Severe human herpesvirus-8 primary infection in a renal transplant patient successfully treated with anti-CD20 monoclonal antibody.
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Antibodies, Monoclonal↗
Biomedical subjects
Françoise Valensi
Publications and source records attributed to Françoise Valensi.
Deciphering leukemic B-cell chronic lymphoproliferative disorders.
Diagnosis of leukemic B-cell chronic lymphoproliferative disorders (B-CLPD) is a frequent challenge in hematology. In this multicentric study, we prospectively studied 165 new consecutive leukemic patients with B-CLPD selected on the basis of Royal Marsden Hospital scoring system < or =3. The primary aim of the study was to try to decipher the atypical cases and identify homogenous subgroups. Overall, morphological examination contributed to diagnosis in only 20% cases, all of them CD5 negative. Thirty additional cases were CD5 negative suggestive of leukemic marginal zone lymphoma in most cases. The significantly poorer survival of the 26 cyclin D1 positive cases justifies recommending its systematic determination among atypical B-CLPD. CD20 expression segregated clearly two subgroups among CD5 positive cyclin D1 negative B-CLPD. The 17 patients with the CD20 dim profile represent a homogeneous subgroup very close to typical B-cell chronic lymphocytic leukemia (B-CLL) on morphological, phenotypical and cytogenetical criteria. In contrast, the subgroup of 51 patients with a CD20 bright profile is heterogeneous. Their significantly lower p27 expression level suggest the presence of a proliferative component, underlying a more aggressive disease. Further genomic studies are warranted to establish their precise nature. These cases should not be included in the same therapeutic trials as B-CLL.
Aged↗
Absence or low expression of fas-associated protein with death domain in acute myeloid leukemia cells predicts resistance to chemotherapy and poor outcome.
In acute myeloid leukemia (AML), coexpression of death receptors and ligands of the tumor necrosis factor (TNF) receptor/TNF-alpha superfamily on leukemic cells after chemotherapy is not always accompanied by apoptosis, suggesting that the apoptotic death receptor signaling pathway is disrupted. Because Fas-associated protein with death domain (FADD) is the main adaptor for transmitting the Fas, TNF-related apoptosis-inducing ligand receptors, and TNF receptor 1 death signal, expression of FADD was analyzed by Western blot and immunocytochemistry in leukemic cells of 70 de novo AML patients treated with the European Organization of Research and Treatment of Cancer AML-10 randomized trial before initiation of induction chemotherapy. Thirty seven percent of patients (17 of 46) with FADD negative/low (FADD(-/low)) leukemic cells had a primary refractory disease compared with 12% of FADD(+) patients (3 of 24; P = 0.05). FADD(-/low) expression was significantly associated with a worse event-free survival [EFS (P = 0.04)] and overall survival (P = 0.04). In multivariate analysis, FADD(-/low) protein expression was independently associated with a poor EFS and overall survival (P = 0.002 and P = 0.026, respectively). Importantly, FADD(-/low) protein expression predicted poor EFS even in patients with standard- or good-risk AML (P = 0.009). Thus, we identified low or absent expression of the FADD protein in leukemic cells at diagnosis as a poor independent prognostic factor that can predict worse clinical outcome even for patients with standard- or good-risk AML.
Adaptor Proteins, Signal Transducing↗
Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity?
Hepatitis C virus (HCV) has been associated with the development of B-cell non-Hodgkin lymphomas. We recently reported the regression of splenic lymphoma with villous lymphocytes (SLVL) in patients with HCV after antiviral treatment, demonstrating a direct role of HCV in lymphomagenesis. This study expands our previous results in 18 patients with chronic HCV and SLVL. Mixed cryoglobulinemia (MC) was present in all cases and was symptomatic in 13 (72%). All patients were treated with interferon alone or in association with ribavirin. Hematologic and virologic responses were correlated. Fourteen (78%) patients achieved a sustained complete hematologic response after clearance of HCV RNA. Two patients had a virologic partial response and achieved a complete hematologic response. Two virologic nonresponders achieved partial hematologic response. Regardless of the response, monoclonal immunoglobulin gene rearrangement persisted after treatment. This study underscores the role of HCV in the lymphomagenesis and the benefit of antiviral treatment for patients presenting with HCV-driven lymphoproliferations.
Cryoglobulinemia↗
Hemophagocytic syndrome as a presenting sign of transformation of smoldering to acute adult T-cell leukemia/lymphoma: efficacy of anti-retroviral and interferon therapy.
A 55-year-old Caribbean woman with a 6-year history of smoldering adult T-cell leukemia/lymphoma presented with clinical and biological symptoms of hemophagocytic syndrome. An extensive search for infectious diseases was negative. A lymph node biopsy showing large T-cell lymphoma (CD4-, CD25+) and findings of high LDH count and severe lymphocytosis led to the diagnosis of acute adult T-cell leukemia/lymphoma. Anti-retroviral therapy combining zidovudine, lamivudine, and interferon-alpha was started, resulting in rapid control of both hemophagocytic syndrome and symptoms of acute adult T-cell leukemia/lymphoma. Thus, we propose that adult T-cell leukemia/lymphoma must be added to the spectrum of etiologies of hemophagocytic syndrome.
Antineoplastic Agents↗
CD4+ CD56+ lineage negative malignancies: a new entity developed from malignant early plasmacytoid dendritic cells.
BACKGROUND AND OBJECTIVES: The CD4+ CD56+ lin- immunophenotype characterizes rare malignancies, so far considered as arising from the transformation of NK progenitors, and therefore classified as blastic NK-cell leukemia/lymphoma by the WHO committee. Recently it was formally demonstrated that such malignancies do, in fact, develop from plasmacytoid dendritic cells (pDC), according to immunophenotypic and functional criteria. The clinico-biological features of this neoplasm were moreover recently summarized from a large series of 23 patients. INFORMATION SOURCES: The main symptoms at presentation were cutaneous lesions and bone marrow failure, due to invasion by blastic cells, all of which were EBV negative and agranular. Most patients were initially sensitive to chemotherapy regimens, but they rapidly relapsed and died within 3 years. Only 2 allotransplanted patients were long survivors. Recurrent chromosomal aberrations involving chromosomes 5q, 6q, 12p, 13q, 15q and 9 were described and it was characteristic that these were associated in the same cell. In the present review we compared these findings to those in the literature. STATE OF THE ART AND PERSPECTIVES: The concordant characteristics led us to confirm that this neoplasm actually represents a new entity, that we propose to rename early pDC leukemia/lymphoma. The diagnosis is primarily based on a characteristic immunophenotypic profile i.e. CD4+ CD56+ CD3- CD13- CD33- CD19-. Complementary analyses assessing the expression of more specific pDC-related markers showed the cells to be HLA-DR+, CD123high, CD116low, CD45RA+, BDCA-2+ or BDCA-4+. Such complementary investigations are necessary only in the case of an atypical phenotype, in order to confirm a pDC origin and exclude another hematologic disease. This presently regards the expression of CD33 or cytoplasmic CD3e (cyCD3e) and the negativity of CD56.
Adolescent↗
Analysis of TCR, pT alpha, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment.
T-acute lymphoblastic leukemias (T-ALLs) derive from human T-lymphoid precursors arrested at various early stages of development. Correlation of phenotype and T-cell receptor (TCR) status with RAG-1 and pT alpha transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid development. Half the TCR alpha beta lineage T-ALLs expressed a pre-TCR, as evidenced by RAG-1, pT alpha, and cTCR beta expression, absence of TCR delta deletion, and a sCD3(-), CD1a(+), CD4/8 double-positive (DP) phenotype, in keeping with a population undergoing beta selection. Most TCR gamma delta T-ALLs were pT alpha, terminal deoxynucleotidyl transferase (TdT), and RAG-1(lo/neg), double-negative/single-positive (DN/SP), and demonstrated only TCR beta DJ rearrangement, whereas 40% were pT alpha, TdT, and RAG-1 positive, DP, and demonstrated TCR beta V(D)J rearrangement, with cTCR beta expression in proportion. As such they may correspond to TCR alpha beta lineage precursors selected by TCR gamma delta expression, to early gamma delta cells recently derived from a pT alpha(+) common alpha beta/gamma delta precursor, or to a lineage-deregulated alpha beta/gamma delta intermediate. Approximately 30% of T-ALLs were sCD3/cTCR beta(-) and corresponded to nonrestricted thymic precursors because they expressed non-T-restricted markers such as CD34, CD13, CD33, and CD56 and were predominantly DN, CD1a, pT alpha, and RAG-1 low/negative, despite immature TCR delta and TCR gamma rearrangements. TCR gene configuration identified progressive T-lymphoid restriction. T-ALLs, therefore, provide homogeneous expansions of minor human lymphoid precursor populations that can aid in the understanding of healthy human T-cell development.
Adolescent↗
Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection.
BACKGROUND: Some epidemiologic studies suggest a link between hepatitis C virus (HCV) infection and some B-cell non-Hodgkin's lymphomas. We undertook this study after a patient with splenic lymphoma with villous lymphocytes had a hematologic response after antiviral treatment of HCV infection. METHODS: Nine patients who had splenic lymphoma with villous lymphocytes and HCV infection were treated with interferon alfa-2b (3 million IU three times per week) alone or in combination with ribavirin (1000 to 1200 mg per day). The outcomes were compared with those of six similarly treated patients with splenic lymphoma with villous lymphocytes who tested negative for HCV infection. RESULTS: Of the nine patients with HCV infection who received interferon alfa, seven had a complete remission after the loss of detectable HCV RNA. The other two patients had a partial and a complete remission after the addition of ribavirin and the loss of detectable HCV RNA. One patient had a relapse when the HCV RNA load again became detectable in blood. In contrast, none of the six HCV-negative patients had a response to interferon therapy. CONCLUSIONS: In patients with splenic lymphoma with villous lymphocytes who are infected with HCV, treatment with interferon can lead to regression of the lymphoma.
Adult↗
Clinical and biologic features of CD4(+)CD56(+) malignancies.
CD4(+)CD56(+) malignancies are rare hematologic neoplasms, which were recently shown to correspond to the so-called type 2 dendritic cell (DC2) or plasmacytoid dendritic cells. This study presents the biologic and clinical features of a series of 23 such cases, selected on the minimal immunophenotypic criteria defining the DC2 leukemic counterpart, that is, coexpression of CD4 and CD56 in the absence of B, T, and myeloid lineage markers. Clinical presentation typically corresponded to cutaneous nodules associated with lymphadenopathy or spleen enlargement or both. Cytopenia was frequent. Circulating malignant cells were often detected. Massive bone marrow infiltration was seen in 20 of 23 (87%) patients. Most tumor cells exhibited nuclei with a lacy chromatin, a blastic aspect, large cytoplasm-containing vacuoles or microvacuoles beside the plasma membrane, and cytoplasmic expansions resembling pseudopodia. Other immunophenotypic characteristics included both negative (CD16, CD57, CD116, and CD117) and positive (CD36, CD38, CD45 at low levels, CD45RA, CD68, CD123, and HLA DR) markers. The prognosis was rapidly fatal in the absence of chemotherapy. Complete remission was obtained in 18 of 23 (78%) patients after polychemotherapy. Most patients had a relapse in less than 2 years, mainly in the bone marrow, skin, or central nervous system. Considering these clinical and biologic features, the conclusion is made that CD4(+)CD56(+) malignancies constitute a genuine homogeneous entity. Furthermore, some therapeutic options were clearly identified. Finally, relationships between the pure cutaneous indolent form of the disease and acute leukemia as well as with the lymphoid/myeloid origin of the CD4(+)CD56(+) malignant cell are discussed.
Adolescent↗
all-trans-Retinoic acid in the treatment of Kimura's disease.
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Adjuvants, Immunologic↗
Recurrence of OTT-MAL fusion in t(1;22) of infant AML-M7.
Translocation t(1;22)(p13;q13) is associated with a peculiar subtype of acute megakaryocytic leukemia (M7) occurring in infants. We have recently characterized a fusion gene, OTT-MAL, resulting from this translocation. We now report three additional cases and show that this gene fusion is present in all five t(1;22) cases studied to date. Nucleotide sequence analysis of two translocation breakpoints suggests a nonhomologous end joining mechanism in the genesis of this translocation and reveals a noncanonical topoisomerase II-like consensus sequence within the OTT gene. FISH and PCR techniques described in this work are useful for identifying t(1;22) associated with M7.
Amino Acid Sequence↗