Intensity Of Neutropenia Research Articles

Homeopathic supportive care protocol for oral inhibitors of cyclin dependent kinases 4 and 6 (CDK 4/6) in postmenopausal hormone-receptor-positive advanced breast cancer

Summary Cyclin-dependent kinase inhibitors 4 and 6 are a new therapeutic class and are indicated for the treatment of postmenopausal hormone-receptor-positive, HER-2-negative, advanced breast cancer. Generally well tolerated, the major side effect is grade 3 neutropenia, which occurs in two-thirds of patients, requiring reduction, spacing out, or even discontinuation of treatment. The study of the physio-pathological mechanism of hematopoietic toxicity, the comparison with homeopathic Materia Medica and our clinical experience enabled us to identify and retain a specific homeopathic therapeutic protocol. The combination of Natrum muriaticum 7c, 3 pills in the morning, Meduloss 8 DH, 15 drops in the afternoon and Silicea 7c, 3 pills in the evening, prescribed as soon as possible and for the whole duration of the treatment, makes it possible to reduce the intensity of neutropenia and concomitant infections. The daily addition of the hetero-isotherapic anti-CDK 4/6 in 7c has sometimes been necessary in cases of persistent neutropenia. Well tolerated by patients and without drug interference, this homeopathic protocol can be prescribed by any doctor. In our experience, homeopathic support treatment makes it possible to avoid the spacing out of sessions, the reduction of dosage, and so represents increased opportunities for the patients. Clinical studies will be needed to verify the favourable clinical results obtained.

Impact of the D-index deduced from duration and intensity of neutropenia following chemotherapy on the risk of invasive fungal infection in pediatric acute myeloid leukemia.

Pediatric patients with acute myeloid leukemia (AML) are at high risk of invasive fungal infection (IFI). In adult patients, the D-index, which reflects the duration and intensity of neutropenia, was reported as a predictive factor of IFI after induction therapy for AML. The aim of this study was to assess whether the D-index is a predictive factor for IFI in pediatric AML. We define the D-index as the area over the neutrophil curve during neutropenia. Ninety-two courses of chemotherapy performed for 24 consecutive patients with AML undergoing chemotherapy at Sapporo Hokuyu Hospital between April 2007 and March 2017 were analyzed. We also evaluated the utility of the cumulative D-index (c-D-index) from the start of neutropenia until the clinical manifestation of IFI in these patients. The D-index and c-D-index were compared between courses with and without IFI episodes. The median D-index and c-D-index in 6 courses with IFI episodes were 12,816 (range 9500-27,412) and 7250 (range 3987-16,273), respectively, which was not statistically higher than the median D-index [10,127 (range 3788-20,897)] in 86 courses without IFI episodes (P = 0.081 and P = 0.108, respectively). Unlike in adult cases, neither the D-index nor c-D-index reflected the risk of IFI in pediatric AML.

First Year Experience Of Subcutaneous Bortezomib Use In a University Teaching Hospital

IntroductionSubcutaneous (SC) injection of bortezomib was reported to be safe and effective in myeloma patients. In September 2012, we standardised all bortezomib containing-protocols at our centre and changed the route of administration form intravenous (IV) to subcutaneous. This way of administration is more convenient for patients and staff and is reported to decrease the rate of peripheral neuropathies. ObjectivesThis retrospective study aimed to describe the safety of this new administration technique, specifically regarding change in blood pressure and hematologic toxicity. Blood pressure (BP) was measured before and after each SC injection to evaluate the risk of hypotension, an adverse reaction frequently reported with IV bortezomib administration. Secondly, we wanted to analyse the rate of neutropenia and thrombocytopenia during the treatment to see if a complete blood count (CBC) is needed before every injection, versus only once weekly. Other adverse events were also collected. MethodsThis retrospective study included all patients who received bortezomib for multiple myeloma or amyloidosis at the Centre hospitalier de l'Université de Montréal (CHUM) between June 1, 2012 and May 31, 2013. Date was collected through medical and pharmaceutical patient records. Our local ethics board approved this study. ResultsA total of 45 patients received bortezomib for MM or amyloidosis with a median age of 68 years (SD ± 9.3) and 53.3 % were male. Patients received bortezomib in various protocols including Vel-Dex (42.2%), VMP (44.4%) and CyBorD (13.3%). The median starting dose of bortezomib was 1.3 mg/m2(SD ± 0.13). Patients received SC only bortezomib injections (71.1%) or IV only (15.6%) or were switched from IV to SC (13.3%) for a total of 157 cycles (786 doses). A total of 444 BP values before and 425 BP values after SC bortezomib were analysed. No significant difference was detected between the average systolic BP (125 vs 125; p=0.76), diastolic BP (70 vs 71; p=0.77) or heart rate (79 vs 78; p=0.89) between the 2 measurements. Hypotension, defined as a drop of 20 mmHg of systolic BP, occurred 18 times (4.2%) but systolic BP was never below 90 mmHg. One patient had a severe dysautomia, possibly related to bortezomib that required the discontinuation of the treatment. At our center, CBC are performed prior to each bortezomib dose. Neutropenia occurred in 10 % of the total doses received. Risk factors influencing neutropenia were the use of oral alkylating agent (melphalan and cyclophosphamide) in the regimen and baseline neutrophil count less than 2.0 x 109. Many patients also received bortezomib for a relapsed / refractory disease and were previously exposed to many lines of therapy. Thrombocytopenia occurred in 7,2% of doses received. Cutaneous toxicity occurred mostly with the first patients treated with the SC technique. With time, nursing changed their technique and further skin reactions were less reported. Neuropathy occurred in 21 patients (13 SC, 4 IV, 4 IV to SC), caused dose reductions in 7 patients (2 SC, 2 IV, 3 IV to SC) and treatment discontinuation in 2 patients (SC).Table IRates and intensity of hematological problems of patients taking SC bortezomibCharacteristicsCyBorD SCVel-Dex SCVMP SCTotalNumber of patients6161638Number of doses75223241539Neutropenia (all grades)23 (30.7%)7 (3.1%)24 (10.0%)54 (10.0%)Grade II (n = 1.0 – 1.49)15 (20.0%)6 (2.7%)17 (7.1%)38 (7.1%)Grade III (n = 0.5 – 0.99)8 (10.7%)1 (0.4%)5 (2.1%)14 (2.6%)Grade IV (n < 0,5)0 (0.0%)0 (0.0%)2 (0.8%)2 (0.4%)Thrombocytopenia (all grades)9 (12.0%)9 (4.0%)21 (8.7%)39 (7.2%)Grade II (Plt = 50 – 74)5 (6.7%)6 (2.7%)15 (6.2%)26 (4.8%)Grade III (Plt = 25 – 49)2 (2.7%)3 (1.3%)3 (1.2%)8 (1.5%)Grade IV (Plt < 25)2 (2.7%)0 (0.0%)3 (1.2%)5 (0.9%) ConclusionOur results demonstrate SC bortezomib was well tolerated. The rates of hypotension was quite low. Also rates and intensity of neutropenia and thrombocytopenia varied among different bortezomib containing regimens. Because of the low rate of profound neutropenia, Vel-Dex and VMP protocols can be modified to decrease the number of CBC to once weekly during the cycle rather than before every injection. More data are needed with CyBorD protocol before drawing any conclusions. Disclosures:Adam:Jansen Ortho: Honoraria. Lemieux-Blanchard:Celgene: Honoraria. Lemieux:Jansen Ortho: Honoraria.

MCP-1 and VCAM-1 As Pathological Markers In a Patient With Infection Induced Hemophagocytic Syndrome After Stem Cell Transplantation

The origin of macrophage in HPS after SCT was also very interesting to be examined. Material and MethodThe characteristics of the patients and the information of infections were summarized in Table 1. [Display omitted] 1. IL6, MCP|1, VCAM-1, TNF-a, RANTES, sE-selectin and HMGB1were measured by immunosorbent assay of cryopreserved blood samples.2. In situ hybridization was performed to paraffin sections of aspirated bone marrow cells whose sex chromosome were dyed in different colors to detect the Y chromosome in macrophages.Result yperferritinemia and high levels of serum soluble interleukin-2 receptor were recognized. On day14, initial neutrophil engraftment and complete chimerism were successfully achieved. High dose mPSL 1000mg/day was administered several times but phagocytosis was little better and finally peripheral bloods were completely deprived (secondary graft failure). About sex chromosome, mononuclear cells had XX (donor type) but the phagocytes held original chromosome XY (recipient type). MCP-1 and VCAM-1 were rising up steadily but another adhesion molecule E-selectin or cytokines were not elevated (Fig1.). The same movement of MCP-1 and VCAM-1 was recognized in the case of patient#4 EBV-associated HPS who had immunological dysfunction with Bechet disease. The following two cases, patient #2 and #3 who received haplo-mini-SCT showed completely different cytokine movement. Patient #3 who was 75y.o.female with AM/MDS was infected with multiple candida species after haplo-mini-transplantation. MPC-1 inversely decreased less than 400 pg/ml. Patient#2 who was 60y.o. female with AML(M1) de Montréal (CHUM) between June 1, 2012 and May 31, 2013. Date was collected through medical and pharmaceutical patient records. Our local ethics board approved this study. ResultsA total of 45 patients received bortezomib for MM or amyloidosis with a median age of 68 years (SD ± 9.3) and 53.3 % were male. Patients received bortezomib in various protocols including Vel-Dex (42.2%), VMP (44.4%) and CyBorD (13.3%). The median starting dose of bortezomib was 1.3 mg/m2(SD ± 0.13). Patients received SC only bortezomib injections (71.1%) or IV only (15.6%) or were switched from IV to SC (13.3%) for a total of 157 cycles (786 doses). A total of 444 BP values before and 425 BP values after SC bortezomib were analysed. No significant difference was detected between the average systolic BP (125 vs 125; p=0.76), diastolic BP (70 vs 71; p=0.77) or heart rate (79 vs 78; p=0.89) between the 2 measurements. Hypotension, defined as a drop of 20 mmHg of systolic BP, occurred 18 times (4.2%) but systolic BP was never below 90 mmHg. One patient had a severe dysautomia, possibly related to bortezomib that required the discontinuation of the treatment. At our center, CBC are performed prior to each bortezomib dose. Neutropenia occurred in 10 % of the total doses received. Risk factors influencing neutropenia were the use of oral alkylating agent (melphalan and cyclophosphamide) in the regimen and baseline neutrophil count less than 2.0 x 109. Many patients also received bortezomib for a relapsed / refractory disease and were previously exposed to many lines of therapy. Thrombocytopenia occurred in 7,2% of doses received. Cutaneous toxicity occurred mostly with the first patients treated with the SC technique. With time, nursing changed their technique and further skin reactions were less reported. Neuropathy occurred in 21 patients (13 SC, 4 IV, 4 IV to SC), caused dose reductions in 7 patients (2 SC, 2 IV, 3 IV to SC) and treatment discontinuation in 2 patients (SC).Table 1Rates and intensity of hematological problems of patients taking SC bortezomibCharacteristicsCyBorD SCVel-Dex SCVMP SCTotalNumber of patients6161638Number of doses75223241539Neutropenia (all grades)23 (30.7%)7 (3.1%)24 (10.0%)54 (10.0%)Grade II (n = 1.0 – 1.49)15 (20.0%)6 (2.7%)17 (7.1%)38 (7.1%)Grade III (n = 0.5 – 0.99)8 (10.7%)1 (0.4%)5 (2.1%)14 (2.6%)Grade IV (n < 0,5)0 (0.0%)0 (0.0%)2 (0.8%)2 (0.4%)Thrombocytopenia (all grades)9 (12.0%)9 (4.0%)21 (8.7%)39 (7.2%)Grade II (Plt = 50 – 74)5 (6.7%)6 (2.7%)15 (6.2%)26 (4.8%)Grade III (Plt = 25 – 49)2 (2.7%)3 (1.3%)3 (1.2%)8 (1.5%)Grade IV (Plt < 25)2 (2.7%)0 (0.0%)3 (1.2%)5 (0.9%) ConclusionOur results demonstrate SC bortezomib was well tolerated. The rates of hypotension was quite low. Also rates and intensity of neutropenia and thrombocytopenia varied among different bortezomib containing regimens. Because of the low rate of profound neutropenia, Vel-Dex and VMP protocols can be modified to decrease the number of CBC to once weekly during the cycle rather than before every injection. More data are needed with CyBorD protocol before drawing any conclusions. [Display omitted] Disclosures:Adam: Jansen Ortho: Honoraria. Lemieux-Blanchard: Celgene: Honoraria. Lemieux: Jansen Ortho: Honoraria.

Valoración inicial del paciente neutropénico con fiebre: cuantificación del riesgo

Infection in immunocompromised hosts represents a serious clinical situation due the high morbidity and mortality it produces and is one of the most frequent complications in patients with cancer. In patients treated with chemotherapy the risk of infection mainly depends on the duration and intensity of neutropenia. It is essential to evaluate which pathogens are involved so that the most appropriate treatment can be selected a priori, as well as to determine the patient's general clinical status so that more or less aggressive treatment can be provided from the beginning, bearing in mind that "low risk" patients can be managed in the home. These questions can be determined by evaluating the patient's clinical history, physical examination, laboratory investigations, and radiological tests. Prompt initiation of broad-spectrum antibiotic therapy adapted to the the patient's risk is crucial.

Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE)

Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in which infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. We have retrospectively analyzed 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patients died due to infectious complications. The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens.

Virulence ofPseudomonas aeruginosain a Murine Model of Gastrointestinal Colonization and Dissemination in Neutropenia

Pseudomonas aeruginosa bacteremia in cancer patients develops from initial gastrointestinal (GI) colonization with translocation into the bloodstream in the setting of chemotherapy-induced neutropenia and GI mucosal damage. We established a reproducible mouse model of P. aeruginosa GI colonization and systemic spread during neutropenia. Mice received 2 mg of streptomycin/ml of drinking water and 1,500 U of penicillin G/ml for 4 days and then ingested 10(7) CFU of P. aeruginosa per ml of drinking water for 5 days. After GI colonization levels were determined, cyclophosphamide (Cy) was then injected intraperitoneally (i.p.) three times every other day or an antineutrophil monoclonal antibody, RB6-8C5, was injected i.p. once. Dissemination was defined by the presence of P. aeruginosa in spleens of moribund or dead mice. In this mouse model, P. aeruginosa colonizes the GI tract and then disseminates systemically once Cy or RB6-8C5 is administered. The duration and intensity of neutropenia, related to Cy dose, was found to be a means to compare the virulence of different P. aeruginosa strains, as exhibited by comparisons of strains lacking or producing the virulence-enhancing ExoU cytotoxin. The lipopolysaccharide outer core polysaccharide and O side chains were critical in establishing GI colonization, and P. aeruginosa mutants lacking the aroA gene (necessary for synthesizing aromatic amino acids) were able to establish GI colonization but unable to disseminate. Both the colonization and dissemination phases of P. aeruginosa pathogenesis can be studied in this model, which should prove useful for evaluating pathogenesis, therapies, and associated means to control P. aeruginosa nosocomial infections.

Mechanism-based models for topotecan-induced neutropenia

A semiphysiologic pharmacokinetic-pharmacodynamic model was applied to describe topotecan-induced neutropenia, to quantify interindividual and intraindividual pharmacodynamic variability, and to study the effect of covariates on the model. Data were obtained from patients treated with topotecan given either orally (118 patients) or intravenously (71 patients), according to different schedules (5 to 21 consecutive days), with or without cisplatin. The model mimics the maturation chain of neutrophils. Topotecan concentration-time profiles affected the proliferation of neutrophil precursors (sensitive cells) through an inhibitory linear model (topotecan is assumed to induce cell loss by a function, E drug, proportional to the topotecan concentration in the central compartment: E drug = Slope . Concentration). The topotecan plasma concentration versus time profile was generated for each patient by modeling the data according to a 2-compartment pharmacokinetic model and first-order absorption for oral administration by use of NONMEM. The model described the time course of neutrophil values well. Topotecan neutropenic effect exhibited a large interpatient variability (coefficient of variation of 82% for the slope values). The oral route was associated with a 43% lower value for slope, corresponding to a lower toxicity. The combination with cisplatin increased the neutropenic effect compared with topotecan alone by a factor 3.5. The intrapatient variability between cycle 1 and cycle 2 on slope was lower for the intravenous administration than for the oral administration. By application of the model to a new weekly schedule of topotecan, neutrophil values at the nadir were consistent with those observed during a phase I study of this regimen. This model can be used to describe both the duration and intensity of neutropenia; the area between the curve of neutrophil count versus time and a critical neutrophil count (such as 0.500 x 10(3) /mm 3 ) would be a better toxic endpoint than the unique observed value of neutrophil at nadir. The model may be used to predict neutropenia corresponding to regimens of topotecan not yet explored.