INTRODUCTION:Primary effusion lymphoma is a rare type of B-cell lymphoproliferative disorder which is mainly observed in patients with HIV infection. Lymphomatous cells bridge features of immunoblastic and anaplastic cells with a non-B non-T phenotype and are characterized by the presence of the human herpesvirus 8 genome. We report on the retrospective analysis of 12 cases.PATIENTS AND METHODS:: Twelve HIV-infected patients with serous effusions containing large HHV8(+) lymphomatous cells were extensively evaluated to disclose associated visceral involvement. Clonality was assessed by IgH gene rearrangement PCR analysis (n = 11) or Southern blot (n = 1). EBV and HHV8 DNA sequences were detected by PCR analysis. Cytogenetics studies were performed in seven cases using RHG-banding.RESULTS:Extraserous localizations of lymphoma were present in six cases (50%): mediastinal (n = 2), mesenteric (n = 2), pancreatic (n = 1), and bone marrow involvement (n = 1). A monoclonal rearrangement of IgH genes was demonstrated in six cases, an oligoclonal pattern in one, whereas no clonality could be detected in five. High HHV8 copy numbers were demonstrated in all effusion fluids, with EBV-co-infection in all cases but one. Cytogenetic analysis displayed a complex karyotype in all cases without recurrent abnormalities. Eight patients have died. Three patients are in complete remission at 28, 53 and 55 months after high-dose chemotherapy (n = 1), cidofovir and alpha-interferon combination therapy (n = 1), and antiretroviral therapy alone (n = 1).CONCLUSION:The clinical and molecular pattern, as well as the response to therapy suggest that primary effusion lymphoma represents an heterogenous type of virus-induced B-cell lymphoproliferative disorder, sharing pathophysiological features with that induced by the Epstein-Barr virus and occurring in immunocompromised patients.

T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia associated with chromosomal rearrangements implicating MTCP1 or TCL1 genes. These genes encode two homologous proteins, p13(MTCP1) and p14(TCL1), which share no similarity with other known protein. To determine the oncogenic role of MTCP1, mice transgenic for MTCP1 under the control of CD2 regulatory regions (CD2-p13 mice) were generated. No abnormality was detected during the first year after birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13 mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid hemopathies, occurring in the three transgenic lines, were characterized by lymphoid cells with an irregular nucleus, a unique and prominent nucleolus, condensed chromatin, a basophilic cytoplasm devoid of granules, and an immunophenotype of mature T cells. The molecular characterization of Tcrb rearrangements demonstrated the monoclonal origin of these populations. Histopathological analysis of the cohort demonstrated early splenic and hepatic infiltrations, whereas lymphocytosis and medullar infiltrations were found infrequently. The engraftment of these proliferations in H2-matched animals demonstrated their malignant nature. Cumulative incidence of the disease at 20 months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in the control group. The level of expression of the transgene, as estimated by Western blotting in the transgenic lines correlated with the tumoral incidence, with the highest expression of p13(MTCP1) being found in F3 mice. CD2-p13 transgenic mice developed an hemopathy similar to human T-PLL. These data demonstrate that p13(MTCP1) is an oncoprotein and that CD2-p13 transgenic mice represent the first animal model for mature T-PLL.

Trisomy 14 as single karyotype aberration was detected in three patients, two with acute myeloblastic leukemia, AML-M2 type, and one with aplastic anemia. These new observations and the 28 previously reported cases confirm that trisomy 14 is a primary non random change, mostly confined to myeloid disorders.

According to French and European experience, hyperleukocytosis occurs during ATRA differentiation therapy in about 70% of de novo and 25% of relapsed APL cases. The most frequently suggested cause for this side-effect is an ATRA-induced proliferation of APL cells. However, no definite explanation for such a proliferative effect has been clearly established. Another mechanism directly related to the differentiation of marrow leukemic cells could be a change in their microrheology, allowing their release from the bone marrow and their transfer toward peripheral blood (PB) and tissues. Using a single cell aspiration assay into a glass restrictive channel, we measured APL cell viscosity values in five de novo APL patients. A deformability index (DI) was defined as the ratio of mean normal neutrophil viscosity x 100/mean APL cell viscosity. Results were the following: (1) at diagnosis, two patients had high marrow DI (96 and 250%) and three patients had low marrow DI (16, 17, and 40%); (2) when PB and marrow APL cells were simultaneously tested, PB APL cells display higher DI than marrow APL-cells; (3) the two patients with high initial marrow DI experienced an ATRA-induced hyperleukocytosis after only 1 day of treatment; (4) in the three patients with low initial marrow DI, the DI was increasing during ATRA therapy and hyperleukocytosis seemed to occur when a large amount of maturing APL cells reached a viscosity value similar to that of mature neutrophils. These results suggest that an asynchronism between rheological and morphological maturation in each APL cell might explain the occurrence of hyperleukocytosis in some patients during ATRA differentiation therapy.

APL-associated hemostasis disorders result from at least two distinct mechanisms due to the release of procoagulant activities and plasminogen activators from the leukemic cells. These two mechanisms (thrombin activation and plasmin activation) may cleave the fibrinogen molecule, but their respective roles in low fibrinogen levels and bleeding diathesis genesis remain in dispute. In vivo ATRA therapy induces a rapid correction of both low fibrinogen level and bleeding tendency, but no clear explanation of this beneficial effect has been proposed. We prospectively investigated 27 APL patients at presentation for diffuse intravascular coagulation (DIC) markers (prothrombin activation fragment and thrombin/antithrombin complexes) and plasmin-dependent primary fibrinogenolysis markers (alpha 2 plasmin inhibitor consumption +/- plasmin/alpha 2 plasmin inhibitor complexes). Fourteen of these patients were then serially studied during the first 2 weeks of ATRA therapy. Four of them, however, developed an hyperleukocytosis requiring additional chemotherapy before the end of the 2nd week. At presentation, low level of fibrinogen was clearly associated with alpha 2 plasmin inhibitor deficiency (p < 0.01), while DIC was equally present in fibrinogenopenic and non-fibrinogenopenic patients. Moreover, we observed a rapid simultaneous correction of low fibrinogen levels and plasmin activation markers in APL patients undergoing ATRA therapy (before day 5), but a more prolonged persistence of DIC markers (until day 14). Initial bleeding syndrome seemed more frequent in patients with initial low fibrinogen level. These data indicate that plasmin-dependent primary fibrinogenolysis is the major etiologic factor of low fibrinogen level in APL patients. In vivo differentiation ATRA therapy induces a rapid decrease in the plasmin activation and a normalization of fibrinogen level, while DIC may in vivo persist for several weeks. Prospective studies evaluating antifibrinolytic agents as therapy of APL-associated hemostasis disorders should be considered. Additionally, prophylactic heparin therapy might be useful after day 5 in patients undergoing ATRA therapy, since they present a prolonged procoagulant tendency.

In multiple myeloma increased osteodastic activity causes degradation of organic and inorganic bone matrix. In some patients the increased osteoclastic activity is outbalanced by an increased osteoblastic activity, and these patients do not develop lytic bone destructions. Besides this remodeling disorder in bone 20-30 X of the patients develop bone marrow fibrosis, which is of prognostic importance. The organic bone matrix consists mainly of type I collagen, whereas the extracellular matrix of the bone marrow consists of type I and type III collagen along with hyaluronan. During degradation of type I collagen a cross-linked telopeptide, ICTP, is liberated into the circulation. Correspondingly, the C-terminal propeptide of procollagen I, PICP, and the N-terminal propeptide of procollagen III. PIIINP, are liberated during synthesis of type Iand type Kl collagen, respectively. The present smdy was performed to provide information concerning hyaluronan and the peptides related to collagen metabolism in serum in multiple myeloma, and to evaluate the prognostic value of these metabolites according to bone morbidity and survival. We examined 15 consecutive patients before start of treatment and 15 sexand age-matched controls. In the myeloma group we found significant elevations in serum of ICTP (median 6.2 vs. 2.4 pgfl; P < 0.01), PIIINP (median 5.2 vs. 2.9 pgA; P < 0.01) and hyaluronan (median 122 vs. 45 pgll; P < 0.01). PICP in serum was elevated in only three patients. ICTP in serum correlated significantly with radiologically assessed bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated closely to serum PIIINP (P < 0.01) and serum &-microglobulin (P < 0.01), whereas there were no significant correlations between the serum levels of hyaluronan and any of the collagen derived peptides, &-microglobulin or the paraprotein level. The myeloma group was followed for 9 to 25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that ICTP in serum seems to be a sensitive and easy accessible marker of osteoclastic activity and bone morbidity in multiple myeloma. Furthermore ICTP in serum may be of prognostic value. Elevation of hyaluronan in serum is common in multiple myeloma, the significance of which is unknown.

British Journal of HaematologyVolume 81, Issue 4 p. 620-621 t(14;18) AND BCL-2 GENE REARRANGEMENT IN A B-CHRONIC LYMPHOCYTIC LEUKAEMIA Ph. Jonveaux, Ph. Jonveaux INSERM U.301, Paris Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorJ. Hillion, J. Hillion INSERM U.301, ParisSearch for more papers by this authorA. L. Bennaceur, A. L. Bennaceur Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorM. F. D'Agay, M. F. D'Agay Laboratorie d'Anatomo-pathologie, Hôpital Saint-LouisSearch for more papers by this authorP. Brice, P. Brice Polyclinique d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorM. T. Daniel, M. T. Daniel Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorF. Sigaux, F. Sigaux Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorR. Berger, R. Berger INSERM U.301, ParisSearch for more papers by this author Ph. Jonveaux, Ph. Jonveaux INSERM U.301, Paris Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorJ. Hillion, J. Hillion INSERM U.301, ParisSearch for more papers by this authorA. L. Bennaceur, A. L. Bennaceur Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorM. F. D'Agay, M. F. D'Agay Laboratorie d'Anatomo-pathologie, Hôpital Saint-LouisSearch for more papers by this authorP. Brice, P. Brice Polyclinique d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorM. T. Daniel, M. T. Daniel Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorF. Sigaux, F. Sigaux Laboratoire d'Hématologie, Hôpital Saint-LouisSearch for more papers by this authorR. Berger, R. Berger INSERM U.301, ParisSearch for more papers by this author First published: August 1992 https://doi.org/10.1111/j.1365-2141.1992.tb03006.xCitations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume81, Issue4August 1992Pages 620-621 RelatedInformation

Retinoic acid, the active metabolite of vitamin A has been shown to differentiate in vitro human leukaemic cells from patients with acute promyeolocytic leukaemia (APL). The results obtained in vivo with the 13-cis isomer of retinoic acid in combination with or after chemotherapy in four cases of APL are described. More recently Huang et al from the Shangai Institute of Haematology have treated 24 cases of APL with all-trans retinoic acid alone. They obtained 24 complete remissions. This success prompted us to treat patients with APL and a contra-indication to chemotherapy with all-trans retinoic acid. The results confirm the great efficacy of all-trans retinoic acid in APL.

Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.

A systematic cytogenetic study was started in 1977 to investigate the incidence, types, and possible relations with prognosis of childhood acute nonlymphocytic leukemia (ANLL). We report on the findings of 130 de novo childhood ANLL studied at diagnosis in one department and in the same laboratories for cytology and cytogenetics between September 1977 and December 1986.

Letters and Corrections1 May 1988Fine-Needle Aspiration and Cryptococcosis in the Acquired Immunodeficiency Syndrome (AIDS)JEAN-MICHEL MOLINA, M.D., ERIC OKSENHENDLER, M.D., MARIE-THERESE DANIEL, M.D., JEAN-PIERRE CLAUVEL, M.D.JEAN-MICHEL MOLINA, M.D.Search for more papers by this author, ERIC OKSENHENDLER, M.D.Search for more papers by this author, MARIE-THERESE DANIEL, M.D.Search for more papers by this author, JEAN-PIERRE CLAUVEL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-5-772_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their evaluation of fine-needle aspiration biopsies of lymph nodes in patients with the acquired immunodeficiency syndrome (AIDS)-related conditions, Bottles and colleagues (1) emphasize the usefulness of this method for diagnosing malignancy, Kaposi sarcoma, and mycobacterial infection. We report a case in which the diagnosis of disseminated cryptococcosis was made on the basis of a routine May-Grünwald-Giemsa-stained lymph node specimen from fine-needle aspiration biopsy.A 33-year-old black patient from Angola had lost weight and had night sweats and fever. Physical examination showed cervical, nontender small lymph nodes (0.5 to 1 cm). Mild splenomegaly was present....References1. BOTTLESMCPHAULVOLBERDING KLP. Fine-needle aspiration biopsy of patients with the acquired immunodeficiency syndrome (AIDS): experience in an outpatient clinic. Ann Intern Med. 1988;108:42-5. LinkGoogle Scholar2. ENGBISHBURGSMITHKAPILA RESR. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med. 1986;81:19-23. CrossrefMedlineGoogle Scholar3. ZUGERLOUIEHOLZMANSIMBERKOFFRAHAL AERMJ. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1986;104:234-40. LinkGoogle Scholar4. WITTMCKAYSCHWAMGOLDSTEINGOLD DDLDJ. Acquired immune deficiency syndrome presenting as bone marrow and mediastinal cryptococcosis. Am J Med. 1987;82:149-50. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hôpital Saint-Louis 75475 Paris cedex 10 France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHuman CryptococcosisAtypical Micromorphology and Uncommon Location of Cryptococcosis: A Histopathologic Study Using Special Histochemical Techniques (One Case Report)AIDS and fungal infections 1 May 1988Volume 108, Issue 5Page: 772-772KeywordsAIDSBiopsyCryptococcosisFeversKaposi sarcomaLymph nodesSplenomegalySweat Issue Published: 1 May 1988 PDF DownloadLoading ...

D uring the last 10 years, there has been growing evidence that viral infection might be an important clue to hematologic malignancies end disorders of the immune system. Adult T-cell leut emia (ATL), a distinct clinical entity initially described in Japan in 1977 [1], is the first human malignancy recognized as being associated with a retrovirus, HTLV-I (human Tcell leukemia/lymphoma virus type 1) [2]. Human immunodeficiency viruses type 1 and type 2 (HIV-1 and HIV-2) were described in 1983 and 1986, respectively, as agents responsible for the acquired immunodeficiency syndrome (AIDS) [3,4]. Recently, a novel lymphotropic herpesvirus, designated human herpesvirus 6 (HHV-6), has been suspected of playing a role in human lymphoproliferative disease [5]. Herein we describe a case of a young African woman with ATL, noteworthy for simultaneous infection with HTLV-I, HIV-2, and HHV-6, three viruses exhibiting tropism for human lymphoid cells. Since the epidemiology of the diseases thought to be linked to these viruses in Africa is still partly unknown, the results of a serologic study among the relatives of the patient will be presented.

Cytogenetic studies performed on 130 consecutive childhood acute non lymphoblastic leukemias (ANLL) and investigated in the same center between 1977 and 1986 have been studied for their prognostic value. Clonal chromosome changes were detected in 68.5% (89/130) of the cases prior to treatment. Complete remission rate and median survival were significantly lower in patients with only abnormal metaphases than in patients with only normal metaphases (NN) or a mixture of normal and abnormal mitoses (AN). The ANLL with translocation t(8;21), which were 58.6% of the M2 ANLL, were not associated with a particularly long survival (16 months) when compared with AN and NN ANLL. The longest survival (26 months) was observed in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. Cytogenetic analysis have a prognostic value in childhood ANLL.

We report a case of acute adult T-cell leukemia associated with HTLV1 infection in a young African woman. The leukemic proliferation consisted of CD4-, CD25-positive lymphoid cells with typically convoluted nuclei and monoclonal integration of the HTLV1-proviral DNA. The clinical course was characterized by a rapid progression of the leukemia with development of hypercalcemia, resistance to chemotherapy, and the presence of multiple opportunistic infections. The additional finding of a seropositivity for HIV2 raises the problem of the respective contribution of the two retroviruses in this patient's disease.

Six patients with Philadelphia-positive (Ph1+) acute nonlymphocytic leukemia (ANLL) were studied by morphological, immunological, cytogenetic, and molecular techniques. Seven Ph1+ acute lymphocytic leukemia (ALL) cases were also studied for comparison. Three of ANLL cases were classified in M1, M2, and M4 groups of the FAB nomenclature, while the three other cases do not fit with any FAB subgroup and are described as M0. Immunophenotypical marker studies, double immunolabeling, and combined immunological and cytogenetic studies of metaphases showed that these ANLL expressed several lineage differentiation antigens. Rearrangements of immunoglobulin heavy chain gene (C mu) were detected in the six ANLL cases and in the seven ALL cases studied, as well as, in most cases, rearrangement of T cell receptor beta chain genes and/or T cell rearranging gamma genes. The results favored the assumption that the Ph1 translocation originated from a multipotent stem cell in Ph1+ ANLL. A common t(9;22) translocation was found in all cases, and additional chromosomal abnormalities were present in the six ANLL cases and in five of the seven ALL cases. Molecular studies of bcr gene configuration and c-abl transcription allowed two groups of Ph1+ ANLL to be distinguished. Three cases had bcr rearrangement and c-abl mRNA expression comparable to those reported in Ph1+ chronic myeloid leukemia, while three others had not detectable bcr rearrangement and a 7.2-7.5 kb c-abl mRNA. The existence of Ph1+ ALL with and without classical bcr rearrangement was confirmed.

We describe herein the occurrence of a T cell-derived blast crisis of chronic myelocytic leukemia which presented as a typical T cell leukemia on clinical (thymic mass and high white blood cells) and immunological grounds (T6+ T4+ T8+), with rearranged T cell receptor genes and germ line immunoglobulin genes. A Philadelphia chromosome was detected in all blast cell mitoses. The significance of T cell involvement during the chronic and acute phases of chronic myelocytic leukemia is discussed.

A total of 32 patients with acute myelomonocytic leukemia and abnormal bone marrow eosinophils (LAM4 Eo) have been treated at this Institute since 1977. Abnormalities of chromosome 16 have been noted in 14 of 22 evaluable cases. After a median follow-up of 4 years, median duration of complete remission was 46 months and median duration of survival had not been reached; 8 patients have been receiving no therapy for between 1 and 6 years. These results compare favorably with LAM4 without abnormal bone marrow eosinophils (median duration of complete remission: 12 months; median duration of survival: 14 months). LAM4 Eo constitute a particular entity, with a special hematological presentation, the incidence of abnormalities of chromosome 16, and a particularly good prognosis.

Morphometric analysis of nuclear sizes and shapes was carried out on semithin sections of lymph node for 21 patients suffering from non-Hodgkin's peripheral T-cell malignant lymphoma (ML) (excluding mycosis and Sézary syndrome). Twenty cases of B-cell ML and three cases of Sézary syndrome with massive lymph node infiltration were also studied as references. Wright and Isaacson's recent proposals were applied to classify the peripheral T-cell MLs into monomorphic medium-cell ML (eight cases), pleomorphic ML (nine cases), and monomorphic large-cell ML (four cases). These three classes were readily distinguishable by morphometric analysis of nuclear sizes. Nuclear areas and their coefficients of variation were higher in pleomorphic MLs than in monomorphic medium-cell MLs (p less than 0.01). Large-cell monomorphic MLs were set apart by the histograms of their nuclear sizes. The mitoses were evaluated on histological sections and found to be more numerous in pleomorphic ML than in monomorphic medium-cell ML (p less than 0.05). Nuclear irregularity in the 21 cases of peripheral T-cell ML was lower than in Sézary cells. Morphometry clearly demonstrates the morphological distinctiveness of the subclasses of peripheral T-cell ML. Their biological significance has yet to be determined.