ABSTRACT
BACKGROUND: Results from recent studies show that less intravitreal injections are often performed in everyday practice than in controlled trials, which subsequently leads to worse treatment success. In this study we analyzed the introduction of a more stringent organization of treatment using workflow optimization and new IT systems and analyzed the effect on treatment continuity. MATERIAL AND METHODS: In the second quarter of 2019 a new medical practice management software and a software for automated injection planning were implemented. There was also a change of the treatment regimen from pro re nata (PRN) to treat and extend (T&E ). We analyzed the results of the patients regarding the frequency of injections and treatment controls three quarters before (Q3/2018-Q1/2019) and three quarters after the change (Q2/2019-Q4/2019). Treatment-naive and pretreated patients were analyzed. RESULTS: In group 1 (Q3/2018-Q1/2019) the average number of injections per quarter was 1.74 (SDâ¯= 0.4). Eyes of patients from group 2 (Q2/2019-Q4/2019) received on average 2.17 (SDâ¯= 0.3) injections. The number of check-ups per quarter was 1.71 (SDâ¯= 0.3) before the introduction, and thereafter 2.16 (SDâ¯= 0.3). There was a significant increase in the number of OCTs from 1.18 (SDâ¯= 0.2) to 1.98 (SDâ¯= 0.3). The visual acuity was stable in both groups. CONCLUSION: We were able to show that the introduction of the medical practice management software and the change of the regimen from PRN to T&E can achieve numbers of injections, check-ups and OCT similar to those in studies. A standardized procedure facilitates efficient treatment planning and enables a better patient management.
Subject(s)
Angiogenesis Inhibitors , Ranibizumab , Angiogenesis Inhibitors/therapeutic use , Follow-Up Studies , Humans , Intravitreal Injections , Retrospective Studies , Tomography, Optical Coherence , Treatment OutcomeABSTRACT
BACKGROUND: We introduced a video consultation (VC) during the coronavirus (COVID-19) pandemic in an ophthalmology practice with eight doctors to ensure continuous ophthalmological care, infection prophylaxis and to compensate a decreased number of patient presentations. OBJECTIVE: Evaluation of the most common reasons for patient presentations in the VC, the proportion of re-presentations in the practice despite VC, practical challenges associated with the introduction of VC and patient satisfaction. MATERIAL AND METHODS: Patients with a recent acute visual deterioration and severe eye pain were excluded from the VC. The VC were carried out by a trained specialist in ophthalmology. A questionnaire with eight questions was completed after the VC appointment in order to evaluate the proportion of completed VC and patient satisfaction. RESULTS: We included 29 (13 male, Ø 52.6 years, 16 female, Ø 64.7 years) patients in this analysis. The VC could be performed with 68.97% of the participants who rated their overall experience with an average grade of 1.6 (1 very good to 6 insufficient) and all of them indicated that they would recommend the VC. Of presentations in VC 70% were related to the symptoms of the anterior eye segment. In 70% of the cases no re-presentations took place in the unit. CONCLUSION: Our study represents a significant practical application of VC for the management of non-urgent ocular conditions with maximum infection prophylaxis. The introduction of VC was severely limited by technological or user-related issues by the establishment of video connections. Patient satisfaction with VC was high to very high.
Subject(s)
COVID-19 , Ophthalmology , Telemedicine , Female , Humans , Male , Pandemics , Patient Satisfaction , SARS-CoV-2ABSTRACT
BACKGROUND: We introduced a video consultation (VC) during the coronavirus (COVID-19) pandemic in an ophthalmology practice with eight doctors to ensure continuous ophthalmological care, infection prophylaxis and to compensate a decreased number of patient presentations. OBJECTIVE: Evaluation of the most common reasons for patient presentations in the VC, the proportion of re-presentations in the practice despite VC, practical challenges associated with the introduction of VC and patient satisfaction. MATERIAL AND METHODS: Patients with a recent acute visual deterioration and severe eye pain were excluded from the VC. The VC were carried out by a trained specialist in ophthalmology. A questionnaire with eight questions was completed after the VC appointment in order to evaluate the proportion of completed VC and patient satisfaction. RESULTS: We included 29 (13 male, Ø 52.6 years, 16 female, Ø 64.7 years) patients in this analysis. The VC could be performed with 68.97% of the participants who rated their overall experience with an average grade of 1.6 (1 very good to 6 insufficient) and all of them indicated that they would recommend the VC. Of presentations in VC 70% were related to the symptoms of the anterior eye segment. In 70% of the cases no re-presentations took place in the unit. CONCLUSION: Our study represents a significant practical application of VC for the management of non-urgent ocular conditions with maximum infection prophylaxis. The introduction of VC was severely limited by technological or user-related issues by the establishment of video connections. Patient satisfaction with VC was high to very high.
Subject(s)
Betacoronavirus , Coronavirus Infections , Ophthalmology , Pandemics , Patient Satisfaction , Pneumonia, Viral , COVID-19 , Female , Humans , Male , Middle Aged , SARS-CoV-2 , TelemedicineABSTRACT
Background: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC. Patients and methods: Patients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1 : 1 : 1) nab-P 125 mg/m2 plus C AUC 2, nab-P 125 mg/m2 plus G 1000 mg/m2, or G 1000 mg/m2 plus C AUC 2, all on days 1, 8 q3w. Phase II primary end point: investigator-assessed progression-free survival (PFS); secondary end points included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety. Results: In total, 191 patients were enrolled (nab-P/C, n = 64; nab-P/G, n = 61; G/C, n = 66). PFS was significantly longer with nab-P/C versus nab-P/G [median, 8.3 versus 5.5 months; hazard ratio (HR), 0.59 [95% CI, 0.38-0.92]; P = 0.02] or G/C (median, 8.3 versus 6.0 months; HR, 0.58 [95% CI, 0.37-0.90]; P = 0.02). OS was numerically longer with nab-P/C versus nab-P/G (median, 16.8 versus 12.1 months; HR, 0.73 [95% CI, 0.47-1.13]; P = 0.16) or G/C (median, 16.8 versus 12.6 months; HR, 0.80 [95% CI, 0.52-1.22]; P = 0.29). ORR was 73%, 39%, and 44%, respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic. Conclusions: First-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile versus nab-P/G or G/C.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Triple Negative Breast Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Albumins/administration & dosage , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/methods , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Mastectomy , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Progression-Free Survival , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology , GemcitabineABSTRACT
This study was performed to estimate the effect of the retrieval process on mortality for patients admitted to a mixed adult intensive care unit (ICU) compared with propensity-matched, non-retrieved controls. Patients retrieved to the Royal Adelaide Hospital (RAH) ICU between 2011 and 2015 were propensity-score matched for age, gender, Aboriginal and Torres Strait Islander status, Acute Physiology and Chronic Health Evaluation (APACHE) III score and diagnostic group with non-retrieved ICU patients to estimate the average treatment effect of retrieval on hospital mortality. Factors associated with mortality in those retrieved were assessed by multiple logistic regression. Retrieved patients comprised 1,597 (14%) of 11,641 index ICU admissions; this group were younger, mean (standard deviation) 53 (18.5) versus 59 (17.7) years, had higher APACHE III scores, 61 (30.3) versus 56 (27.5), were more likely to be Indigenous (5.1% versus 3.7%) and to have sustained trauma (34% versus 9%). The average treatment effect for retrieval on hospital mortality, risk difference (95% confidence interval), was -0.7% (-2.8% to 1.3%), P=0.50. Variables independently associated with hospital mortality in those retrieved included age, APACHE III score and diagnostic category. Time from retrieval team activation to arrival with the patient, rural location, radial distance from the RAH and population size at the retrieval location were not significantly associated with mortality. The hospital mortality for retrieved patients was not significantly different when compared with propensity-matched controls. Mortality in those retrieved was associated with increasing age, APACHE III score and diagnostic category; however, was independent of time from team activation to arrival with the patient.
Subject(s)
Critical Care , Hospital Mortality , Patient Transfer , Adult , Age Factors , Aged , Female , Humans , Length of Stay , Logistic Models , Male , Middle Aged , Propensity ScoreABSTRACT
SETTING: Haiti has the highest burden of tuberculosis (TB) in the Americas, with an estimated prevalence of 254 per 100 000 population. The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, GHESKIO) conducted active case finding (ACF) for TB at the household level in nine slums in Port-au-Prince. OBJECTIVE: We report on the prevalence of undiagnosed TB detected through GHESKIO's ACF campaign. DESIGN: From 1 August 2014 to 31 July 2015, we conducted a retrospective cohort analysis using GHESKIO's ACF campaign data. All individuals who reported chronic cough (cough î¶2 weeks) were tested for TB at GHESKIO, and those aged î¶10 years were included in the analyses. RESULTS: Of 104 097 individuals screened in the community, 5598 (5%) reported chronic cough and satisfied the study inclusion criteria. A total of 1110 (20%) were diagnosed with active TB disease (prevalence of 1066/100 000). Of the 5472 (98%) patients tested for human immunodeficiency virus (HIV), 528 (10%) were HIV-positive; 143 (3%) patients were diagnosed with both diseases. CONCLUSION: Household-level screening for cough with TB and HIV testing for symptomatic patients was a high-yield strategy, leading to the detection of a prevalence of undiagnosed disease exceeding national estimates by more than four-fold for TB, and by five-fold for HIV.
Subject(s)
HIV Infections/diagnosis , Mass Screening/methods , Poverty Areas , Tuberculosis/diagnosis , Adolescent , Adult , Child , Chronic Disease , Cohort Studies , Cough/diagnosis , Cough/etiology , Female , HIV Infections/epidemiology , Haiti/epidemiology , Humans , Male , Prevalence , Retrospective Studies , Tuberculosis/epidemiology , Young AdultABSTRACT
AIM: For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. METHODS: Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. RESULTS: From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P <0.001) and significantly more grade ≥3 neutropenia events were documented (respectively 30.7% vs 4.0%, P <0.001). The prophylactic use of G-CSF was similar; 26.0% in Asians and 28.0% in Caucasian (P = 0.764). There were no differences in nonhematological toxicities. No significant difference in disease-free survival was observed between Asians and Caucasians (log-rank P = 0.910). CONCLUSIONS: Ethnic differences in toxicity profile exist between Asian and Caucasian patients given adjuvant TC. Over 30% Asians but less than 5% Caucasians experienced grade ≥3 neutropenia.
Subject(s)
Breast Neoplasms/drug therapy , Taxoids/adverse effects , Asian People , Breast Neoplasms/pathology , Docetaxel , Female , Humans , Middle Aged , Retrospective Studies , White PeopleABSTRACT
Despite a paucity of data regarding both the incidence of ocular candidiasis and the utility of ophthalmic examination in critically ill patients, routine ophthalmic examination is recommended for critically ill patients with candidaemia. The objectives were to estimate the incidence of ocular candidiasis and evaluate whether ophthalmic examination influenced subsequent management of these patients. We conducted a ten-year retrospective observational study. Data were extracted for all ICU patients who were blood culture positive for fungal infection. Risk factors for candidaemia and eye involvement were quantified and details regarding ophthalmic examination were reviewed. Candida species were cultured in 93 patients. Risk factors for ocular candidiasis were present in 57% of patients. Forty-one percent of patients died prior to ophthalmology examination and 2% of patients were discharged before candidaemia was identified. During examination, signs of ocular candidiasis were only present in one (2.9%) patient, who had a risk factor for ocular candidiasis. Based on these findings, the duration of antifungal treatment for this patient was increased. Ocular candidiasis occurs rarely in critically ill patients with candidaemia, but because treatment regimens may be altered when diagnosed, routine ophthalmic examination is still indicated.
Subject(s)
Candidemia/complications , Candidiasis/epidemiology , Eye Infections, Fungal/epidemiology , Adult , Aged , Candidiasis/drug therapy , Candidiasis/etiology , Critical Illness , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/etiology , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
We investigated treatment effects by oestrogen receptor (ER) status among women with metastatic breast cancer (MBC) receiving capecitabine (C) plus docetaxel (D) or D alone in a randomised phase III trial. Data were retrospectively analysed from patients whose disease had recurred following (neo)adjuvant anthracyclines. ER status was identified in 356/506 patients. In patients with ER-positive tumours, median overall survival from enrolment was 17.7 months with CD versus 12.5 months with D (hazard ratio [HR] 0.65, 95% confidence interval [CI]: 0.47-0.89; P = 0.007) and median time to progression (TTP) was 6.8 and 5.4 months, respectively (HR 0.62, 95% CI: 0.46-0.84; P = 0.002). For patients with ER-negative tumours, significantly longer TTP was seen with CD (5.2 versus 3.5 months; HR 0.73, 95% CI: 0.53-0.98; P = 0.038). Whether there is an additional C to D treatment benefit in ER-positive versus ER-negative MBC requires further evaluation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/chemistry , Breast Neoplasms/drug therapy , Receptors, Estrogen/analysis , Taxoids/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Disease-Free Survival , Docetaxel , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Kaplan-Meier Estimate , Middle Aged , Proportional Hazards Models , Receptors, Progesterone/analysis , Retrospective Studies , Taxoids/administration & dosage , Taxoids/adverse effects , Time FactorsABSTRACT
NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling pathways involved in tumor cell proliferation and metastasis and enhances anti-tumor immune responsiveness in tumor models. The addition of NOV-002 to chemotherapy has been shown to increase anti-tumor efficacy in animal models and some early phase oncology trials. We evaluated the clinical effects of NOV-002 in primary breast cancer, whether adding NOV-002 to standard preoperative chemotherapy increased pathologic complete response rates (pCR) at surgery, and determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and whether levels of myeloid derived suppressor cells (MDSC) were predictive of response. Forty-one women with newly diagnosed stages II-IIIc HER-2 negative breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC â T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered to detect a doubling of pCR rate from 16 to 32% with NOV-002 plus AC â T (α = 0.05, ß = 80%). Weekly complete blood counts were obtained as well as circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients with 40 evaluable tumors, 15 achieved a pCR (38%), meeting the primary endpoint of the trial. Concurrent NOV-002 resulted in pCR rates for AC â T chemotherapy higher than previously reported. Patients with lower levels of circulating MDSCs at baseline and on the last cycle of chemotherapy had significantly higher probability of a pCR (P = 0.02). Further evaluation of NOV-002 in a randomized study is warranted.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Doxorubicin/administration & dosage , Drug Combinations , Female , Glutathione Disulfide/administration & dosage , Humans , Immunity, Cellular/drug effects , Kaplan-Meier Estimate , Mastectomy , Middle Aged , Neoadjuvant Therapy , Neoplasm Invasiveness , Neoplasm Staging , Taxoids/administration & dosage , Treatment Outcome , Young AdultSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Estrogen Receptor Modulators/therapeutic use , Receptors, Estrogen/metabolism , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Methotrexate/administration & dosage , Precision Medicine , Randomized Controlled Trials as TopicABSTRACT
Soluble forms of some cell adhesion molecules (CAM), sICAM-1, sVCAM-1, and sE-selectin, are elevated in the sera and plasma of patients with inflammation, arthritis, diabetes, and cancer. Increased levels of these soluble molecules in patients with cancer have been shown to correlate with disease progression and survival. This suggests that increased expression of the soluble forms of CAMs may play an important role in cancer cell growth and metastasis and may be prognostic and/or predictive of malignant disease. In this retrospective study, we assessed the clinical significance of sICAM-1, sVCAM-1, and sE-selectin in 95 patients with metastatic breast cancer enrolled in clinical trials of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). The significance of soluble HER-2 (sHER-2) and sFAS status, determined in previous studies for this group of patients, was also included in this analysis. Univariate analysis showed that sICAM-1, sVCAM-1, sFas, sHER-2 positive status, and the presence of liver metastases were significant prognostic factors for both progression-free survival (PFS) and overall survival (OS) in the total patient group. In multivariable analysis, HER-2 and sFAS were shown to be independent prognostic factors for PFS and OS. Within the various treatment groups examined, sICAM-1 was a prognostic factor for clinical outcome for patients with metastatic breast cancer enrolled in trials with cyclophosphamide- and carboplatin-based or vinblastine-based HDC, but not in trials with paclitaxeland cyclophosphamide-based HDC.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms , E-Selectin/blood , Intercellular Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/blood , Adult , Breast Neoplasms/blood , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Clinical Trials, Phase II as Topic , Disease Progression , Female , Humans , Middle Aged , Neoplasm Metastasis , Prognosis , Receptor, ErbB-2/blood , Retrospective Studies , Stem Cell Transplantation , Survival Rate , Transplantation, Autologous , fas Receptor/bloodABSTRACT
Cryopreservation of stem cells after collection from peripheral blood or bone marrow for autologous transplantation necessitates protection with dimethyl sulfoxide (DMSO). Unfortunately, DMSO, when infused with the thawed cell suspension, may induce serious complications and side effects. To assess whether depletion of DMSO before autografting affects safety and efficacy, 56 consenting consecutive patients treated with high-dose chemotherapy and autologous blood stem cell transplantation were assigned to obtain either an untreated or DMSO-depleted autograft. On the day of transplantation, the cryopreserved cells were thawed and infused to the patient either immediately or after washing 3 times in normal saline supplemented with 6% anticoagulant citrate dextrose solution. Cell count with viability, clonogenic assay, and phenotyping were performed before and after thawing and after washing. Hematologic recovery, side effects, and complications were recorded. The in vitro and clinical data on 56 patients show that the depletion of DMSO in vitro before autografting does not induce a significant loss of cell number, viability, colony-forming unit-granulocyte-macrophage activity, or number of CD34(+) cells. Furthermore, it leads to a safe and sustained engraftment. The complications and side effects, as recorded by continuous monitoring, were substantially less; however, the procedure takes 3 to 4 hours of laboratory work per patient.
Subject(s)
Breast Neoplasms/therapy , Cryopreservation , Dimethyl Sulfoxide/adverse effects , Hematopoietic Stem Cells/cytology , Peripheral Blood Stem Cell Transplantation/methods , Adolescent , Adult , Breast Neoplasms/complications , Cell Count , Cell Survival , Female , Graft Survival , Hematopoietic Stem Cells/drug effects , Humans , Kinetics , Middle Aged , Peripheral Blood Stem Cell Transplantation/adverse effects , Transplantation Conditioning/methods , Transplantation, AutologousABSTRACT
The presence of cancer cells in autografts of breast cancer patients has been described to have prognostic value or directly lead to relapse. Previously, we demonstrated that apheresis products (APs) collected after induction chemotherapy have a significantly lower likelihood of tumor cell contamination. Here, we examine the prognostic value of micrometastases in autografts. Data from 83 patients with breast cancer treated with autologous blood stem cell transplantation were analyzed. Pan-cytokeratin-FITC conjugated antibodies were used to detect contaminating breast cancer cells in the APs. Progression and survival data analyzed on the basis of three or fewer cancer cells showed no significant differences in outcomes. Of the 83 patients, 11 had more than three cancer cells detectable in their APs. In total, 72 patients were shown to have less than three cells detectable. When patients with more than three cells were compared to patients with 0-3, we found statistically significant differences in progression-free survival. We also found a significant difference in overall survival (OS) between the two groups. No difference was observed in OS since the time of diagnosis. We conclude that patients with more than three contaminating cells in their APs have micrometastases and represent a poor prognosis group.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Component Removal , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Neoplasm Metastasis/pathology , Peripheral Blood Stem Cell Transplantation/mortality , Adult , Aged , Antibodies , Antigens, Neoplasm/blood , Antigens, Neoplasm/immunology , Breast Neoplasms/therapy , Cell Count , Disease-Free Survival , Female , Humans , Keratins/blood , Keratins/immunology , Middle Aged , Neoplastic Cells, Circulating/pathology , Prognosis , Retrospective Studies , Survival Analysis , Survival Rate , Transplantation, AutologousABSTRACT
Treatment of primary central nervous system lymphoma (PCNSL) with combined high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. In an attempt to improve upon these dismal results, we treated seven PCNSL patients with HD-MTX-based induction therapy followed by thiotepa, busulfan, cyclophosphamide (TBC), and autologous stem cell transplant (ASCT), without WBRT. Six of these patients had at least one of the following poor prognostic features: Karnofsky performance status (KPS)
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/therapy , Lymphoma/therapy , Stem Cell Transplantation , Adolescent , Adult , Brain/pathology , Brain Neoplasms/radiotherapy , Busulfan/administration & dosage , Central Nervous System Neoplasms/drug therapy , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma/drug therapy , Magnetic Resonance Imaging , Male , Prognosis , Radiotherapy/adverse effects , Thiotepa/administration & dosage , Transplantation, Homologous , Treatment OutcomeABSTRACT
INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a widely used technique for axillary staging in breast cancer patients. The principle to evaluate the axillary status of a breast cancer patient with a less invasive surgery than axillary lymph node dissection (ALND) meets the new minimally invasive concept in breast cancer surgery. Some breast cancer centers proceed to SLNB without ALND in SLN-negative patients. PATIENTS AND METHODS: Between March 1998 and March 2002, 500 SLNBs were performed. After a learning period with SLNB and ALND in 75 patients with a sensitivity of 96.2% and a false-negative rate of 3.8%, SLNB alone without further ALND was performed in a group of patients. In addition, the feasibility of SLNBin patients with locally advanced breast cancer, in patients after neoadjuvant chemotherapy and in patients with multicentricity was evaluated. The combined method with blue dye and technetium-99m-labeled human albumin for identification of SLNs was applied. RESULTS: 500 SLNBs were performed. The identification rate was 86.2%. After exclusion of patients with neoadjuvant chemotherapy and patients with multicentricity, the identification rate was 94.5%. SLNs were positive in 41.3% of patients and negative in 58.7% of patients. DISCUSSION: SLNB is an excellent method for axillary stag-ing and an alternative for ALND in a certain group of breast cancer patients.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Sentinel Lymph Node Biopsy , Axilla , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/surgery , Combined Modality Therapy , Feasibility Studies , Female , Humans , Lymph Node Excision , Lymph Nodes/pathology , Neoadjuvant Therapy , Neoplasm Staging , Predictive Value of Tests , Reproducibility of ResultsABSTRACT
Interstitial collagenase activity stimulates bone resorption by mouse marrow osteoclasts [1]. Here, we show that collagenase activity promotes bone resorption by activating adherent osteoclasts to resorb bone. Inhibition of interstitial collagenase activity, either with peptidomimetic hydroxymates or with a specific anti-interstitial collagenase inhibiting antibody, reduced bone resorption by 73-92%. Equal numbers of osteoclasts adhered to bone in the presence of collagenase inhibitors and osteoclast survival was unaffected. In contrast, formation of actin rings and polarization of the vacuolar-H+-ATPase (V-ATPase) to ruffled membranes, two indicators of osteoclast activation, were decreased by inhibiting collagenase activity and stimulated in the presence of cleaved or heat-denatured type I collagen in proportion to increases and decreases of bone resorptive activity. Addition of excess recombinant osteoprotegerin-ligand to cultures did not restore bone resorption in the presence of interstitial collagenase inhibitors. These data support the hypothesis that cleaved collagen stimulates osteoclastic bone resorption by triggering cytoskeletal reorganization and transport of V-ATPase from cytoplasmic stores to ruffled membranes.
Subject(s)
Actins/metabolism , Bone Resorption , Cell Membrane/metabolism , Matrix Metalloproteinase 1/metabolism , Osteoclasts/enzymology , Actins/drug effects , Animals , Antibodies, Blocking/pharmacology , Bone Marrow Cells , Carrier Proteins/pharmacology , Cell Membrane/drug effects , Cell Survival/drug effects , Cells, Cultured , Dentin/drug effects , Macrophages , Matrix Metalloproteinase 1/immunology , Matrix Metalloproteinase Inhibitors , Membrane Glycoproteins/pharmacology , Mice , Oligopeptides/pharmacology , Osteoclasts/cytology , Osteoclasts/drug effects , Protease Inhibitors/pharmacology , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , Vacuolar Proton-Translocating ATPases/metabolismABSTRACT
Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and 'short course' methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II-IV was 19 +/- 6% vs 36 +/- 8%, grade III-IV 10 +/- 6% vs 18 +/- 7%, chronic GVHD 44 +/- 8% vs 51 +/- 8%, non-relapse mortality 15 +/- 5% vs 8 +/- 4% at 100 days, 28 +/- 8% vs 36 +/- 7% at 3 years. At 3 years, relapse was 45 +/- 7% vs 42 +/- 7%, and disease-free survival 39 +/- 7% vs 37 +/- 7%. None of these differences are significant. Three-year overall survival was identical at 42 +/- 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 +/- 10% after UD BMT vs 59 +/- 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 +/- 7% and 21 +/- 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.
Subject(s)
Antilymphocyte Serum/administration & dosage , Bone Marrow Transplantation/methods , Bone Marrow Transplantation/immunology , Bone Marrow Transplantation/mortality , Disease-Free Survival , Female , Genotype , Graft vs Host Disease/prevention & control , Histocompatibility Testing/methods , Humans , Male , Matched-Pair Analysis , Prognosis , Recurrence , Survival Rate , Tissue Donors , Transplantation, Homologous , Transplantation, Isogeneic , Treatment OutcomeABSTRACT
We report three cases of post-transplant lymphoproliferative disorder (PTLD) in the context of autologous stem cell transplantation (ASCT) for multiple myeloma (MM) and non-Hodgkin's lymphoma. The first two cases received ASCT for MM, one with a CD34-selected autograft and the other with an unmanipulated autograft. Both these cases of PTLD achieved a complete response following treatment with IVIG, gancyclovir, solumedrol and interferon (IFN). The third case received ASCT with an unmanipulated autograft for relapsed angioimmunoblastic lymphoma. He also achieved a complete response but only after rituximab was added to IVIG, gancyclovir, solumedrol and IFN. None of these patients experienced a relapse of their PTLD with follow-up ranging from 1.5 to 5 years. These cases highlight the importance of considering PTLD in the differential diagnosis of lymphadenopathy and fever post ASCT. They also demonstrate the possibility of durable complete remission of post-ASCT PTLD following antiviral and immune modulating therapy.
Subject(s)
Lymphoproliferative Disorders/drug therapy , Peripheral Blood Stem Cell Transplantation/adverse effects , Adult , Antineoplastic Agents/administration & dosage , Antiviral Agents/administration & dosage , Diagnosis, Differential , Humans , Immunoblastic Lymphadenopathy/complications , Immunoblastic Lymphadenopathy/therapy , Immunotherapy , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/therapy , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/therapy , Remission Induction/methods , Transplantation, Autologous/adverse effectsABSTRACT
BACKGROUND: Since the development of techniques to cultivate DC from peripheral blood, there has been a great deal of interest in the use of these cells in immunotherapeutic strategies. In a clinical setting, delays often occur between when blood is drawn and when it is processed. We therefore investigated the effect of overnight storage on the yield, morphology and phenotype of DC cultured from the peripheral blood of healthy volunteers. METHOD: Blood was processed either immediately, or after storage for 24 h in the fridge (4 degrees C) or at room temperature (RT, 20 degrees C). Samples were compared for starting cell number, DC yield and characteristics (morphology and phenotype). RESULTS: The number of PBMC that could be obtained was significantly lower from the refrigerated samples compared with both the freshly processed sample and that stored at RT. Samples processed after overnight storage at RT yielded cells morphologically identical to DC cultured from freshly processed samples. Only when samples were both stored and processed cold did the cultured cells not have typical DC morphology. DC cultured from the refrigerated samples showed a significant reduction in MHC II expression compared with samples processed fresh or stored at RT. This expression increased slightly when the sample was first warmed. Total DC yield and the percentage yield of cultured DC was not significantly different for any of the groups. DISCUSSION: We conclude that, if immediate processing of blood for in vitro generation of DC is not possible, samples should be stored at room temperature (approximately 20 degrees C).