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1.
Hematol Oncol Stem Cell Ther ; 16(4): 379-387, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37363983

RESUMO

BACKGROUND AND OBJECTIVES: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce. The study aimed to determine the rates of GVHD and survival outcomes for patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA-matched related donors (MRD) receiving PTCy-based GVHD prophylaxis and compare these outcomes with those of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis. PATIENTS AND METHODS: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic hematopoietic cell transplantation (allo-HCT) were analyzed prospectively. These patients received PTCy and CSA as a GVHD prophylaxis (therapeutic group) and their outcomes were compared with those of 75 retrospectively collected patients who received methotrexate and CsA as a GVHD prophylaxis (historical group) from the same two transplant centers. RESULTS: The median recipient age was significantly lower in the MTX/CsA group at 28 years compared to 34 years in the PTCy/CSA group. Peripheral blood was the only graft source used. All patients had a complete MRD, with two patients having a one-antigen mismatched related donor within the PTCy/CsA group. The 1-year cumulative incidence (CI) of chronic GVHD was 13.4% with PTCy/CsA and 38.6% with MTX/CsA (P = .001). Acute GVHD CI across all grades did not differ between the groups, with 10.7% for PTCy/CsA and 14.7% for MTX/CsA (P = .46). At two years, the overall survival (OS) (54.4% vs 67.2%, P = 0.282), disease-free survival (DFS) (54.1% vs 66.1%, P = 0.358), relapse rates (27.4% vs 20.1%, P = 0.245), and non-relapse mortality (NRM) (29.3% vs 25%, P = 0.904) did not differ between PTCy/CsA and MTX/CsA, respectively. CONCLUSION: PTCy-based GVHD prophylaxis in MRD transplant is feasible and leads to lower chronic GVHD rates without causing a significantly different risk of relapse or survival than MTX/CsA. More extensive studies are needed to confirm our results.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Ciclosporina/uso terapêutico , Metotrexato/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/métodos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle
2.
J Chemother ; 34(6): 381-390, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34895107

RESUMO

High dose methotrexate (HDMTX) is an essential agent in chemotherapeutic regimens used in various hematological malignancies in Egyptian adults. The research for the impact of gene polymorphism on HDMTX induced toxicities and delayed elimination is an important ongoing objective in many studies, variable and conflicting results produced in the past years to clarify that impact. This study aimed to investigate the role of ABCB1 3435 C > T rs1045642 and MTHFR 677 C > T rs1801133 polymorphisms on HDMTX induced toxicity outcomes and delayed elimination in Egyptian adult patients with hematological malignancies. A prospective, observational cohort study was conducted on a total of 62 Egyptian adult patients with hematological malignancies age ≥ 18-years-old. All demographic, medical, and laboratory data were continuously collected from the patients' medical files in an up-to-date follow-up in selected clinics during the period from April 2018 to March 2020. Venous blood samples were collected for the purpose of genotyping, DNA extraction, and measurement of MTX levels. All the relevant data were statistically analyzed. The studied patients' median age was 25 years old with a range of (18-62) years. Forty-six patients were males with about 74%, and 16 were females with about 26%. Eighty-nine percent of the patients diagnosed with acute lymphoblastic leukemia 'ALL', 5% of the patients had B cell non-hodgkin lymphoma 'B-NHL' and 3% diagnosed with primary central nervous system lymphoma 'PCNSL' and Burkitt's lymphoma 'BL' Hematological, hepatic, renal and gastrointestinal toxicities observed post-HDMTX were recorded with the hematological toxicities toping on all the others, also patients with delayed elimination at 72 hours post the HDMTX dose were determined. Statistical analysis revealed a significant association between ABCB1 3435 C > T rs1045642 and HDMTX delayed elimination with about 10 times higher risk among the minor allele 'T' carriers (p-value = 0.006) (odds ratio [OR]: 10.470; 95% CI: 1.961-55.904). No significant association observed between the studied gene polymorphisms: MTHFR 677 C > T rs1801133, ABCB1 3435 C > T rs1045642, and different toxicity outcomes. According to our best knowledge, this study is the first to conclude a significant association between ABCB1 3435 C > T rs1045642 gene polymorphism and HDMTX delayed elimination at 72 hours post HDMTX infusion; also, it is the first study to analyze the association between ABCB1 3435 C > T rs1045642 polymorphism with HDMTX toxicity and delayed elimination in adult Egyptian patients with hematological malignancies.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Neoplasias Hematológicas , Metotrexato , Metilenotetra-Hidrofolato Redutase (NADPH2) , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Egito , Feminino , Neoplasias Hematológicas/induzido quimicamente , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Humanos , Masculino , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Prospectivos , Adulto Jovem
3.
Clin Lymphoma Myeloma Leuk ; 20(7): 459-467, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32229198

RESUMO

BACKGROUND: Core binding factor acute myeloid leukemia (CBF-AML) encodes 2 recurrent cytogenetic abnormalities, t(8;21) and inv(16), which carries an overall good prognosis. However, some patients will develop a relapse. We sought define the unfavorable group of CBF-AML by analysis of (c-KIT and FLT3-ITD) and to correlate them with treatment outcome. PATIENTS AND METHODS: We performed a prospective study of 70 patients with CBF-AML diagnosed and managed at the medical oncology department of the (National Cancer Institute), Cairo University, with analysis of c-KIT and FLT3 mutations. All patients had received "3 + 7" induction, followed by 3 to 4 courses of high-dose cytarabine consolidation. The institutional review board approved the present study. RESULTS: The median patient age was 31 years (range, 18-60 years), with a male/female ratio of 4:3. Of the 70 patients, 42 (60%) had t(8;21) and 28 had inv(16) (40%). c-KIT mutations (exons 8 and 17) were detected in 10 of 52 tested patients, and FLT3-ITD was detected in 3 of 70 patients. Patients with inv(16) experienced more lymphadenopathy and splenomegaly, had a higher median initial leukocyte count. Hepatitis C antibody positivity (8 of 42) was exclusively present in patients with t(8;21). The median overall survival (OS) was 19.5 months, and the median disease-free survival (DFS) was not reached. Patients with inv(16) had near-significant (P = .07) better DFS than patients with t(8;21). c-KIT mutations had no significant effect on OS or DFS. However, reverse tyrosine kinase mutations had a negative effect on DFS but not OS (P = .04). CONCLUSION: CBF-AML with reverse tyrosine kinase mutation conveys a worse prognosis. Hepatitis C virus antibody positivity might be associated with t(8;21) AML and inv(16) with more extramedullary disease.


Assuntos
Leucemia Mieloide Aguda/genética , Proteínas Tirosina Quinases/metabolismo , Adolescente , Adulto , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
4.
Curr Pharm Biotechnol ; 21(13): 1394-1401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196445

RESUMO

BACKGROUND: Multiple Myeloma (MM) is a complex hematologic malignancy, driven by several genetic and epigenetic alterations. MiRNAs as biomarkers have become a rapidly growing research area in the last decade. AIM: The aim was to study the expression pattern of selected miRNAs and to explore the impact of cytogenetic aberrations in MM patients for therapeutic tools. PATIENTS AND METHODS: Forty Egyptian adult patients were selected for the study with symptomatic newly diagnosed MM disease. Bone marrow samples were collected to investigate twelve miRNAs selected according to their relation to the most common cytogenetic aberrations with relevant prognostic value. The relative expression of the selected miRNAs was determined using a real-time PCR technique. Fluorescence In Situ Hybridization (FISH) technique was performed for cytogenetic analysis. RESULTS: Eight miRNAs were down-regulated [miR-15a (p<0.001), miR214-3p (p<0.001), miR135b (p<0.001), miR19a-3p (p<0.001), miR19b-3p ((p=0.026), miR30e-5p (NS), miR133a (NS), miR146a- 5p (p<0.001)]. Four miRNAs were up-regulated [miR99b-5p (p=0.028), miR125a-3p (p=0.004), let7b- 5p (p<0.001), let7c-5p (p<0.001)]. Significant relation was observed between positive 14q32 rearrangement using the break apart re-arrangement probe for 14q32.33 locus and lower expression levels of miR15a (p= 0.014), 214-3p (p=0.046), 99b-5p (p=0.014), 146a-5p (p=0.041). A higher expression level of miR30e-5p was significantly related to positive 14q32 rearrangement. CONCLUSION: Deregulated miRNAs were identified and the association with 14q32 rearrangement and MM pathogenesis has been determined.


Assuntos
Biomarcadores Tumorais/genética , Medula Óssea/patologia , Aberrações Cromossômicas , MicroRNAs/genética , Mieloma Múltiplo/genética , Adulto , Regulação para Baixo , Egito , Feminino , Perfilação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
5.
Clin Lymphoma Myeloma Leuk ; 20(3): 156-167, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32033928

RESUMO

BACKGROUND: Acute promyelocytic leukemia (APL) has a characteristic peculiar morphologic and genetic features as well as a more favorable outcome. We studied the differential effect of bcr-1 and bcr-3 isoforms of the promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) transcript together with FLT3 internal tandem duplication (FLT3-ITD) mutation status on the outcome of newly diagnosed de novo APL patients. PATIENTS AND METHODS: This cohort study included all patients diagnosed with APL at outpatient medical and pediatric oncology clinics of the National Cancer Institute, Cairo University, Cairo, Egypt, from May 2012 to January 2018. RESULTS: The study included 118 patients with APL, 71 adults (60.2%) and 47 children (39.8%). Median (range) age was 25 (1.5-70) years. Children had significantly higher total leukocyte count (≥10 × 109/L), disseminated intravascular coagulation (DIC), and thrombocytopenia (< 40 × 109/L) than adults (P = .04, .03, and .04, respectively), while the latter group had significantly higher hemorrhage than children (P = .04). FLT3-ITD mutation was detected in the whole group, children, and adults in 23.7%, 30.6%, and 24.6%, respectively. FLT3-ITD mutation was significantly associated with leukocytosis in the whole group (P = .039). bcr-3 was significantly associated with FLT3-ITD mutation in the whole APL cohort and in adults (P = .011, P = .022). All children (both bcr-1 and bcr-3) and all adult patients with bcr-3 experienced CR, while 22 (78.5%) of 28 patients with bcr-1 experienced CR (P = .04). APL patients with DIC and hemorrhage had significantly lower overall survival (P = .002 and < .001, respectively). Overall survival for APL in children was significantly better than in adults (P = .005). Multivariate analysis indicated that age was an independent prognostic variable affecting survival (hazard ratio = 2.6; 95% confidence interval, 1.3-5.3; P = .007) (adults had hazard ratio of death 2.6 times higher than children). DIC and FLT3-ITD were independent prognostic variables affecting survival in children with APL (hazard ratio = 12.3; 95% confidence interval, 1.46-104.61; P = .021; and hazard ratio = 5.2; 95% confidence interval, 1.01-26.95; P = .048, respectively). CONCLUSION: Age is an independent prognostic factor for APL. bcr-3 is significantly associated with FLT3-ITD in adults with APL. DIC and FLT3-ITD are adverse prognostic factors in children with APL. Despite children being at higher risk, outcome is better than in adults.


Assuntos
Leucemia Promielocítica Aguda/genética , Isoformas de Proteínas/genética , Proteínas Proto-Oncogênicas c-bcr/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Leucemia Promielocítica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Adulto Jovem
6.
Andrologia ; 51(10): e13384, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31483058

RESUMO

Prostate cancer (PC) is considered as the fifth cause of cancer deaths worldwide. The exact etiopathogenesis is unclear; however, genetic predisposition, hormonal influencers, lifestyle and environmental factors act as major contributors. It has been found that several miRNAs may play a crucial role in cancer initiation and progression. Here, in this study, we evaluated the peripheral blood levels of miR-21, miR-141, miR-221 and miR-18a expression among 80 prostate cancer patients (50 localised and 30 metastatic) and 30 benign prostatic hyperplasia patients compared to 50 normal control subjects, using RT-PCR. Our results of analysis of miR-21, miR-141, miR-18a and miR-221 in the plasma of PC patients showed that miR-18a is a powerful discriminator of PC patients from healthy controls as it had the highest AUC (0.966; 95% CI, 0.937-1.000), while miR-221 provided better differentiation of metastatic from localised PC (sensitivity was 92.9% at 100% specificity), and when we combine miR-18a and miR-221 for differentiating patients with MPC, it will increase the sensitivity to 96.4% at a specificity of 100% (AUC, 0.997; 95% CI, 0.988-1.0) (p < .000). This current study recommends that analysis of these miRNAs might have clinical value in enhancing PSA testing.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , MicroRNAs/sangue , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Egito , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/sangue , Hiperplasia Prostática/genética , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Curva ROC
7.
Clin Lymphoma Myeloma Leuk ; 19(7): e406-e413, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31031147

RESUMO

BACKGROUND: Early blast clearance to induction chemotherapy in acute myeloid leukemia (AML) is an important prognostic indicator of treatment outcome in addition to genetics and molecular genetics. We evaluated the prognostic value of bone marrow aspiration (BMA) at day 14 (D14) and impact on outcome to asses the timing of a second induction. PATIENTS AND METHODS: This retrospective study included 303 adult AML patients managed at the National Cancer Institute, Cairo University, from the beginning of 2010 to the end of 2014. RESULTS: Median age was 34 years (range, 18-67 years). Sixty-six percent had early blast clearance with < 5% blasts and 34% had ≥ 5% blasts at BMA D14; 38 patients died early during or shortly after induction. Initial blast load (bone marrow and peripheral blood) and initial platelet count were significantly higher in those with disease that did not respond to therapy compared to those whose disease did respond to therapy at D14 (P < .001, .035, and .006, respectively). The median disease-free survival for early blast clearance at D14 was 18.5 months, versus 18.7 months for those with late response to therapy (day 28), and was only 1.3 months for patients who received immediate second-line therapy on the basis of BMA D14 (P < .001). The median overall survival for early blast clearance was 13.6 months, versus 7.2 months for those with late response to therapy, and only 1.3 months for patients who received immediate second-line therapy on the basis of BMA D14 (P < .001). CONCLUSION: BMA D14 has a significant prognostic impact on the therapeutic outcome of AML patients (complete remission, disease-free survival, and overall survival); however, a second induction in patients with BMA D14 blasts > 5% should be delayed until neutrophil recovery to minimize death in aplasia.


Assuntos
Medula Óssea/patologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Adolescente , Adulto , Idoso , Biópsia por Agulha , Gerenciamento Clínico , Feminino , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
8.
Clin Lymphoma Myeloma Leuk ; 19(6): e281-e290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30926392

RESUMO

BACKGROUND: Genotypic mutation of fms like tyrosine kinase 3 (FLT3), Nucleophosmin (NPM1), and DNA-methyltransferase 3A (DNMT3A) has been involved in the leukemogenesis of acute myeloid leukemia (AML), with the well known poor prognostic role of FLT3 and DNMT3A and favorable role for the NPM1 mutation. PATIENTS AND METHODS: A total of 123 patients with AML treated at the National Cancer Institute, Cairo University were examined for mutations in DNMT3A, FLT3, and NPM1 using polymerase chain reaction (PCR) for detecting FLT3 internal tandem duplication (ITD) and allele-specific PCR to detect DNMT3A and NPM1A mutations. Two-way direct sequencing and Gene Mapper version 4.0 software (Fred Hutchinson Cancer Research Center) sequencing were used as confirmatory tests for DNMT3A and NPM1A mutations, respectively. RESULTS: DNMT3A, FLT3-ITD, and NPM1A gene mutations were detected in 22 (17.9%), 22 (17.9%), and 24 (19.5%) patients, respectively. DNMT3A/FLT3, NPM1A/FLT3, and DNMT3A/NPM1A combined mutant genotypes were detected in 5 (4.1%), 9 (7.3%), and 3 (2.4%) patients, respectively. Two patients (1.6%) had triple mutant genotypes (DNMT3A/FLT3/NPM1A). FLT3 and DNMT3A mutations had a significant negative effect on complete response (CR) rates (P = .016). FLT3-ITD mutation was significantly associated with older age (P = .029), and lower overall survival (OS) rates (P = .046). DNMT3A/FLT3 combined mutant genotypes were significantly associated with a lower OS rate (P = .016). Mutant NPM1/wild type FLT3, wild type DNMT3A/FLT3, and mutant NPM1A/wild type DNMT3A combinations were significantly associated with higher CR rates (P = .006, P = .006, and P = .023, respectively). CONCLUSION: DNMT3A, FLT3-ITD, and NPM1A are frequent mutations in Egyptian AML. FLT3-ITD mutations are frequent in older patients. DNMT3A and FLT3-ITD mutations were associated with an unfavorable prognosis, but the NPM1A mutation has tendency to indicate a good prognosis.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Duplicação Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Mutação , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Criança , Pré-Escolar , DNA Metiltransferase 3A , Egito , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Nucleofosmina , Fenótipo , Prognóstico , Análise de Sobrevida , Adulto Jovem
9.
Mediterr J Hematol Infect Dis ; 7(1): e2015058, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26543527

RESUMO

Cladribine induces durable complete remission (CR) in approximately 85% of hairy cell leukemia (HCL) patients. In Egypt, cladribine is mainly used as IV continuous infusion at a dose of 0.1 mg/kg/day for 7 days and as SC bolus injection at a dose of 0.14 mg/kg/day for 5 days. We aimed to compare the outcome and toxicity between these two regimens. We retrospectively collected data from HCL patients treated at the National Cancer Institute and its affiliated center, Nasser Institute, Cairo, Egypt. Forty-nine patients were identified, 18 treated with the IV regimen (IV group) and 31 with the SC regimen (SC group). Forty-one patients were newly diagnosed. Patient characteristics were balanced across the two groups. The CR rates in the IV and the SC group were 94% and 97%, respectively. The main complications in the IV group and the SC were neutropenia G3-4 (67% vs. 87%), mucositis mainly G1-2 (67% vs 32%) and infections (mainly viral, 78% vs 34%). In the IV group, five patients died, three of progression and infection, one of unknown cause and one of late heart failure. In the SC group, one patient died of disease progression and one of second cancer. After 33.5 months, median follow-up, the 3-year event free survival was 60% and 96%, respectively (p=0.104). The 3-year overall survival was 81% and 100%, respectively (p=0.277). In conclusion, SC cladribine is an excellent alternative to the IV regimen for the treatment of HCL.

10.
Hematology ; 20(6): 328-35, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25232917

RESUMO

INTRODUCTION: Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes. AIM: To study the impact of p53, p21, and mdm2 gene polymorphisms on the clinical outcome in adult AML patients treated at the National Cancer Institute (NCI) - Cairo University. METHODS: Forty-eight adult AML patients presented to the Medical Oncology Department, NCI, from April 2010 till November 2011. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving P53, MDM2, and P21 single-nucleotide gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism coupled analysis. RESULTS: The mean age was 35.7 years. After a median follow-up period of 12 months, 28 patients (58.4%) achieved complete remission (CR) and the overall survival (OS) was 8.7 months. Patients with homozygous Arg/arg at codon 72 of P53 had a better median OS months than Arg/Pro and Pro/Pro (13.4 vs. 8.4 vs. 1.5 months, respectively; P = 0.045). P53/p21 combination had a better median OS and disease-free survival (DFS) of 12.1 and 13.7 months for wild type cases (GG + Ser/ser) and 20.3 and 20.7 months for patients with either variant genes (GC + Ser/arg) compared with 1.1 and 1.9 months for patients with both variant genes (CC + arg/arg), (P = 0.037 and 0.004). The presence of wild genotype of either P21 or MDM2 may abolish the effect of P53 homozygous variant genotype on the OS. Neither p21nor mdm2 polymorphism alone showed an impact on OS or DFS. CR was not affected by any of the three gene polymorphisms. CONCLUSION: The p53 pathway gene polymorphisms may affect the OS of adult AML patients.


Assuntos
Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Genes p53 , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
J Egypt Natl Canc Inst ; 26(3): 127-37, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25150128

RESUMO

BACKGROUND AND AIMS: To study the clinico-pathological features, treatments and outcomes of gastric carcinoma (GC) in the elderly (⩾65 years) and the non-elderly Egyptian patients. METHODS: This retrospective cohort study included 168 patients with histologically confirmed GC treated at Tanta Cancer Center between 2003 and 2007. RESULTS: Compared to the non-elderly, elderly patients had significantly higher proportion of tumors involving the cardia (p=0.034) and of adenocarcinoma NOS histology (p=0.032). Treatments were largely comparable in the two groups. Response to palliative chemotherapy was achieved in 44.4% of the elderly and 25.5% of the non-elderly patients (p=0.417). The median overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 6, 17 and 3 months, respectively. The median OS was 4 months in the elderly compared to 9 months in the non-elderly (p=0.005). The median DFS was 4 months in the elderly compared to 20 months in the non-elderly (p=0.004). The median PFS was 2 months in the elderly compared to 3 months in the non-elderly (p=0.685). In multivariate analysis, poor performance status was an independent predictor of poor OS, DFS and PFS. Non-curative or no surgery and lack of chemotherapy use were independent predictors of poor OS. Age was an independent predictor of poor DFS. CONCLUSIONS: Compared to the non-elderly, GC in the elderly has similar clinico-pathological characteristics and exhibits comparable outcomes with the same treatment options. Treatments should be tailored to each patient.


Assuntos
Neoplasias Gástricas/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Comorbidade , Egito/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Resultado do Tratamento , Adulto Jovem
12.
J Egypt Natl Canc Inst ; 26(2): 103-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24841162

RESUMO

INTRODUCTION: Female germ cell tumors (GCTS) are rare tumors that carry a good prognosis. AIM: To report the experience of the Egyptian National Cancer Institute (ENCI) in managing female GCTs. METHODS: This retrospective study included 19 females with ovarian GCTs presenting to the ENCI between 2006 and 2010. RESULTS: The median age was 23years. Ovaries were the primary site in all patients. Dysgerminoma and teratoma were the predominant pathologies followed by mixed GCT in females. Unilateral ovariectomy or ovarian tumorectomy were the classic surgical procedures with R0 resection being feasible in most cases. Surveillance was adopted in six patients with stage I disease. Chemotherapy was administered in 63% of ovarian GCTs with BEP being the commonest regimen with reasonable tolerability and good response rates. The median OS and EFS were not reached. The projected 5-year OS rate was 93.8%. Both OS and EFS were better in patients responding to chemotherapy than non-responders (p<0.002). Stage of disease did not significantly affect OS or EFS. CONCLUSIONS: Female GCTs rarely affect Egyptian females. They have good prognosis.


Assuntos
Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Resultado do Tratamento , Adolescente , Adulto , Idoso , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Prognóstico , Estudos Retrospectivos
13.
Asian Pac J Cancer Prev ; 13(9): 4315-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23167335

RESUMO

BACKGROUND: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. AIM OF THE STUDY: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. RESULTS: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR= 6.807, 95% CI= 1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value= 0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. CONCLUSION: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/ MDM2 might be genetic susceptibility factors in the pathogenesis of AML.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Transdução de Sinais/genética , Adulto Jovem
14.
J Egypt Natl Canc Inst ; 19(2): 106-13, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19034340

RESUMO

BACKGROUND: Despite important advances in the therapy of acute myeloid leukemia (AML), the majority of patients die of their disease, unless bone marrow transplantation (BMT) is done. Infection and hemorrhage are still the major causes of mortality in AML patients. Progress in therapy and supportive care has led to gradual improvement in the overall results, but further improvements are still needed. PATIENTS AND METHODS: The aim of this study is to identify the outcome and costs of adult AML patients treated with conventional chemotherapy (CCT) at the National Cancer Institute (NCI), Cairo University during the time period from April 1999 to January 2002. Clinical, laboratory characteristics were all recorded. Data regarding different types of therapies given for these patients including response, outcome and costs were also collected. RESULTS: The median age of 82 identified AML patients was 34 years. The complete remission (CR) rate after induction with CCT was 52% (42/82 patients) with a median CR duration of 9 months. Twenty-eight percent of patients who achieved CR subsequently relapsed. By January 2003, fifty-eight patients were dead (70.7%). Infections were the major mortality cause, followed by disease progression then bleeding (65% , 28% and 7% respectively). The median treatment cost per patient was 33158 Egyptian Pounds (LE). It was higher for patients who achieved CR compared to those who relapsed and/or died. Drugs contributed by 78 % to the total treatment cost, while hospitalization, investigations and blood-component therapy contributed by 6%, 7% and 8% respectively. CONCLUSIONS: Outcome of patients with AML treated at NCI- Cairo University can be enhanced by improvement of supportive therapy; mainly infection control and expanding BMT programs to accommodate all eligible patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/economia , Adolescente , Adulto , Idoso , Egito , Feminino , Custos de Cuidados de Saúde , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
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