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Biomedical subjects

A Polliack

Publications and source records attributed to A Polliack.

At least 37 records · Page 2Linked to original sources
PubMed1999

Salvage chemotherapy using a combination of fludarabine and cyclophosphamide for refractory or relapsing indolent and aggressive non-Hodgkin's lymphomas.

The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) after primary therapy is poor and multi-drug salvage treatments are associated with less than 60% response rates, usually of short duration. Here we report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP-Cy) combination as a salvage failure regimen in refractory and relapsing low-grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had received up to 4 regimens prior to therapy with FAMP-Cy were treated with fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving complete responses (CR) and 7 partial responses (PR). All patients with low-grade NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR lasting for a median of 5 months. The main toxicity encountered was moderate myelosuppression. Three patients had febrile neutropenia, one had drug-induced fever and a single patient developed severe neurotoxicity. Opportunistic infections due to lymphopenia were not seen. The combination of fludarabine and cyclophosphamide used as a salvage regimen showed an impressive response in a small group of heavily pretreated low-grade NHL patients who had previously received a large number of prior regimens. FAMP-Cy had limited effect in a similar group of intermediate-grade NHL patients. Results with this "failure" regimen are encouraging, however further studies are needed in order to confirm these observations in a larger series of patients.

Adolescent↗
PubMed1999

Treatment of hairy-cell leukemia: current views.

Although hairy-cell leukemia (HCL) is uncommon, remarkable progress has been made in the treatment of patients with this disease. Because of their unique mechanisms of action, the purine analogs, 2'-deoxycoformycin (2'-DCF) and 2-chlorodeoxyadenosine (2-CdA), are naturally targeted to lymphocytes and are cytotoxic to both resting and dividing cells. Both of these agents induce durable complete remissions (CRs) in the overwhelming majority of patients. Remarkably, equally high rates of durable CR are achieved in both untreated and previously treated patients. Furthermore, patients with large tumor burdens fare as well as those with minimal disease. Therefore, these agents have emerged as the treatments of choice for all patients with hairy-cell leukemia and have supplanted earlier treatments such as splenectomy and interferon-alpha (IFN-alpha). Since a single 7-day cycle of 2-CdA leads to excellent outcomes and is associated with few toxicities other than culture-negative fever, this agent is particularly attractive and may offer some advantages. However, given the indolent natural history of HCL, long-term follow-up study will be required to determine if one purine analog offers a survival advantage over the other.

Antibiotics, Antineoplastic↗
PubMed1998

A novel translocation (1;2)(p34;p21-22) in acute myelomonoblastic leukemia.

A novel and as yet unrecorded translocation, (1;2)(p34;p21-22), detected in a patient with acute myeloid leukemia (AML) is reported. The leukemia--in this case, AML-M4--showed a rapidly progressive fatal course despite an early transient response to aggressive chemotherapy. In this patient, the leukemic cells showed a novel balanced translocation, (1;2)(p34;p21-22), in most of the metaphases at the time of diagnosis and during subsequent relapse. Interferon-inducible double-stranded RNA-dependent protein kinase (ds RNA-PK) is located in the chromosome region, 2p21-22, that was involved in the translocation in this case. The possible role of ds RNA-PK in leukemogenesis is briefly mentioned.

Adolescent↗
PubMed1998

Differences in rhodamine-123 efflux in B-type chronic lymphocytic leukemia suggest possible gender and stage variations in drug-resistance gene activity.

Peripheral blood samples from 61 patients (36 male, 25 female) with all stages of B-type chronic lymphocytic leukemia (CLL) were studied for MDR1 phenotype using monoclonal antibodies and rhodamine-123 dye exclusion, a functional assay of MDR1 expression. The duration of the disease varied from 1 month to 22 years at the time of initial study. Overall, 74% of the patients were positive for rhodamine-123 exclusion. When analyzed by gender, significantly more men than women were positive (89% versus 48%, p<0.001). There were more positive men than women for every stage of the disease. Female patients were found to be either MDR1 phenotype positive or negative at any stage of the disease. In contrast, all male patients with early (stages 0-II) disease were MDR1 phenotype positive. One early-stage (stage II) male patient converted from rhodamine-efflux positive to rhodamine-efflux negative as he progressed from stage-II to stage-IV disease. We suggest that some of the differences in disease biology of male versus female CLL patients (women having a more benign course) may be due to gender-dependent differences in drug-resistance gene activity, including MDR1. Our results also emphasize the need to take into account gender in evaluating the clinical course of patients with CLL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Two-way referral bias: evidence from a clinical audit of lymphoma in a teaching hospital.

The objective of this study was to evaluate the effect of referral bias in a clinical audit of lymphoma in a university hospital. We compared demographic and clinical characteristics as well as survival for Jerusalem residents (local) and referred (distant) patients diagnosed from 1987 to 1992 and treated in our institution. Referred patients were younger (p < 0.0001), and less likely to be immigrants (p < 0.0001), than local patients. Aggressive non-Hodgkin's lymphomas (NHL) were more common in the referred population (p = 0.015). Survival for Hodgkin's disease was consistently better for local patients, but for patients with NHL the findings were reversed. In this study referred patients differed in their clinical and sociodemographic characteristics but did not consistently exhibit a worse outcome than that of local patients. The unpredictable nature of referral bias may be due to better functional status or resources among referred patients, or to selective referral for procedures such as bone marrow transplantation. While reports on the natural history of disease from tertiary institutions may be biased by referral patterns, the direction of the bias is not uniform.

Adolescent↗
PubMed1998

Cutaneous lymphoma in Israel, 1985-1993: a population-based incidence study.

The incidence rate of cutaneous lymphomas (CL) [including mycosis fungoides (MF) and non-mycosis fungoides (non-MF)] for the period 1985-93 in Israel was determined using data from the population-based Cancer Registry supplemented by a field survey that covered approximately 80% of lymphoma cases. After the field survey, corrected rates were 49% and 24% higher for MF and non-MF respectively (37% for CL overall). The age-adjusted incidence rates per 100,000 were 1.18 and 0.63 for Jewish men and women respectively. MF rates (0.77 in men and 0.35 in women) were higher than non-MF (0.41 and 0.28 respectively). Rates of CL were significantly lower in non-Jews. There were no significant differences in incidence among Jewish ethnic subgroups. However, the lack of variability in the incidence of these neoplasms among subpopulations is in contrast with findings for cutaneous malignant melanoma; the observed high rates of CL could, nonetheless, be consistent with the sunlight exposure hypothesis, operating perhaps through a different mechanism.

Cohort Studies↗
PubMed1998

The contribution of multiple data sources to a clinical audit of lymphoma in a teaching hospital.

OBJECTIVE: To assess the independent contribution of data sources used for case ascertainment in a clinical audit of the outcome of lymphoma patients in our institution. DESIGN: In the absence of a unified register of lymphoma patients diagnosed and/or treated in our institution, we used an elective approach to case ascertainment. Sources included two internal databases (computerized discharge data for hospitalizations and outpatient oncology database) and one external (Israel Cancer Registry) database. Histologic diagnosis was confirmed by search of on-line pathology files or discharge summaries. Demographic, histologic and survival characteristics were compared among patients identified through each data source. Survival was assessed via record linkage with the Population Registry. SETTING: A tertiary care university teaching hospital. STUDY PARTICIPANTS: Seven hundred and twelve patients with lymphoma diagnosed between 1987 and 1992. RESULTS: All three sources contributed independently to the total, with the majority (583 or 82%) via hospitalizations. Overlap among the sources was minimal with only 73 (10.3%) of the patients being common to all three sources. Differences (P < 0.05) in the age distribution, country of birth and population groups (defined by religion) as well as histologic diagnoses among the sources were noted. In addition, survival of those ascertained via the outpatient database was higher than those ascertained from other sources (P=0.02 for Hodgkin's disease) even after controlling for age. CONCLUSIONS: The use of multiple data sources for case ascertainment in clinical audit is justified when no patient register exists. The results indicate that use of a single internal data source would have resulted both in an underestimate of the scope of lymphoma in our institution and significant bias in terms of patient characteristics and outcome.

Adolescent↗
PubMed1998

Intravascular lymphomatosis--an indolent or aggressive entity?

Intravascular lymphomatosis (IVL) is a rare malignancy characterized by neoplastic proliferation of lymphoid cells within the lumens of arteries, small veins and capillaries. We report four patients with IVL and review the recent world literature, relating to incidence, clinical features and possible therapy. In these cases diagnosis was established coincidentally in one patient after prostatectomy. This patient eventually had central nervous system involvement. In two other patients IVL was diagnosed from skin lesions. In the fourth case the diagnosis was established at post-mortem examination, where involvement of most organs was evident but particularly kidneys, myocardium, gastrointestinal tract and lymph nodes. Therapy was given to three patients, but the disease progressed in two and they both died with evidence of central nervous system involvement, while the third patient has had a good partial response to combination chemotherapy but has relapsed within two months of completing chemotherapy. As evident from our patients and the literature review IVL has a variable clinical course and currently, there appears to be no effective therapy for this rare disorder.

Aged↗
PubMed1998

Correlation of serum levels of interleukin-1 family members with disease activity and response to treatment in hairy cell leukemia.

Hairy cell leukemia (HCL) is a well-recognized chronic lymphoproliferative disorder of B cell lineage, which may be regulated by growth factors including cytokines and cytokine antagonists. Previous studies have shown a good correlation between circulating soluble interleukin-2 receptor (sIL-2R) levels and disease activity and response to therapy was always associated with a decrease in sIL-2R levels. The interleukin-1 (IL-1) family of agonists and antagonists may also be involved in the regulation of hematopoietic malignancies. In the present study, we evaluated members of the IL-1 family (IL-1beta, IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptors Type I and Type II (IL-1sRI and IL-1sRII) in 23 patients with HCL. Patients were classified according to the clinical state of their disease. Most were treated with 2-chloro-2'-deoxyadercosine (2-CDA) and treatment was associated with a significant decrease in the serum levels of sIL-2R, IL-1beta and IL-1sRII in patients achieving a complete or partial response. In contrast to the above, levels of IL-1Ra increased during response to treatment and clinical response to 2-CDA was associated with an increase of 122% in IL-1Ra levels, in parallel with a decrease of 63% in IL-1beta and 47% in IL-1sRII levels. These results suggest that the balance between IL-1beta, IL-2 and their soluble receptors or antagonists may be involved in the pathogenesis and immunoregulation of HCL. Serum levels of these cytokines may therefore be used to monitor therapeutic efficacy of therapy in HCL and to detect any residual disease.

2-Chloroadenosine↗
PubMed1997

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): report of a patient with isolated renotesticular involvement after cure of non-Hodgkin's lymphoma.

Sinus histiocytosis with massive lymphadenopathy (SHML)-Rosai-Dorfman disease-is a rare but well-defined benign histiocytic proliferative disorder. We report an unusual patient, cured of non-Hodgkin's lymphoma, who presented 12 years later with renotesticular SHML associated with IgA monoclonal gammopathy, but without any evidence of relapsed lymphoma. The genitourinary manifestations of this disorder with massive lymphadenopathy and its rare association with malignant lymphoma are reviewed.

Adult↗
PubMed1997

Cancer patterns in the Middle East--special report from the Middle East Cancer Society.

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.

Adult↗
PubMed1997

Pathways controlling the expression of surface CD21 (CR2) and CD23 (Fc(epsilon)IIR) proteins in human malignant B cells.

The aim of the present study was to analyze the pathways regulating the expression of CD21 and CD23 B-cell differentiation antigens on human malignant B cells. Exposure of Farage cells, derived from a human B-cell lymphoma, to phorbol 12-myristate 13-acetate (PMA) down-regulated CD21 and CD23 expression, while interleukin 4 (IL4) inhibited the expression of CD21 but augmented CD23 expression. When Farage cells were stained with either anti-CD21 or anti-CD23 monoclonal antibodies (mAb), subsequent exposure to IL4 failed to change the staining of the cells, indicating that IL4 did not affect the turnover of CD21 and CD23 molecules. Inhibition of protein synthesis with cycloheximide (CXM) had no effect on the expression of CD21 molecules, but abrogated their down-regulation by IL4, suggesting that IL4 induced the synthesis of proteins which modify the processing of CD21 molecules. The inhibitory effect of IL4 on the expression of CD21 and its augmentary effect on the expression of CD23 was abrogated by H7 (1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine), an inhibitor of serine protein kinase. Staurosporine, an additional inhibitor of serine kinases also abrogated the effect of IL4 on CD23 expression. H8 (N-(2-[Methylamino]ethyl)-5-isoquinolinesulfonamide), a preferential inhibitor of protein kinases A and G, and genistein, an inhibitor of tyrosine kinases had no effect on IL4-induced modulation of CD21 and CD23 in Farage cells. The exposure of B-chronic lymphocytic leukemia (CLL) cells to PMA reduced the expression of CD21, but increased the expression of CD23. IL4 had no effect on the expression of CD21 on CLL-cells but strongly enhanced the level of CD23. H7, H8 and genistein each abrogated to a different extent the effect of IL4 on the expression of CD23 by CLL-cells. These data indicate that activation of serine/threonine kinases in malignant B cells inhibited the production of CD21 proteins, while different protein kinases appeared to be involved in up- and down-regulation of CD23 in different B lymphocytes.

B-Lymphocytes↗
PubMed1997

De novo acute myeloid leukemia with near-pentaploidy: diploid karyotype and lymphoblastic phenotype at relapse.

Hyperploidy is a rare finding in leukemias, with isolated cases of tetraploidy reported in acute myeloblastic and acute lymphblastic leukemias. We report the first case of acute myeloid leukemia with near-pentaploidy (5 n+/-) which was present in 100% of metaphases at diagnosis. By light microscopy, the leukemic blasts were exceptionally large and coarsely granulated. Following one cycle of induction chemotherapy, complete morphologic and cytogenetic remission was documented. Four weeks later relapse occured, at which time the karyotype was diploid and the morphological and immunophenotypic characteristics were those of a lymphoid leukemia. However, the presence of three aberrant chromosomes (5q+, 6q+ and 20q+) confirmed that this was clonal evolution of the original myeloid leukemia. To the best of our knowledge, this case represents the first report of near-pentaloidy in de novo, pretreatment human leukemia.

Acute Disease↗
PubMed1997

Hairy cell leukemia and allied chronic lymphoid leukemias: current knowledge and new therapeutic options.

This review deals mainly with the essentials of hairy cell leukemia (HCL) detailing clinical aspects, laboratory findings and morphology. Rare manifestations of HCL are listed. Newer aspects relating to cytokines, soluble interleukin receptors and TNF are reviewed. Differential diagnosis including HCL-variant, SLVL, PLL and CLL/PLL are discussed. Prognostic factors and in particular therapeutic aspects are detailed with particular emphasis on the new purine analogues Pentostatin and 2-CdA. A list of suggested reading is offered.

Antineoplastic Agents↗
PubMed1997

Sweat analysis following pressure ischaemia in a group of debilitated subjects.

This article examines the application of a simple technique for the collection of sweat to the investigation of tissue metabolites in 11 debilitated subjects attending a rehabilitation unit. It is applicable to subjects with a range of clinical conditions. Sweat was collected at the sacrum with the subjects either seated in a wheelchair or lying in bed, which was representative of their usual daily routine. The tissues could be loaded during sweat collection by sacral support in either of these positions. Collections were made for about 10 hours and interface pressures were recorded on at least two occasions. After the prescribed period, the sweat pads were removed and a quantitative analysis of a range of metabolites was performed. Metabolite concentrations may reflect local tissue viability and responses to loading. In unloaded tissues the metabolite concentrations were similar to those observed in nondisabled subjects in an earlier study. During prolonged loading at relatively low levels of pressure, there was elevation in the levels of some metabolites; for example 39 and 28% increases for lactate and urea respectively. Successive measurements on an individual over a period of months showed variations, which were small compared to those observed in either groups of nondisabled or debilitated subjects. These observations suggest that the technique may be best applied in clinical practice to monitor sequential changes in individual subjects.

Adult↗
PubMed1996

Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype.

During the last decade the frequency of therapy-related acute leukemia (t-leuk) and myelodysplastic syndrome (t-MDS) has been increasingly observed. Over the past 15 years, we treated 56 patients with t-leuk who had received prior chemotherapy (39%), radiotherapy (11%), or both (45%). The drugs received included alkylating agents and topoisomerase II inhibitors. The primary tumors included hematological malignancies (49%) and solid tumors such as breast or ovarian cancer. The median age at diagnosis of the primary tumor was relatively young (43 years +/- 18). Twelve patients had more than one primary tumor and 31 patients had a family history of malignancy. Karyotypic abnormalities were found in 91% of the patients. Prognosis was uniformly poor, with an overall median survival of 10 months. Twelve of the 18 patients examined (67%) had a multidrug resistance phenotype. P53 genes of the leukemic cells, as well as the original tumors, were analyzed in 21 patients using polymerase chain reaction (PCR) with single-stranded conformation polymorphism analysis followed by sequencing. P53 mutations were identified in 38% of these patients, a relatively high prevalence compared with other forms of MDS or de novo acute myeloid leukemia. Mutations were nongermline and restricted to the leukemic cells. We identified different p53 mutations in the various primary tumors of individual patients. The presence of a mutator phenotype was assessed by PCR analysis of microsatellites in eight loci (one trinucleotide repeat sequence, four dinucleotide, and three mononuclear repeat sequences). Microsatellite instability in two to seven loci were found in 15 of 16 (94%) of the patients. This instability is compatible with a mutator phenotype, which predisposes the patients to the development of malignancies including t-leuk.

Adult↗