Abrahão Elias Hallack Neto

Interim fluorine-18 fluorodeoxyglucose PET-computed tomography and cell of origin by immunohistochemistry predicts progression-free and overall survival in diffuse large B-cell lymphoma patients in the rituximab era.

ObjectiveThe aim of this study was to analyze the prognostic value of the interim PET (iPET)-computed tomography (CT) (iPET-CT) after two cycles of immunochemotherapy with the R-CHOP protocol in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with a curative intent in combination with the neoplastic cell origin defined by Hans’s immunohistochemstry algorithm followed in a reference center for cancer treatment in Brazil. Materials and methodsWe prospectively evaluated 147 DLBCL patients treated with R-CHOP-21 to assess the value of the International Prognostic Index, iPET-CT, and cell of origin by immunohistochemistry as prognostic markers in the rituximab era. Fluorine-18 fluorodeoxyglucose PET-CT was performed after two cycles (iPET-CT) and at the end of treatment in 111 patients. Lymphoma cases were categorized into germinal center (GC) and nongerminal center subtypes by immunohistochemistry according to Hans’s algorithm. ResultsThe median age of GC-DLBCL patients (52.7 years) was lower than that of nongerminal center-DLBCL patients (59.4 years) (P=0.021); in addition, it was lower in patients with negative iPET-CT findings (52.7 years) versus positive findings (59.4 years) (P=0.031). The overall survival at 48 months was 100% for iPET-CT-negative GC-DLBCL patients and 61.2% for iPET-CT-positive GC-DLBCL patients (P=0.002). Progression-free survival at 30 months was 100% for iPET-CT-negative GC-DLBCL patients and 60.3% for iPET-CT-positive GC-DLBCL patients (P=0.001). ConclusionWe conclude that iPET-CT associated with cell origin identified a very good prognostic group in DLBCL patients treated with R-CHOP. Video Abstract: http://links.lww.com/NMC/A59

Azidothymidine is Effective Against Human Multiple Myeloma: A New Use for an Old Drug?

Azidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-κB pathway. As multiple myeloma (MM) presents with constitutive activation of NF-κB, we analyzed the effect of AZT on human MM cell lines. We evaluated the cytotoxic effect of AZT in human MM cell lines sensitive (8226/S) or resistant to doxorubicin (8226/DX5) and human T cell lymphoblast-like cells, uterine sarcoma cells, and HUVEC using MTT assay. Cytotoxicity was also evaluated in vivo in nude mice xenografted with 8226/S tumor. The effect of AZT on the expression of genes involved in cell proliferation, apoptosis, angiogenesis, and the NF-κB pathway was analyzed in the xenografts using real-time polymerase chain reaction. AZT was effective against both 8226/S and 8226/DX5 cells in a dose and time-dependent manner (p = 0.02) in vitro and promoted cell cycle arrest in S phase in these cells. The tumor volume was lower in mice treated with AZT compared to untreated mice (p = 0.0003). AZT down-regulated the pro-proliferative genes encoding AKT1, MYC, STAT1, MAPK8, MAPK9, CCL-3, Bcl-3, and cyclin D2; pro-angiogenenic genes encoding VEGF and IL8; and genes involved in cell adhesion (ICAM1 and FN1) and the NF-κB pathway. AZT up-regulated the expression of tumor suppressor gene FOXP1 and the pro-apoptotic genes encoding BID, Bcl-10, and caspase-8. Thus, we demonstrated the cytotoxic effect of AZT in human MM cell lines for the first time. Our data may provide the rationale for future clinical trials of AZT for treating MM.

Estratificação de risco em linfoma difuso de grandes células B

Diffuse large B-cell lymphoma is a heterogeneous clinical pathological entity which accounts for about 30% to 35% of all non-Hodgkins lymphoma cases. It is considered to be aggressive due to the patients short survival time when incorrect treatment is provided. Since 1993, treatment has been carried out according to IPI, which has been validated in several studies. However, since there are different responses from patients with the same IPI submitted to similar therapies, new prognostic markers are needed for these patients. As the biological nature of such lymphomas is becoming better known, other variables are starting to be used in order to stratify risk. In this review we will approach the key biological markers used as prognostic factors to treat diffuse Large B-Cell Lymphoma patients.

Quimioterapia associada à terapia anti-retroviral de alta eficácia no tratamento dos linfomas não-Hodgkin agressivos relacionados à Síndrome da Imunodeficiência Adquirida

AbstractNon-Hodgkin lymphoma is one of the most frequent oncologicalcomplications in patients with the Acquired Immune-DeficiencySyndrome (AIDS). In other countries, after the introduction ofthe Highly Active Antiretroviral Therapy (HAART), the drop inthe incidence of systemic aggressive lymphomas was belowexpectations, although the survival of these patients rose. InBrazil, little is known about the clinical behavior and survival ofthe patients with lymphoma and AIDS in the post-HAART era.The aim of this study was to retrospectively evaluate 25 patientswith lymphomas and AIDS, treated with the combination ofchemotherapy and HAART. In agreement with the literature mostof the patients were male (20 patients - 80%) with a median ageof 39 years. We observed a predominance of the Diffuse Large BCell Lymphoma subtype (13 patients - 52%), advanced stage(15 patients - 60%), with extra-nodal disease (22 patients - 88%)and B symptoms (18 patients - 72%). Previous AIDS diagnosiswas present in 14 patients (56%), higher than that reported inother series. Fifty-two percent achieved CR, the estimatedprobability of overall survival and disease-free survival at 3years were 54% e 42%, r espectively. The median overall survivaltime was 15 months. Hematological toxicity and infections werefrequently observed, but no toxicity-related deaths were seen.Therefore we conclude that the combined chemotherapy-HAARTtreatment is feasible in Brazilian patients and can provide simi-lar overall survival than that described for some internationalgroups, with an acceptable toxicity profile. Rev. bras. hematol.hemoter. 2004;26(3):177-182.Key words: Lymphoma; AIDS; Highly active antiretroviraltherapy; chemotherapy.

LEAM versus CBV for conditioning in autologous hematopoietic stem cell transplantation for lymphoma

We previously accessed the safety and efficacy of lomustine in combination with etoposide, cytarabine, and melphalan (LEAM) for 4 days, in a Phase 1 study with 3+ 3 design, defining the maximum tolerated dose (MTD) of lomustine at 300 mg/m [1]. This study was a single arm, phase 1/2 multicenter (three Brazilian centers), dose-escalation for investigating lomustine administered in combination with etoposide, aracytin, and melphalan as conditioning regimen in relapsed/refractory non Hodgkin lymphoma and Hodgkin lymphoma for auto-hematopoietic stem cell transplantation (HSCT). The local Ethical Committee, number 139-420-2011, CAAE 0102.0.420.000-11, approved the study. Phase 1 primary objective was to identify the MTD of lomustine. Phase 2 objective was to evaluate the overall survival (OS) and progression-free survival (PFS) of LEAM regimen. Secondarily, we also assessed the safety and tolerability of this regimen in comparison with historical control series of patients submitted to auto-HSCT with CBV as conditioning in our institution. A total of 42 consecutive lymphoma patients were treated with LEAM protocol followed by auto-HSCT, 12 patients being in the dose-escalation phase and the remaining 30 patients in the expansion of the MTD. Enrollment occurred between 2011 and 2016. Of the first 14 patients, six patients received Lomustine 200 mg/m, two patients received lomustine 400 mg/m, and six patients received lomustine 300 mg/m as previously reported [1]. The following 28 patients received lomustine (300 mg m2) on day −4, etoposide (1000 mg/m2) on day −3, aracytin (4000 mg/m2) on day −2, and melphalan (140 mg/m2) on day −1. The infusion of hematopoietic stem cells occurred 24 h after the end of the melphalan intake. The data were collected prospectively, from the first day of hospitalization until hospital discharge and then during the outpatient follow-up at three Brazilian institutions. The data were compared with the historical series of 71 patients treated at the University Hospital of the Federal University of Juiz de Fora (HU-UFJF) with CBV (carmustine, etoposide, and cyclophosphamide) between 2004

Advances in cellular technology in the hematology field: What have we learned so far?

Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-the-art concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research.

Allogeneic hematopoietic stem cell transplantation in mycosis fungoides.

Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.