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Biomedical subjects

M Shtalrid

Publications and source records attributed to M Shtalrid.

At least 19 recordsLinked to original sources

Successful treatment of aggressive HIV-associated non-Hodgkin's lymphoma with combination chemotherapy, biotherapy with rituximab and HAART: presentation of a therapeutic option.

The incidence of non-Hodgkin's lymphoma (NHL) in individuals infected with human immunodeficiency virus (HIV) is more than 60 times higher than in matched controls. In the vast majority of cases aggressive pathological subtypes and advanced stages prevail, extranodal sites are involved and systemic symptoms are present. The prognosis of HIV-NHL remains poor and the optimal therapeutic approach has yet to be defined. We report a 48-year-old Ethiopian woman with advanced-stage HIV infection, who developed diffuse large cell, immunoblastic type B-cell NHL and was treated with a modified CHOP-like chemotherapy combined with Rituximab and supported with growth factor. Highly active antiretroviral therapy (HAART) and opportunistic infections prophylaxis were administered concomitantly. The patient completed 6 cycles of therapy and currently, 76 weeks after diagnosis, is in complete clinical remission. Despite the fact that there was a transient decrease in the CD4-positive cell number and a 1.5 log increase in plasma viral load there were no opportunistic infections, nor was life-threatening toxicity seen. Rituximab seems a well-tolerable and advantageous adjunct to chemotherapy and HAART in the treatment of aggressive HIV-associated NHL andshould be investigated in large trials in the future.

Antibodies, Monoclonal↗

Primary effusion lymphoma (PEL) in HIV-negative patients--a distinct clinical entity.

Primary effusion lymphoma (PEL) is a recently described rare type of non-Hodgkin's lymphoma occurring almost exclusively in HIV infected people. Human herpesvirus 8 (HHV-8), has been linked with PEL, and a causative relationship has been suggested. In the vast majority of PEL cases Epstein-Barr virus (EBV) has been found in the tumour cells. We describe here an elderly human immune deficiency (HIV) seronegative man with intractable chest pain and pleural effusion. The diagnosis of malignant lymphoma was suggested cytologically and confirmed histologically following pleural biopsy. No lymphadenopathy or organ involvement with lymphoma was found. Systemic chemotherapy with a modified CHOP regimen with G-CSF support gradually led to the resolution of the chest pain and ultimately resulted in a complete clinical remission (CCR). The presence of HHV-8 was demonstrated by PCR using paraffin-embedded tissue samples from the involved pleura, whereas EBV-associated genetic material was absent. The patient remained in CCR for 18 months and died of an unrelated cause (cerebrovascular event). Only 11 other cases with clinical and virological features similar to those of our patient have been reported in the literature. Analysis of these rare cases suggests HIV-negative EBV-negative PEL to be a distinct clinical entity with epidemiological features resembling classical KS and supports an EBV-independent role for HHV-8 in the pathogenesis of PEL.

Aged↗

Over-expression of the functional interleukin-11 alpha receptor in the development of B-cell chronic lymphocytic leukemia.

Several cytokines have been found to play a role in the pathogenesis of B-CLL. In the present study using reverse-transcriptase polymerase chain reaction (RT-PCR), FACS analysis and immunofluorescence we have shown the constitutive expression of IL-11 and IL-11R alpha in B-chronic lymphocytic leukemia (B-CLL). The expression level of IL-11R alpha in B-CLL cells is much higher than in PBL of normal donors. Recombinant human IL-11 (rhIL-11) activates B-CLL cells, leading to morphologic alterations of the cells and increase in cell number and size. Short-term cultivation in the presence of rhIL-11 did not lead to quantitative changes in the ratio of the living vs apoptotic and dead cells. However, in contrast to rhIL-6, pretreatment with rhIL-11, did not cause B-CLL cells to be resistant to the action of dexamethasone. These data suggest an essential role for the IL-11/IL11 R alpha system in the pathogenesis of the malignant B-CLL cells.

Aged↗

Facial diplegia as the presenting manifestation of acute lymphoblastic leukemia.

A 36-year-old man with recent onset of unilateral peripheral 7th nerve paresis presented ten days later with involvement of the other side of his face. Physical examination was otherwise normal, and since blood tests and imaging were also normal, he was considered to have bilateral Bell's palsy. However, unexpected headaches and worsening of the paresis led to a gallium-67 scan which revealed uptake in the mediastinum. A repeat lumbar puncture revealed cells which were identified as lymphoblasts. T-cell acute lymphoblastic leukemia (T-ALL) was diagnosed, although the peripheral blood smear was normal. The differential diagnosis of bilateral 7th nerve palsy and of mononuclear cerebrospinal fluid pleocytosis is discussed, as well as this rare central nervous system presentation of acute leukemia.

Adult↗

[Effective treatment with Lamivudine of patients with reactivation of hepatitis B following chemotherapy administration].

Chemotherapy administration to patients with lymphoproliferative diseases that are carriers of hepatitis B can be complicated by reactivation of Hepatitis B. This may lead to morbidity and mortality due to liver failure. We report 2 cases, treated recently. The first case is that of a 63-year-old female with a diagnosis of immunoblastic lymphoma. The patient was treated with the ProMACE-CytaBOM protocol. During treatment Hepatitis B was reactivated and after termination, of chemotherapy she developed fulminant hepatitis with hyperbilirubinemia, coagulopathy, hypoalbuminemia and ascites. The second case is that of a 34 years old male with a diagnosis of T-ALL who was treated according to the BFM 95 protocol. He had reactivation of Hepatitis B during induction therapy. These two patients were treated with Lamivudine with resolution of the hepatitis and disappearance of HBV DNA from the sera. Prophylactic administration of Lamivudine enabled reinduction of chemotherapy in the first case after relapse of the lymphoma and continuation of BFM 95 protocol in the second patient. Lamivudine inhibits replication of hepatitis B virus and prevents reactivation of Hepatitis B during immunosuppression induced by chemotherapy and probably ameliorates the severity of already reactivated hepatitis.

Adult↗

Advanced Hodgkin's disease in a pregnant HIV seropositive woman: favorable mother and baby outcome following combined anticancer and antiretroviral therapy.

We describe a 33 y/o HIV(+) woman who developed advanced Hodgkin's disease (HD) during the 2nd trimester of her pregnancy. Combination chemotherapy and antiretroviral treatment along with opportunistic infection prophylaxis were administered. At term, while in partial remission, she delivered by a Caesarian section a healthy baby, PCR-negative for HIV. A complete remission was later achieved upon completion of the chemotherapy regimen. Since both the incidence of HD and the proportion of young women among the HIV(+) individuals are increasing, it seems important to recognize that successful completion of pregnancy with no deterioration of accepted surrogate parameters of HIV disease progression is achievable in a carefully treated HIV(+) pregnant woman with advanced HD.

Adult↗

Autologous T cells control B-chronic lymphocytic leukemia tumor progression in human-->mouse radiation chimera.

B-chronic lymphocytic leukemia (B-CLL) is characterized by the clonal accumulation of CD5+ B cells. It has been suggested that CLL cells may be regulated by inhibitory and growth-promoting signals exerted by autologous T cells. We have recently described a model for human B-CLL in which peripheral blood mononuclear cells (PBMCs) are transplanted into the peritoneal cavity of lethally irradiated mice radioprotected with bone marrow from mice with severe combined immunodeficiency. In this model, adoptive transfer of low-stage PBMCs leads to marked engraftment of T cells or combined T and CLL cell engraftment, whereas infusion of high-stage PBMCs leads to dominance of CLL cells with a miniscule level of T-cell engraftment. This mutual exclusive pattern of engraftment indicated that T cells might control the expansion of tumor cells in the peritoneum of recipient BALB/c mice. In the present study, we further investigated this question and we demonstrate that in vivo T-cell depletion, using OKT3 antibody, markedly enhances the engraftment of B-CLL cells from patients with early-stage disease. In mice receiving PBMCs from 11 donors with advanced-stage disease, the results were more heterogeneous. In five patients the results were similar to those observed in early stage, whereas in two cases no CLL cell engraftment was found in the absence of T cells. The addition of purified T cells to PBMCs led to a substantial decrease of CLL engraftment in three advanced-stage cases. These results strengthen the working hypothesis that autologous T cells can actively suppress the expansion of the pathological cells in human-->mouse radiation chimera. This effect is prominent in early-stage disease, whereas in advanced stage suppressive and/or stimulatory effects may occur in different patients. The interaction of T cells with tumor cells and the potential of autologous T cell/immune-therapy in CLL can be further explored in this model.

Aged↗

B-cell prolymphocytic leukemia: a survey of 35 patients emphasizing heterogeneity, prognostic factors and evidence for a group with an indolent course.

We report a retrospective survey of 35 patients (18 males and 17 females) with B-Prolymphocytic leukemia (B-PLL) followed for a median of 63 months. Twelve patients fulfilled Galton's original clinical and hematological criteria, presented with prominent splenomegaly and hyperleukocytosis and showed rapid progression soon after diagnosis. Twelve cases with gradually increasing spleen size and prolymphocyte count had an indolent course. Seven of this group are alive 68 to 164 months after diagnosis, whereas five died from causes unrelated to PLL. Eleven patients who never developed impressive leukocytosis had a variable prognosis. In the group of 17 patients treated with chlorambucil and prednisone (CP) or cyclophosphamide, vincristine, prednisone (COP) 8 achieved a partial remission (PR) with a median response of 32 months. In the group of six cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) treated patients one achieved a complete remission and two PR (median response was maintained for 30 months). Three patients treated with 2CdA achieved good PR. Six patients remained untreated. Median survival was 65 months and the probability of overall survival for 3, 5, and 10 years was 63%, 56% and 35%, respectively. Anemia < 11 g/dl and lymphocytosis > 100 x 10(9)/l were predictors of shorter survival in this group of patients. Age over 70, gender, B-symptoms at presentation, spleen size, thrombocytopenia, low IgG and complement levels, presence of paraproteinemia and the pattern of bone marrow infiltrate were not significant. Our findings show that all B-PLL may not have such a poor prognosis as described in earlier reports. The existence of prior symptoms evolving gradually after years to obvious PLL and cases with mild prolymphocytosis could possibly lead to underdiagnosis of the entity. Identification and follow-up of such cases may suggest a different natural history, variable prognostic features and different survival curves for B-PLL patients. In the light of the above, we suggest that the therapeutic approach for B-PLL should always relate to the severity of the disease.

Adult↗

Ultrastructural characteristics and lysozyme content in hypergranular and variant type of acute promyelocytic leukaemia.

We investigated the electronmicroscopic (EM) features and cellular lysozyme (LZ) content in 16 cases of acute promyelocytic leukaemia (APL): 11 cases of the hypergranular form (M3) and five cases of the microgranular variant (M3-V). The main EM features in all cases were: irregular, folded or bilobed nuclei, many cytoplasmic granules, distended rough endoplasmic reticulum (RER) cisternae which, in some cases, presented as stellate forms (more frequent in M3-V), and bundles of cytoplasmic microfilaments. Many Auer rods were present in M3 cases and few in M3-V; most of these disclosed parallel tubular arrays (PTA) with a varied periodicity ranging from 13 to 26 nm. There was a significant difference between M3 and M3-V (P<0.0001) in both the number of granules per cell section (62.9 +/- 34.5 v 38.0 +/- 23.6) and in the granule section area (0.044 +/- 0.033 v 0.026 +/- 0.015 microm2). In some cases, mainly in M3-V, we found cells with large granules containing PTA which probably represent poorly developed Auer rods. Intracellular LZ content assayed by a post-embedding immunogold method, showed high granular LZ density (in the range of that found in M4 and M5) in M3 cells and very low granular LZ content in M3-V. This study adds new objective parameters for the diagnosis of these two types of APL and provides new information on their LZ pattern of expression.

Endoplasmic Reticulum, Rough↗

Acute femoral artery thrombosis associated with functional protein C deficiency as the presenting manifestation of acute monocytic leukemia.

Acute leukemia may be linked to disturbances of the coagulation system, which are usually due to hyperviscosity because of disseminated intravascular coagulation or a high white cell count. We report a unique case of femoral artery thrombosis as the beginning symptom of acute monocytic leukemia (M5) associated with a low level of functional protein C. The patient had multiple recurrent episodes of thrombosis with low levels of functional protein C associated with the relapse of the leukemia. A review of the literature shows that this is an extremely rare phenomenon.

Acute Disease↗