The following represent additions to UpToDate, since the last version, that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.

ACUTE GRAFT VERSUS HOST DISEASE

Mesenchymal stem cells — A phase II study evaluated the use of unmatched mesenchymal stem cells plus standard glucocorticoid therapy in 31 patients with grade II-IV acute graft-versus-host disease (GVHD) [1]. Overall and complete response rates were 94 and 77 percent, respectively. No infusional toxicities or ectopic tissue formations were reported. (See "Treatment of acute graft-versus-host disease: Clinical trials", section on 'Steroid-resistant acute GVHD'.)

ACUTE MYELOID LEUKEMIA

Increased dose daunorubicin for induction — Two randomized phase III trials in patients with previously untreated acute myeloid leukemia, one in younger adults and one in older adults, investigated the use of induction therapy with seven days of continuous infusion cytarabine (100 mg/m2 per day) plus three once-daily doses of daunorubicin at either 45 or 90 mg/m2 [2,3]. In both trials, patients assigned to the higher dose of daunorubicin had higher complete remission rates with no significant increased toxicity when compared with patients assigned to the lower dose of daunorubicin. Younger adults assigned to the higher dose of daunorubicin also demonstrated longer median overall survival rates [2]. (See "Treatment of acute myeloid leukemia in older adults", section on 'Intensive chemotherapy' and "Induction therapy for acute myeloid leukemia in younger adults", section on 'Cytarabine plus daunorubicin'.)

ANTICOAGULATION

Change in heparin potency — Because of the use of a new reference standard, unfractionated heparin products manufactured in the United States after October 8, 2009 will be 10 percent less potent [4]. This reduction in potency may have clinical significance in some situations, such as when heparin is administered as a bolus intravenous dose and an immediate anticoagulant effect is clinically important. (See "Therapeutic use of heparin and low molecular weight heparin", section on 'Effect of the change in heparin potency'.)

CHRONIC LYMPHOCYTIC LEUKEMIA

Chlorambucil versus fludarabine in older adults — A phase III trial in older adults (median age 70) with symptomatic, previously untreated chronic lymphocytic leukemia reported that, when compared with single agent chlorambucil, single agent fludarabine resulted in significantly higher response rates, but similar rates of progression-free and overall survival with higher rates of severe myelotoxicity [5]. (See "Initial treatment of chronic lymphocytic leukemia", section on 'Older adults'.)

Bendamustine versus chlorambucil — A phase III trial of 319 patients with previously untreated symptomatic chronic lymphocytic leukemia randomly assigned treatment with chlorambucil or bendamustine for up to six cycles [6]. Patients who were treated with bendamustine had significantly higher rates of overall response (68 versus 31 percent) and longer median progression-free survival (21.6 versus 8.3 months). To date, there is no difference in overall survival, but longer term follow-up is needed to determine any differential impact on survival. (See "Initial treatment of chronic lymphocytic leukemia", section on 'Bendamustine'.)

CHRONIC MYELOID LEUKEMIA

Dasatinib

Efficacy in accelerated phase disease — The START-A phase 2, open-label, single-arm clinical trial of dasatinib 70 mg twice daily in 174 patients with accelerated phase chronic myeloid leukemia (CML) who were resistant to or intolerant of imatinib reported rates of major hematologic, complete hematologic, and complete cytogenetic response of 64, 45, and 32 percent, respectively [7]. The median time to major hematologic response was 64 days. Sixty-six percent of patients were progression-free at 12 months. (See "Treatment of chronic myeloid leukemia in accelerated phase", section on 'Dasatinib'.)

Dosing in accelerated phase disease — A randomized phase III trial of dasatinib 140 mg once daily versus 70 mg twice daily reported similar response rates, but decreased toxicity with the once daily dose when given to patients with accelerated phase chronic myeloid leukemia intolerant of or resistant to imatinib [8]. Specifically, patients assigned to once-daily treatment had significantly fewer pleural effusions (20 versus 39 percent, respectively). (See "Treatment of chronic myeloid leukemia in accelerated phase", section on 'Dasatinib'.)

Bleeding — Platelet aggregation studies performed on samples from patients receiving tyrosine kinase inhibitors suggest that bleeding, which occurs in up to 25 percent of patients receiving dasatinib therapy, may be due to impaired platelet aggregation in the context of normal platelet counts and coagulation studies [9]. (See "Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia", section on 'Bleeding'.)

HEMATOPOIETIC CELL TRANSPLANTATION

Minimal intensity conditioning — Patients with DNA/telomere repair defects may not tolerate even reduced intensity conditioning prior to hematopoietic cell transplantation (HCT) and may be candidates for MINIMAL intensity conditioning. This was tested in 16 patients undergoing HCT for primary combined immunodeficiency. The regimen included two anti-CD45 antibodies, an anti-CD52 antibody, fludarabine, and low-dose cyclophosphamide [10]. Fifteen of the 16 patients engrafted; no grade 4 toxicities were noted. At 40 months post-HCT, 81 percent were alive and cured of their underlying disease. (See "Preparative regimens for hematopoietic cell transplantation", section on 'Antibody-based minimal intensity conditioning'.)

LYMPHOMA

Stroke in Hodgkin lymphoma survivors — Irradiation of the neck and/or mediastinum, especially when administered at a young age, has been associated with an increased risk of stroke and transient ischemic attack among Hodgkin lymphoma survivors [11]. (See "Monitoring of the patient with Hodgkin lymphoma during and after therapy", section on 'Cardiac and vascular disease'.)

Temsirolimus for mantle cell — A randomized phase III trial in 162 patients with relapsed or refractory mantle cell lymphoma reported that, compared with patients who were treated with other agents, those who received temsirolimus had a significantly longer median progression-free survival (3.4 to 4.8 months versus 1.9 months, respectively) [12]. (See "Treatment of relapsed or refractory mantle cell lymphoma", section on 'Temsirolimus'.)

FLIPI two — A new prognostic score for patients with follicular lymphoma, the Follicular lymphoma international prognostic index 2 (FLIPI2), has identified the following five parameters of prognostic value [13]:

• Age >60 years
• Bone marrow involvement
• Hemoglobin level <12.0 g/dL
• Longest diameter of the largest node >6cm
• Serum beta-2 microglobulin level > upper limit of normal

While the role of the FLIPI2 in clinical practice is unclear at this time, this system supports the prognostic value of these factors, some of which were not part of the original FLIPI score. (See "Evaluation, staging, and prognosis of non-Hodgkin lymphoma", section on 'Follicular lymphoma IPI (FLIPI)',).

Pralatrexate for peripheral T cell lymphoma — Pralatrexate was approved for use in relapsed or refractory peripheral T cell lymphoma (PTCL) by the United States Food and Drug Administration in the fall of 2009. Preliminary results from an international, open label phase II registration trial (the PROPEL trial) of pralatrexate in 115 heavily pretreated patients with PTCL noted an overall response rate of 27 percent with 10 percent complete responses [14]. The most common severe (grade 3/4) toxicities were thrombocytopenia (32 percent) and mucosal inflammation (21 percent). (See "Treatment of relapsed or refractory peripheral T cell lymphoma", section on 'Pralatrexate'.)

Interim PET scans — While some studies have suggested that positive interim positron emission tomography (PET) scans are associated with inferior outcomes, there appears to be substantial inter-reader variability, even among nuclear medicine experts. A prospective trial that evaluated the interpretation of 38 interim PET scans in patients with diffuse large B cell lymphoma reported complete agreement by ECOG and London criteria in only 68 and 71 percent of cases, respectively [15]. (See "Initial treatment of diffuse large B cell lymphoma", section on 'Response evaluation'.)

Primary CNS lymphoma — The first completed randomized trial in primary central nervous system lymphoma (PCNSL) was an international phase II trial of 79 patients randomly assigned treatment with four cycles of either methotrexate or the same dose of methotrexate plus cytarabine [16]. When compared with those assigned to methotrexate alone, patients assigned the combination of methotrexate plus cytarabine had significantly higher rates of complete (46 versus 18 percent) and overall response (69 versus 40 percent), but with higher rates of severe (grade 3/4) hematologic toxicity (92 versus 15 percent) and infection. (See "Treatment and prognosis of primary central nervous system lymphoma", section on 'Methotrexate'.)

MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE

Pesticide use — In a prospective cohort study of men who work as pesticide applicators, the age-adjusted prevalence of monoclonal gammopathy of undetermined significance (MGUS) was 1.9-fold (95% CI 1.3-2.7) higher than that of men from the general population [17]. Some of the chemicals implicated in this study have also been associated with excess multiple myeloma risk. (See "Monoclonal gammopathy of undetermined significance", section on 'Incidence and clinical characteristics'.)

MULTIPLE MYELOMA

Response evaluation — Despite advances in multiple myeloma disease detection with the serum free light chain assay (FLC), it is still important to include a bone marrow examination in the evaluation of complete response to therapy. Up to 10 percent of patients demonstrating a normal serum FLC ratio and negative immunofixation of the urine and serum will have 5 percent or greater plasma cells in the bone marrow and therefore not fulfill the criteria for complete response [18]. (See "Evaluating response to treatment of multiple myeloma", section on 'Response criteria'.)

MYELODYSPLASTIC SYNDROME

Long-term effect of treatment with erythropoietin — The issue of worsened survival in cancer patients treated with erythropoietin (EPO) or darbepoetin has been raised. However, during long-term follow-up of a phase III ECOG trial, subjects with myelodysplastic syndrome (MDS) who were treated with EPO ± granulocyte colony-stimulating factor, when compared with those receiving supportive care only, had similar overall survival and a similar incidence of transformation to acute myeloid leukemia [19]. (See "Treatment and prognosis of the myelodysplastic syndromes", section on 'Effect on survival'.)

Toxicity of the iron chelating agent deferasirox — The United States FDA has notified healthcare professionals of an Early Communication regarding an ongoing review of safety issues with the orally-active iron chelating agent deferasirox (Exjade). New safety data suggest there may be a greater number of adverse events and deaths in patients using this agent who are >60 and have myelodysplastic syndrome [20]. (See "Treatment and prognosis of the myelodysplastic syndromes", section on 'Red cell transfusions and iron chelation'.)