Francesco Marchesi

High density of CD68+/CD163+ tumour‐associated macrophages (M2‐TAM) at diagnosis is significantly correlated to unfavorable prognostic factors and to poor clinical outcomes in patients with diffuse large B‐cell lymphoma

To the Editor Tumour-Associated Macrophages (TAM) may have both anti-tumoural and tumour-promoting functions, depending on their acquired immunophenotype (M1 or M2). Recent studies have shown that TAM expression was related with prognosis in hematologic malignancies, particularly in Hodgkin’s lymphoma [1]. However, the role of microenvironment in diffuse large B-cell lymphoma (DLBCL) has been less studied in the last years, and contrasting results about the role of TAM concentration on prognosis were obtained. Hasselblom et al. demonstrated that it is not possible to predict worse clinical outcomes in terms of disease-free survival (DFS) and overall survival (OS) in DLBCL patients just evaluating CD68+ TAM concentration [2], whereas other studies showed that high TAM density was significantly related to poor prognosis [3] and worse therapy-response [4]. More recently, Nam et al. suggested that an increase ofM2-TAM predicts poor outcome in DBLCL patients treated with R-CHOP regimen [5]. The aim of this study is to quantify TAM concentration making use of a double immunofluorescence in DLBCL patients at diagnosis and to evaluate the presence of a significant correlation between the prevalent subtype of macrophages, clinical and biological disease features and clinical outcomes in terms of therapy response, DFS and OS. Sixty-one patients diagnosed with de novo DLBCL were enrolled in our study. Fifty-seven patients were treated with R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone), whereas the remaining four received R-CHOP-like regimens (with liposomal Doxorubicin). Every patient gave an informed written consent to authorize sensitive data processing for scientific purposes; this study has been approved by a local Ethical Committee. Treatment responses were evaluated according to Cheson’s criteria [6]. Different subtypes of macrophage infiltration were identified by a double indirect immunofluorescence for CD68/CD163 (M2) and CD68/HLA-DR (M1). Antibodies against CD68 were used as primary antibodies to recognise CD68+ cells. Then we used a secondary antibody (Ab) binding the Fc fragment of the primary Ab. The secondary Ab was marked with Alexa Fluor 488 fluorochrome (Life

Cytogenetic abnormalities in adult non-promyelocytic acute myeloid leukemia: A concise review

Cytogenetic abnormalities are found in 50-60% of newly diagnosed acute myeloid leukemia (AML) of adult patients. Cytogenetic analysis of bone marrow leukemic cells is an important pre-treatment evaluation for a correct prognostic stratification of patients, that permit to separate AML patients in three broad prognostic categories: high, intermediate and low risk. The determination of cytogenetic features of AML remains a corner stone in predicting outcome although today its use needs to be integrated by molecular and immunophenotypic data, particularly in cytogenetically normal (CN) group of patients. In this review we perform a concise description of more recurrent cytogenetic aberrations found in AML, theirs correlations with biological and clinical data and theirs strong impact with outcome of patients, useful for therapeutic decision.

The potential role of pre-transplant HBcIgG seroposivity as predictor of clinically relevant cytomegalovirus infection in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation: A study from the Rome Transplant Network

Despite the increased use of intensive immunosuppressive chemo‐immunotherapies in patients with lymphoma observed in the last decade, current data on cytomegalovirus (CMV) infection following autologous stem cell transplantation (Auto‐SCT) are very limited. To address this peculiar aspect, a retrospective study on a cohort of 128 adult patients consecutively transplanted for lymphoma in three Hematology Institutions was performed with the aim to determine the incidence of and the risk factors for CMV symptomatic infection and/or end‐organ disease. Sixteen patients (12.5%) required specific antiviral therapy and 4/16 died (25%); transplant‐related mortality (TRM) was significantly influenced by CMV infection (P = 0.005). In univariate analysis, a pre‐transplant HBcIgG seropositivity, HBV infection according to clinical–virological definitions, a pre‐transplant Rituximab treatment, a diagnosis of B‐cell non‐Hodgkin lymphoma, and age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection. In multivariate analysis, only a pre‐transplant HBcIgG seropositivity (P = 0.008) proved to be an independent predictor of a clinically relevant CMV infection. These results suggest that a pre‐transplant HBcIgG seropositivity could be considered as an independent predictor factor of clinically relevant CMV infection after Auto‐SCT.

A case of primary MALT lymphoma of the endometrium presenting as an asymptomatic polyp

Dear Editor,Herein, we present the case of an 81-year-old Caucasianwoman who received a diagnosis of breast cancer in March2006. During staging procedures, a transvaginal echogra-phy revealed an endometrial polyp that was removed a fewmonths later, after the completion of the breast cancertherapeutic program.At microscopic examination, the polyp was character-ized by numerous cystically dilated glands, mainly locatedat its periphery (Fig. 1). The stalk was diffusely infiltratedby a lymphomatous population consisting of small-sizedelements with slightly indented nuclei, moderately dis-persed chromatin, inconspicuous nucleoli, and a narrow rimof clear cytoplasm (Fig. 1). Such population tended tofocally invade the glandular component giving rise tolymphoepithelial lesions and to colonize and substitutepreexisting germinal centers. As a consequence of the latterevent, a few centroblasts were scattered throughout theneoplastic growth. At immunohistochemistry, the lympho-matous population expressed the B-cell markers CD20 andCD79a, as well as the marginal zone-associated moleculeimmune receptor translocation associated 1 (IRTA1; Fig. 1).In the areas corresponding to germinal center colonization,neoplastic cells—always CD10 negative—showed faintpositivity for Bcl-6, in contrast to residual germinal centerB-cells that strongly expressed both Bcl-6 and CD10 (Fig.1). The Ki-67 marking accounted for less than 5% of thewhole neoplastic population (Fig. 1). Based on thesefindings, a diagnosis of extranodal marginal zone B-celllymphoma of mucosa-associated lymphoid tissue (MALTlymphoma) arising in an endometrial polyp was made.Fever, night sweating, loss of weight, and local signs orsymptoms were absent at diagnosis. The blood cell countrevealed only a mild normocytic and normochromic anemiaassociated with a mild increase of erythrocyte sedimenta-tion rate. Serum

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant‐related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T‐cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High‐dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first‐line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high‐risk patients.

Cryotherapy reduces oral mucositis and febrile episodes in myeloma patients treated with high-dose melphalan and autologous stem cell transplant: a prospective, randomized study

Cryotherapy reduces oral mucositis and febrile episodes in myeloma patients treated with high-dose melphalan and autologous stem cell transplant: a prospective, randomized study

Relapse of IgA λ Multiple Myeloma Presenting as Obstructive Jaundice and Abdominal Pain

Background: Only few cases of pancreatic involvement of multiple myeloma (MM) have been reported in the medical literature. Patients and Methods: We here report a case of devastating extramedullary relapse of IgA/λMM (stage IA) treated at diagnosis with a dexamethasone, adriamycin, vincristine (DAV) regimen followed by high-dose therapy and autologous stem cell transplantation (ASCT), achieving a partial remission. After 6 years of stable disease, the patient presented symptoms of obstructive jaundice determined by a large mass of the head of the pancreas. An ultrasound-guided fine-needle aspiration cytology of the pancreatic mass revealed the presence of myeloma plasma cells. A chest X-ray demonstrated a massive right pleural effusion, and the cytomorphologic evaluation of the pleural effusion showed the presence of abnormal plasma cells. Results: We observed a progression of disease despite an aggressive treatment with high-dose cyclophosphamide. Conclusions: Our case shows that extramedullary relapses of MM after ASCT are very resistant to conventional chemotherapy. The role of new drugs and the optimal treatment strategy in these cases remain to be defined.

Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant

We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.

Campylobacter jejuni Fatal Sepsis in a Patient with Non-Hodgkin’s Lymphoma: Case Report and Literature Review of a Difficult Diagnosis

Campylobacter jejuni (C. jejuni) bacteremia is difficult to diagnose in individuals with hematological disorders undergoing chemotherapy. The cause can be attributed to the rarity of this infection, to the variable clinical presentation, and to the partial overlapping symptoms underlying the disease. Here, we report a case of a fatal sepsis caused by C. jejuni in a 76-year-old Caucasian man with non-Hodgkin’s lymphoma. After chemotherapeutic treatment, the patient experienced fever associated with severe neutropenia and thrombocytopenia without hemodynamic instability, abdominal pain, and diarrhea. The slow growth of C. jejuni in the blood culture systems and the difficulty in identifying it with conventional biochemical phenotyping methods contributed to the delay of administering a targeted antimicrobial treatment, leading to a fatal outcome. Early recognition and timely intervention are critical for the successful management of C. jejuni infection. Symptoms may be difficult to recognize in immunocompromised patients undergoing chemotherapy. Thus, it is important to increase physician awareness regarding the clinical manifestations of C. jejuni to improve therapeutic efficacy. Moreover, the use of more aggressive empirical antimicrobial treatments with aminoglycosides and/or carbapenems should be considered in immunosuppressed patients, in comparison to those currently indicated in the guidelines for cancer-related infections supporting the use of cephalosporins as monotherapy.

Changes in the incidence of candidemia and related mortality in patients with hematologic malignancies in the last ten years. A SEIFEM 2015-B report

The epidemiology of invasive fungal infections (IFI) among patients with hematologic malignancies who are undergoing either conventional chemotherapy or hematopoietic stem cell transplantation (HSCT) is changing due to the introduction of new, effective antifungal agents for both prophylaxis and