Renata de Oliveira Costa

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.

Resistant and disseminated Strongyloides stercoralis infection in a young patient with adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell malignancy associated to the human T-cell lymphotropic virus type 1 (HTLV-1). There are between 10 and 20 million HTLV-1 carriers worldwide, particularly in Southwest Japan, the Caribbean, Central Africa, South America and Papua New-Guinea.

Disease progression after R-CHOP treatment associated with the loss of CD20 antigen expression

A case of a follicular lymphoma transformed into a CD20+ is described which progressed with the loss of CD20 expression after 8 cycles of R-CHOP. This phenomenon is not a rare event and has shown poor prognosis. Our purposes are to describe this event and suggest biopsy in relapsed or progressive disease

Primary nodal peripheral T-cell lymphomas: diagnosis and therapeutic considerations

Nodal peripheral T-cell lymphomas are a rare group of neoplasms derived from post-thymic and activated T lymphocytes. A review of scientific articles listed in PubMed, Lilacs, and the Cochrane Library databases was performed using the term “peripheral T-cell lymphomas”. According to the World Health Organization classification of hematopoietic tissue tumors, this group of neoplasms consists of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+), and a provisional entity called anaplastic large cell lymphoma-anaplastic lymphoma kinase negative (ALCL-ALK−). Because the treatment and prognoses of these neoplasms involve different principles, it is essential to distinguish each one by its clinical, immunophenotypic, genetic, and molecular features. Except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, which has no adverse international prognostic index, the prognosis of nodal peripheral T-cell lymphomas is worse than that of aggressive B-cell lymphomas. Chemotherapy based on anthracyclines provides poor outcomes because these neoplasms frequently have multidrug-resistant phenotypes. Based on this, the current tendency is to use intensified cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) regimens with the addition of new drugs, and autologous hematopoietic stem cell transplantation. This paper describes the clinical features and diagnostic methods, and proposes a therapeutic algorithm for nodal peripheral T-cell lymphoma patients.

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m2, for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4×109/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment due to liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

CD20-Positive T-Cell Large Granular Lymphocytic Leukemia: A Case Report and Literature Review

T-cell large granular lymphocytic leukemia (T-cell LGLL) is a rare disorder characterized by the monoclonal expansion of CD3-positive cytotoxic T cells. Cell morphology and immunophenotyping are the main tools for diagnosis. Typical phenotypic findings include the expression of markers CD3+, CD5+dim, CD8+, CD16+, CD57+, and T-cell receptor (TCR) αβ (+). However, a few cases may present with the CD3+/CD4+ phenotype or the double expression of CD4 and CD8. Similarly, in 20% of cases, TCRγ/δ is positive. In this study, we aimed to describe a rare, unusual case of T-cell LGLL that exhibited expression of the B-cell antigen, CD20. Additionally, we performed a literature review to compare the clinical characteristics of our patient to those of other patients with CD20-positive T-cell LGLL and to seek new therapeutic possibilities.

Risk stratification for indolent lymphomas

Indolent B-cell lymphomas account for approximately 40% of all non-Hodgkin lymphomas (NHLs). Advances in technology have contributed to improvements in the diagnosis and classification of indolent non-Hodgkin lymphomas. Follicular Lymphomas are the most common although the frequency varies significantly throughout the world. The description of the Follicular Lymphoma International Prognostic Index (FLIPI) was an important step in identifying patient subgroups, but its use in the clinical practice has not been established yet. The use of a larger number of paraffin active monoclonal antibodies for immunohistochemistry, molecular cytogenetic studies including standard cytogenetics, multi-color fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus-specific fluorescence insitu hybridization as well as developments in high-resolution techniquesincluding microarray gene expression profiling allow more accurate diagnosis andprecise definition of biomarkers of value in risk stratification. The identification ofdiseasespecific gene lists resulting from expression profiling provides a number ofpotential protein targets that can be validated using immunohistochemistry. Analysesof gene expression profiles or constitutive gene variations may also provide additional insight for prognostication in the near future. A comprehensive understanding of the biology of these distinct lymphoid tumors will allow us to identify novel diseaserelated genes and should facilitate the development of improved diagnosis, outcome prediction, and personalized approaches to treatment.