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Biomedical subjects

Hussain I Saba

Publications and source records attributed to Hussain I Saba.

6 recordsLinked to original sources
PubMed2006

Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia.

Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2 subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P < .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS.

Aged↗
PubMed2005

Decitabine in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders that are multifactorial in their etiology. Aberrant DNA hypermethylation is now thought to be involved in MDS, as numerous tumor-suppressor genes have been identified that are silenced in these patients. Thus, the use of DNA methyltransferase inhibitors, such as 5-aza-2'-deoxycytidine (decitabine, Dacogen, MGI Pharma Inc, Bloomington, MN), for reversal of this process appears to be a rational intervention that may influence the course of the disease. Several phase I/II studies have been conducted using a low-dose schedule of decitabine in MDS patients. Based on these studies, decitabine appears to be effective and generally well tolerated, especially in those patients with worse prognostic indicators. Recent results of a phase III study also confirmed that patients treated with decitabine compared to standard supportive care had higher overall response rates and longer time to AML transformation. Decitabine appears to be a promising new therapy for the treatment of MDS; however, defining the optimal dosing schedule and exploring the possible use in combination with other agents such as the histone deacetylase inhibitors need further evaluation.

Azacitidine↗
PubMed2003

Thromboembolism preceding cancer: a correlation study.

Thromboembolic (TE) events preceding cancer have been observed. Some studies failed to find this correlation. We retrospectively examined the cancer incidence following thromboembolic events in patients at our medical center. Medical records of 183 patients with established thromboembolic events documented in their records were selected and reviewed. Time interval between primary, secondary, and recurrent TE events preceding cancer diagnosis was analyzed. Two hundred age- and sex-matched controls seen during the same period and without any evidence of TE were randomly selected and charts reviewed for malignancy. Cancer occurred after TE in 48 of 183 patients (26.2%). In controls, cancer was diagnosed in 23 (11.5%). This was statistically significant with an odds ratio of 2.736 (1.586, 4.720). In the 64 primary TE patients, the cancer incidence was 37.5%. The 63 patients with recurrent TE had an incidence of 35.4%, and 56 secondary TE patients had an incidence of 27.1%. Time between initial TE and cancer diagnosis was <6 months in 27 (56.3%) patients, between 6 months and 1 year in 12 (25.0%), 1-5 years in 5 (10.4%), and >5 years in 4 (8.3%). Fourteen (31.1%) TE patients presented with metastatic cancer. This study indicates that thromboembolic events are important predictors of cancer. Cancer in this population occurs within a year in the majority of patients. Cancer screening in patients without identifiable risk factors for thrombosis could be helpful for early detection, diagnosis, and management of cancer.

Adult↗
PubMed2003

Acute myeloid leukemia mimicking primary testicular neoplasm. Presentation of a case with review of literature.

We describe a new unique case of acute myeloid leukemia (AML) in a 21-yr-old male presenting with abdominal pain, bilateral testicular masses and gynecomastia. Further work-up with computed tomography of the chest, abdomen and pelvis revealed massive retroperitoneal, peripancreatic and mediastinal lymphadenopathy, suggesting primary testicular neoplasm. The patient was subjected to right orchiectomy that showed infiltration of testicular tissue with malignant cells, originally misinterpreted as undifferentiated carcinoma. Immunohistochemistry studies, however, showed these cells to be strongly positive for myeloperoxidase and CD45, indicating a myeloid cell origin. Bone marrow (BM) aspirate and biopsy demonstrated replacement of marrow with immature myeloid cells. Both the morphology and immunophenotype of the blast cells were consistent with AML type M4 (acute myelo-monocytic leukemia), using French-American-British (FAB) classification. The patient received standard induction chemotherapy with cytosine arabinoside (ARA-C) and daunorubicin followed with two cycles of consolidation therapy with high dose ARA-C, which resulted in remission of BM disease and resolution of lymphadenopathy and left testicular masses. After the second cycle of consolidation therapy, the patient developed sepsis that was complicated by refractory disseminated intravascular coagulopathy. He expired with a clinical picture of multiple organ failure. The unique features of this case are presented and the related literature is reviewed.

Abdominal Pain↗