Analysis of the Clinical Impact of the Use of Palifermin in Patients Undergoing Autologous Peripheral Blood Progenitor Cell Transplantation for Multiple Myeloma and Relapsed Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4332-4332
Author(s):  
Kari Kolm ◽  
Ronan Foley ◽  
Jolanta Jeziorowska ◽  
Deborah C Marcellus ◽  
Ann Benger ◽  
...  
Keyword(s):  
Keratinocyte Growth Factor ◽  
Clinical Status ◽  
Underlying Disease ◽  
Entire Group ◽  
High Dose ◽  
Heparin Binding ◽  
Number Of Patients ◽  
Conditioning Regimens ◽  
Relapsed Lymphoma ◽  
Severe Mucositis

Abstract Severe mucositis remains a serious complication of autologous PBPC transplantation. Keratinocyte growth factor/KGF (Palifermin) is a 28kd heparin-binding glycoprotein that specifically binds the KGF receptor resulting in a range of biological events including increased mucosal epithelial thickness. Administration of palifermin to patients undergoing TBI-based autologous PBPC transplantation has been shown to reduce the incidence and duration of severe mucositis. In the current study we retrospectively evaluated the use of palifermin in patients with myeloma and relapsed lymphoma undergoing non-TBI autologous PBPC transplantation with high-dose melphalan and BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimens respectively. Palifermin was given at a dose of 60 mcg/kg/day on days −5 to −3 in patients with myeloma, days −10 to −8 in patients with lymphoma, and days 0 to +2 in all patients. Depending on clinical status and distance from our centre, patients had the opportunity of early discharge on day +1 with outpatient follow-up. G-CSF was administered (5 mcg/kg/day) starting on day +5 in all patients. Of a total of 81 patients, 32 patients received palifermin (23 myeloma, 9 lymphoma) and were compared to a concurrent non-palifermin treated population of 49 patients (27 myeloma, 22 lymphoma). Patients were comparable with respect to age (overall mean 54.5 years), except that patients with myeloma receiving palifermin were slightly older (mean 60 vs. 55 y, p=0.04), and the numbers of infused CD34 positive cells per kg were similar. There were 46 male and 35 female patients. Administration of palifermin was safe and generally well tolerated with 97% of patients receiving all scheduled doses; rash was seen in 32% of cases. The use of palifermin did not influence engraftment of leukocytes or platelets in either myeloma or lymphoma patients. Analysis of length of stay (LOS) following reinfusion in the entire group suggested a difference of 2 days favouring the palifermin group (mean 11.8 vs 13.8 days), but this was not statistically significantly different. There were also no statistically detectable differences in LOS in palifermin treated or untreated patients with myeloma (mean 13.5 vs 10.5 days) or lymphoma (mean 7.7 vs 17.9 days) respectively, although the number of patients with lymphoma receiving palifermin was small. Patients with myeloma appeared to have higher rates of significant mucositis compared with lymphoma (74% vs 48%, p=0.03) but this was not significant in an exploratory logistic regression analysis when age, gender, underlying disease, administration of palifermin and infused number of PBPC were included in the analysis. We conclude that palifermin can be safely administered to patients undergoing non-TBI high dose therapy and autologous PBPC transplantation. Although there was a suggestion of some improvements in LOS with palifermin, the small numbers of patients limit the strength of such conclusions. Further prospective studies in non-TBI conditioning regimens will help to further define the potential benefits of palifermin in reducing mucositis and its consequences.

scholarly journals Invasive aspergillosis in children and adolescents with solid tumors: clinical cases and registry analysis

2019 ◽  
Vol 14 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Yu. V. Dinikina ◽  
O. V. Shadrivova ◽  
M. B. Belogurova ◽  
Yu. E. Melekhina ◽  
S. M. Ignatyeva ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Children And Adolescents ◽  
Solid Tumors ◽  
Wilms Tumor ◽  
Underlying Disease ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Additional Risk ◽  
Number Of Patients

We presented two cases of invasive aspergillosis (IA) in children with solid tumors, data of IA patients register, and a literature review. In theregister of patients with IA (1997–2018), we found 57 patients with IA from 0 to 18 years. It was established that the number of patients with solid tumors was 15.7 %. Background diseases were: central nervous system tumors – 33.5 %, neuroblastoma – 33.5 %, osteosarcoma – 11.0 %, Wilms tumor – 11.0 %, hemangioblastoma – 11.0 %. Chemotherapy-induced neutropenia was reported in 100 % of IA cases in children and adolescents with solid tumors. The additional risk factors were treatment in intensive care unit – 22.2 %, high-dose chemotherapy with autologous hematopoietic stem cell transplantation – 22.2 %, concomitant bacterial infection – 33.0 %. Surgical intervention for the underlying disease was performed in 77.7 % of patients. The most common clinical site of IA was the lungs – 88.9 %. The predominant clinical sign was fever – 66.7 %, cough and respiratory failure were seen less frequently – 33.4 % and33.4 %, respectively. The etiologicalagents of IA were Aspergillus fumigatus – 33.3 %, Aspergillus nidulans – 33.3 % and Aspergillus ustus – 33.3 %. 88.9 % of patients received antimycotic therapy, voriconazole predominantly – 66.7 %. Combination therapy was used in 33.3 % of patients. The overall 12-week survival in children and adolescents with IA in case of solid tumors was 77.8 %.

Severe Mucositis Adversely Affects Survival after Autologous Stem Cell Transplantation (ABMT) for Lymphoid Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 837-837
Author(s):  
Brian Bolwell ◽  
Matt Kalaycio ◽  
Ronald Sobecks ◽  
Steven Andresen ◽  
Lisa Rybicki ◽  
...  
Keyword(s):  
Negative Impact ◽  
Surrogate Marker ◽  
Disease Status ◽  
Entire Group ◽  
High Dose ◽  
Prior Chemotherapy ◽  
Lymphoid Malignancies ◽  
Transplant Patients ◽  
Cox Analysis ◽  
Severe Mucositis

Abstract Mucositis is a well known short term complication of ABMT. Many studies of mucositis in ABMT, however, are flawed due to heterogeneity of both mobilizing regimens and high-dose preparative regimens. There is also sparse data on the long term consequences of mucositis after ABMT. This study retrospectively reviews all patients with lymphoid malignancies undergoing ABMT from 5/2000 to 2/2005 at our institution that received a uniform mobilizing regimen of VP-16 plus G-CSF and a uniform high dose preparative regimen of busulfan, cyclophosphamide and VP-16. 191 patients fit the entry criteria into this study. Mucositis was graded using the OMAS mucositis grading scale, which has a scoring range of 0–2.0. Severe mucositis for the purposes of this study was designated as having a maximal OMAS scale of ≥ 1.0. 87 patients experienced severe mucositis and 104 did not. Median age for patients was 52 years; underlying diagnoses were non-Hodgkin’s Lymphoma (n=155) and Hodgkin’s Disease (n=36). The two groups (developing severe mucositis vs not) were balanced with respect to disease status at transplant, number of courses of prior chemotherapy, prior exposure to radiation therapy of any kind, and elevated LDH at the time of transplant. Median CD34+ cell dose collected for the entire group was 8.5 x 106 /kg; there was no difference between the 2 groups. Severe mucositis correlated with mortality within 100 days of transplant. Patients with a maximal OMAS scale of < 1.0 had 99% 100-day survival (103/104) as compared to 92% (80/87) for those with an OMAS scale ≥ 1.0 (p=0.015). To date, 30% of patients have relapsed with no difference in the two groups. However, Kaplan-Meier estimates of survival reveal that severe mucositis has a profound negative impact on survival (p=0.002) as shown graphically below: Figure Figure One of the key drivers of this difference in survival was the fact the patients with severe mucositis were more likely to experience pulmonary or multi-organ failure as a cause of death: 8 patients with severe mucositis died of these toxicities, as compared to zero in the less severe mucositis group. Multivariable Cox analysis was performed to analyze risk factors for mortality. Three variables were found to be significant: elevated LDH at transplant (p=0.03), number of prior chemotherapy regimens (for one regimen increase, p=0.024) and severe mucositis (p=0.003). In conclusion, patients that develop severe mucositis have a higher risk of mortality after ABMT. The etiology is likely multi-factorial; mucositis may directly contribute to mortality risk, and may also be a surrogate marker of other organ toxicities.

Phase II study of caphosol oral rinse for prevention of oral mucositis (OM) in sarcoma patients (pts) receiving multicycle doxorubicin-based chemotherapy (CT): Randomized study with cross-over to palifermin for severe OM.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19520-e19520
Author(s):  
Saroj Vadhan-Raj ◽  
Dejka M. Araujo ◽  
Jonathan C. Trent ◽  
Xiao Zhou ◽  
Joseph A. Ludwig ◽  
...  
Keyword(s):  
Keratinocyte Growth Factor ◽  
Randomized Study ◽  
Study Drug ◽  
Weighted Kappa ◽  
Secondary Prophylaxis ◽  
High Dose ◽  
Serious Adverse Event ◽  
Oral Rinse ◽  
Experienced Grade ◽  
Severe Mucositis

e19520 Background: Mucositis is a common complication in cancer pts receiving CT. We have shown that palifermin (recombinant Keratinocyte Growth Factor), administered as single dose prior to CT, alleviated severe mucositis in pts receiving doxorubicin-based CT (Ann Int Med 2010). Caphosol is a supersaturated electrolyte solution of calcium phosphate that has been indicated as oral rinse for xerostomia and as an adjunct to treat OM induced by radiation or high-dose CT. Purpose of the study was to evaluate the preliminary efficacy of Caphosol in pts receiving CT. Methods: Pts were randomized 1:1 to Caphosol vs. baking soda (control) as an oral rinse five times daily from initiation of CT. All pts received doxorubicin (75 or 90 mg/m2 by continuous infusion over 3 days) with ifosfamide (10 gm/m2) or cisplatin (120 mg/m2). Pts that experienced Grade (Gr) > 3 mucositis received palifermin (180 mcg/kg) iv 3 days before CT in subsequent cycles. Results: 28 of 30 pts received treatment and were evaluble; 15 men and 13 women, with median age 51 (range, 20-65 yrs). Incidence of Gr > 2 OM was 57% (8 of 14 pts) for Caphosol vs. 86% (12 of 14) for control (P=0.21). Incidence of Gr > 3 OM was 29% (4/14) for Caphosol vs. 43% (6/14) for control (P=0.43). However, the benefit was limited to oral but not other GI mucosal sites. Of 10 pts (Caphosol: 4, BS: 6,) with Gr > 3 OM, 6 crossed over to palifermin (Caphosol: 3, BS: 3); the other 4 pts (Caphosol: 1, BS: 3) came off the study. All 6 pts, that received palifermin, avoided severe OM in the next cycle. The median duration of Gr > 2 OM in the cycle before cross-over was 8 days (range: 5-12) vs. 0 days (0-3) in palifermin cycle (p=0.0032) and Gr > 3 OM was 5 days (2-7) vs. 0 days (p=0.0015). Oral assessment and the pts-reported outcome were in substantial agreement for the OM grading (weighted kappa, 0.78, 95% CI: 0.44-0.87, p<0.0001). No serious adverse event related to the study drug was observed. Conclusions: There was a trend for less severe OM with Caphosol vs. control. Secondary prophylaxis with palifermin alleviated severe mucositis in all pts who previously experienced severe mucositis during multi-cycle CT.

scholarly journals Brown Bowel Syndrome: An Exceedingly Rare Condition with Longstanding Malabsorption and an Unusual Cause of Colon Pseudo-Obstruction

2021 ◽  
pp. 960-965
Author(s):  
Adnan Alkurdi ◽  
Diana Rubin ◽  
Alexander Seelhoff ◽  
Hermann Herbst
Keyword(s):  
Vitamin E ◽  
Periodic Acid ◽  
Clinical Status ◽  
Smooth Muscles ◽  
Rare Condition ◽  
Underlying Disease ◽  
High Dose ◽  
Muscularis Mucosa ◽  
Periodic Acid Schiff ◽  
Lipofuscin Granules

Brown bowel syndrome (BBS) is an exceedingly rare condition usually associated with longstanding malabsorption of any etiology. As a result of vitamin E deficiency and subsequent mitochondrial degeneration due to oxidative stress induced by free radicals, lipofuscin granules accumulate in the smooth muscles of the gastrointestinal tract resulting in myopathy and dysmotility with underlying disease aggravation. The current study reports a BBS case in a 64-year-old female patient who had undergone jejunoileal bypass surgery as a bariatric procedure. The patient was admitted with signs of malabsorption and ileus in computed tomography imaging. Endoscopic workup revealed no stenosis or obstruction. The colon histologically showed periodic acid-Schiff-positive lipofuscin granules in the lamina muscularis mucosa consistent with BBS. The vitamin E level in the patient was extremely low. Moreover, clinical improvement was documented following high-dose substitution. BBS should be considered in patients with malabsorption of any cause especially with signs of gastrointestinal dysmotility. Vitamin E substitution may improve clinical status and prevent further deterioration.

scholarly journals Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lydia Ntari ◽  
Christoforos Nikolaou ◽  
Ksanthi Kranidioti ◽  
Dimitra Papadopoulou ◽  
Eleni Christodoulou-Vafeiadou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Therapeutic Effect ◽  
Expression Analysis ◽  
Mode Of Action ◽  
Gene Expression Analysis ◽  
Kinase Inhibitors ◽  
High Dose ◽  
Dependent Manner ◽  
Combination Therapies ◽  
Number Of Patients

Abstract Background New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients. Methods We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy. Results Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy. Conclusion Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.

scholarly journals Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia—A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (6) ◽  
pp. 1244
Author(s):  
Stinne Tranekær ◽  
Dennis Lund Hansen ◽  
Henrik Frederiksen
Keyword(s):  
Haemolytic Anaemia ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Underlying Disease ◽  
Age At Diagnosis ◽  
Autoimmune Haemolytic Anaemia ◽  
Sex Distribution ◽  
Number Of Patients ◽  
Study Results ◽  
Full Text Review

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.

scholarly journals 577. Incidence and Outcomes of Positive Outpatient Surveillance Blood Cultures in Hematopoietic Stem Cell Transplant (HSCT) Patients with Graft Versus Host Disease (GvHD) On High Dose ≥ 0.5 mg/kg/day (HD) and Low Dose < 0.5mg/kg/day (LD) Steroid Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S353-S354
Author(s):  
Sarah Perreault ◽  
Molly Schiffer ◽  
Jennifer Zhao ◽  
Dayna McManus ◽  
Francine Foss ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
Central Line ◽  
Blood Cultures ◽  
High Dose ◽  
Cell Transplant ◽  
Coagulase Negative Staphylococci ◽  
Hematopoietic Stem ◽  
Surveillance Cultures ◽  
Number Of Patients ◽  
Clinically Significant

Abstract Background Treatment of GvHD with steroids increases the risk of infection in HSCT patients due to additive immunosuppression and may delay the diagnosis of infection due to lack of symptoms. Outpatient surveillance blood cultures in HSCT with GvHD being treated with HD steroids has demonstrated a blood culture positivity rate of 3.5%. Currently, the utility of surveillance cultures in patients receiving LD steroid therapy is unknown. Our practice includes weekly outpatient surveillance cultures for all GvHD patients treated with steroids regardless of the dose. The primary endpoint of this study was to assess the incidence of positive surveillance blood cultures in GvHD patients receiving HD or LD steroids. Secondary endpoints included number of patients treated, hospitalization, 30 day mortality due to infection, and organisms isolated. Methods This was a single-center, retrospective review of GvHD patients at Yale New Haven Hospital between January 2013 and May 2019. Patients were excluded if: lack of signs or symptoms of GvHD, treatment with steroids for any indication other than GvHD, and active GvHD without central line. Cultures from patients receiving antibiotics for concurrent infection were also excluded. Results A total of 71 patients met criteria with 901 blood cultures. On HD, eight patients (14%) had 12 positive cultures (4%), and on LD, 16 patients (25%) had 22 positive cultures (4%) (p=0.15). Treatment occurred in six patients (75%) with four (24%) requiring hospitalization on HD, and 12 patients (75%) with 10 (83%) requiring hospitalization on LD (p=0.45). The median duration of steroid therapy was 93 and 236 days with a median dose of steroids of 1mg/kg/day and 0.15mg/kg/day, respectively. The number of positive cultures/1000 steroid days was 1.2 on HD and 0.5 on LD (RR 2.2). 30 day mortality was only noted in one patient (8%) on LD. The most common organism in both groups was Coagulase-negative staphylococci with all six cultures on HD classified as contaminants and 6/10 cultures requiring treatment on LD. Conclusion Although the relative risk of positive surveillance blood cultures in HD patients compared to LD was twofold higher, there were clinically significant infections identified in the LD group. Disclosures All Authors: No reported disclosures

Potential for Single High-Dose Influenza Immunization in Unprimed Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (6) ◽  
pp. 982-986 ◽  
Author(s):  
Peter A. Gross ◽  
Gerald V. Quinnan ◽  
Pureza F. Gaerlan ◽  
Carolyn R. Denning ◽  
Anne Davis ◽  
...  
Keyword(s):  
New York ◽  
Influenza A ◽  
Standard Dose ◽  
Geometric Mean ◽  
High Dose ◽  
York Metropolitan Area ◽  
Reaction Index ◽  
Number Of Patients ◽  
Sibling Control ◽  
High Concentrations

High concentrations of split-product vaccine (SPV) are more immunogenic than lower concentrations. These studies were verified with another influenza strain, B/Singapore/22/79. Two ether-treated SPVs were compared in 80 children and young adults. The vaccine strains were influenza A/Bangkok/79, A/Brazil/78, and B/Singapore /79; 44 patients received a high-dose SPV containing 7, 7, and 60 µg each of the respective hemagglutinins (HA) and 36 received a standard dose SPV containing 7, 7, and 7 µg of HA, respectively. Among persons initially seronegative by hemagglutination inhibition (HAI) tests, the geometric mean titer (GMT) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one standard dose (P &lt; .05). Furthermore, 87% of high-dose recipients had HAI titer ≥ 40 vs 44% of standard dose recipients. In initially seropositive persons, GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one standard dose (P &lt; .05). Immune response to the other two virus strains was comparable for the two vaccines. The reaction index for the high dose vaccine was 0.70 vs 0.45 for the standard dose (P = NS). An A/Bangkok epidemic struck the New York metropolitan area. The attack rate in unvaccinated matched sibling control subjects was 35% (15/43). There were no vaccine failures. In conclusion, in the small number of patients studied, a 60-µg HA dose of B/Singapore/79 was significantly more immunogenic than a standard 7-µg HA dose without an increase in reactogenicity.

Consensus document on radiotherapy in patients with implantable pacemakers and cardioverter – defibrilators

2018 ◽  
Vol 2 (47) ◽  
pp. 27-31
Author(s):  
Lidia Chmielewska-Michalak ◽  
Ewelina Konstanty ◽  
Przemysław Mitkowski
Keyword(s):  
Current Knowledge ◽  
Clinical Status ◽  
Electronic Devices ◽  
Heart Rhythm ◽  
Complex Care ◽  
Consensus Document ◽  
Cardiac Implantable Electronic Devices ◽  
Number Of Patients ◽  
High Level ◽  
Emergency Mode

The number of patients with cardiac implantable electronic devices (CIED), who require oncological management including radiotherapy (RT) is still increasing. According to current knowledge the most frequent device dysfunction related to exposition to ionizing radiation is reprogramming to emergency mode (soft reset). There are uncommon cases of complete, irreversible device damage. CIED dysfunction during RT can be observed in approximately 3% of patients. In majority of cases they are asymptomatic, although in literature there are descriptions of deterioration of clinical status due to bradycardia or exacerbation of heart failure. The most important factor of device malfunction is radiotherapy with photons of energy >10 MV or protons despite energy used. So far there were no cases published with inadequate ICD therapies due to the presence of electromagnetic field interference during RT. Because patients with CIED undergoing RT need complex care to achieve high level of safety, experts of Heart Rhythm Society establish document, published in 2017 which summarized current knowledge about this group of patients. The document contains guidelines on peri-radiotherapy care of patients with CIED.

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