Francis J. Giles

Mylotarg™ (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation

Mylotarg™ (Wyeth‐Ayerst Laboratories, St. Davids, PA) is the brand name for a calicheamicin‐conjugated humanized anti‐CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA‐676) and has been approved recently for the treatment of a subset of elderly patients who have relapsed acute myeloid leukemia (AML). Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this patient population. Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy.

Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis

Little is known regarding long‐term prognosis among patients with Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0% Ph‐positive cells) after treatment with interferon‐α.

Chronic myelogenous leukemia in nonlymphoid blastic phase: Analysis of the results of first salvage therapy with three different treatment approaches for 162 patients

The prognoses of patients with chronic myelogenous leukemia in blastic phase (CML‐BP) are extremely poor. Treatment of patients with nonlymphoid CML‐BP is associated with very low response rates, a median survival of 2–3 months, and significant toxicities. The aim of this study was to evaluate the results of therapy in CML‐BP with different treatments in relation to response rate, survival, and toxicity.

Plasma vascular endothelial growth factor levels have prognostic significance in patients with acute myeloid leukemia but not in patients with myelodysplastic syndromes

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are positive regulators of angiogenesis. Increased levels in urine, serum, plasma, or malignant tissue have been associated with an adverse prognosis in patients with solid tumors.

Phase II study of SU5416 - A small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor - In patients with refractory myeloproliferative diseases

Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with myeloproliferative disorders (MPD), including agnogenic myeloid metaplasia (AMM), chronic myeloid leukemia in blastic phase (CML‐BP), and chronic myelomonocytic leukemia (CMML). VEGF is a soluble, circulating, angiogenic molecule that acts through receptor tyrosine kinases (RTK), including VEGF receptor 2 (VEGFR‐2). SU5416 is a small‐molecule RTK inhibitor (RTKI) that targets VEGFR‐2, c‐kit, and fms‐related tyrosine kinase Flk2.

Thalidomide therapy for myelofibrosis with myeloid metaplasia.

Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies.

Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia

Therapy for patients with Richter syndrome (RS) or fludarabine‐refractory chronic lymphocytic leukemia (CLL) is unsatisfactory. A Phase II study was conducted to evaluate an alternating combination cytotoxic regimen given with rituximab and granulocyte‐macrophage–colony stimulating factor (GM‐CSF) in these patients.

High-dose chemotherapy in high-risk myelodysplastic syndrome: Covariate-adjusted comparison of five regimens

Antileukemic chemotherapy has been used for two decades to treat high‐risk myelodysplastic syndrome (refractory anemia with excess of blasts [RAEB] and RAEB in transformation into acute leukemia [RAEB‐t]) patients. Because the results of standard regimens have been disappointing, high‐dose chemotherapeutic regimens were investigated recently. In the absence of randomized trials, the relative merits of various treatment regimens are unknown.

Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes

Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are major regulators of angiogenesis, which plays a key role in the growth and dissemination of solid tumors and hematologic neoplasms.

Phase II study of sphingosomal vincristine in patients with recurrent or refractory adult acute lymphocytic leukemia

Outcomes with salvage therapy for patients with recurrent or refractory acute lymphocytic leukemia (ALL) are poor, with complete response (CR) rates reported to be 20–30% and a median survival ranging from 2–6 months. New agents are needed to reduce the recurrence rate after frontline chemotherapy. Vincristine is an important component of ALL therapy. In animal models, the encapsulation of vincristine into sphingomyelin liposomes or “sphingosomes” for injection (SV) has improved efficacy compared with conventional vincristine.