Sameh Shamaa

Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study.

PURPOSE We performed a prospective, randomized, controlled study to compare intravesical epirubicin and doxorubicin as adjuvant therapy after endoscopic resection of superficial bladder tumor. MATERIALS AND METHODS We randomly allocated 253 eligible patients to 4 study arms. Seven to 14 days after transurethral bladder tumor resection instillation of the intravesical agent was instituted, including 50 and 80 mg. epirubicin in study arms 1 and 2, respectively, and 50 mg. doxorubicin in arm 3. Control arm 4 included patients who underwent transurethral bladder tumor resection alone. Instillation was repeated weekly for 8 weeks and monthly thereafter to complete 1 year of treatment. All patients were followed every 3 months by cystourethroscopy, urine cytology and deoxyribonucleic acid flow cytometry for 12 to 48 months (mean 30.1). RESULTS Rates of recurrence were significantly lower in the chemotherapy groups than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.02). In arms 1 to 4 recurrence rates were 25, 17.6, 36.7 and 65.6%, respectively. Recurrence rates per 100 patient months were 0.83, 0.60, 1.18 and 2.73, respectively, which were significant statistically, and lower after chemotherapy in general and epirubicin in particular (p < 0.05). Mean interval to first recurrence was 16, 15.4, 18.9 and 6.3 months, respectively, with a significant difference between the chemotherapy and control groups (p < 0.05). Progression to muscle invasive disease occurred in 7 (10.9%), 3 (4.4%), 6 (10%) and 5 patients (8.2%), respectively, in arms 1 to 4 (p > 0.05). We studied the relationships among different risk factors, and patterns of recurrence and progression. For pT1 tumors recurrence rates in arms 1 to 4 were 26.3, 17.8, 39.3 and 70.9%, respectively, which were significantly lower in the chemotherapy group than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.01). Toxic and untoward side effects developed in 10 (15.6%), 16 (23.5%) and 25 (41.7%) patients in chemotherapy arms 1 to 3, respectively, with a marginal insignificant difference between low and high dose epirubicin (p = 0.3), and significantly lower toxicity rates in arms 1 and 2 than in 3 (p = 0.002). A contracted bladder developed in 2.1% of all patients who received chemotherapy. CONCLUSIONS This study demonstrates that epirubicin has better efficacy and lower toxicity than doxorubicin when used as an intravesical agent.

Diagnostic and Prognostic Utility of t(14;18) in Follicular Lymphoma

Background: Follicular lymphoma (FL) is one of the most common non-Hodgkin’s lymphomas of B cells, being closely associated with a t(14;18) translocation. Detection of t(14;18), which is present in 70–95% of FL, might aid in FL diagnosis. Objective: To compare the efficacy of routine polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques in detecting t(14;18) in paraffin-embedded tissue samples of FL patients at different stages. Combined with other immunophenotypic biological determinants, detection of t(14;18) might help to determine patients at increased risk according to the FL International Prognostic Index (FLIPI) and therefore facilitate appropriate treatment. Design and Methods: This study was mainly based on a retrospective examination of formalin-fixed, paraffin-embedded lymph nodes. We selected fixed tissue samples of 21 FL patients treated at the National Cancer Institute Center in the period from 2000 to 2001. Results: FISH techniques could detect 14 of 18 FL cases with a sensitivity of 77.8%, while the PCR technique could detect only 11 of 18 FL cases with a sensitivity of 61.1%, resulting in a statistically significant difference between both techniques (p = 0.004). According to the FLIPI index, 9 of the 18 FL patients were categorized into the high-risk group (50%), 5 in the intermediated-risk group (27.8%) and 4 in the low-risk group (22.2%). Conclusion: The sensitivity of FISH is superior to that of PCR in the detection of the t(14;18) translocation in paraffin-embedded tissue samples. There is a statistically significant correlation between both CD10 and FISH with FLIPI.

Prognostic implications of NPM1 mutations and FLT3 internal tandem duplications in Egyptian patients with cytogenetically normal acute myeloid leukemia

Abstract Nucleophosmin (NPM1) and fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) gene mutations represent the most frequent molecular aberrations in patients with cytogenetically normal-acute myeloid leukemia (CN-AML). We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML. NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by polymerase chain reaction and GeneScan assays of bone marrow samples obtained from newly diagnosed 104 CN-AML patients. FLT3-ITD+ and NPM1mut were detected in 36 (34.6%) and 30 (28.8%) out of 104 subjects, respectively, 16 cases (15.4%) had double NPM1mut/FLT3-ITD+. The incidence of FLT3-ITD+ was significantly higher in the NPM1mut group than in the NPM1 wild (NPM1wt) group (P = 0.018). Statistical analysis revealed that isolated NPM1mut group had a better clinical outcomes in terms of higher complete response (CR) rate (P = 0.01) and a trend towards favorable overall survival (OS) and disease-free survival (DFS) (P = 0.28, 0.40, respectively). In contrast, the isolated FLT3-ITD+ group had an unfavorable outcome in terms of lower CR rate (P = 0.12), shorter OS, and DFS (P < 0.0001 for both). The NPM1mut/FLT3-ITD-group had the best OS and DFS, while the NPM1wt/FLT3-ITD+ group had the worst OS and DFS than other groups (NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD−) (P < 0.0001 for both). Multivariate Cox regression analysis showed that age and FLT3/ITD+ were independent poor prognostic factors for OS (P = 0.006, <0.0001, respectively), while FLT3/ITD+ was independent predictor for DFS (P = 0.04). However, NPM1mut did not have a significant impact on OS and DFS. In conclusion, adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD−. Patients with NPM1mut/FLT3-ITD− had the best prognosis in terms of higher CR, OS, and DFS, while those with NPM1mut/FLT3-ITD+ had the worst CR rate, and NPM1wt/FLT3-ITD+ had the lowest OS and DFS.

A Metastatic Signet Ring Cell Carcinoma Presented as Acquired Thrombotic Thrombocytopenic Purpura: A Case Report

Microangiopathic hemolytic anemia (MAHA) may occur as a paraneoplastic syndrome in some solid tumors, but MAHA accompanied by signet ring cell carcinoma (SRCC) of an unknown origin is very rare. We report a patient who presented with an acute onset of Coombs negative hemolytic anemia and frequent schistocytes in the peripheral blood smear which are typical for MAHA as initial presentation of metastatic SRCC. Our patients fulfilled the criteria of thrombotic thrombocytopenic purpura (TTP) and received the specific treatment for TTP without improvement.

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report and Clinicopathological Review

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is aggressive hematopoietic malignancy derived from the precursors of plasmacytoid dendritic cells. The present study reported a case of a 35-year-old BPDCN patient, who presented with scalp lesions without extracutaneous involvement of the lymph nodes (LNs), peripheral or bone marrow. Histopathological examination of scalp lesion revealed monomorphous diffuse infiltrate of small to medium-sized cells with irregular nuclear contours, pleomorphic nuclei, finely dispersed chromatin, inconspicuous nucleoli and scant amount of cytoplasm. Immunohistochemical staining showed diffuse positivity for CD45, CD4, CD 56, CD45 and negative for CD3, CD5, CD7, CD8, CD19, CD20, CD30, CD33, CD34, CD79a, CD99, CD117, TDT, and myeloperoxidase. Patient started treatment with acute lymphoblastic lymphoma protocol (Hyper-CVAD). Reevaluation after the second course showed marked regression of scalp lesion. The patient continued Hyper-CVAD protocol and planned for allogeneic stem cell transplant.

Prognostic significance of serum monoclonal immunoglobulin in B-chronic lymphocytic leukemia

Background Serum immunoglobulin (Ig) paraprotein can be detected in a subset of patients with chronic lymphocytic leukemia (CLL) by serum protein electrophoresis and immunofixation electrophoresis. CLL with Ig paraproteinemia had an inferior survival compared with patients with CLL without serum paraprotein. Participants and methods The present study was carried out on 100 patients with B-CLL (60 men and 40 women) ranging in age from 33 to 75 years. The staging of CLL was performed according to the Binet staging system. Venous blood samples were obtained from B-CLL patients for a complete blood count. Serum was separated for the measurement of lactate dehydrogenase (LDH), β 2 -microglobulin (β 2 -MG) levels by ELISA, and Ig paraprotein. Bone marrow aspiration was carried out for all B-CLL cases. Prognostic markers of CD38 and z-chain-associated protein kinase-70 (ZAP-70) expression were also analyzed. Results Twenty-two patients had Ig paraproteinemia of a total of 100 untreated patients with CLL, frequency 22%. There was a highly significant elevation in LDH, β 2 -MG, CD38, ZAP-70, IgG, and IgM in CLL with monoclonal paraprotein versus CLL without monoclonal paraprotein. There were positive correlations of serum IgG paraprotein and serum IgM paraprotein with advanced Binet stage ( P P =0.00), high level of β 2 -MG ( P =0.00 and 0.00) and LDH ( P =0.00 and 0.00), CD38 positivity ( P =0.00 and 0.02), and ZAP-70 positivity ( P =0.00 and 0.01). Also, there was a positive correlation between high serum β 2 -MG concentration with Binet stage ( P =0.00), high level of LDH ( P =0.00), CD38 positivity ( P =0.00), and ZAP-70 positivity ( P =0.02). After a follow-up of 60 months, 15 patients (15%) died. Eight (36.3%) patients with Ig paraproteinemia died during the observation period, whereas among the 78 patients without Ig paraproteinemia, seven (8.9%) died. Conclusion β 2 -MG and Ig paraprotein serve as poor prognostic markers for B-CLL. Patients with CLL with serum Ig paraprotein represent a heterogeneous group with an inferior clinical outcome. Serum Ig paraprotein might be applied for the assessment of prognosis in patients with CLL.

Stratification of Patients with Follicular Lymphoma

Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is derived from mutated germinal center B cells and exhibits a nodular or follicular histologic pattern. It is typically composed of a mixture of small, cleaved follicle center cells referred to as centrocytes and large noncleaved follicular center cells referred to as centroblasts. FL accounts for about 20 % of all lymphomas with the highest incidence in the USA and Western Europe. In Asia and in the developing countries the incidence is much lower [1].

A study for evaluation of different diagnostic approaches in acute leukemia in Egypt

Abstract Cytomorphology, cytochemistry, immunophenotyping, in addition to cytogenetic and molecular analyses have specific roles in the diagnosis and management of acute leukemias. This work was designed as a comparative study of different available methods for diagnosis of acute leukemia. The study comprised 47 cases with acute leukemia (21 cases with ALL and 26 cases with AML). Peripheral blood and bone marrow samples were subjected to through morphological examination of Leishman-stained smears, cytochemical analysis, immunophenotyping, conventional cytogenetic banding analysis, fluorescence in situ hybridization (FISH) for selected cases, and RT-PCR for detection of BCR-ABL rearrangement. The results of the study revealed that careful examination of Romanowsky-stained peripheral blood and BM films is fundamental in the diagnosis of acute leukemias, and when considered together with clinical and hematological features, indicates which of the more specialized techniques are most likely to be useful. The major role of cytochemistry was in the diagnosis of AML, while the major role of immunophenotyping was in the diagnosis of acute leukemia, which is not obviously myeloid. Apart from identification of chromosomal abnormalities unique to specific subtypes of leukemia, cytogenetic analysis had a salient impact on anticipating the prognosis and treatment outcome in acute leukemias. We could conclude that the techniques used in this study are considered complementary rather than alternatives and that stepwise employment of strategies is more cost effective than doing all the tests simultaneously.