Elisabetta Cerchiara

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

High incidence of post‐transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib‐based regimens: a survey from the Rome Transplant Network

The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post‐engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib‐based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.

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.

Comparison between biosimilar filgrastim vs other granulocyte‐colony stimulating factor formulations (originator filgrastim, peg‐filgrastim and lenograstim) after autologous stem cell transplantation: a retrospective survey from the Rome Transplant Network

Acar, K., Sucak, G.T., Yagci, M., Tunca, Y. & Haznedar, R. (2006) Translocation (2;11)(p21; q23) in a patient with polycythemia vera: a novel clonal chromosome abnormality. American Journal of Hematology, 81, 891. Bousquet, M., Quelen, C., Rosati, R., Mansat-De Mas, V., La Starza, R., Bastard, C., Lippert, E., Talmant, P., Lafage-Pochitaloff, M., Leroux, D., Gervais, C., Viguie, F., Lai, J.L., Terre, C., Beverlo, B., Sambani, C., Hagemeijer, A., Marynen, P., Delsol, G., Dastugue, N., Mecucci, C. & Brousset, P. (2008) Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t (2;11)(p21;q23) translocation. The Journal of Experimental Medicine, 205, 2499–2506. Bousquet, M., Harris, M.H., Zhou, B. & Lodish, H.F. (2010) MicroRNA miR-125b causes leukemia. Proceedings of the National Academy of Sciences of the United States of America, 107, 21558–21563. Chapiro, E., Russell, L.J., Struski, S., Cave, H., Radford-Weiss, I., Valle, V.D., Lachenaud, J., Brousset, P., Bernard, O.A., Harrison, C.J. & Nguyen-Khac, F. (2010) A new recurrent translocation t(11;14)(q24;q32) involving IGH@ and miR-125b-1 in B-cell progenitor acute lymphoblastic leukemia. Leukemia, 24, 1362–1364. Malcovati, L., Della Porta, M.G., Pietra, D., Boveri, E., Pellagatti, A., Galli, A., Travaglino, E., Brisci, A., Rumi, E., Passamonti, F., Invernizzi, R., Cremonesi, L., Boultwood, J., Wainscoat, J.S., Hellstrom-Lindberg, E. & Cazzola, M. (2009) Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Blood, 114, 3538–3545. Royer-Pokora, B., Hildebrandt, B., Redmann, A., Herold, C., Kronenwett, R., Haas, R., Drechsler, M. & Wieland, C. (2003) Simultaneous occurrence of a t(9;22) (ph) with a t(2;11) in a patient with CML and emergence of a new clone with the t(2;11) alone after imatinib mesylate treatment. Leukemia, 17, 807–810. Scott, L.M. (2011) The JAK2 exon 12 mutations: a comprehensive review. American Journal of Hematology, 86, 668–676. So, A.Y., Zhao, J.L. & Baltimore, D. (2013) The yin and yang of microRNAs: leukemia and immunity. Immunological Reviews, 253, 129–145. Swerdlow, S., Campo, E., Harris, N.L., Jaffe, E., Pileri, S. & Stein, H. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, Lyon, France. Thorsen, J., Aamot, H.V., Roberto, R., Tjonnfjord, G.E., Micci, F. & Heim, S. (2012) Myelodysplastic syndrome with a t(2;11)(p21;q23-24) and translocation breakpoint close to miR-125b-1. Cancer Genetics, 205, 528–532.

Early Diastolic Dysfunction after Cancer Chemotherapy: Primary Endpoint Results of a Multicenter Cardio-Oncology Study

Asymptomatic diastolic dysfunction (DD) with preserved left ventricular ejection fraction (LVEF) is suspected to precede late cardiac events in cancer survivors treated by chemotherapy. We conducted the first multicenter study of early DD induced by chemotherapy. Patients who were candidates for standard dose chemotherapy were screened for the absence of cardiovascular risk factors, LVEF ≥50%, normal-for-age diastolic function at echocardiography (E/A ratio, E wave deceleration time; DT), normal levels of potential DD biomarkers like Nt-proBNP (≤125 pg/mL), and cardiac troponin I (cTnI, ≤0.05 ng/mL). Mitral Doppler (E/E’) was left at the investigator’s discretion. Chemotherapy-induced DD with preserved LVEF was diagnosed for patients showing LVEF ≥50% and any of the following: Nt-proBNP > 125 pg/mL, cTnI > 0.05 ng/mL, and out-of-range E/A and DT. Eighty patients (68 males, 12 females, median age 49 years) were evaluated at 1 week after chemotherapy (T1). Thirty-three protocol-defined diastolic events were observed (15 Nt-proBNP > 125 pg/mL, 14 grade I DD by E/A and DT, 4 cTnI > 0.05 ng/mL). The events occurred in 29 asymptomatic patients with LVEF ≥50% (36% incidence of DD with preserved LVEF). Interactions occurred between biomarkers and grade I DD. E/E’ abnormalities were not observed. Both anthracycline-based and nonanthracycline regimens induced DD. These findings show that biomarkers and echocardiography intercept early DD in otherwise asymptomatic low-risk cancer patients treated by standard dose chemotherapy. These findings therefore call for the adequate cardiac management of cancer patients.

A Case of Transplantation-Associated Thrombotic Microangiopathy with Cardiac Involvement Successfully Treated with Plasma Exchange

Transplantation-associated thrombotic microangiopathy (TA-TMA) is occasionally described as a serious complication after allogeneic and, more rarely, autologous stem cell transplantation (SCT). It is characterized by poor outcome with high mortality rate. Plasma exchange (PE) has been reported as successful first-line therapy in other thrombotic microangiopathies. However, unlike to idiopathic forms, response to PE are usually suboptimal in TA-TMA and the use of PE remains controversial, because the exact mechanism of injury is not yet understood. The kidney is the most commonly affected organ and injury has rarely been reported elsewhere in the body, such as in lungs and gastrointestinal tract. Although several case reports have documented myocardial infarctions in patients presenting classic thrombotic thrombocytopenic purpura (TTP), there are no reports documenting cardiac involvement in TA-TMA. We describe a case of a 66-year-old man who experienced TA-TMA accompanied by cardiac ischemia after autologous SCT for multiple myeloma, successfully treated with PE. The immediate start of PE induced a complete remission of TA-TMA and disappearance of cardiac ischemic signs and symptoms except of a residual chronic renal failure.

Sytemic strongyloidiasis and primary aspergillosis of digestive tract in a patient with T-cell acute lymphoblastic leukemia.

Invasive strongyloidiasis is a rare event occurring in patients aving a deficient cellular immunity, as in hematologic maligancies; digestive tract is frequently involved as secondary ocalization in cases of systemic invasive aspergillosis, but priary aspergillosos of digestive tract is a very rare. We describe a ase of severe unrecognized strongyiloidiasis associated to primary spergillosis of the upper gastrointestinal tract occurring during nduction treatment of a patient with T-cell acute lymphoblastic eukemia (T-ALL).

Hematologic Issues in Cervical Spine Surgery

Soon after a diagnosis of anemia has been made, the next step is to take an accurate clinical history and perform a physical examination to evaluate the signs and symptoms of anemia. These signs and symptoms may be: (a) directly related to anemia , and therefore, may present in all patients, independently from the cause of anemia, such as pallor, anorexia, fatigue, roaring in the ears, tachycardia, heart murmur, arrhythmia; until when Hematologic Issues in Cervical Spine Surgery