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Purpose: Granulocyte colony-stimulating factor (G-CSF) administered prophylactically after chemotherapy reduces the duration and severity of neutropenia. This randomized crossover study was designed to assess whether a lower dose of G-CSF is as effective as a standard dose of 5 microg/kg daily., Patients and Methods: Patients who received standard-dose chemotherapy regimens expected to cause neutropenia received G-CSF (lenograstim) that started the day after chemotherapy for 14 days or until the absolute neutrophil count (ANC) recovered to greater than 10 x 10(9)/L. The lenograstim dose was randomly allocated to be 2 or 5 microg/kg daily in the first cycle of chemotherapy and crossed over to the alternate dose for the second cycle. The study was designed to accrue 40 assessable patients to provide a power of 80% to detect a difference in duration of neutropenia of 1 day. Fifty-two patients were randomized to treatment and 43 patients completed two cycles of identical chemotherapy., Results: There was little neutropenia irrespective of the dose used. Twenty-three patients (53%) had no grade III or IV neutropenia and 30 patients (70%) had no grade IV neutropenia. Crossover trial methodology was used to assess the difference in outcome caused by the lower dose compared with the standard dose (estimated treatment effect). There was no significant difference in the measures of neutropenia, hospitalization, or other clinical outcomes. The 95% confidence interval (one-sided) for the additional duration of neutropenia caused by the lower dose of lenograstim was 0.43 days or less for grade III or IV neutropenia and 0.34 days or less for grade IV neutropenia., Conclusion: Lenograstim 2 microg/kg provides similar protection to 5 microg/kg against neutropenia that complicates standard-dose chemotherapy. The use of a lower dose has important implications for the cost-effectiveness of prophylactic G-CSF therapy.

The Australian Leukaemia Study Group has performed a randomized trial of interferon alpha-2A (Roferon-A) as a co-induction agent together with intensive combination chemotherapy and as maintenance following completion of 12 cycles of induction treatment. When used as a co-induction agent, interferon-alpha did not improve response rates, time-to-treatment failure, or overall survival. Patients who had interferon together with intensive combination therapy (PCAB: prednisone 60 mg/m2 days 1-5, cyclophosphamide 600 mg/m2 day 1, BCNU 30 mg/m2 day 1, doxorubicin 30 mg/m2 day 1, repeated every 28 d for a total of 12 cycles) had more leucocyte and granulocyte toxicity and received a lower dose intensive of cytotoxic drugs than those patients who received PCAB without interferon. There was a trend towards prolongation of plateau phase which did not reach significance. Interferon, however, did improve the survival of patients who achieved plateau; for those patients interferon was associated with a 33% decrease in the rate of death after adjusting for initial beta-2 microglobulin level.

Background: Selection of patients for a clinical trial is affected by awareness of the existence of the trial, interest in the study question and clinical practices and views of the clinicians., Aims: To investigate the selectivity that may have occurred at Peter MacCallum Cancer Institute (PMCI) during the ANZ Lymphoma Group trial of MACOP-B vs CHOP in non-Hodgkin's lymphoma (NHL)., Methods: NHL patients at PMCI in the study period were assessed against the trial's eligibility criteria. Comparisons were made between eligible (except for consent) non-trial patients and all patients actually randomised into the trial., Results: Of 497 patients presenting during the trial period, 320 (64%) did not meet the specified eligibility criteria, 102 (21%) were unsuitable on other grounds (age and medical) and 75 (15%) were eligible. Of those eligible, 43 (57%) were entered into the trial and 32 (43%) were not. Four non-trial patients had inappropriate application of eligibility criteria and 13 unknown reason. Eligible non-trial patients were similar to trial patients in most patient and tumour characteristics and overall survival. Significantly more non-trial patients had higher stage disease (p = 0.02). More non-trial patients had lower grade histology, but this was not significant., Conclusions: Physician selectivity occurred with respect to patient entry, but trial and non-trial patients were similar in most characteristics. Eligibility criteria should specify that patients can withstand all trial drugs and patient availability for treatment and follow-up. PMCI trial accural could have been up to 33% greater. These results suggest the trial accrual period could have been 25% shorter. Patient entry into this trial by PMCI clinicians compared favourably with other centres.

The aim of this study was to assess the influence of dose and dose intensity (DI) of induction and consolidation chemotherapy on relapse rates in 264 de novo patients with acute nonlymphocytic leukemia (ANLL). Patients were randomised to receive cytosine arabinoside (ARAC) 100 mg/m2 continuous infusion for 7 days and daunorubicin (DNR) 50 mg/m2 IV day 1-3 (7-3) or the same drugs with the addition of etoposide 75 mg/m2 IV days 1-7 (7-3-7). Cox proportional hazards regression models were used throughout to identify prognostic factors, including dose delivery parameters, influencing the rate of relapse. Of 152 patients who achieved a complete remission (CR), 104 have relapsed with a median duration of CR of 15.8 months. Actual dose delivered was prospectively documented. Cox regression analysis identified the most significant prognostic factors jointly influencing duration of CR as performance status groups (p < 0.0001), percentage peripheral blasts (p = 0.0015), 7-3-7 arm (p = 0.0075), age < 40 years (p = 0.022) and induction dose ARA-C plus DNR (p = 0.029). In this analysis patients randomized to the 7-3-7 arm had an estimated 43% reduction in the relapse rate and each 10% reduction of doses ARA-C and DNR was associated with an estimated 45% increase in the relapse rate. The number of induction courses, delays in treatment and induction dose intensity did not significantly influence the duration of CR nor did any of the consolidation treatment parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients receiving outpatient chemotherapy, without cisplatin, were randomised to receive four doses of either domperidone 60 mg or prochlorperazine 25 mg suppositories every 4 h, starting 30 min before the chemotherapy. They were crossed over for the next chemotherapy cycle. To enable analysis of 100 patients who had received identical chemotherapy in each course, 136 patients were randomised. Patients experienced a higher grade of nausea on domperidone (P = 0.05). Only 18% of patients vomited on domperidone and 14% on prochlorperazine, but the number of vomits was higher on domperidone (P = 0.003) and the duration was significantly increased (P = 0.02). Patients experienced significantly more diarrhoea on domperidone (P < 0.0001), although it was predominantly mild. Patients were significantly more sedated on prochlorperazine on the second course (P = 0.006), but not on the first course (P = 0.9). More patients preferred their second course (P < 0.0001), and were significantly less anxious (P = 0.0002). Patients reported tolerating their treatment similarly for both antiemetics, but more patients preferred prochlorperazine (P = 0.003), mainly due to reductions in nausea and vomiting and other side-effects, particularly diarrhoea.

A total of 22 patients with superficial transitional cell carcinoma of the bladder, uncontrolled cystoscopically and unsuitable for or having failed intravesical therapy, received 50 mg. oral methotrexate per week for 12 months. Of the patients 7 (32%) achieved or remained in complete remission and 5 achieved a partial response, while 4 remained stable, 3 had progression and 3 were not evaluable. Patients who were still alive had a median followup of 2.5 years. Two patients with complete remission had relapse at 16 and 26.4 months, and 5 were disease-free at 34.5, 31.3, 18.6, 17.8 and 16.8 months, respectively. The methotrexate was generally well tolerated but 2 patients discontinued therapy because of dyspnea (1 subsequently died of respiratory failure that was possibly related to the methotrexate) and 1 because of persistent grade 2 mucositis. Grade 3/4 toxicities occurred in 3 patients: 1 each with reversible increases in creatinine and aspartate aminotransferase, and 1 with gastric bloating. There was little hematological toxicity. Reversible skin lesions developed in 4 patients. This oral treatment may provide an effective alternative to intravesical therapy but can be associated with severe toxicity.

Sixty-seven patients with advanced breast cancer were prospectively entered into a Phase II trial of cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously (i.v.) on day 1, 5-fluorouracil 600 mg/m2 i.v. on day 1, and prednisolone 40 mg/m2 orally on days 1-14 (CMFP) rapidly alternating with doxorubicin 25-30 mg/m2 i.v. on day 8 and vincristine 1.4 mg/m2 i.v. on day 8 (AV). Complete responses (CR) were seen in 7 patients, partial responses (PR) in 25 (CR + PR, 48%), stable disease in 24, and progressive disease in 9. The median time to disease progression was 9.8 months, and the median survival 19.4 months. Neutropenia was the major toxicity with WHO grade 3 or 4 neutropenia in 50% of patients. CMFP/AV is a well-tolerated, effective regimen in advanced breast cancer but does not appear to be superior to CMFP alone.

Introduction: Multiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells in bone marrow. Upfront identification of tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established a molecular classification by stratifying multiple myeloma into two subtypes with a different prognosis based on a gene module co-expressed with MCL-1 (MCL1-M). Methods: Gene Ontology (GO) analysis with differentially expressed genes was performed to identify signal pathway. Drug sensitivity was analyzed using the OncoPredict algorithm. Drug sensitivity of different myeloma cell lines was detected by CCK8 and flow cytometry. RNA-seq was performed on drugsensitive cell lines before and after adriamycin treatment. RT-qPCR was used to further verify the sequencing results. The expression of g-H2AX and dsDNA in sensitive and resistant cell lines was detected by immunofluorescence method. Results: In our study, we demonstrated that MCL1-M low MM were more sensitive to anthracyclines. We treated different myeloma cell lines with doxorubicin in vitro and discovered the association of drug sensitivity with IFN signaling. Herein, we demonstrate that the doxorubicin-sensitive myeloma cell line showed significant DNA damage and up-regulated expression of genes related to the IFN response, which was not observed in drug-insensitive cell lines. Discussion: Our results suggest that the active IFN signaling pathway may serve as a marker for predicting chemotherapy sensitivity in patients with myeloma. With our MCL1-M molecular classification system, we can screen patients with a potentially good response to the interferon signaling pathway and provide individualized treatment for MM. We propose IFN-a as adjuvant therapy for patients with myeloma sensitive to anthracyclines to further improve the therapeutic effect and prolong the survival of patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy.Methods: This dose-finding, non-comparative study investigated the antiemetic effect and safety of increasing doses (2.5, 7.5 and 20 mg) of amisulpride against acute nausea and vomiting in the period 0-24 h after initiation of cisplatin-based chemotherapy. The 20 mg dose was also investigated in combination with the 5-HT3-receptor antagonist, ondansetron. The primary parameter was complete response (0-24 h), defined as no emesis and no need for rescue antiemetics. Secondary parameters were number of emetic episodes, severity of nausea and time to first emetic episode and start of nausea.Results: A total of 51 patients were enrolled and evaluable. None of the 10 patients in the 2.5 and 7.5 mg groups obtained a CR. In the 20 mg monotherapy cohort, two of the 18 subjects (11%) had a CR, 3/18 (17%) had no emesis and 12/18 (67%) had no significant nausea. Seven subjects (39%) had no nausea at all (a VAS score < 5 mm). In the combination (ondansetron plus amisulpride) cohort, 19/23 (83%; 90% confidence interval: 65-94%) had a CR and 14/23 (61%) had no nausea at all.Conclusions: Amisulpride has antiemetic effect against cisplatin-induced acute nausea and vomiting. The effect against nausea is of particular interest. Randomised studies are warranted to further explore the effect and safety of amisulpride. [ABSTRACT FROM AUTHOR]

The survival of patients with multiple myeloma ( MM) has improved substantially since the introduction in the late 1980s of high-dose chemotherapy ( HDT) supported by autologous stem cell transplantation ( ASCT). Further improvements have been observed following the availability of immunomodulatory drugs ( IMiD) such as thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib. Here, we summarise the recommendations of the Medical Scientific Advisory Group to the Myeloma Foundation of Australia for patients considered suitable for HDT + ASCT as part of initial therapy. These recommendations incorporate the various phases of treatment: induction, HDT conditioning and maintenance therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is effective in accelerating neutrophil recovery after intensive chemotherapy for acute myeloid leukemia (AML). However, the optimal G-CSF dosage for patients with AML has not been determined. To the authors' knowledge, G-CSF dosages have not been compared in a randomized AML study. METHODS: Patients who were enrolled on the St. Jude AML97 protocol and remained on study after window therapy were eligible to participate. The effect of the dosage of G-CSF given after induction chemotherapy Courses 1 and 2 was analyzed in 46 patients who were assigned randomly in a double-blinded manner to receive either 5 µg/kg daily or 10 µg/kg daily of G-CSF. The number of days of G-CSF treatment, neutropenia (an absolute neutrophil count <0.5 x 109/L), and hospitalization; the number of episodes of febrile neutropenia, grade 2 through 4 infection, and antimicrobial therapy; transfusion requirements; the cost of supportive care; and survival were compared between the 2 study arms. RESULTS: No statistically significant differences were observed between the 2 arms in any of the endpoints measured. CONCLUSIONS: The higher G-CSF dosage (10 µg/kg daily) offered no greater benefit than the lower dosage (5 µg/kg daily) in patients who were receiving intensive chemotherapy for AML. [ABSTRACT FROM AUTHOR]

Lenograstim (Granocyte®, Neutrogin®, Myelostim®) is a glycosylated recombinant human granulocyte colony-stimulating factor. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of lenograstim, mainly focusing on its use in chemotherapy-induced neutropenia, acceleration of neutrophil recovery following haematopoietic stem cell transplantation (HSCT), and peripheral blood stem cell (PBSC) mobilization in patients with cancer and healthy donors. In randomized, multicentre trials in patients with solid tumours, lymphoma or multiple myeloma, the durations of chemotherapy-induced neutropenia, hospitalization for infection and intravenous antibacterial therapy were significantly shorter in patients receiving lenograstim prophylaxis than in those receiving placebo. The time to neutrophil recovery was also significantly shorter in patients with acute myeloid leukaemia or acute lymphoblastic leukaemia who received lenograstim than in those who received placebo or no treatment, according to the results of randomized, multicentre trials. In addition, lenograstim prophylaxis facilitated the administration of dose-intense or dose-dense chemotherapy regimens, with improved clinical outcomes seen in some trials. In patients with cancer undergoing HSCT, lenograstim accelerated neutrophil recovery post-HSCT and shortened the duration of hospitalization. according to the results of randomized, multicentre trials. Lenograstim effectively mobilized PBSCs in patients with cancer, demonstrating generally similar efficacy to filgrastim or molgramostim in five randomized trials (although lower dosages of lenograstim than filgrastim were administered in four of the trials). Lenograstim also provided effective PBSC mobilization in healthy donors and was more effective than filgrastim when both drugs were administered at a dosage of 10μg/kg/day. The efficacy and safety of lenograstim for PBSC mobilization in healthy donors was supported by the results of a prospective, longer-term study involving almost 4000 healthy donors. Lenograstim was generally well tolerated across a variety of treatment settings, including PBSC mobilization in healthy donors, with bone pain being one of the most commonly reported adverse events. In conclusion, lenograstim remains an important option for use in chemotherapy- induced neutropenia, acceleration of neutrophil recovery following HSCT, and PBSC mobilization. [ABSTRACT FROM AUTHOR]

Objectives: Patients with multiple myeloma (MM) often have pronounced symptoms and substantially reduced quality of life. The aims of treatment are to control disease, maximise quality of life and prolong survival. Hence, health-related quality of life (HRQOL) should be an important end-point in randomised controlled trials (RCTs) in addition to traditional endpoints. We wanted to evaluate whether trials reporting HRQOL outcomes have influenced clinical decision making and whether HRQOL was assessed robustly according to predefined criteria. Methods: A systematic review identified RCTs in MM with HRQOL assessment as a study end-point. The methodological quality of these studies was assessed according to a checklist developed for evaluating HRQOL outcomes in clinical trials. The impact of the HRQOL results on clinical decision making was assessed, using published clinical guidelines as a reference. Results: Fifteen publications presenting RCTs with HRQOL as a study end-point were identified. In 13 trials, the author stated that HRQOL results should influence clinical decision making. We found, however, that the HRQOL data only had a limited impact on published treatment guidelines for bisphosphonates, high-dose treatment, interferon, erythropoiesis-stimulating agents and novel agents. Conclusion: The present review indicates that the there are still few RCTs in MM including HRQOL as a study end-point. Systematic incorporation of HRQOL measures into clinical trials allows for a comparison of treatment arms that includes the patients’ perspective. Before the full impact on clinical decisions can be realised, the quality and methodology of collecting HRQOL data must be further improved and the results rendered more comprehensible to clinicians. [ABSTRACT FROM AUTHOR]

In cancer care in Australia, we are very reliant on an array of expensive pharmaceuticals. Our use of these treatments is often based on multinational or foreign clinical studies. Oncologists are, to varying degrees, reliant on how the studies are interpreted by the writers of journal editorials, clinical guidelines and opinion pieces. Therefore it is important that these guidelines are balanced and evidence based. We have examined in detail one of the most influential and wide ranging clinical guidelines used in oncology, The American Society of Clinical Oncology (ASCO) 2006 Update of Recommendations for the use of White Blood Cell Factors: An Evidence-Based Clinical Practice Guideline. We have discussed in detail some of the controversial recommendations in this guideline and have exposed what we believe are some flaws in these recommendations. We would urge that we continue to be rigorous in our oversight of international research agendas and international clinical guidelines in the future. [ABSTRACT FROM AUTHOR]

Combination chemotherapy used to treat patients with aggressive non-Hodgkin's lymphoma is associated with neutropenia and subsequent infection, hospital admission and treatment delays. Haematopoietic growth factors (HGF) can prevent neutropenia and improve quality of life. We undertook a meta-analysis of six randomised and one nonrandomised trials to quantify the effect in previously untreated patients, and a simple cost-effectiveness analysis. The trials compared HGF plus chemotherapy with chemotherapy alone. In total, there were 779 patients aged between 15 and 82 years. Haematopoietic growth factors was associated with a statistically significant 44% reduction in the incidence of severe neutropenia (neutrophil count <0.5 × 109?l-1), a 60% reduction in the number of hospital admissions due to infection, an 80% reduction in the number of patients who had a treatment delay due to neutropenia and a 50% reduction in hospital stay. These data together with UK G-CSF drug costs were combined to develop a simple cost-effectiveness model, based on direct costs. Given the current cost of G-CSF, it would only be cost-effective among patients in which high rates of hospital stay due to neutropenia or infection are expected. Alternatively, if the cost could be reduced then all patients may be able to obtain the benefits. However, the evidence that prophylactic HGFs are clinically worthwhile is clear.British Journal of Cancer (2004) 90, 1302-1305. doi:10.1038/sj.bjc.6601708 www.bjcancer.com Published online 2 March 2004 [ABSTRACT FROM AUTHOR]

G-CSF is used to enhance hemato- poietic recovery after autologous stem cell transplantation (ASCT), but the optimal dose of G-CSF during engraft- ment has not been established. The medical cost of ASCT is a serious financial burden in developing countries, and G-CSF is the most costly drug used in this procedure. We evaluated whether a lower, vial-size fitted dose of lenograstim is clinically equivalent to a higher fixed dose. A prospective randomized study was performed on 33 patients (11 non-Hodgkin's lymphoma, 8 multiple myeloma, 14 breast cancer) undergoing ASCT. Patients were randomly administered 100 µg or 250 µg lenograstim daily starting on the next day of ASCT, with a minimum infusion of 3 × 106 CD34+ cells per kg. For both lenograstim doses, median time to neutrophil engraftment was 9 days and median time to PLT engraftment was 11 days. Episodes of clinically documented infections were 10 per 379 patient-days in the 100 µg per day group and 10 per 320 patient-days in the 250 µg per day group. There were no between-group differences in requirements for transfusion of RBCs or PLTs. Duration of hospitalization was 16 days for the 100 µg per day group and 17 days for the 250 µg per day group. Daily lenograstim dose per patient's body weight and total amount of lenograstim used during ASCT were both significantly lower in the 100 µg per day group. Administration of 100 µg per day of lenograstim showed comparable clinical efficacy to 250 µg per day lenograstim for immediate hematopoietic recovery after ASCT. Use of the lower dose was associated with lower overall lenograstim usage and lower cost. [ABSTRACT FROM AUTHOR]

In children and adolescents, prophylactic application of G-CSF after myelosuppressive chemotherapy reduces the duration of neutropenia, of hospitalization, and of parenteral antibiotic treatment. In acute lymphoblastic leukemia, non-Hodgkin lymphoma, and solid tumors, G-CSF support allows dose intensification of chemotherapy. On the other hand, each G-CSF injection causes pain and costs. We set up the hypothesis that besides strategies as restricted indications, delayed start, lower doses, and stringent rules for discontinuation, individualized timing of blood count might optimize G-CSF prophylaxis. We randomized 64 cycles of G-CSF prophylaxis in eight children and adolescents being treated for acute lymphoblastic leukemia or solid tumors to standard twice a week or to individually timed blood counts. Primary study endpoints were the numbers of G-CSF doses and of blood counts, and the total costs of G-CSF support. Per cycle, individual timing of blood count resulted in a median of one G-CSF injection fewer [estimated population median (EPM) 1.40, 95% confidence interval (CI) 0.57–2.20] and one blood count fewer (EPM 1.00, 95% CI 0.74–1.33). The total costs of G-CSF support and of blood counts were thereby reduced by a median of US $ 152 per cycle (EPM 191, 95% CI 97–318). The results of this study suggest that individual timing of blood counts during prophylactic G-CSF support in children and adolescents undergoing chemotherapy for malignant disease can significantly reduce the number of injections and blood counts performed, thus resulting in less pain and lower costs. These findings need confirmation in a larger randomized trial. [ABSTRACT FROM AUTHOR]

Rectally administered medications are essential in palliative medicine, particularly in the last days of life. They are underutilized. The pharmacology of rectally administered medications relates not only to the medication but also to the suppository base, additives, drug ionization, p K a, absorptive surface of the rectum, and rectal health. The pharmacokinetics may differ from those of orally administered medications owing to reduced hepatic first-pass clearance. In this review the pharmacology of rectally administered palliative medications is reviewed and the use of individual drugs is outlined. [ABSTRACT FROM AUTHOR]

The aim of this trial was to compare the severity of neutropenia, the frequency of hospital admission for fever or infection, and the use of antibiotics among patients treated with a standard dose of lenograstim (263 µg/day of Euprotin) and others treated with half of this dose (131.5 µg/day) and the cost-effectiveness of each of the two doses. In this single-center study, 44 patients with solid tumors, who were all receiving standard-dose chemotherapy regimens following previous neutropenia or were at high risk of neutropenia, were randomized to receive lenograstim at a dose of 263 µg or 131.5 µg daily in the first cycle and then crossed over to the alternate dose for the following cycle. Crossover to the alternate dose was repeated for patients who received more than two cycles. Lenograstim was administered from day +5 to day +14. The absolute neutrophil count (ANC) was assessed on days +5, +8, +12 and +15 of each cycle. Statistical analysis was performed using a general lineal model for repeated samples. In all, 120 cycles were administered, with a median of 3 cycles (range 1–6). Only 4 patients received only 1 cycle. No statistically significant difference ( P=0.324) in ANC was observed between standard-dose (mean 5.3, 10.7, 8.3, 11.4×109/l) and low-dose (5.0, 8.6, 5.4, 7.5×109/l) treatment at days +5, +8, +12 and +15. Neutropenia grade III–IV was more common in patients receiving the low than in those receiving the standard dose of lenograstim (20% vs 12%, respectively), but the difference did not reach statistical significance ( P=0.1). The incidence of fever and frequency of hospital admission were not affected by the dose of lenograstim: 3 patients presented with fever with the standard dose (all of those were admitted to hospital) and 2 patients with the low dose (1 was admitted). ANC in both groups (standard and low doses) was independent of chemotherapy line (first versus second or more). Lenograstim at a dose of 131.5 µg/day is as effective as the standard dose in limiting the severity of neutropenia and in preventing episodes of fever and hospital admissions after chemotherapy for solid tumors. The lower dose of lenograstim is cost-effective in neutropenia prophylaxis. Starting its administration on day +5 reduces costs while maintaining efficacy. [ABSTRACT FROM AUTHOR]

Lenograstim is the glycosylated recombinant form of human granulocyte colony stimulating factor. The drug is used to reduce the risk of life-threatening infection in patients with neutropenia, particularly after cytotoxic chemotherapy. Lenograstim accelerates neutrophil recovery significantly after chemotherapy, with beneficial effects on clinical end-points such as incidence of laboratory-confirmed infection and length of hospital stay. Chemotherapy dose intensity has also been increased in patients receiving lenograstim, notably those with breast or small cell lung cancer, although improvements in tumour response and survival have not been demonstrated. Lenograstim also assists neutrophil recovery in patients undergoing bone marrow transplantation, and stimulates the production of peripheral blood stem cells (PBSCs) for autologous transfusion after aggressive chemotherapy. Lenograstim also mobilises CD34+ cells more efficiently in unit dose terms than filgrastim and has been used successfully to mobilise PBSCs from healthy donors for allogeneic transplantation. Randomised trials have shown increases in rates of disease remission after lenograstim therapy in patients with acute myeloid leukaemia, with no evidence of stimulation of malignant blasts. The drug has also shown potential in the mobilisation of nonmalignant PBSCs for autotransplantation in patients with chronic myeloid leukaemia. Other studies show efficacy of lenograstim in patients with acute lymphoblastic leukaemia, aplastic anaemia, in children with severe chronic neutropenia and in the reversal of neutropenia related to antiretroviral therapy in patients with AIDS, although data are not extensive. Cost analyses of lenograstim have been carried out from a hospital perspective, although results have been inconclusive. Cost-effectiveness or cost-benefit data are lacking at present. Lenograstim is well tolerated, with bone pain and injection site reactions being reported most frequently in clinical trials. Conclusions: Lenograstim has been confirmed as a valuable adjunct to minimise the haematological toxicity of myelosuppressive chemotherapy in patients with malignant disease. The drug also enhances neutrophil recovery in patients undergoing stem cell rescue, and assists PBSC mobilisation. Data indicate clinical benefit with lenograstim in myeloid disorders, with no evidence of malignant blast cell proliferation. Further studies are required to assess more fully the pharmacoeconomic implications of the use of lenograstim and other recombinant growth factors, to provide more data on the efficacy of the drug in the management of disease-related neutropenia, and to clarify fully its position relative to filgrastim. [ABSTRACT FROM AUTHOR]

Clonal T cell populations with idiotype specificity are present in the peripheral blood of a proportion of patients with multiple myeloma. We have identified the presence of both T cell sub-populations with a specificity for autologous immunoglobin fragments and T cell receptor β gene rearrangements in peripheral blood samples of patients with myeloma. T cell receptor β gene rearrangements were detected in 38 of 119 patient samples (32%) and were more common in progressive disease (70%), than at diagnosis (25%) or in stable disease (23%). The 38 patients who had T cell receptor β gene rearrangements detected at any time had a better overall survival (median not yet achieved) than the patients who never had rearrangements detected (median 45 months, n = 49; χ[SUP2] = 6.2, P < 0.01). All 12 patients with T cell receptor β gene rearrangements at diagnosis are still alive whereas the median survival for 28 patients with a germline configuration at diagnosis was 40 months (χ[SUP2] = 5.8, P > 0.01). The presence of T cell receptor β gene rearrangements even conferred a survival advantage during progressive disease (median survival 44 months vs 19 months; χ[SUP2] = 8.7, P < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin fragments demonstrated idiotype-reactive T cells in the peripheral blood of five out of 15 patients all of whom had T cell gene rearrangements. The remaining 10 patients had neither idiotype-reactive T cells nor a detectable T cell receptor β gene rearrangement in concurrent samples. Thus in patients with myeloma there was a good correlation between the presence of T cell receptor β gene rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell receptor β gene had a significantly better prognosis. [ABSTRACT FROM AUTHOR]

Induction therapy of acute myeloid leukaemia (AML) with standard-dose chemotherapy will result in approximately 64% of patients achieving a complete remission (CR). New drugs which are active in induction therapy in randomised clinical trials are etoposide, idarubicin and high dose cytarabine. Intensification of induction treatment with etoposide or high-dose cytarabine does not appear to alter the CR rate but prolongs remission and has some impact on survival. High-dose cytarabine in induction combinations increase relapse-free survival compared to standard approaches. These induction results appear to parallel results obtained with post-remission therapies intensified with high-dose cytarabine. These studies provide clinical evidence that intensified induction with cytarabine in AML influences subsequent outcome but is more toxic, gives more profound myelosuppression post-remission and has benefit confined to younger patients. [ABSTRACT FROM AUTHOR]

Discusses the use of colony stimulating factors (CSFs) to reduce the duration of chemotherapy-induced neutropenia. High cost of CSFs; Study to determine if lower dosages were as effective as the standard dose; Conclusion that lower than conventional doses are comparable in clinical efficacy to standard doses in patients with prolonged cytotoxic-induced neutropenia.