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Samra, MOHAMED A., Hossam K. Mahmoud, Thoraya M. Abdelhamid, Nahla M. El Sharkawy, Yasser H. Elnahass, Mossaad Elgammal, Rafaat M. Abdelfattah, Salem Eid, Fayek M. Ghaleb, and Azza M. Kamel. "The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia." Journal of the Egyptian National Cancer Institute 25, no. 3 (2013): 135-42. Abstract

BACKGROUND: Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse.

OBJECTIVES: We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients.

PATIENTS AND METHODS: Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS).

RESULTS: Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017).

CONCLUSION: MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.

Farghaly, Thoraya A., and Huda K. Mahmoud. "Synthesis, tautomeric structures, and antitumor activity of new perimidines." Archiv der Pharmazie 346, no. 5 (2013): 392-402. Abstract

New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides. In addition, 8,10-disubstituted-[1,2,4]triazolo[4,3-a]perimidines (20a-m) were prepared through the reaction of perimidine-2-thione (15) with hydrazonoyl chlorides. The structures of the newly synthesized compounds were established on the basis of spectral data and elemental analyses. Some products were investigated for their antitumor activities against the human breast cancer cell line MCF-7 and the liver carcinoma cell line HEPG-2, and the results of some derivatives showed promising activity.

Mossallam, Ghada I., Thoraya M. Abdelhamid, and Hossam K. Mahmoud. "Prognostic significance of WT1 expression at diagnosis and end of induction in Egyptian adult acute myeloid leukemia patients." Hematology (Amsterdam, Netherlands) 18, no. 2 (2013): 69-73. Abstract

BACKGROUND: Wilms' tumor (WT1) gene overexpression has been reported in the majority of acute myeloid leukemia (AML) patients at diagnosis and has been evaluated as prognostic and minimal residual disease (MRD) marker.

PATIENTS AND METHODS: WT1 overexpression was evaluated in 68 adult AML patients at diagnosis and at the end of induction using quantitative real-time polymerase chain reaction (PCR).

RESULTS: No significant associations were encountered between WT1 overexpression at diagnosis and other prognostic factors. Complete remission (CR) was achieved in 74% of the patients with WT1 overexpression compared to 80% of patients with normal levels (P = 0.5). No significant associations were encountered between WT1 overexpression at diagnosis and disease-free survival (DFS) or overall survival (OS) (P = 0.6 and 0.3, respectively). At the end of induction, the median duration of DFS in patients achieving ≥ 2 log reduction was not reached compared to only 5 months (range: 2.1-7.9 months) in those attaining <2 log reduction (P = 0.2). The median duration of OS in patients achieving ≥ 2 log reduction was 13 months (range: 0-33.3 months) compared to 7.5 months (5.4-9.6 months) in those attaining <2 log reduction (P = 0.2). The survival at 1 year in patients achieving ≥ 2 log was double the group with <2 log reduction (67% compared to 33%).

CONCLUSION: Our results, although not reaching the level of significance, probably due to the small sample size, still suggest that the early assessment of WT1 transcript level at the end of induction in patients in CR may have a prognostic significance on clinical outcome and may thus be a useful marker for risk stratification especially in patients lacking disease-specific marker.

SO, Ahmed, Ghavamzadeh A, Zaidi SZ, Baldomero H, Pasquini MC, Hussain F, Alimoghaddam K, Almohareb F, Ayas M, Hamidieh A et al. "Trends of hematopoietic stem cell transplantation in the Eastern Mediterranean region, 1984-2007." Biol Blood Marrow Transplant (2011). Abstractcu_pdf.pdfWebsite


M, Aljurf, Zaidi SZ, Hussain F, Ghavamzadeh A, Alimoghaddam K, Jahani M, Mahmoud HK, Haddad A, Adil S, Ben Othman T et al. "Status of hematopoietic stem cell transplantation in the WHO Eastern Mediterranean Region (EMRO)." Transfus Apher Sci (2010). Abstractcu_pdf.pdfWebsite


Mahmoud, Hossam K., Yasser El Nahas, Mohamad Abdel Moaty, Raafat Abdel Fattah, Mohamad El Emary, and Wafaa El Metnawy. "Kinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival." International journal of biomedical science : IJBS 5, no. 3 (2009): 223-8. Abstract

PURPOSE: To assess the kinetics of molecular response to Imatinib Mesylate (IM) therapy in predicting progression free survival (PFS), sustained hematological, and cytogenetic responses in CPCML.

METHODS: Ninety five newly diagnosed CPCML Egyptian patients were treated with IM 400 mg daily dose. Cytogenetic analysis was performed at diagnosis and every 6 months. Molecular monitoring by RT-QPCR was performed at diagnosis and every 3 months during a median follow-up period (FUp) of 26 months. Mutation detection of ABL domain was performed by ASO-PCR.

RESULTS: Hematological response was 98% after three months of IM therapy. Out of 95 patients 59 showed 2 log reduction of BCR-ABL/ABL ratio after 6 months of whom 49 (83%) had complete cytogenetic response (CCyR) and 42 (71%) had major molecular response (MMR) at 12 months. BCR-ABL transcripts remained undetectable in 22 patients (39%) at 26 months. Among the remaining 34 patients not achieving 2 log reduction at 6 months only 5 (15%) had CCyR and MMR by 12 months. ABL domain mutations were detected in 11/15 (73%) resistant and suboptimal responding patients. Achieving 2 log reduction after 6 months of IM therapy significantly correlated with sustained cytogenetic and molecular responses (p<0.0001), with PFS at 2 years (p<0.03) and inversely with ABL gene mutations (p<0.001).

DISCUSSION: These data demonstrated the predictive value of early molecular response to IM in CPCML regarding disease course and PFS. A 2 log reduction at 6 months of IM treatment could be a cut off level predicting resistance, CCyR, or suggesting IM dose modification.

MD, Aljurf, Zaidi SZ, El Solh H, Hussain F, Ghavamzadeh A, Mahmoud HK, Shamsi T, Othman TB, Sarhan MM, Dennison D et al. "Special issues related to hematopoietic SCT in the Eastern Mediterranean region and the first regional activity report." Bone Marrow Transplant (2009). Abstractcu_pdf.pdfWebsite


H, Mahmoud, El-Haddad A, Fahmy O, El-Emary M, Nassar A, Abdel-Mooti M, Sobhy A, and Sultan A. "Hematopoietic stem cell transplantation in Egypt." Bone Marrow Transplant 42 (2008): 76-80. Abstractbmt2008136a.pdfWebsite


AM, Kamel, El-Sharkawy N, Mahmoud HK, Khalaf MR, Elhaddad A, Fahmy O, El Fattah RA, and Sayed D. "Impact of CD34 subsets on engraftment kinetics in allogeneic peripheral blood stem cell transplantation." Bone Marrow Transplant 35 (2005): 129-136. AbstractWebsite


MH, El-Sayed, El-Haddad A, Fahmy OA, Salama II, and Mahmoud HK. "Liver disease is a major cause of mortality following allogeneic bone-marrow transplantation." Eur J Gastroenterol Hepatol (2004). AbstractWebsite
DW, Beelen, Haralambie E, Brandt H, Linzenmeier G, M? KD, Quabeck K, Sayer HG, Graeven U, Mahmoud HK, and Schaefer UW. "Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation." Blood (1992). AbstractWebsite
DW, Beelen, Quabeck K, Mahmoud HK, Sayer HG, Kraft J, Graeven U, Grosse-Wilde H, Quast U, and Schaefer UW. "[Maintenance of remission in acute myeloid leukemia by allogeneic or autologous bone marrow transplantation]." Dtsch Med Wochenschr (1991). AbstractWebsite
K, Quabeck, Beelen DW, Mahmoud HK, Sayer HG, Graeven U, Schaefer UW, Schmidt CG, and Hossfeld DK. "Bone marrow transplantation for myeloblastoma." Eur J Haematol (1988). AbstractWebsite
DW, Beelen, Quabeck K, Mahmoud HK, Schaefer UW, Becher R, Schmidt CG, Bamberg M, Quast U, Grosse-Wilde H, Haralambie E et al. "Allogeneic bone marrow transplantation for acute leukaemia or chronic myeloid leukaemia in the fifth decade of life." Eur J Cancer Clin Oncol (1987). AbstractWebsite
UW, Schaefer, Beelen DW, Mahmoud HK, Quabeck K, Becher R, Schmidt CG, Bamberg M, Quast U, Haralambie E, Linzenmeier G et al. "Bone marrow transplantation in acute leukemia." Haematol Blood Transfus (1987). AbstractWebsite
HK, Mahmoud, Beelen DW, Neumann MC, Thraenhart O, Quabeck K, and Schaefer UW. "Cytomegalovirus hyperimmunoglobulin and substitution with blood products from antibody-negative donors. A pilot study in bone marrow transplant recipients." Haematol Blood Transfus (1987). AbstractWebsite
H, Grosse-Wilde, Doxiadis I, V? U, Mahmoud HK, Sch? UW, Beelen DW, and Ploegh HL. "An HLA lost mutation may lead to leukemic relapse of recipient type six years after bone marrow transplantation." Haematol Blood Transfus (1987). AbstractWebsite
DW, Beelen, Quabeck K, Mahmoud HK, Grosse-Wilde H, Shaefer UW, and Schmidt CG. "Influence of underlying disease and donor sex on the incidence of graft-versus-host disease in allogeneic bone marrow transplantation." Br J Haematol (1987). AbstractWebsite
R, Becher, Schaefer UW, Mahmoud HK, and Schmidt CG. "Persistence of recipient cells after syngeneic BMT of Ph-positive CML." Blut (1987). AbstractWebsite
DW, Beelen, Mahmoud HK, Mlynek ML, Schmidt U, Richter HJ, Schaefer UW, Reinhardt V, and Pauleikhoff D. "Toxoplasmosis after bone marrow transplantation." Haematol Blood Transfus (1987). AbstractWebsite
K, Quabeck, Beelen DW, Mahmoud HK, Schaefer UW, Schmidt CG, Henneberg-Quester KB, and Luboldt W. "[ABO incompatibility in allogeneic bone marrow transplantation]." Beitr Infusionther Klin Ernahr (1987). AbstractWebsite