Guillermo Garcia-Manero

Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome.

Elderly patients (age ≥ 65 years) with acute myeloid leukemia (AML) generally have a poor prognosis. AML‐type therapy results are often derived from studies in younger patients and may not apply to elderly AML. Many investigators and oncologists advocate, at times, only supportive care or frontline single agents, Phase I–II studies, low‐intensity regimens, or ‘targeted’ therapies. However, baseline expectations for outcomes of elderly AML with ‘standard’ AML‐type therapy are not well defined. The aim was to develop prognostic models for complete response (CR), induction (8‐week) mortality, and survival rates in elderly AML, which would be used to advise oncologists and patients of expectations with standard AML type therapy, and to establish baseline therapy results against which novel strategies would be evaluated.

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.

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders.

Imatinib mesylate is a selective tyrosine kinase inhibitor of c‐abl, bcr/abl, c‐kit, and platelet‐derived growth factor‐receptor (PDGF‐R). c‐kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD).

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.

Chronic myelogenous leukemia: A review and update of therapeutic strategies

DOI 10.1002/cncr.11520

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.

Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

Older age is a consistent poor prognostic factor in patients with Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML). Whether this is related to an intrinsic worse disease biology or to inadequate drug delivery or excessive treatment‐associated toxicity is unknown. The availability of imatinib mesylate, a selective, Bcr‐Abl‐targeted therapy that is administered orally with minimal side effects, may clarify whether older age would remain an adverse factor (thus, implying a different age‐related CML biology).

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.

Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia

Aberrant methylation of promoter‐associated cystosine‐guanine (CpG) islands is an epigenetic modification of DNA frequently observed in adult patients with acute lymphocytic leukemia (ALL). This epigenetic modification has been associated with gene silencing, malignant transformation, and aging. It is not known whether there are epigenetic differences between pediatric patients and adult patients with ALL.