Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) patients aged ≥ 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%.

Intravenous iron replacement for persistent iron deficiency anemia after Roux-en-Y gastric bypass.

Background: Iron deficiency is a major postoperative complication of Roux-en-Y gastric bypass surgery. Oral replacement can fail to correct the deficiency. Thus, recourse to parenteral iron administration might be necessary.

Activity of azacitidine in chronic myelomonocytic leukemia.

Background: Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML.

Fetal-maternal microchimerism in normal parous females and parous female cancer patients.

Objective: The prevalence of male microchimerism (MC) in parous females, nonparous females, and parous female cancer patients was examined.

Materials And Methods: DNA extracted from peripheral blood leukocytes and male Y-chromosomal DNA was amplified using a sensitive two-stage polymerase chain reaction technique. Controls prepared by mixing human male and female cell lines demonstrated the sensitivity of the technique to be in the range of 1 male cell per 1 million female cells.

Recent advances in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrow disorders characterized by both bone marrow failure and a propensity for development of acute myeloid leukemia. The incidence of these conditions has risen sharply over the past several years, making them the most common malignant bone marrow disorders. While the majority of patients are diagnosed with low-grade disease, approximately two-thirds will succumb to complications of peripheral blood cytopenias or progression to acute leukemia.

Multiple unit HLA-unmatched sex-mismatched umbilical cord blood transplantation for advanced hematological malignancy.

We investigated the effect of multiple-unit umbilical cord blood (UCB) transplantation on engraftment in the setting of severe human leukocyte antigen (HLA) mismatch. Ten poor-risk adult patients with hematological malignancy received multiple unit, HLA-unmatched, sex-mismatched, unrelated UCB transplantation after a reduced intensity-conditioning regimen (RICR) with engraftment as the primary endpoint. The median age of the patients was 55 years with a range of 28-67.

Posterior reversible encephalopathy syndrome in infection, sepsis, and shock.

Background And Purpose: The cause of "posterior reversible encephalopathy syndrome" (PRES) is not established. We recently encountered several patients who developed PRES in the setting of severe infection. In this study, we comprehensively reviewed the clinical and imaging features in a large cohort of patients who developed PRES, with particular attention to those with isolated infection, sepsis, or shock (I/S/S).

A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease.

Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers.

Treatment of acute myelogenous leukemia with outpatient azacitidine.

Background: Patients older than 55 years of age with acute myelogenous leukemia (AML) are less likely to achieve complete remission and more likely to experience toxicity with conventional induction chemotherapy than younger patients. Azacitidine administered in the outpatient setting is well tolerated and can induce complete hematological remission in patients with myelodysplastic syndromes (MDS). At higher doses, azacitidine has activity in AML.

Variable incidence of cyclosporine and FK-506 neurotoxicity in hematopoeitic malignancies and marrow conditions after allogeneic bone marrow transplantation.

Introduction: This study examines whether malignant disease under treatment influences the incidence of cyclosporine or FK-506 neurotoxicity after myeloablative conditioning and allogeneic bone marrow transplantation (allo-BMT).

Methods: Review of 290 patients who received myeloablative conditioning prior to allo-BMT and cyclosporine/FK-506 identified 21 (7.2%) patients with neurotoxicity confirmed by computed tomography or magnetic resonance.

Pretransplantation conditioning influence on the occurrence of cyclosporine or FK-506 neurotoxicity in allogeneic bone marrow transplantation.

Background And Purpose: Transplantation conditioning regimens have been shown to affect the brain imaging appearance in patients with cyclosporine or FK-506 neurotoxicity. We assessed whether the occurrence of neurotoxicity was affected by the choice of conditioning regimen used before allogeneic bone marrow transplantation (allo-BMT).

Methods: An allo-BMT was performed in 290 patients conditioned before transplantation with myeloablative therapy.

Localized lymphoid relapse in the pancreas following allogeneic hematopoietic stem cell transplant for chronic myelogenous leukemia.

The incidence of isolated extramedullary disease (EMD) following allogeneic hematopoietic stem cell transplant (allo-HSCT) for chronic myelogenous leukemia (CML) is not fully known. One review found the incidence of isolated myeloid EMD, or granulocytic sarcoma (GS), in an allo-HSCT treated CML/myelodysplastic subgroup to be just 0.22%.

Factors affecting purification of CD34(+) peripheral blood stem cells using the Baxter Isolex 300i.

A total of 201 patients with breast cancer, ovarian cancer, or hematological malignancies underwent mobilization of peripheral blood stem cells (PBSC) using chemotherapy and granulocyte-colony stimulating factor (G-CSF). Stem cell products were collected using the Baxter CS3000 pheresis machine. The Baxter Isolex 300i was used to perform 240 CD34(+) cell separations on the apheresis products.

Treatment of myelodysplastic syndromes with 5-azacytidine.

Patients with myelodysplastic syndromes (MDS) who were anemic and/or thrombocytopenic were treated with 5-azacytidine (5-AZA) at a dose of 75 mg/m(2) per day SQ x 7 days. This cycle was repeated every 28 days. Forty-eight patients who received at least one cycle of 5-AZA were evaluable for response.

Etiology of cortical and white matter lesions in cyclosporin-A and FK-506 neurotoxicity.

Background And Purpose: The etiology of the neurotoxicity associated with cyclosporin-A (CsA) and FK-506 treatment is not fully understood. At our institution, we noticed a distinct, abrupt change in the imaging characteristics of CsA and FK-506 neurotoxicity, which consisted of a shift in lesion morphology from a white matter abnormality to a mixed cortical and white matter pattern. The purpose of this study was to assess clinical parameters that might explain this change.

Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP).

Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease that is treated with plasma exchange and typically with replacement with fresh frozen plasma (FFP). This approach results in an approximate 50% response rate following 1 week of therapy and 80% survival. Cryoprecipitate poor plasma (CPP) is plasma from which the cryoprecipitate fraction is removed.

Ex vivo expansion of human umbilical cord blood and peripheral blood CD34(+) hematopoietic stem cells.

The proliferation and expansion of human hematopoietic stem cells (HSC) in ex vivo culture was examined with the goal of generating a suitable clinical protocol for expanding HSC for patient transplantation.HSC were derived from umbilical cord blood (UCB) and adult patient peripheral blood stem cell collections. HSC were stimulated to proliferate ex vivo by a combination of two growth factors, flt-3 ligand (FL) and thrombopoietin/c-mpl ligand (TPO/ML), and assessed for expansion by flow cytometry.

Mobilization and transplantation of peripheral blood stem cells.

Two hundred nineteen patients underwent peripheral blood stem cell (PBSC) transplantation from 1990 to 1997. Stem cells were mobilized with cyclophosphamide (CY), or with CY plus Taxol or etoposide, followed by cytokines, and collected when leukocyte counts > or = 1,000/microl, or when CD34+ counts > or = 20/microl. On average, four to five collections were needed to obtain sufficient PBSC for engraftment.

Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein.

Mice deficient for the transcription factor, interferon consensus sequence binding protein (ICSBP), are immunodeficient and develop disease symptoms similar to human chronic myeloid leukemia (CML). To elucidate the hematopoietic disorder of ICSBP(-/-) mice, we investigated the growth, differentiation, and leukemogenic potential of ICSBP(-/-) myeloid progenitor cells in vitro, as well as by cell-transfers in vivo. We report that adult bone marrow, as well as fetal liver of ICSBP-deficient mice harbor increased numbers of progenitor cells, which are hyperresponsive to both granulocyte macrophage colony-stimulating factor (GM-CSF) and G-CSF in vitro.

Calpain activity in bone marrow transplant-associated thrombotic thrombocytopenic purpura.

The pathophysiology of thrombotic thrombocytopenic purpura (TTP) is not well understood. Recent studies have described a platelet aggregating factor which has been characterized as a calcium-dependent cysteine protease (calpain) in patients with TTP. A type of TTP, sometimes called secondary TTP, has been associated with bone marrow transplantation (BMT).