Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

BACKGROUND: Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). METHODS: In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups. RESULTS: After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006). CONCLUSIONS: Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML

Investigating rare haematological disorders - A celebration of 10 years of the Sherlock Holmes symposia

The Sherlock Holmes symposia have been educating haematologists on the need for prompt recognition, diagnosis and treatment of rare haematological diseases for 10 years. These symposia, which are supported by an unrestricted educational grant from Sanofi Genzyme, encourage haematologists to consider rare disorders in differential diagnoses. Improvement in rare disease awareness is important because diagnostics and the availability of effective therapies have improved considerably, meaning that rare haematological diseases can be accurately diagnosed and successfully managed, particularly if they are identified early. The Sherlock Holmes symposia programme includes real-life interactive clinical cases of rare haematological disorders that require awareness from the physician, to be diagnosed at an early stage. The audience are encouraged to examine each case as if they were detectives, look for clues from the clinical history and presentation, consider the potential causes, assess which tests would be required to make a definitive diagnosis and suggest optimal treatment options. To celebrate the 10-year anniversary of the Sherlock Holmes symposia, this article describes a number of clinical cases that include anaemia, thrombocytopaenia and splenomegaly among the presenting symptoms, to illustrate the importance of rigorous differential diagnosis in the identification of rare haematological disorders

Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study

Purpose: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. Methods: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment (“watch and wait”), chlorambucil treatment only, and patients with other treatment(s). Results: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. Conclusions: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment

Distress and quality of life after autologous stem cell transplantation: a randomized clinical trial to evaluate the outcome of a web-based stepped care intervention

Background Psychological distress (i.e. depression and anxiety) is a strong predictor of functional status and other aspects of quality of life in autologous stem cell transplantation following high-dose chemotherapy. Treatment of psychological distress is hypothesized to result in improvement of functional status and other aspects of quality of life. The aim is to evaluate the outcome of stepped care for psychological distress on functional status and other aspects of quality of life in patients with hematological malignancy treated with autologous stem cell transplantation. Methods/Design The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention program versus care as usual. Patients are randomized immediately pre transplant. Stepped care and care as usual are initiated after a 6 weeks buffer period. Outcome is evaluated at 13, 30, and 42 weeks post transplant. In the experimental group, the first step includes an Internet-based self-help program. If psychological distress persists after the self-help intervention, the second step of the program is executed, i.e. a diagnostic evaluation and a standardized interview, yielding a problem analysis. Based on this information, a contract is made with the patient and treatment is provided consisting of individual face-to-face counseling, medication, or referral to other services. Care as usual comprises an interview with the patient, on ad hoc basis; emotional support and advice, on ad hoc basis; if urgent problems emerge, the patient is referred to other services. Primary outcome variables are psychological distress and functional status. Data are analyzed according to the intention to treat-principle. Discussion This study has several innovative characteristics. First, the outcome of the intervention for psychological distress in patients with hematological malignancy treated with autologous stem cell transplantation is evaluated in a randomized controlled study. Second, the impact of the intervention on functional status is evaluated: it is hypothesized that reduction of psychological distress results in improved functional status. Furthermore, the intervention concerns an Internet-based treatment in the first step. Finally, the intervention is characterized by an emphasis on self-management, efficiency, and a multi-disciplinary approach with nurses taking up a central role

Treatment of myeloma: Recent developments

Melphalan was the first described treatment for patients with multiple myeloma in the 1960s and is still being used in clinical practice. However, the use of melphalan in combination with prednisone resulted in a median survival of only 2-3 years. Therefore, the dose of melphalan has been intensified since then (140-200 mg/m(2)). In order to diminish treatment-related morbidity and mortality due to severe myelosuppression induced by these regimens, high-dose melphalan is currently supported with autologous stem cells. Indications for high-dose therapy and the role of further intensification by performing second or allogeneic transplantations are discussed. Furthermore, new therapeutic modalities, such as inhibitors of angiogenesis, also showing direct antiproliferative, cytokine-related and immunomodulatory effects on plasma cells (thalidomide and its newer derivatives), inhibitors of the transcription factor NF-kappa B (proteasome inhibitors) and immunotherapy are describe

[Intravenous high-dose methylprednisolone efficacy for treatment of idiopathic thrombocytopenic purpura in adults]

Objective. To determine the efficacy of a short intravenous course of high-dose methylprednisolone compared with the standard treatment with prednisone for adult patients with idiopathic thrombocytopenic purpura (ITP). Design. Retrospective. Methods. For all patients diagnosed with ITP between January 1rst 1988 and January 1rst 1998 in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands, data were obtained until June 1rst 1998. These patients had received a brief course of treatment with methylprednisolone i.v. (1 g per day on three successive days in the outpatient department) or the standard treatment (protracted oral treatment with prednisone). A response was defined as a rise in platelet count of > 50 x 109/l. When a remission lasted more than a year a patient was defined as longterm responder. Results. The results concerned 41 patients. The prednisone group comprised 7 males and 20 females, mean age 39 years, the methylprednisolone group comprised 2 males and 12 females, mean age 43 years. Initial treatment with prednisone or methylprednisolone resulted in equal response rates of, respectively, 63% (17/27 patients) and 64% (9/14 patients). The number of longterm responders was 8 of 27 patients in the prednisone group and 2 of 14 patients in the methylprednisolone group. At time of relapse 22 patients were treated with the other treatment modality. The response rate in the group of patients treated with prednisone after first-line treatment with methylprednisolone, was 67% (6/9), for methylprednisolone after first-line treatment with prednisone the response rate was 23% (3/13). Conclusion. A short intravenous course of high-dose methylprednisolone is effective as initial treatment of adults with ITP. Toxicity of longterm treatment with prednisone can be avoided in a number of patients with ITP. In patients refractory to treatment with methylprednisolone, the response rate to second-line treatment with prednisone was not negatively influenced, since two thirds of these relapsing patients subsequently responded to prednisone