Biomedical subjects

Emil Freireich

Publications and source records attributed to Emil Freireich.

5 recordsLinked to original sources

PubMed2006

Arsenic derivatives in hematologic malignancies: a role beyond acute promyelocytic leukemia?

The importance of arsenic trioxide (As2O3) has been underscored over the last decade due to its efficacy against acute promyelocytic leukemia (APL), a disease in which this agent has been associated with complete hematologic and molecular remission rates of 87% and 83%, respectively. The different molecular mechanisms of action of As2O3 suggest its applicability in hematologic malignancies other than APL. However, responses obtained thus far have consisted of improvements in signs and symptoms without the elimination of a given disease. Toxicities derived from As2O3 are significant but manageable and reversible. However, the risk/benefit ratio of As2O3 in hematologic malignancies other than APL is still unclear. The development of new generations of orally bioavailable inorganic, as well as new organic, arsenic compounds with improved toxicity profiles may bolster the therapeutic application of arsenic derivatives in hematologic malignancies such as leukemia, multiple myeloma and myelodysplastic syndromes.

Administration, Oral↗

PubMed2003

Relative increase in leukemia-specific DNA in peripheral blood plasma from patients with acute myeloid leukemia and myelodysplasia.

Using loss of heterozygosity (LOH) and X-chromosome inactivation, we compared peripheral blood (PB) plasma with bone marrow (BM) cells in detecting genomic abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We detected LOH in the PB plasma of all 45 patients who had cytogenetically documented chromosomal abnormalities (5q-, 7-, +8, 17-, or 20-). BM cells from the same patients showed LOH in 89% of patients with MDS and 70% of patients with AML. Posttherapy samples from 16 of these patients demonstrated complete concordance between LOH and cytogenetics in detecting residual disease in 15 samples. Of the 16 samples, 4 showed LOH in plasma with normal BM morphology. Using X-chromosome inactivation, clonality was detectable in 19 (73%) of 26 BM samples, whereas all PB plasma samples showed clonality. These data support the conclusion that PB plasma is enriched by tumor-specific DNA and can replace BM cells for studying genomic abnormalities.

Adult↗

PubMed2003

Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase.

BACKGROUND: Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-alpha), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-alpha, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS: Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m(2) IFN-alpha subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m(2) by continuous infusion over 24 hours daily x 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS: With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to < or = 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-alpha dose was 1.6 MU/m(2) daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS: The sequence of IFN-alpha, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.

Adult↗

PubMed2003

Sudden onset of the blastic phase of chronic myelogenous leukemia: patterns and implications.

BACKGROUND: Therapeutic options in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph-positive CML) in chronic phase include allogeneic stem cell transplantation (SCT) and treatments other than allogeneic SCT. The choice of therapy often depends on the mortality risk of allogeneic SCT. Delaying SCT until the disease demonstrates resistance to other strategies (e.g., imatinib mesylate or interferon-alpha) entails the risk of the development of a sudden blastic phase, which may not permit enough time to perform a SCT. METHODS: The current study was performed to define the incidence and patterns of sudden-onset blastic-phase CML in relation to the risk inherent in delaying allogeneic SCT. Of a study group of 1286 patients who were referred in early chronic-phase CML between 1981-2001 and who received therapies other than allogeneic SCT, 1093 patients had regular follow-up at the study institution. A sudden onset of blastic phase was defined as having its onset within 3 months from a previously documented complete hematologic response. RESULTS: Among the 1093 patients, 183 patients developed blastic-phase disease, which was of sudden onset in 46 patients (25%; 4% of the total). The incidence of sudden blastic phase was 0.4% in the first year, 1.8% in the second year, and 2.6% in the third year. Patients with sudden blastic-phase disease were found to have more often low-risk features at the time of presentation, including low incidences of blasts and thrombocytosis. Sudden blastic-phase CML was found to be associated with a higher incidence of lymphoid blastic morphology (67% vs. 22%; P < 0.0001), which resulted in a higher response rate to blastic-phase therapy (70% vs. 29%; P < 0.0001) and significantly longer survival from the onset of blastic-phase disease (median of 12 months vs. 6 months; P < 0.01). Twenty-four of the 42 patients with sudden blastic-phase disease who were treated at the M. D. Anderson Cancer Center were able to undergo allogeneic SCT in second chronic phrase (n = 13) or transformed phase (n = 11); at the time of last follow-up, 6 patients were alive without evidence of disease at a median of 18 months. CONCLUSIONS: The low rates of sudden blastic transformation in the first 3 years of the course of disease for CML and the salvage rate of these patients with allogeneic SCT should be considered in relation to the transplantation mortality in patients with early chronic-phase disease and the early promising results with imatinib mesylate therapy.

Adult↗

PubMed2002

Differences in CD33 intensity between various myeloid neoplasms.

We measured the concentration of CD33 antigen on the surface of cells in 315 bone marrow (BM) samples and 114 corresponding peripheral blood (PB) samples from patients with various leukemias (acute myeloid leukemia [AML], chronic myelogenous leukemia [CML], myeloproliferative disorder [MPD] other than CML, myelodysplastic syndrome [MDS]) and from control subjects. Overall CD33 intensity in total CD33+ cells was significantly higher in BM than in PB. CD33 intensity in total BM CD33+ cells differed significantly with the type of disease. The median number of CD33 molecules per cell was highest in AML, followed by MDS, CML, and control subjects and lowest in MPD. When only CD34+/CD33+ cells were examined, CD33 molecules per cell were highest in CD34+ cells in AML and lowest in MPD (P = .027). Patients with AML or MDS younger than 60 years had significantly higher intensity of CD33 expression on CD34+ cells than patients 60 years or older. Levels of CD33 intensity did not correlate with cytogenetics in patients with AML or MDS. There was no correlation between CD33 intensity and response to therapy or overall survival in 35 patients treated with protocols including Mylotarg. These data demonstrate variation in CD33 intensity between various leukemias.

Aminoglycosides↗