infection. In particular, we put attention in selection of a properly matching control group and in the role of age as a confounding variable.

Are blood donors an adequate control group to ascertain HCV prevalence in non-Hodgkin’s lymphoma patients?

CD146+ bone marrow osteoprogenitors increase in the advanced stages of primary myelofibrosis

Abstract CD146+ bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. In this study we used immunohistochemical analysis to investigate the contribution of CD146+ bone marrow osteoprogenitors to the stromal remodeling occurring in the different stages of primary myelofibrosis. We found that CD146+ cells sited at the abluminal side of the bone marrow vessels and branching among hematopoietic cells significantly increased in the advanced stages of primary myelofibrosis (p<0.001), paralleling the extent of fibrosis (r=0.916, p<0.0001) and the microvascular density (r=0.883, p<0.0001). Coherently with a…

How I diagnose and treat splenic lymphomas.

Abstract The incidental finding of an isolated splenomegaly during clinical assessment of patients evaluated for unrelated causes has become increasingly frequent because of the widespread use of imaging. Therefore, the challenging approach to the differential diagnosis of spleen disorders has emerged as a rather common issue of clinical practice. A true diagnostic dilemma hides in distinguishing pathologic conditions primarily involving the spleen from those in which splenomegaly presents as an epiphenomenon of hepatic or systemic diseases. Among the causes of isolated splenomegaly, lymphoid malignancies account for a relevant, yet probably underestimated, number of cases. Splenic lymphoma…

Paroxysmal nocturnal haemoglobinuria: When delay in diagnosis and long therapy occurs

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by hemolytic anemia, bone marrow failure and thrombosis, caused by a somaticmutation in PIG-A gene that results in theabsence of CD55 and CD59, two important complement regulatory proteins. In thispaper, a case of PNH is retrospectively examined looking for clinical and laboratory features, and the entire course of the disease from the onset of the symptoms isdescribed, together with an adequate follow-up over a 7-years treatment period. Inthis case, the not specificity and the limited clinical relevance of the symptoms led to adelay in diagnosis. After thrombosis, Eculizumab therapy has been shown to be effec…

Efficacy of bendamustine and rituximab in splenic marginal zone lymphoma: results from the phase II BRISMA/IELSG36 study.

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method. The primary endpoint was complete response rate. Fifty-six patients with SMZL diagnosis confirmed on central revis…

Splenic marginal zone lymphoma with or without villous lymphocytes

BACKGROUND Splenic marginal zone lymphoma (SMZL) is a well defined pathologic entity. However, questions regarding the bone marrow infiltration rate, the minimal diagnostic data set, and therapy remain unanswered. METHODS Clinical-pathologic features and outcomes of 57 consecutive patients who had splenomegaly with no clinically significant lymphadenomegaly and who were diagnosed with SMZL with or without (±) villous lymphocytes (VL) were reviewed. RESULTS SMVL ± VL occurred mostly in elderly males (median age, 62 years ± 10 years; male-to-female ratio, (1.85). Anemia was recorded in 49% of patients, and 30% of patients had moderate thrombocytopenia. Leukocytosis and leukopenia were found i…

Hepatosplenic γδ T-cell lymphoma: complete response induced by treatment with pentostatin

Higher frequency of HCV in patients with non-Hodgkin lymphoma: Is it enough to suggest an association with B-cell NHL?

Successful treatment of resistant thrombotic thrombocytopenic purpura/hemolytic uremic syndrome with autologous peripheral blood stem and progenitor (CD34+) cell transplantation

The first-line treatment of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS syndrome) induces a response and survival rate of approximately 85%, even if a considerable number of patients relapse; nevertheless, a number of these patients are resistant to conventional management. Immunoablation followed by stem cell transplantation has been shown to be capable of inducing remissions in a large spectrum of experimental autoimmune disorders. We report here the case of a 20-year-old male patient with the TTP-HUS syndrome who was resistant to conventional treatment and was transplanted with autologous immunoselected CD34+ PBPC after conditioning with cyclosphosphamide, anti…

FIRST APPLICATION OF MINIMAL RESIDUAL DISEASE ANALYSIS IN SPLENIC MARGINAL ZONE LYMPHOMA TRIALS: PRELIMINARY RESULTS FROM BRISMA/IELSG36 PHASE II STUDY

Pre-Emptive Treatment with Cidofovir for Cytomegalovirus Antigenemia in Autologous Bone Marrow Recipient and CLL Patients on Therapy with Alemtuzumab.

Abstract Cytomegalovirus (CMV) is an important cause of morbidity and mortality in patients who have undergone severe immunosuppressive therapy. Ganciclovir continues to be the first choice for pre-emptive therapy, but it needs multiple intravenous daily administration for three weeks and may cause myelosuppression. Cidofovir is a non myelotoxic nucleotide analogue effective against CMV; its favourable pharmacokinetic profile allows a once-a-week dosing. We reviewed a database on 110 consecutive Autologous Stem Cell Transplant (ASCT) and that of 15 Chronic Lymphocytic Leukemia (CLL) patients treated with alemtuzumab. All patients were virologically monitored by quantification of pp65 antige…

Use of intrapleural bortezomib in myelomatous pleural effusion [1]

Gamma-delta T-cell lymphomas.

Peripheral T-cell lymphomas (TCLs) are uncommon neoplasms, accounting for about 12% of all lymphoid tumors worldwide. TCLs in which gammadelta T-cell receptors are expressed (gammadelta TCLs) are extremely aggressive and rare (<1% of lymphoid neoplasms). gammadelta TCLs originate from gammadelta T cells, a small subset of peripheral T cells with direct antigen recognition capability acting at the interface between innate and adaptive immunity. Two distinct gammadelta TCL entities are recognized: hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous gammadelta T-cell lymphoma (PCGD-TCL). HSTL is a well-characterized extranodal lymphoma that has a disguised onset, secondary to intrasinus…

Prognostic features of splenic lymphoma with villous lymphocytes

Different immunophenotypical apoptotic profiles characterise megakaryocytes of essential thrombocythaemia and primary myelofibrosis.

Aims: Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as “key-cells”. The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders. Methods: Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax,…

Re: ?Splenic marginal zone B-cell lymphoma associated with primary Sj�gren?s syndrome?

We describe a 67-year-old woman with primary Sjögren's syndrome who developed a splenic marginal zone B-cell lymphoma, and complained of a dry mouth and Raynaud's phenomenon. She had splenomegaly, swollen lymph nodes and monoclonal IgM-kappa cryoglobulin. After splenectomy, Raynaud's phenomenon had improved with the decrease of cryoglobulin. This is the first case of primary Sjögren's syndrome with splenic marginal zone B-cell lymphoma to be reported.

Bone marrow biopsy in hemophagocytic syndrome.

Abstract Aims. Hemophagocytic syndrome (HPS) is a severe and acute clinical event occurring with fever, hepatosplenomegaly, and pancytopenia due to uncontrolled phagocytosis of blood cells and precursors. Although HPS represents a secondary phenomenon, it can mask the underlying condition, generally a neoplastic or infective disease, thus making the patient management rather difficult. The aims of this study were to point out the main pathological features useful to highlight the primary disease and show the eventual discrepancies among the different cases. Methods and results. Bone-marrow biopsies (BMBs) of 26 patients with HPS were morphologically and immunophenotypically evaluated; the p…

Continuous intravenous infusion of dipyridamole as adjunctive therapy in the treatment of thrombotic thrombocytopenic purpura.

Abstract Thrombotic thrombocytopenic purpura (TTP) is an uncommon hematologic thrombotic disorder characterized by fever, hemorrhagic and neurologic signs. The advent of plasma exchange has dramatically improved the prognosis of this disease, which was once inevitably fatal. However, mortality rates remain significant. Antiplatelet drugs have been widely used in combination with plasma exchange. In this pilot study we investigated the effects of an adjunctive therapy consisting of the continuous, intravenous infusion of dipyridamole, a modality of administration that has not been previously tested in this setting. Sixteen untreated TTP patients, diagnosed consecutively at our clinic, receiv…

Response-based chemotherapy and involved field radiation for intermediate stage Hodgkin disease. A GISL/NHLSG trial.

Abstract Background. Most of the patients with advanced stage Hodgkin lymphoma can be cured with a standard course of six cycle of ABVD chemotherapy plus involved field (IF)radiotherapy. Patients with less advanced stage or with a more responsive disease could possibly achieve a cure with a shorter course of chemotherapy. In 1992, in the pre-PET era, the GISL addressed the issue of the proper number of chemotherapy cycles planning a response-oriented, ABVD-based study for intermediate-stage Hodgkin’s lymphoma patients. Patients and Methods. From January 1992 to December 2002, 218 patients younger than 70 were enrolled. Eligible patients had histologically confirmed and clinically staged Hod…