Ombretta Annibali

Treatment of 72 newly diagnosed Waldenström macroglobulinemia cases with oral melphalan, cyclophosphamide, and prednisone: Results and cost analysis

Current treatment regimens for Waldenström macroglobulinemia (WM) are based on the use of oral alkylating agents. Recently, however, other more costly agents have been proposed for the treatment of WM. In the current study, the authors report on results obtained using oral melphalan, cyclophosphamide, and prednisone (MCP) to treat 72 patients with WM, and they compare these results (and the associated costs) with those observed using more aggressive protocols.

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.

IgM multiple myeloma: report of four cases and review of the literature.

The differential diagnosis between multiple myeloma (MM) and Waldenströms macroglobulinemia (WM) is generally well defined. Consistent with a diagnosis of MM is the presence of a non-IgM monoclonal gammopathy associated to multiple osteolytic lesions and plasma cell infiltration of the bone marrow. Characteristic of WM is the presence of an IgM monoclonal gammopathy associated to lymphoadenopathy, hepatosplenomegaly, anemia and hyperviscosity syndrome in the presence of a monoclonal lymphoplasmacytoid proliferation in the bone marrow. Nonetheless, few cases of IgM myeloma have been reported that display clinico-pathologic features intermediate between MM and WM. Here, this study describes four of 317 (1.2%) patients with an IgM monoclonal gammopathy in whom the morphologic and clinical features were consistent with a diagnosis of IgM myeloma.

Fibrin glue for refractory hemorrhagic cystitis after unrelated marrow, cord blood, and haploidentical hematopoietic stem cell transplantation.

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) are particularly exposed to the risk of developing hemorrhagic cystitis (HC), which is characterized by symptoms ranging from macroscopic hematuria to renal failure. Although HC significantly affects the quality of life and in a few cases becomes intractable leading to patient death, its therapeutic management has not been established. Fibrin glue (FG), a hemostatic agent derived from human plasma, has been largely employed in different surgical settings including urologic procedures.

Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa

Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8–34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the “quality of life” matter is of primary importance.

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.

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

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.

Incidence of venous thromboembolism and use of anticoagulation in hematological malignancies: Critical review of the literature

Venous Thromboembolism (VTE) frequently complicates the course of hematologic malignancies (HM) and its incidence is similar to that observed in high-risk solid tumors. Despite that, pharmacologic prophylaxis and treatment of VTE in patients with HM is challenging, mainly because a severe thrombocytopenia frequently complicates the course of treatments or may be present since diagnosis, thus increasing the risk of bleeding. Therefore, in this setting, safe and effective methods of VTE prophylaxis and treatment have not been well defined and hematologists generally refer to guidelines produced for cancer patients that give indications on anticoagulation in patients with thrombocytopenia. In this review, besides to summarize the incidence and the available data on prophylaxis and treatment of VTE in HM, we give some advices on how to use antithrombotic drugs in patients with HM according to platelets count.

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.