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ABSTRACT: Plasma cell leukemia (PCL) is a rare form of plasma cell malignancy, few large series reported underlying genetic abnormalities. We systematically evaluated the genomic aberrations in 41 PCL patients by combining fluorescence in situ hybridization with cytoplasmic light chain immunofluorescence and correlated with their clinical outcome. The genomic aberrations in the 15 primary PCL (pPCL) and 26 secondary PCL (sPCL) were compared with 220 newly diagnosed multiple myeloma (MM) patients. There was no significant difference in the prevalence of genetic abnormalities in pPCL and sPCL but del(13q), t(4;14), 1q21 amplification and del(1p21) were more common in PCL than MM. Patients with pPCL had higher creatinine and beta(2)-microglobulin levels and tended to have a longer overall survival than patients with sPCL. In univariant analysis, PCL patients with t(4;14) (p=0.006) and del(1p21) (p=0.003) had shorter overall survivals. In multivariant analysis adjusting for all tested genetic factors as well as clinico-biologically relevant factors including C-reactive protein, calcium and beta(2)-microglobulin, t(4;14) remained a significant predictor for adverse overall survival in PCL (p=0.008).
Leukemia research 09/2008; 33(2):259-62. · 2.36 Impact Factor
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ABSTRACT: Prognostic studies of T-cell lymphoblastic leukemia/lymphoma (T-ALL) have been performed in small patient cohorts with conflicting results. We systematically reviewed 67 adult T-ALL patients diagnosed and treated at our institute to identify clinical and pathologic prognostic factors. The median initial WBC was 21.3 x 10(9)/l. Blasts expressed at least one myeloid-associated antigen in 33%. Karyotypes were abnormal in 32% of the cases. Fifty-six of 64 patients (88%) achieved complete remission (CR). In univariate analysis, age, gender, initial WBC, CD10, CD34 and abnormal karyotype did not predict CR. Patients expressing at least one myeloid-associated antigen had a CR of 74% compared to 94% (p = 0.04) for those not expressing myeloid antigens. None of the above factors affected relapse-free or overall survival in this cohort. Our study indicates that expression of myeloid-associated antigens is associated with a lower CR rate in adult T-ALL and may be considered in risk stratification for induction chemotherapy.
Acta Haematologica 01/2008; 120(1):5-10. · 1.35 Impact Factor
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ABSTRACT: The genetic events that lead to tumour progression in plasma cell dyscrasia are not well understood. Interphase cytoplasmic fluorescence in situ hybridisation was used to investigate the CKS1B amplification status (at 1q21) in clonal plasma cells from 123 patients: 23 monoclonal gammopathy of undetermined significance (MGUS), 75 multiple myeloma (MM) and 26 plasma cell leukaemia (PCL). While CKS1B amplification was absent in MGUS patients, such amplification (3-8 copies) was detected in 36% of newly diagnosed MM, 52% relapsed MM and 62% PCL (P < 0.001). Our results suggest that CKS1B amplification is associated with transformation from MGUS to MM and progression to PCL.
British Journal of Haematology 10/2006; 134(6):613-5. · 4.94 Impact Factor
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ABSTRACT: Clonal plasma cells from patients with multiple myeloma (MM), plasma cell leukemia (PCL) and human myeloma cell lines (HMCLs) were analyzed for deletions/mutations of the tumor suppressor gene PTEN. By interphase-FISH, hemizygous PTEN deletions were detected in 4 (5.6%) of 71 MM patients, 2 (20%) of 10 PCLs, and 2 (20%) of 10 HMCLs. PTEN deletions were detected in 4 MM patients at diagnosis with stage III disease (Durie-Salmon). Of the six cases with PTEN deletions, 1 MM had a 13q deletion, 1 PCL had a t(11;14), and the other PCL had a t(14;16), a 13q deletion and a p53 deletion. Sequencing analysis did not detect PTEN mutations in 11 primary MM and 5 PCL cases. Our results indicate that alterations of PTEN are uncommon in MM patients, and PTEN deletions tend to occur in advanced disease suggesting that they are secondary, rather than primary, events in the pathogenesis of MM.
Leukemia Research 04/2006; 30(3):262-5. · 2.92 Impact Factor
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ABSTRACT: By immunohistochemistry, the CD56-positive myeloma cells were detected in three (38%) bone marrow (BM) and one (13%) cerebrospinal fluid (CSF) samples from eight patients with multiple myeloma involving the central nervous system (CNS MM). Of the three patients with CD56-positive BM myeloma cells, two had CSF myeloma cells negative for CD56. In a control cohort of 84 MM patients without CNS involvement, the BM myeloma cells were CD56-positive in 68 (80%) cases (P < 0.0001). The prevalence of CD56-negative myeloma cells in the BM and CSF of our patients suggests that CD56 downregulation may play a role in the pathogenesis of CNS MM.
British Journal of Haematology 06/2005; 129(4):539-41. · 4.94 Impact Factor
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ABSTRACT: A combination of cytoplasmic immunofluorescence to detect the immunoglobulin light chain and an interphase fluorescence in situ hybridization technique was used to study the recurrent genetic abnormalities in 14 patients with plasma cell leukemia (PCL). Of the 14 patients studied, 5 had primary and 9 secondary PCL. Chromosomal abnormalities were detected in all 14 patients (100%). Deletions of 13q14 were detected in 11 (78%) cases and deletions of 17p13.1(TP53) in 6 (43%) cases. Translocations (11;14), (4;14), and (14;16) were found in 5 (35%), 2 (14%), and 1(7%) cases, respectively. Except for an association between t(4;14) and 13q14 deletions, no association was identified among the genetic abnormalities. Our study revealed that recurrent genetic changes are more frequent in PCL than in multiple myeloma. The frequent TP53 deletions may represent a marker of genetic instability giving rise to an increased propensity for myeloma cells to emigrate from the bone marrow environment and enter leukemic phase.
Cancer Genetics and Cytogenetics 02/2005; 156(2):150-3. · 1.39 Impact Factor
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ABSTRACT: We evaluated the frequency and prognostic significance of extramedullary infiltrates (EMI) at presentation of acute myeloid leukemia (AML) in adult patients. Of 331 cases with de novo AML, 101(30.5%) had extramedullary infiltrates at diagnosis. The extramedullary manifestations included: lymphadenopathy, splenomegaly, hepatomegaly, gingival hypertrophy, skin infiltrates and involvement of central nervous system (CNS). Patients with EMI had a high initial WBC count and a high proportion of M4/M5 morphological variants. The complete remission rate (CR) with induction chemotherapy was lower in patients with EMI (P=0.0077) and their overall survival was also inferior (P=0.0017). Flow cytometric evaluation of the surface antigens expressed by the leukemic blasts for CD34, TdT, HLADR, CD7, CD19 and CD56 found that only CD56 expression was associated with EMI. The association of CD56 expression with lymphadenopathy was statistically significant (P=0.035). Abnormal karyotypes were found in 50.6% of patients with EMI and 49.7% of patients without EMI. Only 11q23 abnormalities were associated with specific sites of EMI; lymphadenopathy (P=0.0111) and gingival hypertrophy (P=0.0016). Our study of adult AML patients demonstrates that EMI at diagnosis is associated with CD56 expression by leukemic blasts, 11q23 karyotypic abnormalities, low complete remission rate and poor overall survival.
Leukemia Research 11/2004; 28(10):1007-11. · 2.92 Impact Factor
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ABSTRACT: We investigated the prognostic relevance of immunophenotype and other clinical pathological features in 379 adult patients with de novo (acute myeloid leukemia) AML diagnosed and treated at our institution during an 8-year period. Acute promyelocytic leukemia (APL) cases were excluded because they received different treatment. The overall complete remission (CR) rate post-induction therapy with Ara-C and daunorubicin (DNR) was 60% with a median disease free survival (DFS) of 72 weeks, and a median overall survival (OS) of 54 weeks. At diagnosis, CD34, deoxynucleotidyl transferase (TdT), CD7, CD56, HLADR and CD19 were expressed in 65, 19, 32, 15, 87 and 5%, respectively, of 379 evaluable cases. CD34 positive patients had a significantly lower CR rate (P=0.0003) than CD34 negative patients and there was a trend to a lower remission rate in HLADR positive patients (P=0.067). In multi-variate analysis, co-expression of CD34 and HLADR was an independent adverse factor for achieving CR (P=0.0364). CD56 expression was associated with a significantly shorter overall survival (P=0.0262), but did not affect remission rate or disease free survival. Neither TdT nor CD7 expression was associated with treatment outcome. Age (60 years or older) and cytogenetic features (classified by favorable, intermediate and unfavorable groups) were associated with a lower CR rate, shorter disease free survival and shorter OS. Patients with higher white cell counts (WBC) also had a significantly lower remission rate (P=0.0064) and OS (P=0.0127). We propose a prognostic score for achieving CR in AML patients based on age, WBC, cytogenetics and CD34/HLADR status as four independent factors. Defined by number of factors, this score system may help to stratify AML patients to alternative treatment for better outcome.
Leukemia Research 02/2004; 28(1):43-8. · 2.92 Impact Factor
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ABSTRACT: A 26-year-old woman, diagnosed with diffuse large B-cell lymphoma, was treated with CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone), rituximab and radiotherapy. She developed transfusion-dependant anaemia, which persisted following chemotherapy. Bone marrow aspirate and biopsy were consistent with pure red cell aplasia and parvovirus infection. Serology was negative for previous or acute infection but parvovirus DNA was detected by polymerase chain reaction. Administration of intravenous immunoglobulin (1 g/kg) resulted in reticulocytosis and recovery of her haemoglobin. We hypothesize that rituximab caused depletion of her normal B cells, resulting in an inability to mount a primary immune response to parvovirus infection.
British Journal of Haematology 11/2002; 119(1):125-7. · 4.94 Impact Factor
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ABSTRACT: this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734
05/2001;
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ABSTRACT: The serum prostate specific antigen (PSA), having been a valid marker for prostate cancer in 2 patients at the time of their diagnosis, ultimately became undetectable (<0.1 ng/ml) despite evidence of disease progression. This was documented by isotope bone scans and the results of subsequent CT guided bone biopsies. In both biopsy specimens, immunohistochemical staining for PSA was negative, but positive for prostate acid phosphatase after microwave antigen enhancement. In both cases the serum prostate acid phosphatase (PAP) had remained within normal limits. We would caution that prostate cancer may recur and progress with an undetectable serum PSA after antiandrogen therapy.
The Canadian Journal of Urology 10/1998; 5(4):620-622. · 0.64 Impact Factor
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