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Ehab Atallah

Publications and source records attributed to Ehab Atallah.

6 recordsLinked to original sources
PubMed2007

The role of decitabine in the treatment of myelodysplastic syndromes.

Supportive care with red cell and platelet transfusions and use of growth factors has long been the standard of care for patients with myelodysplastic syndromes (MDS) ineligible for stem cell transplantation. Although these measures improve quality of life, their impact on the natural history of the disease is questionable. Recently, three new agents have been approved for the treatment of MDS. These include: 5-azacytidine, lenalidomide and, more recently, 5-aza-2 -deoxycytidine (decitabine). Decitabine is a hypomethylating agent that is incorporated into DNA and forms irreversible covalent adducts with DNA-methyltransferases. At high concentrations, this leads to cell death. At low concentrations, decitabine is considered to exert its anticancer effects by inducing DNA hypomethylation. This results in reactivation of epigenetically repressed genes, such as tumour suppressor genes and, potentially, cell differentiation. In a randomized, Phase III trial of decitabine versus best supportive care in patients with MDS, the overall response rate with decitabine was 17%, including 9% complete remissions. Patients at high risk had a statistically significant prolongation of time to acute myelogenous leukemia transformation or death. This experience has been followed by a study of low-dose decitabine using a five-times daily 1-h infusion schedule, with significant efficacy in patients with MDS observed. Ongoing studies are evaluating the activity and safety of the combination of decitabine with several histone deacetylase inhibitors and other indications. This article summarizes the experience in with decitabine in MDS.

Azacitidine↗
PubMed2006

Granulocyte transfusion.

PURPOSE OF REVIEW: Granulocyte transfusions have been used for more than four decades. Several issues have complicated the analysis of previous studies, including the utilization of improved antimicrobials, the effects of recipient alloimmunization and variable cell dose. The use of granulocyte colony-stimulating factor for donor stimulation has revived interest in granulocyte transfusion. The aim of this review is to evaluate the most recent studies in granulocyte transfusion therapy and their clinical applicability. RECENT FINDINGS: Granulocyte colony-stimulating factor use has increased the granulocyte yield by approximately fourfold. Multiple recent studies have shown that granulocyte transfusions can be helpful in controlling severe infections progressing despite the use of appropriate antibiotics, with a response rate of 40-80% with variability in results depending on patient characteristics. This benefit is limited to a small patient population as the incidence of prolonged reversible neutropenia is relatively small. Severe side effects have been rare in those studies. SUMMARY: Granulocyte transfusions are beneficial in neutropenic patients with severe uncontrolled infection. The underlying disease process is the major determinant of outcome in these patients. Because granulocyte transfusions are not commonly used, centers are not currently able to provide transfusions in a timely fashion. Nonalloimmunized patients can receive cells from nonmatched ABO compatible donors, while alloimmunized patients should receive granulocytes from either HLA-matched donors or donors selected by leukoagglutination or lymphocytotoxicity crossmatching. Further studies are needed to clarify the optimal starting time and frequency of transfusions, and the best method for identifying donor-recipient compatibility.

ABO Blood-Group System↗
PubMed2005

Treatment of metastatic malignant melanoma.

The rapid increase in incidence of malignant melanoma has not been associated with better therapeutic options over the years. Single-agent chemotherapy or immunotherapy remain the treatments of choice when systemic therapy is offered. Dacarbazine (DTIC) is the chemotherapy of choice with a response rate of 16%. Other chemotherapies, including cisplatinum, paclitaxel, docetaxel and the DTIC analogue temozolomide, have shown activity in this disease. Based on their single-agent activity, several combination chemotherapies have been investigated with preliminary results that appeared promising. However, in randomized phase III trials the two most active chemotherapy combination regimens, cisplatin, vinblastine, and DTIC (CVD) and the Dartmouth regimen (DTIC, cisplatin, bischloroethylnitrosourea , and tamoxifen), did not prove to be superior to single-agent DTIC for overall survival. Immunotherapy with either interleukin (IL)-2 or interferon (IFN) has demonstrated response rates of 10% to 15% in appropriately selected patients. In patients who achieve a complete response, responses can be of greater durability than those with chemotherapy. However, IL-2 and IFN administration are associated with multiple side effects, and only physicians experienced in the management of such therapies should administer them. The potential benefit of combining chemotherapy with immunotherapy has led to multiple phase II trials of biochemotherapy that appeared to be associated with higher response rates and longer median survivals. However, several phase III trials have been completed that have not consistently demonstrated an improvement in either response rates or overall survival, and these approaches to therapy cannot be routinely recommended outside the context of a clinical trial. The surgical resection of isolated metastatic disease has demonstrated an important palliative benefit in those patients who present with solitary single-organ disease with the exception of the liver. Radiation has an important role in the palliative management of brain metastasis and symptomatic bony metastasis. Both stereotactic radiosurgery and whole brain radiotherapy have been used alone and in combination to benefit patients in this troubling clinical circumstance. Isolated limb perfusion and a newer technique, isolated limb infusion have demonstrated high response rates for those uncommon patients who develop recurrent disease isolated to a limb. In our opinion, if complete metastasectomy is not feasible and in the absence of brain metastases, single-agent IL-2 is a good initial treatment choice in appropriately selected patients. Single-agent chemotherapy with DTIC is the treatment of choice for patients who are not candidates for IL-2. Adoptive immunotherapy combining nonmyeloablative chemotherapy with high-dose IL-2 is a potentially promising therapeutic strategy under investigation. Targeted therapy is also an area of promising development as single agents, in combination, and combined with chemotherapy. The latter will be the focus of at least one upcoming cooperative group phase III trial.

Antineoplastic Agents↗
PubMed2002

Chronic myelogenous leukemia in T cell lymphoid blastic phase achieving durable complete cytogenetic and molecular remission with imatinib mesylate (STI571; Gleevec) therapy.

BACKGROUND: A T cell lymphoid blastic phase of chronic myelogenous leukemia (CML) is a rare occurrence, with only a few reported cases worldwide. Standard therapy for such patients is undetermined. Imatinib mesylate, a Bcr-Abl tyrosine kinase inhibitor, has shown activity in CML. METHODS: The authors report on a patient with CML and marrow as well as extramedullary nodal T cell lymphoid blastic phase who was treated with imatinib mesylate. RESULTS: The patient achieved complete morphologic and cytogenetic remission within two months of therapy. Competitive quantitative polymerase chain reaction analysis of marrow cells was negative after 15 months. Response had lasted for 26+ months at the time of writing. CONCLUSIONS: The current data suggest that imatinib mesylate may produce long-term event free survival in patients with T-cell lymphoid blastic phase CML. Its potential role alone or in combinations should be further explored in this condition.

Antineoplastic Agents↗