Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin's lymphoma (NHL) may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP) as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP), not exceeding the total allowed dose of doxorubicin (500 mg/m2). Ten healthy controls were included in our study. Human heart-type fatty acid-binding protein (H-FABP) was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF) of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.
Little is known about burden of CML in Arab countries. The first ALN report demonstrated that age-specific rates for CML in Egypt and Arab nations are lower by at least two decades compared to western populations (Azzazi and Mattar ELN newsletter 2013). Lack of reliable data concerning geographic and ethnic variations and response rates to therapy contribute to the variability of incidences among CML registries. Studies underestimate the true age of CML patients as access to medical services show great diversity in AFME region. ACAs were reported in 5% of CML patients, considered at diagnosis by ELN as a “warning” requiring careful patient monitoring.(Baccarani et al Blood 2013), ACAs emerging during treatment are considered by WHO classification as accelerated phase (AP). There occurrence indicates that the leukemia has become BCR-ABL1 independent by secondary genetic acquisitions. Some ACAs are poor prognostic factors such as the acquisition of additional Ph chromosome (ch) that increases the kinase activity of BCR-ABL1; the isochromosome 17q i(17q) which leads to inactivation of the tumor suppressor gene p53 and impedes the response to Imatinib; the extra 8 which lead to c-Myc over expression that enhances the transformation of leukemic cells and the extra 19 which hinder Imatinib activity via silencing gene promoters. Objectives 1) To Release 5 year follow-up data of second ALN report of CML epidemiology in Egypt. 2) To investigate the low age of CML in Egypt. 3) To evaluate ACAs role in disease and clonal evolution. 4) To build a reliable data base -the ALN- as information / support services. Method We analyzed data of 578 (302 male and 276 female) CML patients (followed-up for 5 years). Data collected according to ELN (Baccarani et al Blood 2013) GIMEMA and EUTOS recommendations via a multicenter web based data registry portal, the ALN. (www.aln-afme.com). To insure lack of bias an independent server for data storage and processing was established in Masaryk University, Institute of Biostatistics and Analyses, in Prague, Czech Republic, other logistics are managed by DMC Healthcare Inc. HQ in Toronto, Canada. Chromosome banding analysis and FISH were performed, for Y-ch, trisomy 8, duplication of Ph, i(17q), trisomy 19, and Deletion of der(9) ch (Luatti et al Blood 2012). Results Patients Median age was 43y, (40y for males, 41y for females), The age specific rates were highest for the age group of 30-35 years. Female patients presented with lower hemoglobin, higher platelet counts and smaller spleen size (P<0.0001). 98% of patients achieved CH respone, 89% PCYR, 87% CCYR, and 83% MMR. At diagnosis 87% patients were in chronic phase (CP) CML, 8.1% in accelerated, and 4.9% in blastic phase. Sokal score: Low risk 57.8% Intermediate 24.5% and High in 17.7%. EURO (Hasford) score (59% Low risk, 28.4%Intermediate risk and 12.6%High risk). 42% of patients received imatinib, 34% nilotinib 20% dasatinib and 4% needed therapies plus TKI). Transplantation rate was 19%, PFS and OS were equal in female and male patients. ACAs were found in 62 (11%) patients, they had lower cytogenetic and molecular response rates and longer response time to TKI and inferior outcome. ACAs were more frequent in younger, imatinib resistant patients, and in blast phase. We identified loss of Y ch in 18 patients (29%), trisomy 8 in 7 (11%), trisomy 19 in12 (19%), i(17q) in 12 (19%), other different single abnormalities in 8 patients (13%), complex karyotype with double ACAs in only 5 patient (8%). Four patient showed variant Ph ch: t(9;22;22)(q34;q11;q11). Deletion of der(9) ch in 17 cases (27%): (10 cases with loss of Y ch, 4 case with del(20)(q11q13), and 3 case with t(X;13) (q13;q32)). The cytogenetic and molecular response rates were uniformly lower in patients with ACAs, overall CCgR and MMR rates were significantly lower in patients with ACAs (68% vs 89% and 55% vs 86% respectively), responses were significantly slower in patients with ACAs, 54 patients presented with ACAs at diagnosis while 8 patients developed ACAs while on treatment. Conclusions: The importance of ethnicity and gender differences in relation to disease incidence, and prognosis are major health policy focus. To investigate the low mean age of CML in Egypt and evaluate role of ACAs on disease and clonal evolution, Data from 10 Centers in Egypt showed a much lower mean age of CML and more frequent (11%) ACAs, they adversely affected time and response rates to Imatinib treatment. Disclosures No relevant conflicts of interest to declare.
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