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Aaron Polliack

Publications and source records attributed to Aaron Polliack.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative flow cytometry of ZAP-70 levels in chronic lymphocytic leukemia using molecules of equivalent soluble fluorochrome.

BACKGROUND: ZAP-70 has emerged as a potential pivotal prognostic marker for patients with chronic lymphocytic leukemia (CLL), which could replace immunoglobulin heavy chain mutation status. Although several flow cytometry assays have been described for assessing ZAP-70 in CLL, certain technical and scientific issues remain unsolved, which have prevented results of this crucial test from being reported, even in the best routine flow cytometry laboratories. In this report, we aimed to solve some of these issues by providing a computerized quantitative flow cytometric assay for ZAP-70 within the entire CLL population, which would be easy to perform and enable standardization between laboratories. METHODS: Intracellular ZAP-70 levels in CLL and normal B cells were assessed by molecules of equivalent soluble fluorochrome (MESF), employing Quantum FITC MESF calibration beads to establish a standard curve relating channel value to fluorescence intensity in MESF units and the QuickCal v. 2.2 program (www.bangslabs.com) and clinical relevance of the data was determined. RESULTS: The average ZAP-70 expression value in the CD19(+)/CD5(+) cells from 35 CLL patients was 103,701 MESF when compared with 12,621 MESF in B cells from 20 normal blood samples. "Low" and "high" ZAP-70 CLL subgroups were defined. Patients with "high ZAP-70 MESF" CLL had a shorter time to disease progression (P = 0.0005) and a more advanced clinical stage (P = 0.0018) when compared with patients in the "low ZAP-70 MESF" CLL subgroup. CONCLUSIONS: This quantitative analysis method can be employed to obtain a more specific and highly accurate assessment of ZAP-70 levels in CLL cells. The method can easily be standardized, in any routine flow laboratory, thereby improving reproducibility and reliability of ZAP-70 analysis.

Aged↗
PubMed2006

The presentation of malignant tumours and pre-malignant lesions incidentally found on PET-CT.

PURPOSE: The purpose of the study was to determine the general and organ-specific presentation of incidental primary tumours on PET-CT. METHODS: PET-CT reports of 2,360 consecutive patients were reviewed and revealed 156 lesions suspicious for a new unexpected malignancy, in 151 patients. One hundred and twenty of these lesions, in 115 patients, were further assessed, by biopsy (n=84 patients) or by clinical and imaging follow-up (n=31 patients) for a mean of 17+/-4 months (range 12-25 months). RESULTS: Forty-four unexpected malignancies were found in 41 of the study patients (1.7%). Twenty-seven of the 44 incidental tumours were identified on the basis of their location, which was uncommon for metastasis of the known malignancy. Eight were detected as a result of either the difference in FDG avidity of the known malignancy and the incidental lesion or the presence of an incidental non-FDG-avid mass on the CT part of the study. Four tumours were synchronous carcinomas in patients with known colorectal malignancy, three were identified by virtue of the discordant response to treatment compared with the known primary tumour and two were detected as new sites of disease after a prolonged disease-free period. There was organ variability in the positive predictive values (PPV) of PET-CT findings for incidental primary malignancy or pre-malignant lesions: 62% for colonic lesions, 54% for lung lesions and 24% for thyroid lesions. CONCLUSION: Incidental primary tumours may be identified on PET-CT based on their location, FDG avidity, response to therapy and time of appearance. The PET and CT parts of the study appear to complement each other and assist in identification of these incidental tumours.

Adult↗
PubMed2006

Diverse niches within multiple myeloma bone marrow aspirates affect plasma cell enumeration.

A basic criterion for the diagnosis of multiple myeloma is plasma cell enumeration within the bone marrow (BM). This report showed that flow cytometry under-estimated the number of plasma cells in BM aspirates by an average of 60%, compared with morphological evaluation. The discrepancy was partially because BM smears contain cells associated with the lipid-enriched spicules. In contrast, flow cytometry is performed on the BM fluid, which is depleted of the lipid-adhesive plasma cells. This discrepancy may point to different plasma cell subpopulations associated with diverse niches within the BM.

Acute Disease↗
PubMed2006

Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia.

BACKGROUND: Recently, it was shown that fat tissue produces and releases inflammatory cytokines, and that obesity may be regarded as a state of low-grade inflammation. In this regard, we aimed to establish an association between obesity and persistent leukocytosis. PATIENTS AND METHODS: We present clinical observations of obese subjects primarily referred for further evaluation of leukocytosis without a cause and validated the link between leukocytosis and elevated body mass index (BMI) in a cross-sectional study. RESULTS: During 1999-2005, 327 patients were referred for further investigation because of persistent leukocytosis. Of these, 15.3% were asymptomatic obese, mostly females, with mild persistent neutrophilia accompanied by elevated acute-phase reactants. After careful evaluation, no recognized cause for leukocytosis was found other than the fact that the patients were obese. During a mean follow-up of 45.6 months, the leukocytosis and the elevated acute-phase reactants persisted and no new causes for leukocytosis were evident. Furthermore, in a cross-sectional analysis of 3716 non-smoker subjects, 62 were found to have leukocytosis. Compared with the population with a normal white blood count range, these subjects with leukocytosis had higher BMI, serum C-reactive protein (CRP) levels, waist circumference, and neutrophil and platelet count (all P < 0.0005). After logistic regression analysis, only BMI was shown to be associated with leukocytosis (P < 0.0005). CONCLUSIONS: Obesity is recognized as a possible cause for reactive leukocytosis. Awareness of this 'obesity-associated leukocytosis' may help the clinician to avoid more extensive and unnecessary diagnostic work-up, particularly in similar obese subjects.

Adipose Tissue↗
PubMed2006

Fatal interstitial pneumonitis related to rituximab-containing regimen.

Rituximab, a chimeric anti-CD20 monoclonal antibody, is commonly being used to treat indolent and aggressive B-cell non-Hodgkin's lymphoma. Rituximab is considered a relatively safe drug, but recently, severe and fatal adverse effects related to this drug have been reported. In this regard, we report an 80-year-old patient with follicular grade 3 non-Hodgkin's lymphoma who developed a fatal interstitial pneumonitis related to treatment with a rituximab/CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) regimen. The pneumonitis was diagnosed on a routine midtreatment positron emission tomography/computed tomography scan when the patient was almost asymptomatic. Pulmonary deterioration occurred as the treatment with rituximab/CHOP was continued. In this article, we also review the literature on rituximab-associated pneumonitis, and we discuss the differential diagnosis with cyclophosphamide-induced lung injury.

Aged↗
PubMed2005

Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells.

Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RARalpha and PLZF-RARalpha fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RARalpha from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells.

Cell Line, Tumor↗
PubMed2005

Chronic lymphocytic leukemia: a review of some new aspects of the biology, factors influencing prognosis and therapeutic options.

This review provides some basic information on chronic lymphocytic leukemia (CLL) and attempts to present some of the newer data which have accumulated in recent years including those relating to familial aggregation of CLL and the detection of monoclonal CD5+ lymphocytosis in the general population and families of CLL patients. Novel data on the pathogenesis and concepts of cell origin in CLL are also reviewed stressing the fact that there is biased IgVH gene usage, and the importance of mutational status of the CLL cell, as reported in recent years by different authors. A brief review of the significance of the microenvironmental interactions between stromal cells and other accessory cells, and the leukemic CLL cells is also provided. Other clinical aspects are discussed including diagnostic criteria, clinical staging, and the newer prognostic factors which influence survival and timing of therapy for CLL patients. We also attempt to outline the therapeutic options available and the principles of planning risk and age-adapted treatment, stressing the importance and the necessity for participating in ongoing and future international clinical trials.

Age Factors↗
PubMed2004

Rapidly progressive diffuse large B-cell lymphoma with initial clinical presentation mimicking seronegative Wegener's granulomatosis.

Here we present a 40-yr-old male patient with an aggressive B-cell lymphoma, who presented 2 yr earlier with polyarthritis, and was responsive to steroids and oral methotrexate. Thereafter he developed skin and lung lesions which on biopsy consisted of mixed 'inflammatory' infiltrates with granulomatous vasculitis. A diagnosis of seronegative Wegener's granulomatosis was made and the patient received a combination of prednisone and cyclophosphamide with clinical improvement and clearance of the radiological lesions in the lungs. The patient was now completely asymptomatic for 1 yr, but then generalized lymphadenopathy appeared, which was shown by histopathology to be large B-cell lymphoma, also involving the bone marrow. Despite intensive chemotherapy, his disease could not be controlled because of primary chemoresistance, which was perhaps in some way related to exposure to the suboptimal doses of chemotherapy given during the 'inflammatory' period before the diagnosis of lymphoma was established. This case illustrates the occasional difficulty in distinguishing between extranodal lymphoproliferative diseases and autoimmune disorders especially when clonality cannot be proved. It also shows the possible risk of 'masking' a true lymphoma by treating non-malignant diseases with immunosuppressive agents, which may eventually contribute to the development of chemoresistant lymphoma.

Adult↗
PubMed2003

Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab.

Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.

Antibodies, Monoclonal↗
PubMed2003

Primary ALK positive anaplastic large cell lymphoma of the pancreas.

Here we present an unusual case of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALCL), appearing as a primary tumor of the pancreas which invaded into the adjacent duodenal wall, causing upper gastrointestinal bleeding. After complete resection of the tumor (Whipple's operation), the patient received 4 cycles of CHOP chemotherapy. Currently, 2 years after diagnosis the patient still remains lymphoma free. Primary ALCL of the pancreas is very rare and has only been reported on one previous occasion. Nevertheless, lymphoma should be considered in the differential diagnosis of pancreatic tumors and an attempt to obtain tissue diagnosis is always necessary before continuing with radical surgery, especially in young patients.

Adult↗
PubMed2003

Coexistence of chronic lymphocytic leukemia and essential thrombocythemia.

The association of chronic lymphocytic leukemia (CLL) with essential thrombocythemia (ET) is an extremely rare event and until now 3 patients with such coexistence have been reported in the literature. We report a 77-year-old white woman in whom these two disorders were diagnosed concomitantly on the basis of peripheral blood count and cytology, bone marrow cytology and histology, immunophenotyping, as well as exclusion criteria. The diagnosis of ET was also supported by spontaneous in-vitro erythroid colony growth and by evaluation of thrombopoietin (TPO) serum level. Interphase FISH analysis allowed to detect 13q14.3 deletion in 98% of lymphocytes nuclei. In contrast this aberration was not observed in the megakaryocytes. The results of PCR analysis of IgG gene rearrangement showed distinct bands characteristic for monoclonal lymphoid population in bone marrow, peripheral blood and inguinal lymph node. The patient was started on hydroxyurea 1 g/day and normalization of the platelet count was achieved. Possible etiopathogenic relationships between both disorders and differential diagnosis of ET and reactive thrombocytosis (RT) are discussed.

Aged↗
PubMed2003

Conventional dose fludarabine-based regimens are effective but have excessive toxicity in elderly patients with refractory chronic lymphocytic leukemia.

The best approach to elderly patients with relapsing chronic lymphocytic leukemia (CLL) or disease refractory to conventional therapy with alkylating agents has not yet been established. Fludarabine and its combination with mitoxantrone and/or cyclophosphamide, which is the most effective treatment in younger patients, has not been extensively utilized in the elderly CLL. Here we report our results with fludarabine-based chemotherapy in 32 previously treated patients over the age of 65 years. The overall response rate was 59% with no complete remission, 3 nodular partial remissions and 16 partial remissions. The median time to progression of disease was 7 months. Only 10 patients completed the entire treatment program, because of poor compliance due to toxicity. Eight patients developed neutropenic fever, 14 severe bacterial infections and 2 patients showed progressive encephalopathy. For comparison, in a younger group of patients with refractory CLL (< 65 years), 38 of 50 patients completed the treatment plan, and the ORR was 80% (10 CR, 11 PR-nodular, 19 PR) with a median response of 12 months. Neutropenic fever was diagnosed in 10 and severe bacterial infection in 4 patients. In conclusion, fludarabine-based chemotherapy is effective for refractory CLL, however, excessive toxicity such as severe infections and neurological complications, do not allow completion of treatment in the majority of the elderly patients. Because maintenance of a good quality of life should be the main goal in the elderly CLL population, dose reduction of fludarabine and the appropriate use of myeloid growth factors and prophylactic antibiotics appear mandatory in this group of patients.

Adult↗
PubMed2003

Treatment of refractory autoimmune diseases with ablative immunotherapy using monoclonal antibodies and/or high dose chemotherapy with hematopoietic stem cell support.

Immunological manipulations are the basis for modern treatments of autoimmune diseases (AID). Targeted immune suppression with lymphopenic based chemotherapy, and monoclonal anti B or T lymphocytic antibodies, are integral part of the conditioning for stem cell transplantation (SCT). Immune manipulation by Cyclophosphamide (Cy), ATG, Campath and recently rituximab (RI), with or without stem cell support are the basis for emerging therapeutic modalities aiming to eradicate the autoreactive clone in various autoimmune disorders. Couple of hundreds of SCTs have been recently performed in various autoimmune disorders, mainly multiple sclerosis (MS), progressive systemic sclerosis (PSS), systemic lupus erythematosis (SLE) and rheumatoid arthritis (RA). Preliminary results are encouraging. Better selection of patients and earlier treatment, before irreversible organ failure develops will probably improve results. Current ongoing multicenter studies are evaluating the role of SCT in MS, RA, SLE, and PSS.

Animals↗
PubMed2003

Rituximab therapy for follicular lymphoma: a comprehensive review of its efficacy as primary treatment, treatment for relapsed disease, re-treatment and maintenance.

BACKGROUND: Advances in the treatment of follicular lymphoma (FL) have been achieved through the development of newer combination regimens, mostly based upon purine analogs and/ or monoclonal antibodies, as well as recent progress in the area of stem cell transplantation. INFORMATION SOURCES: These advances have increased the need to obtain consensus regarding treatment priorities from the various options available, ranging from the traditional palliative approach through to the novel regimens available including stem cell transplantation. STATE OF THE ART: The apparent synergism between chemotherapy and rituximab, which facilitates the achievement of complete clinical (CR) and molecular remission (MR), together with the possible feasibility of maintenance and re-treatment with rituximab have increased the interest in the use of this drug as primary treatment for FL. This review summarizes the available literature and deals with the role of rituximab in refractory/relapsed FL as well as in previously untreated FL patients. The improvement in remission rates and response duration associated with immunotherapy are contrasted with the potential risks, such as the development of rituximab resistance, as well as other less recognized complications related to altered humoral immunity. PERSPECTIVES: Despite all the advances reported, treatment might still have to be individualized for patients with FL, until evidence of an important survival advantage for rituximab over chemotherapy is established. The possible role of autotransplantation for FL and the use of rituximab is also reviewed.

Adjuvants, Immunologic↗