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Nodal marginal zone lymphoma (NMZL) is one of the three well-recognized entities within the broad category of marginal zone lymphoma, representing approximately 10% of the cases in this group. Patients typically present with nodal disease, usually at advanced stages, and a thorough work-up and staging are necessary in order to exclude occult extranodal involvement. NMZL shares many similarities with splenic marginal zone (SMZL) and mucosa-associated lymphoid tissue (MALT) lymphomas, such as cytology, immunophenotype, genetic abnormalities and maybe even a common cell of origin: a post-germinal memory B-cell. NMZL is characterized by an indolent course, but its prognosis is generally considered less favorable than that of SMZL and MALT lymphoma, with reported 5-year overall survival rates ranging between 55% and 89%. Therapeutic recommendations for NMZL are derived from small retrospective series or studies on larger cohorts of indolent lymphomas, which include a limited number of patients with NMZL. For localized disease, radiotherapy appears to be the treatment of choice, while rituximab-containing therapy is recommended for advanced stage disease. Due to the rarity of NMZL it is very difficult to perform prospective trials, and an international collaborative effort is necessary in order to better understand the biological features and provide evidence-based treatment recommendations. [ABSTRACT FROM AUTHOR]

Following chemotherapy and/or the administration of growth factors, such as granulocyte-colony stimulated factor (G-CSF), hematopoietic stem cells (HSC) mobilize from bone marrow to peripheral blood. This review aims to systematically present the structure of the HSC "niche" and elucidate the mechanisms of their mobilization. However, this field is constantly evolving and new pathways and molecules have been shown to contribute to the mobilization process. Understanding the importance and the possible primary pathophysiologic role of each pathway is rather difficult, since they share various overlapping components. The primary initiating event for the mobilization of HSC is chemotherapy-induced endogenous G-CSF production or exogenous GCSF administration. G-CSF induces proliferation and expansion of the myelomonocytic series, which leads to proteolytic enzyme activation. These enzymes result in disruption of various receptor-ligand bonds, which leads to the disanchorage of HSC from the bone marrow stroma. In everyday clinical practice, CXC chemokine receptor-4 (CXCR4) antagonists are now being used as mobilization agents in order to improve HSC collection. Furthermore, based on the proposed mechanisms of HSC mobilization, novel mobilizing agents have been developed and are currently evaluated in preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the toxicity in patients with relapsed hairy cell leukemia who are treated with rituximab.

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 (≤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 ≥45 years, leukocytosis ≥10 × 109/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. [Copyright &y& Elsevier]

Delayed megakaryocytic engraftment occurs in approximately 8 percent of patients undergoing autologous transplantation with PBPCs, and a reliable assay to predict engraftment is not yet available. The correlation between human cell engraftment in a mouse xenotrans- plantation model with the rate of megakaryocytic recovery for individual patients after autologous PBPC transplantation was evaluated. Engraftment into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) and NOD-SCID-β2mnull mice was compared for patients with rapid (11 days) PLT recovery (good engrafters, GEs) versus those with delayed (18 days) PLT engraftment (poor engrafters, PEs). PBPCs (1 × 106 CD34+ cells) were transplanted into sublethally irradiated (300 cGy) mice, and human WBC and human PLT engraftment were analyzed by FACS in the blood weekly. Human WBCs and human CFU-megakaryocytes (Mks) in the marrow were determined 6 to 7 weeks after transplant. Six PEs and five GEs were analyzed. Four of six PEs showed no human cell engraftment, whereas five of five GEs showed multilineage human hematopoiesis including the presence of CFU-Mks. Human WBC engraftment and human CFU-Mks differed significantly between GEs and PEs (p < 0.01). NOD-SCID-β2mnull had significantly higher levels of human engraftment than NOD-SCID mice (p < 0.05). The two PEs whose PBPCs were capable of engrafting in the mice had underlying liver abnormalities that may have played a role in their delayed engraftment. Time to PLT recovery in patients correlates strongly with human PLT and human WBC engraftment and with the number of human CFU-Mks (p < 0.05) in a xenogeneic transplant model. This model may be useful for future studies to test therapeutic strategies for enhancement of engraftment. [ABSTRACT FROM AUTHOR]

Abstract: 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 (FF 2 P). 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 FF 2 P was 24%, while the 10-yr survival after relapse (O 2 S) 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), >=5 involved sites at diagnosis ( P =0.04) and anemia at relapse ( P =0.03) were independent predictors of FF 2 P. 55% of patients had 0 or 1 of these adverse prognostic factors. The 5-yr FF 2 P of patients with 0, 1 or 2 adverse factors was 58%, 34% and 5% ( P <0.0001). The corresponding rates for 10-yr O 2 S 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. [ABSTRACT FROM AUTHOR]

Abstract: 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, CD11α 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 × 109 /l, lymphoma cells 5.0 × 109 /L, and at 6 months post-splenectomy, Ht 43%, platelets 311 × 109 /l and lymphoma cells 3.0 × 109 /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... [ABSTRACT FROM AUTHOR]

Pulmonary involvement in Waldenström’s macroglobulinaemia (WM) occurs in 3–5% of cases, but lung involvement without bone marrow infiltration is extremely rare. We report 2 patients who presented with bilateral consolidations on chest X-ray and non-specific symptoms and were treated for a long period of time for pulmonary infections until the diagnosis was made by open lung biopsy. Both patients presented high monoclonal IgM in the serum and one also had blood lymphoplasmacytosis. Trephine bone biopsy and bone marrow smears were normal and there was no other site of involvement. Along with the presentation of our patients, we review the literature, discuss some of the possible underlying mechanisms and raise the attention of clinicians to this rare manifestation of the disease.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Evaluates the histochemical expression of retinoblastoma gene product (pRb) and WAF1/Cip1 in patients with non-Hodgkin's lymphomas (NHL). Patient characteristics; Detection of pRb in all cases of NHL; Percent of cases with p21 protein detection; Absence of significant prognostic value of pRb and p21 expression.

Determines the efficiency of recombinant human erythropoietin in the restoration of disease-related anemia in B-chronic lymphoproliferative disorders. Demonstration of whether the correction is related to the serum erythropoietin levels before treatment; Comparison of the degree of response with patients' clinical status.

Reports on a patient with primary non-Hodgkin's lymphoma of the gallbladder. Diagnosis of the patient as a T-cell lymphoblastic lymphoma; Inclusion of surgery and postoperative chemotherapy as part of treatment modalities; General prognosis for the disease; Achievement of complete remission.

Evaluates the efficacy of Epirubicin, Bleomycin, Vinblastine and Decarbazine (EBVD) combination chemotherapy followed by low dose involved field radiation therapy in patients with clinical stage I-IIA Hodgkin's disease. Dose administration; Survival rate of patients; Percentage of reduction of tumor load; Response rate.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD. [ABSTRACT FROM AUTHOR]

PET/CT was not performed prior to surgery but the localized nature of the lesion was confirmed by the negative post-surgery PET/CT after the complete resection of the lesion, which had been transformed to anaplastic large cell lymphoma (ALK-negative). It is important to note that there were no other patients within the two cohorts of pediatric and adult cHL patients with 9 and 410 relapsed/refractory cases respectively, in whom a surgery-only approach was applied and failed. At least 70-80% of the patients with Hodgkin lymphoma (HL) can be cured with first-line therapy with the improvement of staging methods and the introduction of increasingly effective chemotherapy regimens during the last 50 years [[1]]. [Extracted from the article]

No abstract available [ABSTRACT FROM AUTHOR]

The article features commentaries on the paper presented by Van Grotel and others on the treatment of pediatric nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL), with only chemotherapy without alkylating agents. While positively commenting on the work, further investigation of the results with the addition of rituximab to the standard anthracycline-based chemotherapy is recommended. NLPHL is considered an indolent disease, and less toxic treatment even in cases of multiple relapses.

Chronic myelogenous leukemia at blast crisis with a T-cell phenotype (T-ALL CML-BC) at diagnosis, without any prior history of CML is extremely rare. After the introduction of tyrosine kinase inhibitors (TKIs), CML patients have a median survival comparable to general population and accelerated/blast crisis are rarely encountered. Most CML patients (80%) transform into acute myeloid leukemia and the rest into B-ALL. Anecdotal cases of Ph+ T-ALL, either de novo or in the context of CML-BC have been reported. Left shift in the blood, the presence of splenomegaly/extramedullary infiltration and the occurrence of BCR::ABL1 rearrangement in both the blastic population, as well as in the myeloid cell compartment are key points in differentiating de novo Ph+ T-ALL from T-ALL CML-BC. The latter is a rare entity, characterized by extramedullary disease, p210 transcript and clonal evolution. Lack of preceding CML does not rule out the diagnosis of T-ALL CML-BC. Prompt TKI treatment with ALL-directed therapy followed by allogeneic stem cell transplantation may offer long-term survival in this otherwise poor prognosis entity. In this paper, we describe a patient with T-ALL CML-BC at presentation, still alive 51 months after diagnosis and we offer a review of the literature on this rare subject. All clinical and laboratory features are provided in order to distinguish de novo Ph+ T-ALL from T-ALL CML-BC, underscoring the prognostic and therapeutic significance of such a differentiation. [ABSTRACT FROM AUTHOR]

Yet, the description of a polymorphic cell infiltration in LN biopsy, the absence of clinical lymphadenopathy at presentation, the history of psoriatic arthritis as well as the preceded treatment with anti-tumor necrosis factor (TNF)- and cyclosporine raised diagnostic concerns. Although the patient could not finally avoid R-CHOP immunochemotherapy, this case highlights that a trial of NBA withdrawal under very close monitoring could be a rational therapeutic choice even in patients with aggressive ID-LPDs. Keywords: diffuse large B-cell lymphoma; psoriasis; infliximab; apremilast; novel biologic agent; anti-TNF EN diffuse large B-cell lymphoma psoriasis infliximab apremilast novel biologic agent anti-TNF 1695 1700 6 10/12/23 20231001 NES 231001 The association of psoriasis with cancer has been a matter of debate, especially in the era of the novel biologic agents (NBA). Lastly, taking into consideration our case with the re-appearance of the lymphoma despite the change of NBA as well as all the other cases described in Table 1, the appearance of LPDs in psoriatic patients is a more complex process influenced by clinical disease duration and extension, the time length of immunosuppression and the nature of the various treatments administered. [Extracted from the article]

The long-term survival of Hodgkin lymphoma (HL) patients treated according to the current standard of care is excellent. Combined-modality schedules (ABVD plus radiotherapy) in early-stage disease, along with treatment intensity adaptation to early metabolic response assessed by PET/CT in advanced stage HL, have been the cornerstones of risk stratification and treatment decision-making, minimizing treatment-related complications while keeping efficacy. Nevertheless, a non-negligible number of patients are primary refractory or relapse after front-line treatment. Novel immunotherapeutic agents, namely Brentuximab Vedotin (BV) and immune checkpoint inhibitors (CPI), have already shown outstanding efficacy in a relapsed/refractory setting in recent landmark studies. Several phase 2 single-arm studies suggest that the addition of these agents in the frontline setting could further improve long-term disease control permitting one to reduce the exposure to cytotoxic drugs. However, a longer follow-up is needed. At the time of this writing, the only randomized phase 3 trial so far published is the ECHELON-1, which compares 1 to 1 BV-AVD (Bleomycin is replaced by BV) with standard ABVD in untreated advanced-stage III and IV HL. The ECHELON-1 trial has proven that BV-AVD is safe and more effective both in terms of long-term disease control and overall survival. Just recently, the results of the S1826 SWOG trial demonstrated that the combination nivolumab-AVD (N-AVD) is better than BV-AVD, while preliminary results of other randomized ongoing phase 3 trials incorporating anti-PD-1 in this setting will be soon available. The aim of this review is to present the recent data regarding these novel agents in first-line treatment of HL and to highlight current and future trends which will hopefully reshape the overall management of this disease. [ABSTRACT FROM AUTHOR]

Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial alliance/CALGB 50303. The latter do not carry concurrent c-myc/bcl-2 and/or bcl-6 rearrangements and usually have the morphology of HGBL with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (HGBL-DLBCL/BL). Dear Editor, In the 2016 WHO classification, HGBL was defined as a separate entity, classified into double/triple-hit lymphomas and HGBL not otherwise specified (HGBL-NOS). [Extracted from the article]

We have analyzed the immunohistochemical expression of a wide range of molecules along with the proliferation rate separately in the proliferation centers (PCs) and in the rest of the tumor area, in lymph node or spleen sections of patients with chronic lymphocytic leukemia (CLL). Fas, FasL and c-FLIP were observed both within and outside the PCs in all cases. However, only the difference in FasL expression between the PCs and the non-PC areas attained statistical significance. Median survivin expression in the PCs was higher compared to the non-PC areas. Cleaved caspase 3 was expressed at very low levels both within and outside PCs, while BCL-2 protein was expressed at high levels in all cases in both tumor compartments. Multivariate analysis demonstrated that concurrent overexpression of Fas/FasL/c-FLIP in the PCs was correlated with worse outcome for progression-free survival as well as for overall survival. [ABSTRACT FROM AUTHOR]

Abstract: Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal stem cell (SC) disorders that mainly affect the elderly population. They are characterized by ineffective hematopoiesis which results in quantitative and qualitative cellular defects and high incidence of leukemic transformation. Recent advances in MDS research have led to the development of novel agents which appears to improve remission rates and survival when compared to best supportive care. Currently azacitidine, decitabine, and lenalidomide are approved by the US FDA for the treatment of MDS, while the activity of other novel agents such as histone deacetylase inhibitors, farnesyl-transferase inhibitors, novel thrombopoietic agents, and anti-angiogenesis molecules is under evaluation. Erythropoietin-stimulating agents, iron chelating therapy and thrombopoietin receptor ligands may also improve quality of life and possibly prolong survival in MDS patients. The only treatment modality that can achieve long-term survival is the allogeneic SC transplantation which is given only in selected patients. Moreover the heterogeneity of MDS and the patient''s advanced age and co-morbidity are significant factors besides cytogenetics, IPSS and WPSS that should be taken into account during the decision-making process. Therefore clinicians should treat patients with MDS on an individual basis aiming the increase of the response rates and the decrease of treatment-associated toxicities. This can only be achieved through the better understanding of the MDS subgroups. If we can better define MDS subgroups we will be able to identify patients who will benefit from the incorporation of the novel agents, as monotherapy or in combinations regimens along with supportive care. [Copyright &y& Elsevier]

The article discusses research which was conducted to determine the validity of the simplified risk stratification/ prognostic score of the Splenic Marginal Zone Lymphoma Working Group in patients with splenic marginal zone lymphoma. Researchers evaluated 177 patients with a median age of 65. They found that the working group's prognositic system was valid.

Summary: The expression patterns and prognostic significance of sterile alpha motif and HD domain‐containing protein 1 (SAMHD1) protein in the neoplastic Hodgkin and Reed Sternberg (HRS) cells of Hodgkin lymphoma (HL) were investigated in a cohort of 154 patients with HL treated with standard regimens. SAMHD1 expression was assessed by immunohistochemistry using diagnostic lymph node biopsies obtained prior to treatment. Using an arbitrary 20% cut‐off, SAMHD1 was positive in HRS cells of 48/154 (31·2%) patients. SAMHD1 expression was not associated with clinicopathologic parameters, such as age, gender, stage or histologic subtype. In 125 patients with a median follow‐up of 90 months (7–401 months), SAMHD1 expression in HRS cells significantly correlated with inferior freedom from progression (FFP) (P = 0·025), disease‐specific survival (DSS) (P = 0·013) and overall survival (OS) (P = 0·01). Importantly, in multivariate models together with disease stage, histology subtype and type of treatment as covariates, SAMHD1 expression retained an independent significant association with unfavourable FFP (P = 0·005) as well as DSS (P = 0·022) and OS (P = 0·018). These findings uncover the significance of a novel, adverse prognostic factor in HL that may have therapeutic implications since SAMHD1 inhibitors are now available for clinical use. [ABSTRACT FROM AUTHOR]

Introduction: Venous blood (VB) sampling for complete blood count (CBC) via venipuncture is the basic method for the daily evaluation of hematological patients. However, several issues during this process, such as venipuncture difficulty and repetitive attempts, may cause pain, phlebitis, hematomas, inadequate sampling, and patient discomfort. Capillary blood (CB) sampling could be an alternative and less painful solution for the patient. The purpose of this study was the comparative evaluation of basic CBC parameters, as counted from venous and capillary blood samples. Methods: During the period 06/2016‐06/2019 in which the study was conducted, 1634 automated counts of VB or CB were performed, derived from 425 hematological hospitalized patients. Bland‐Altman plots were performed to show the agreement of VB and CB counts of common hematological parameters (Hb, Hct, WBC, absolute neutrophil count‐[ANC], RBC, Plt, MCV, MCH), using two different hematology analyzers (Mindray BC‐3000 Plus Auto and Sysmex XE‐5000). Clinical significance of CB sampling was assessed by applying specific clinically significant cutoffs for Hb, ANC, and Plt. Results: All measured parameters revealed a significant correlation (r >.9) between CB and VB samples, irrelatively of the hematology analyzer used. CB measurements of Hb, ANC, and Plt, at different clinically important cutoff levels, showed excellent sensitivity (87%‐100%), specificity (95%‐100%), positive predictive value, and negative predictive value (87%‐100% and 90%‐100%, respectively). Conclusion: Capillary blood and VB counts in hematological patients were equivalent for most basic hematological parameters. Hb, ANC, and Plt CB counts revealed clinically significant performance, indicating that they can reliably substitute VB sampling in the day work. [ABSTRACT FROM AUTHOR]

Marginal zone lymphomas represent approximately 10–12% of all B-cell lymphomas. Extranodal marginal zone lymphomas (EMZL) or mucosa-associated lymphoid tissue (MALT) lymphomas are the most common subtype. Almost half of all MALT lymphomas arise in the gastrointestinal (GI) tract and, while the stomach is the most common site of GI involvement, the small and large intestines can also be involved. Rare cases of MALT lymphoma involving the rectum have been reported; however, to our knowledge, involvement of the anal canal has never been reported in the literature. Here, we describe a unique case of MALT lymphoma of the anal canal. Infectious agents have been implicated in the pathogenesis of MALT lymphomas, possibly through persistent antigenic stimulation of the area; however, in our case no such infection was documented. [ABSTRACT FROM AUTHOR]

The article discusses the treatment of splenic marginal zone lymphoma (SMZL) and the lack of randomized trials, highlighting the use of rituximab infusions for the treatment. It examines the bone marrow for complete response (CR), the impact of rituximab on the disease progression, and the overall survival (OS) rate.

Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients' sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization. Poor mobilizers had significantly higher carboxy-terminal telopeptide of collagen type I (CTX) and lower ANGP-1 at pre-mobilization samples, compared to good ones. CTX, amino-terminal telopeptide of collagen type I (NTX) and ANGP-1 pre-mobilization levels correlated significantly with circulating CD34+ peak cell counts. Our results indicate that bone formation and vessel destabilization are the two major events during human HSC mobilization. Osteoblasts seem to be the orchestrating cells, while osteoclasts are stimulated but not fully active. Moreover, ANGP-1, CTX and NTX may serve as predictors of poor mobilization. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: As the interaction between hematopoietic stem cells (HSCs) and endosteal and endothelial niches in HSCs homing is essential, we aimed to study bone turnover and angiogenesis in 29 patients with lymphoma/multiple myeloma undergoing hematopoietic stem cell transplantation (HSCT). Methods: Serum samples were collected before high‐dose chemotherapy (HDT), at the end of HDT, after HSC infusion, at the nadir of myelotoxicity, and at engraftment. Bone metabolism (CTX, TRACP‐5b, bALP, OC, DKK1, RANKL, OPG), and angiogenesis (Ang1, Ang2) markers were measured. These markers were also measured in 21 control patients before and after conventional chemotherapy. Results and Conclusions: Bone resorption declined during HSCT (decrease in TRACP‐5b [P < .001] and CTX [P = .006]). Bone formation declined as well (decrease in bALP and OC [P < .001 for both]). RANKL/OPG ratio, an indicator of osteoclastic activation, did not change significantly (P = .5). Ang1/Ang2 ratio, a vessel equilibrium marker, decreased significantly (P < .001) suggesting endothelial destabilization. The changes observed in the control group were similar except of bALP and RANKL/OPG ratio. Moreover, Ang1/Ang2 ratio on the day after HSC infusion strongly correlated with time to neutrophil and platelet engraftment (P < .001 for both). Conclusively, bone turnover and vessel destabilization represent important events during HSCT probably reflecting the effect of chemotherapy. [ABSTRACT FROM AUTHOR]

The article presents a case of a 17-year-old white male who developed transient acute myopericarditis without pericardial effusion (PcE) during all-transretinoic acid (ATRA)-based induction. Topics discussed include abnormally granulated promyelocytes having the unique ability to undergo differentiation into mature granulocytes upon exposure to ATRA, increasing incident of coagulopathy-induced hemorrhage, and myocardial enzymes and serum creatinine levels found in limits.

Ibrutinib is a drug used in several lymphohyperplastic diseases. Its use is associated with an increased risk of atrial fibrillation. New-onset atrial fibrillation in this setting is a true challenge as several antiarrhythmic drugs are not indicated and long-term anticoagulation has several limitations. Herein, we describe our experience in treating a 55-year-old patient receiving ibrutinib who presented with new-onset atrial fibrillation and borderline arterial pressure. Since first-line therapies, electrical cardioversion and ablation, could not be performed, rhythm control with intravenous administration of amiodarone was attempted and led to prompt sinus rhythm restoration. We discuss the therapeutic challenges related to sinus rhythm restoration and anticoagulation in this group of atrial fibrillation patients. [ABSTRACT FROM AUTHOR]

The article presents two case studies related to no evidence of splenic disease in patients with splenic marginal zone lymphoma (SMZL) undergoing splenectomy for autoimmune hemolytic anemia after monotherapy with rituximab. Topics include the first case was a 56 year-old male diagnosed with SMZL in September 2012, and the second case of a 60-year old woman first diagnosed with SMZL in May 2010 after she presented with abdominal pain and early satiety.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Monoclonal B-cell lymphocytosis (MBL) is a premalignant condition characterized by the presence of less than 5000/μL 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/μL 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.Thecutoff value of 5000/μL clonal B cells cannot probably be applied in CD5(-) MBL, requiring a new definition to describe those cases. [ABSTRACT FROM AUTHOR]

BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells' surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients' outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P = -0.000021), b2-microglobulin (P = 0.005), anemia (P = -0.03), thrombocytopenia (P = 0.04), Binet stage (P = 0.02), and free light chains ratio (P = 0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P = 0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P = 0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS. [ABSTRACT FROM AUTHOR]

Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients' series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients' follow up was 32months (range 4-228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42%of patients, while the summated FLC-kappa plus FLC-lambda was above 60mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P = 0.0005 and P = 0.000003, resp.) and overall survival (P = 0.05 and P = 0.003, resp.).They also correlated with β2-microglobulin (P = 0.009 and P = 0.03, resp.), serum albumin (P = 0.009 for summated sFLC), hemoglobin (P < 0.001), abnormal LDH (P = 0.037 and P = 0.001, resp.), Binet stage (P < 0.05) and with the presence of beta symptoms (P = 0.004 for summated sFLC). Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters. [ABSTRACT FROM AUTHOR]

The optimal treatment approach for patients with mantle cell lymphoma (MCL) is not well defined. Intensive therapeutic regimens result in high response rates and prolonged progression-free survival but at the expense of significant toxicity. We report here our results of the administration of rituximab plus chlorambucil (R-Chl) as first line treatment in patients with MCL. Twenty consecutively diagnosed patients were treated with this combination in which an induction and a maintenance arm were included. During induction, rituximab was administered at a dose of 375 mg/m2 on day 1, while chlorambucil was given afterward at a dose of 10 mg/day for 10 consecutive days for eight cycles and then as a single agent for an additional four cycles. Maintenance consisted of rituximab administration every 2 months for 1 year. Most patients had indolent disease features such as a low mantle-cell international prognostic index (MIPI) score. The overall response rate was 95% (90% CR, 5% PR). Among patients in CR, 78% presented a molecular remission. The 3-year progression-free survival was 89%. There were no serious side effects. These results show that the R-Chl combination could be an effective therapeutic option as first line treatment in MCL, especially for patients with indolent disease characteristics. [ABSTRACT FROM AUTHOR]

Abstract: We present a cohort of 22 patients with type 2 dendritic cell (DC2) acute leukemia (or blastic plasmacytoid dendritic cell neoplasm-BPDCN, as it has been recently named), diagnosed in Greece over the past 12-year period, according to the main clinical and immunophenotypic features of this entity. Four additional cases are discussed, classified as leukemia of ambiguous lineage (LAL), because of the simultaneous detection of a CD56 negative DC2 population and of a second myeloid precursor cell population. The morphological features and cytogenetic findings of the typical BPDCN cases were similar to those previously described. Acute lymphoblastic leukemia-type chemotherapeutic regimens were more efficient in controlling the disease. Immunophenotyping of typical BPDCN cases revealed CD4+, CD56+, HLA-DR+ and CD123bright neoplastic cells, in the absence of major B-, T- and myeloid-associated markers, while the phenotype of the four cases characterized as LAL highlights the risk of misdiagnosis. Based on our experience, we propose a flow cytometric algorithmic approach for the distinction of typical BPDCN from certain types of acute myeloid leukemia, but also for the identification of acute myeloid leukemia, admixed with CD56 negative DC2 cells, which could be misdiagnosed as BPDCN. [Copyright &y& Elsevier]

Background/Aims: Disease-related anemia in chronic lymphocytic leukemia (CLL) occurs when the obvious causes are excluded while its pathogenesis is still obscure. We investigated its underlying mechanisms in 56 untreated patients with CLL. Methods: Bone marrow (BM) lymphocytic infiltration was estimated in trephine biopsies. Serum erythropoietin (EPO) and tumor necrosis factor-α (TNF-α) levels were measured by ELISA. The potential of BM CD34+ to differentiate into erythroid cells was evaluated by methylcellulose-based assays and in liquid cultures supplemented with EPO, SCF, IL-3 ± TNF-α. The response of erythroid precursors to EPO ± TNF-α was assessed by detecting activated key proteins of EPO-EPO receptor signalling pathway using Western Blot and EMSA. Results: Bone marrow lymphocytic infiltration was not exclusively responsible for disease-related anemia and CD34+ cells were intrinsically capable of generating erythroid precursors. Also, no deficiency of serum erythropoietin (EPO) or defective intracellular response of erythroid precursors to EPO ± TNF-α stimulation was observed. Serum TNF-α levels were found increased in anemic CLL patients and TNF-α appeared to directly inhibit the erythroid development in early stages of erythropoiesis. Conclusion: We concluded that CLL-related anemia was not due to intrinsic defects of erythroid precursors, but might result from the direct suppressive effect of TNF-α on the erythroid production. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Jumping translocations (JT) are rare cytogenetic aberrations in hematological malignancies that include unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to two or more different recipient chromosomes in different cell lines. We report five cases associated with different hematologic disorders and JT to contribute to the investigation of the origin, pathogenesis, and clinical significance of JT. These cases involve JT of 1q in a case of acute myeloblastic leukemia (AML)-M1, a case of Burkitt lymphoma, and a case of BCR/ABL-positive acute lymphoblastic leukemia, as well as a JT of 13q in a case of AML-M5, and a JT of 11q segment in a case of undifferentiated leukemia. To our knowledge, with regard to hematologic malignancies, this study presents the first case of JT associated with AML-M1, the first case of JT involving 13q as a donor chromosome, and the first report of JT involving a segment of 11q containing two copies of the MLL gene, jumping on to two recipient chromosomes in each cell line and resulting in six copies of the MLL gene. Our investigation suggests that JT may not contribute to the pathogenesis but rather to the progression of the disease, and it demonstrates that chromosome band 1q10 as a breakpoint of the donor chromosome 1q is also implicated in AML, not only in multiple myeloma as it has been known until now. [Copyright &y& Elsevier]

In the present study, we assessed the clinical and pathological data of 76 patients with the diagnosis of non-gastric extranodal marginal zone B-cell lymphoma. The most commonly affected sites were salivary glands, skin, ocular adnexa, lung, intestine and Waldeyer's ring. Ann Arbor stage I disease was present in 39 patients (51%), stage II in 10 (13%) and stage IV in 27 (36%). In 17 cases (21%), the lymphoma presented at multiple mucosal sites. Lymph node and bone marrow involvement were present in 21% and 16%, respectively. Most cases were in the low or low-intermediate risk group. Treatment was heterogeneous and included chlorambucil in 59% either alone or in combination with other agents. Complete and partial remission was achieved in 79% and 7%, respectively, with an overall response rate of 86%. The 5- and 10-year overall survival and cause-specific survival rates were 94%, 82% and 95%, 91%, respectively. The 5- and 10-year progression free survival was 56% and 41%, respectively. The only feature associated with inferior outcome was disease localisation to the lung. [ABSTRACT FROM AUTHOR]

The prognostic value of baseline serum free light chain ratio (sFLCR) was investigated in 94 multiple myeloma (MM) patients. sFLCR was calculated as κ/ λ or λ/ κ, depending on the patients’ dominating monoclonal light chain. Median baseline sFLCR was 3·57 in κ-MM patients, 45·09 in λ-MM. ‘High’ sFLCR (≥ the observed median value for κ- and λ-MM respectively) correlated with elevated serum creatinine and lactate dehydrogenase, extensive marrow infiltration and light chain type MM. The 5-year disease-specific survival was 82% and 30% in patients with sFLCR lower than and equal or greater than the median, respectively ( P = 0·0001). sFLCR was an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Assesses different treatment strategies for indolent lymphomas. Use of chemotherapy based treatment when the patient develops constitutional symptoms or symptoms related to tumor burden; Treatment of elderly patients with oral alkylating agents; Production of superior progression free survival rates by adding rituximab to conventional chemotherapy.

Kyrtsonis M-C, Vassilakopoulos TP, Siakantaris MP, Kokoris SI, Gribabis DA, Dimopoulou MN, Angelopoulou MK, Pangalis GA. Serum syndecan-1, basic fibroblast growth factor and osteoprotegerin in myeloma patients at diagnosis and during the course of the disease. Eur J Haematol 2004: 72: 252–258. © Blackwell Munksgaard 2004. Neovascularisation and bone resorption are related to myeloma disease activity. 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. 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. 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 β2M ( 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. 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. [ABSTRACT FROM AUTHOR]

Summary. Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-α (IFN-α). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-α induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-α treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network. [ABSTRACT FROM AUTHOR]

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-α (IFN-α) 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-α 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 the iCNOP arm is of concern. [ABSTRACT FROM AUTHOR]