scholarly journals 346. Eastern Equine Encephalitis and Use of Intravenous Immunoglobulin Therapy and High-Dose Steroids

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S242-S243
Author(s):  
Sarah I Collens ◽  
Douglas R Wilcox ◽  
Shibani Mukerji ◽  
Farrah J Mateen ◽  
Isaac H Solomon
Keyword(s):  
Cerebrospinal Fluid ◽  
Temporal Lobe ◽  
Standard Of Care ◽  
High Dose ◽  
High Morbidity ◽  
Intravenous Immunoglobulin Therapy ◽  
Eastern Equine Encephalitis ◽  
Neuroanatomical Region ◽  
Ivig Administration

Abstract Background Eastern equine encephalitis (EEE) is a mosquito-borne viral infection with significant neurological morbidity and mortality. The clinical presentation and patient outcomes after treatment with IVIG, high-dose steroids, or standard of care alone in EEE remains unclear. Methods A retrospective observational study of patients admitted to two tertiary academic medical centers in Boston, Massachusetts with EEE from 2005 to 2019. Results Of 17 patients (mean [SD] age, 50 [26] years; 10 (59%) male, and 16 (94%) White race), 17 patients had fever (100%), 15 had encephalopathy (88%), and 12 had headache (71%). Eleven of 14 patients with cerebrospinal fluid (CSF) cell count differential had a neutrophil predominance (mean [SD], 60.6% of white blood cells [22.8]) with an elevated protein level (mean [SD], 112 mg/dL [48.8]). Affected neuroanatomical regions included the basal ganglia (n=9/17), thalamus (n=7/17), and mesial temporal lobe (n=7/17). A total of 11 patients (65%) received IVIG; 8 (47%) received steroids. Of the patients who received IVIG, increased time from hospital admission to IVIG administration correlated with worse long-term disability as assessed by modified Rankin Score (mRS) (r=0.72, p=0.02); steroid use was not associated with mRS score. The mortality was 12%. Figure 1. Imaging Characteristics: Typical Pattern of MRI Involvement and Affected Neuroanatomical Regions in Patients with Eastern Equine Encephalitis. All images displayed are the T2-FLAIR sequence. (A) Representative images of pattern of typical neuroanatomical region involved in one patient with demonstrated involvement of the temporal lobe and pons, temporal lobe and midbrain, and basal gangial by T2-FLAIR hyperintensity (panels left to right). (B) Representative images of patients with mild (mRS 0–2), moderate (mRS 3–4), and severe (mRS 5–6) disability score at discharge. (C) Representative images of one patient over course of hospitalization at days 1, 4, and 10 after admission. (D) Quantification of neuroanatomical region involvement in initial MRI of patients with EEE as determined by T2-FLAIR hyperintensity. An area was scored as abnormal only once per patient. Figure 2. Outcomes in Patients with Eastern Equine Encephalitis. Patient disability by modified Rankin Score (mRS) of EEE patients at admission to the hospital, discharge from the hospital, and last recorded follow-up (A). Time to IVIG administration compared to mRS at discharge (B), and most recent clinical follow-up (C). Table 1. Demographics, Clinical Characteristics, and Laboratory Data in Patients with Eastern Equine Encephalitis. Abbreviations: CSF = cerebrospinal fluid, WBC = white clood count, EEG = electroencephalogram, ALT = alanine aminotransferase, AST = aspartate transaminase. Demographic data was collected for all patients with confirmed EEE. Altered mental status included any description of encephalopathy, confusion, or difficulty with attention. Seizures were defined as clinical events with a high-degree of suspicion to be true seizures, and were entirely comprised of generalized tonic-clonic seizures. Conclusion Clinicians should suspect EEE in immunocompetent patients with early subcortical neuroimaging abnormalities and CSF neutrophilic predominance. This study suggests a lower mortality than previously reported, but a high morbidity rate in EEE. IVIG as an adjunctive to standard of care may be considered early during hospitalization. Disclosures All Authors: No reported disclosures

scholarly journals Eastern equine encephalitis and use of IV immunoglobulin therapy and high-dose steroids

2020 ◽  
Vol 8 (1) ◽  
pp. e917
Author(s):  
Douglas R. Wilcox ◽  
Sarah I. Collens ◽  
Isaac H. Solomon ◽  
Farrah J. Mateen ◽  
Shibani S. Mukerji
Keyword(s):  
White Blood Cells ◽  
Standard Of Care ◽  
Immunoglobulin Therapy ◽  
Morbidity Rate ◽  
High Dose ◽  
High Morbidity ◽  
Eastern Equine Encephalitis ◽  
High Morbidity Rate ◽  
Elevated Protein ◽  
Iv Immunoglobulin

ObjectiveTo determine the clinical presentation and patient outcomes after treatment with IV immunoglobulin (IVIG), high-dose steroids, or standard of care alone in Eastern equine encephalitis (EEE), a mosquito-borne viral infection with significant neurologic morbidity and mortality.MethodsA retrospective observational study of patients admitted to 2 tertiary academic medical centers in Boston, Massachusetts, with EEE from 2005 to 2019.ResultsOf 17 patients (median [IQR] age, 63 [36–70] years; 10 (59%) male, and 16 (94%) White race), 17 patients had fever (100%), 15 had encephalopathy (88%), and 12 had headache (71%). Eleven of 14 patients with CSF cell count differential had a neutrophil predominance (mean = 60.6% of white blood cells) with an elevated protein level (median [IQR], 100 mg/dL [75–145]). Affected neuroanatomic regions included the basal ganglia (n = 9/17), thalamus (n = 7/17), and mesial temporal lobe (n = 7/17). A total of 11 patients (65%) received IVIG; 8 (47%) received steroids. Of the patients who received IVIG, increased time from hospital admission to IVIG administration correlated with worse long-term disability as assessed by the modified Rankin Scale (mRS) (r = 0.72, p = 0.02); steroid use was not associated with the mRS score. The mortality was 12%.ConclusionsClinicians should suspect EEE in immunocompetent patients with early subcortical neuroimaging abnormalities and CSF neutrophilic predominance. This study suggests a lower mortality than previously reported, but a high morbidity rate in EEE. IVIG as an adjunctive to standard of care may be considered early during hospitalization.

Total Lymphoid Irradiation and High-Dose Chemotherapy with Autologous Blood Stem-Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Excellent Disease Control and Long-Term Survival Rates

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2024-2024
Author(s):  
Ryan D. Gentzler ◽  
Andrew M. Evens ◽  
Alfred W. Rademaker ◽  
Bharat B Mittal ◽  
Adam M. Petrich ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Survival Rates ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Term Survival

Abstract Abstract 2024 Background: For patients with relapsed or refractory HL, salvage chemotherapy followed by aHSCT is the standard of care. Our group previously reported excellent clinical outcomes with accelerated hyperfractionated TLI followed by high-dose chemotherapy and aHSCT (Ann of Oncol. 16:679, 2007). This strategy has been adopted as the standard at our institution for eligible individuals and we now report long-term outcomes of patients previously reported on the phase I/II clinical trial in addition to those who were subsequently treated as standard of care. Patients and methods: Patients with biopsy confirmed relapsed/refractory classical HL who previously received no more than 20 Gy were eligible. Salvage chemotherapy was chosen by the patient's treating physician. All patients received accelerated hyperfractionated TLI prior to transplantation administered twice daily at 150 cGy, five days/week for 10 days. The morning dose was delivered to all nodal sites including the spleen, and the afternoon dose was delivered to all sites of previous and current disease. The goal was to treat uninvolved nodal sites and spleen to 1500 cGy and sites of current and previous disease to 3000 cGy. Conditioning chemotherapy consisted of high-dose carboplatin, cyclophosphamide, and etoposide. All patients received carboplatin 450 mg/m2 by continuous intravenous infusion (CIV) on days –6 to –4 (total dose = 1350 mg/m2) and cyclophosphamide 60 mg/kg/day over 1 h on days –3 and –2 (total dose = 120 mg/kg). Patients on the phase I portion of the trial received escalating doses of etoposide by CIV from days –6 to –4. Initial dosing levels were 400 mg/m2/day, 450 mg/m2/day, 500 mg/m2/day, 600 mg/m2/day and 700 mg/m2/day. Those treated on the phase II portion of the clinical trial or subsequent to the closing of the trial were treated with etoposide 700 mg/m2/day for a total of 2100 mg/m2. Results: 52 patients with relapsed/refractory HL at Northwestern University were treated with TLI and aHSCT from 1993 to January 2011. One patient was lost to follow-up immediately post-transplant. 51 patients were included in this analysis and had a median follow-up of 47 months (range: 0.07–204 months). Thirty patients were treated on a previously reported prospective phase I/II clinical trial. Most patients had nodular sclerosis histology (n=39, 76%) and more than half had primary induction failure (PIF; n=29). Among patients who achieved a CR with induction, 62% relapsed within one year. The most common salvage regimens were ESHAP and ICE chemotherapy and most had received two lines of chemotherapy prior to aHSCT. Only 21 patients (41%) achieved a complete response (CR) with salvage therapy and in most cases (n=31, 61%), response was determined by functional imaging prior to aHSCT. The 10-year PFS and OS for all patients were 56% and 54%, respectively. Ten-year PFS and OS for patients with PIF was 53%, compared with 63% and 59%, respectively, for those with relapsed disease (p=0.13 and p=0.20, respectively). Patients who had incomplete responses to salvage therapy had a 10-year PFS and OS of 41% and 39%, respectively, compared to 76% and 81%, respectively, for those who achieved a CR (p=0.1 and p=0.056, respectively). Treatment-related mortality within the first 100 days was observed in one patient. Five patients (10%) developed secondary malignancies; three developed MDS (one who had received MOPP induction died with MDS; one had relapsed HL post-aHSCT and died of AML and one is alive with MDS 3+ yrs post-diagnosis). There was one case each of T-cell lymphoma (7 months post-aHSCT) and melanoma. Conclusions: Sequential TLI/chemotherapy conditioning for relapsed/refractory HL for patients with limited or no prior radiotherapy continues to be associated with excellent disease control and long-term survival rates including high-risk populations such as PIF and chemotherapy-resistant disease. Disclosures: No relevant conflicts of interest to declare.

Treatment of Serratia marcescens Meningitis with Prolonged Infusion of Meropenem

2007 ◽  
Vol 41 (6) ◽  
pp. 1077-1081 ◽  
Author(s):  
Anthony M Nicasio ◽  
Richard Quintiliani ◽  
C Andrew DeRyke ◽  
Joseph L Kuti ◽  
David P Nicolau
Keyword(s):  
Case Reports ◽  
High Dose ◽  
High Morbidity ◽  
Prolonged Infusion ◽  
Dosing Interval ◽  
Csf Penetration ◽  
Lumbar Drain ◽  
Days Of Therapy ◽  
The Central Nervous System

OBJECTIVE: To describe the use of and cerebral spinal fluid (CSF) penetration o a prolonged infusion meropenem regimen in a patient with Serratia marcescen meningitis. CASE SUMMARY: A 54-year-old female was diagnosed with S. marcescen meningitis associated with an epidural abscess 57 days after surgery for a herniated spinal disk. Meropenem 2000 mg every 8 hours was administered as a prolonged (3 h) infusion for the purpose of optimizing pharmacodynamic exposure Meropenem concentrations were measured from the patient's blood and CSF (via a lumbar drain). The prolonged infusion regimen resulted in concentrations in both serum and CSF above the meropenem minimum inhibitory concentration (MIC) o 0.047 μg/mL for 100% of the dosing interval. After 6 days of therapy, the patien showed no further signs of infection and was subsequently discharged to a rehabilitation facility. At follow-up, she had completed a 4 week course of the prolonged infused therapy without relapse or adverse events. DISCUSSION: Gram-negative infections of the central nervous system result in high morbidity and mortality. These infections are often difficult to treat because o poor antibiotic penetration coupled with increasing antibiotic resistance. Although there are 2 other case reports that describe the use of prolonged infusion o meropenem, our patient had a lumbar drain in place, thereby allowing us to collect multiple CSF samples and more accurately assess meropenem exposure at the site of infection. CSF penetration was 6.4% in this patient, resulting in 100% time above the MIC throughout the dosing interval. CONCLUSIONS: In this patient with meropenem-susceptible S. marcescensmenin gitis, the use of a high-dose prolonged infusion of meropenem resulted in adequate exposure at the site of infection and a successful clinical response.

scholarly journals Real World Outcomes of Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation and Receive Commercially-Available Salvage Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2893-2893
Author(s):  
Emily C. Ayers ◽  
David J Margolis ◽  
Phyllis A. Gimotty ◽  
Daniel J. Landsburg
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Current Therapy ◽  
High Dose ◽  
Cell Of Origin ◽  
Advisory Committees ◽  
Ecog Ps

Introduction: Salvage immunochemotherapy (IC) followed by high-dose chemotherapy with autologous stem cell transplantation (autoSCT) is standard-of-care second-line therapy (2L) for patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) deemed fit for autoSCT as per the CORAL study (J Clin Oncol. 2010 Sep 20;28(27):4184-90). Optimal therapeutic management of patients with R/R DLBCL who are autoSCT-ineligible is unknown. Here we describe the real-world outcomes of patients with R/R DLBCL who receive palliative intent 2L therapy in community and academic settings and do not receive autoSCT. Methods: This analysis includes de-identified patients from the nationwide Flatiron Health electronic health record-derived database with a histologic diagnosis of DLBCL and R/R disease after frontline IC who do not undergo autoSCT and receive treatment with either bendamustine-based therapy, gemcitabine-based therapy, lenalidomide, or ibrutinib. Patients receiving rituximab/ifosfamide/carboplatin/etoposide (R-ICE) and high-dose cytarabine-containing second-line therapies were excluded. Event free survival (EFS) was defined as the interval between the start of current therapy and start of subsequent therapy if needed, last follow-up on current therapy, or death on therapy. Overall survival (OS) was defined as the time between start of current therapy and death or last follow-up while alive. Results: A total of 250 patients were eligible for inclusion in 2L. Eight patients received autoSCT after gemcitabine therapy and were excluded from this analysis. Clinicopathologic characteristics at time of diagnosis include 56% male, 87% age >60, 55% ECOG performance status >1, 87% stage III-IV disease, 78% IPI >2, 56% germinal center (GCB) of those with cell of origin testing performed, 9% cMYC rearrangement positive when tested, and 29% transformed from indolent disease. A total of 106, 78, 36, and 22 patients received bendamustine, gemcitabine, lenalidomide, and ibrutinib, respectively. For all patients, median EFS was 5.1 months and median OS was 14.3 months in 2L. Median EFS was 7.6, 2.4, 9.1, and 4.2 months, and median OS was 16.0, 9.4, 16.3, and 11 months for bendamustine, gemcitabine, lenalidomide, and ibrutinib in 2L, respectively. Patients receiving bendamustine and lenalidomide demonstrated significantly improved EFS compared to those receiving gemcitabine (p=0.001 and 0.01, respectively), see Figure 1. We observed no difference in EFS (p=0.40) or OS (p=0.89) between lenalidomide and bendamustine in 2L. Univariate analysis demonstrated receipt of gemcitabine, ECOG PS>1, and IPI >2 to have statistically significant increased hazard for treatment failure and ECOG PS>1 to have an increased hazard for death in 2L relative to the reference group. Multivariate analysis demonstrated receipt of gemcitabine (HR 1.57, p=0.03 95% CI: 1.04 - 2.37) and ECOG PS>1 (HR 1.61, p=0.02 95% CI: 1.09-2.38) were associated with an increased hazard for treatment failure in 2L. Median EFS for patients on lenalidomide was 6.7 and 8 months (p=0.26), and median OS was 13.9 and 12.2 months (p =0.48) for patients with nonGCB and GCB cell of origin, respectively. Conclusions: For patients with R/R DLBCL treated with palliative therapy in the 2L, bendamustine- and lenalidomide-based therapies resulted in significantly longer EFS compared to gemcitabine therapy. Although we cannot exclude the possibility that some patients received gemcitabine in 2L with the original intent to proceed with autoSCT, this does not contest our results as this therapy remains inferior to bendamustine and lenalidomide even if given to a potentially more fit patient population. Analysis shows no difference in outcomes by cell of origin if receiving lenalidomide in 2L. These findings may serve as benchmarks for outcomes following receipt of these therapies in the non-investigational setting and suggest both bendamustine and lenalidomide may be considered reasonable standard-of-care therapies for patients unfit for autoSCT in the 2L setting. Figure 1 Disclosures Landsburg: Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Triphase: Research Funding; Takeda: Research Funding; Takeda: Research Funding. OffLabel Disclosure: Outcomes with lenalidomide and ibrutinib in patients with relapsed/refractory DLBCL will be discussed.

Low-dose gemcitabine and radiation alternated to cisplatin/5fu in stage IV squamous cell carcinoma of the head and neck (HN- SCC): A phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6062-6062
Author(s):  
M. Benasso ◽  
V. Vigo ◽  
A. Bacigalupo ◽  
A. Ponzanelli ◽  
M. Marcenaro
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Stage Iv ◽  
Standard Of Care ◽  
High Dose ◽  
Local Toxicity ◽  
Grade 3 ◽  
Present Trial ◽  
Severe Mucositis

6062 Background: At the National Institute for Cancer Research of Genoa, Italy, we conducted two consecutive phase II single-institution trials testing the addition of gemcitabine into an alternating chemo-radiation (CT/RT) regimen that is considered standard of care in our Institute for patients (pts) with loco-regional advanced HN-SCC (NEJM, 327:1115,1992). In the former trial (ALT-G trial; 47 pts) high dose gemcitabine was administered with cisplatin and RT (Annals of Oncology, 15:646,2004). Methods: In the present trial (ALT-g trial) 3 courses of cisplatin, 20 mg/m2/day and 5-fluorouracil, 200 mg/m2/day, days 1–5 (weeks 1, 4, 7) alternated to 3 courses of standard RT (weeks 2–3, 5–6, 8–9) up to 60 Gy and gemcitabine, 40 mg/m2 on monday of each week of RT, were administered to 47 pts with stage IV (42 pts) or relapsed after surgery (5 pts), unresectable SCC of the oral cavity (11 pts), oropharynx (11 pts) hypopharynx-larynx (24 pts). None had previously received CT or RT. Results: Seven pts (15%) did not complete the planned treatment. Four of them died due to pulmonary embolism (2 pts), fulminant pneumonia (1 pt) or uncertain causes (1 pt). Main grade 3–4 other than local toxicities were: neutropenia (11%), neutropenia with fever (6%), thrombocytopenia (30%), anemia (17% grade 3). 27 pts reached a CR (57%). 7 PRs were rendered disease-free by surgery mainly on the neck (final CR rate: 72%). At a median follow-up of 37 months, 3-yr results and acute local toxicity are compared with those from ALT-G trial and from our data-base of pts treated with alternating cisplatin/5-FU and RT without gemcitabine (ALT): Conclusions: In conclusion, the addition of low-dose gemcitabine into a consolidated cisplatin/5FU and RT alternating program may improve the outcomes with an acceptable increase in acute severe mucositis. No significant financial relationships to disclose. [Table: see text]

Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12590-e12590
Author(s):  
Sani Mohammed Bukari ◽  
Muhammad Usman ◽  
Judith Abrams ◽  
Voravit Ratanatharathorn ◽  
Joseph P. Uberti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Locally Advanced ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
High Dose

e12590 Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) > 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.

Increased Number of High Dose Methotrexate Cycles and the Addition of Rituximab Is Associated with Better Outcomes in a Large Primary CNSL Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4125-4125
Author(s):  
Prakirthi Yerram ◽  
Samantha Nicole Reiss ◽  
Lisa Modelevsky ◽  
Lauren Schaff ◽  
Anne Reiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Multivariable Analysis ◽  
Standard Of Care ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Historical Cohort ◽  
Dose Methotrexate

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor confined to the brain, eyes, and cerebrospinal fluid. Over the past few decades, prognosis for PCNSL has significantly improved due to the standard use of high dose methotrexate (MTX) containing treatment regimens. However, it remains unclear if the number of MTX doses and the addition of rituximab has an impact on clinical outcomes. The recent HOVON 105/ALLG NHL 24 study questioned the role of rituximab in the first line setting when combined with a MTX based polychemotherapy using only 4 doses of MTX and 6 doses of rituximab. Over the last 30 years, standard of care at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of MTX doses and those treated with and without rituximab. The purpose of this study was to describe clinical outcomes based on standard of care treatment changes. Methods: This single-center retrospective IRB approved study at MSKCC included patients with immunocompetent PCNSL, age ≥18 years and diagnosed between 1/1983-11/2017. Patients were identified through a departmental database and electronic medical record. The primary objective was to describe overall survival (OS) based on common prognostic markers such as age, KPS, MSKCC prognostic score class (RPA I- III), use of rituximab, and number of methotrexate cycles. Overall survival was calculated from the date of diagnosis to death or last follow-up using Kaplan-Meier methodology. When examining effect of MTX on OS, OS was calculated from date of last MTX cycle until death or last follow-up. Univariable and multivariable analysis for prognostic factors were analyzed using Cox proportional hazards regression. Results: Five hundred and forty-six patients with newly diagnosed PCNSL were identified. Median age at diagnosis was 62 (range 19 to 90), median KPS was 70 (range 10 to 100), and 282 (52%) were men. In total, 472 patients (86.4%) received high dose MTX. Of 460 with known number of MTX cycles, 95 (20.7%) received 1-4 cycles and 365 (79.3%) received ≥5 cycles (5 cycles: 189, 41.1%, 6 cycles: 24, 5.2%, 7 cycles: 74, 16.1%, 8+ cycles: 78, 17%). Rituximab was given to 231 (42.3%). Three hundred and ten (56.8%) patients, treated before 2006, had been reported previously (historic cohort) and 236 (43.2%) served as contemporary cohort. Median OS of the entire population was 4.7 years (95% CI: 3.8-5.7); 3.3 years (95% CI: 2.8-4.1) in the historic and 8.1 years (95% CI: 6.6-no upper limit) in the contemporary cohort. Five-year OS was 40.3% (95% CI: 35.1-46.2) for the historical cohort and 61.8% (95% CI: 55.0-69.5) for the contemporary cohort. Median OS in the contemporary cohort improved in all RPA classes in comparison to patients treated before 2006 (RPA I: not yet reached vs 9.2 years; RPA II: 7.6 years vs 3.5 years; RPA III 2.8 years vs 1.0 year) (Fig. 1). For the historical cohort compared to the contemporary cohort, five-year OS changed from 62.8% to 91.0% in RPA I, 42.0% to 63.0% in RPA II, and 16.3% to 36.9% in RPA III. Patients receiving ≥ 6 cycles of MTX had a better clinical outcome (median OS from last MTX cycle: 7.8 years versus 4.3 years; HR 0.68 (95% CI (0.51 - 0.91), p=0.0085) on multivariable analysis adjusted for age, KPS, sex, RPA classes Additionally, the stratification of rituximab further elucidated the association between MTX cycles and OS, such that in patients receiving rituximab, those treated with ≥ 6 cycles of MTX experienced longer median OS compared to patients receiving < 6 cycles of MTX (13.0 years vs 9.4 years, p=0.001). Furthermore, in patients receiving ≥ 6 cycles of MTX, there was a survival benefit seen in patients who received rituximab compared to those who did not receive rituximab (13.02 years vs 1.61 years, p<000.1) (Fig.2). Conclusions: Overall survival for newly diagnosed PCNSL has improved significantly over the last few decades regardless of age, KPS, RPA class. Patients seem to benefit with the addition of rituximab and when receiving 6 or more cycles of MTX. Disclosures Grommes: BTG: Consultancy; Kite: Consultancy; Squipps: Speakers Bureau.

Myeloablative Conditioning in Myelofibrosis using i.v. Treosulfan and Autologous Peripheral Blood Progenitor Cell Transplantation with High Doses of CD34+ Cells Results in Hematologic Responses - Follow-Up of Three Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5220-5220
Author(s):  
Stefan Fruehauf ◽  
Eike C. Buss ◽  
Julian Topaly ◽  
Hans H. Kreipe ◽  
Anthony D. Ho
Keyword(s):  
Dose Range ◽  
Allogeneic Transplantation ◽  
Morbidity And Mortality ◽  
High Dose ◽  
High Morbidity ◽  
Severe Toxicity ◽  
Post Transplantation ◽  
Myeloid Metaplasia ◽  
Cd34 Cells

Abstract Myelofibrosis with myeloid metaplasia is a chronic myeloproliferative disorder. The only curative therapy to date is myeloablation followed by allogeneic transplantation. This approach, however, is associated with a high morbidity and mortality. Autologous transplantation after myeloablation with high-dose oral busulfan provides a palliative approach which can lead to a long-term relief of symptoms and is associated with acceptable morbidity and mortality (Anderson JE et al. 2001, Blood 98: 586). However, busulfan pharmacokinetics after oral administration can vary between patients and increased toxicity is encountered in some. On the other hand treosulfan, a bi-functional alkylating drug, can be administered safely i.v. with reliable pharmacokinetics up to the myeloablative dose range. In the study presented here, patients were stimulated with G-CSF 16 μg/kg daily for 4 days and subsequent leukapheresis of a minimum of 5 x 106 CD34+ cells/kg was performed. Myeloablation consisted of treosulfan infusions of 14 g/m2 for three consecutive days (total dose 42 g/m2) and subsequent autologous PBPCT. To date we have transplanted 3 patients, all female. Two patients (#1, #3) had symptomatic splenomegaly and severe anemia. Patient #2 had symptomatic splenomegaly and thrombocytopenia (< 100/nl). The WB nadir after treosulfan therapy was 0.06/nl (#1), 0.28/nl (#2) and 0.09/nl (#3). The time to reconstitution of leucocytes > 1/nl post transplantation was 28 days (#1, #2) and 38 days (#3) and the time for reconstitution of thrombocytes > 50/nl was 36 (#1), 22 (#2) and 33 (#3) days. The prolonged reconstitution period may have been due to the myelofibrosis and has also been observed after busulfan conditioning and PBPCT by others. There were no fever or other severe toxicity. Patients did not require total parenteral nutrition. The patients have been followed-up for 18 months post transplantation, now. The first patient (#1), who required erythrocyte transfusions twice weekly pretransplant received her last erythrocyte transfusion on day 56; her Hb-value is 11.2 g/dl at last follow-up. The second patient (#2) recovered to platelet counts higher than pre-transplantation (58/nl) at 3 months.(143/nl) and had 103/nl at last follow-up. Pat. #3 showed a marked reduction of max. spleen size and a rise in Hb from 9 g/dl to 12 g/dl after 12 months, the Hb value at 18 months is 8.7 g/dl and allogeneic transplantation is considered now. We conclude that myeloablation with treosulfan and autologous PBPCT in these three patients with myelofibrosis was safe and useful. Survival of these patients is promising up to date. The results presented warrant further exploration of this approach in a clinical study which has been initiated by our group. (cf. http://leukaemie.krebsinfo.de/kn_home/Studien/studie_101.html).

Induction (Ind) plus concurrent (Con) chemotherapy with high-dose (74 Gy) 3-dimensional (3-D) thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC): Preliminary report of Cancer and Leukemia Group B (CALGB) 30105

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7042-7042 ◽  
Author(s):  
A. W. Blackstock ◽  
M. A. Socinski ◽  
J. Bogart ◽  
L. Gu ◽  
X. Wang ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Stage Iii ◽  
High Dose ◽  
Free Survival ◽  
3 Dimensional ◽  
Randomized Phase Ii ◽  
Group B ◽  
Leukemia Group

7042 Background: Combined chemoradiotherapy is the standard of care in stage III NSCLC. At standard TRT doses, local failures remain problematic and strategies exploiting the dose-response aspect of TRT are warranted. 3-D TRT allows escalation of TRT dose with acceptable toxicity (Socinski et al, J Clin Oncol 22:4341, 2004) and may enhance survival by improving loco-regional control. Methods: This is a two-arm randomized phase II trial evaluating 74 Gy with Con chemotherapy: Arm A- 2 cycles of Ind carboplatin (C) (AUC 6) and paclitaxel (P) (225 mg/m2) followed by weekly Con C (AUC 2/wk) and P (45 mg/m2) and 74 Gy; Arm B- 2 cycles of Ind C (AUC 5) and gemcitabine (G) (1000 mg/m2 d1,8) followed by Con G (35 mg/m2 twice weekly) and 74 Gy. The primary endpoint was a survival rate of ≥50% at 18 months after treatment initiation or med survival time (MST) of ≥18 mos. Results: 69 pts were entered (43 Arm A, 26 Arm B)- med age 61 yrs (39–77), 77% male, PS 0:1 42%:58%, stage IIIA:B 52%:48%. Ind therapy on both arms was well tolerated with no pts experiencing disease progression. ARM A- Overall response rate (RR) to all therapy was 61.9%. Gr 3–4 toxicities during Con therapy were anemia (15%), neutropenia (26%), esophagitis (9%), fatigue (9%), neuropathy (3%) and pulmonary (12%). There was 1 (3%) Gr 5 cardiac event. With med follow-up of 16.4 mos, the med progression-free survival (PFS) is 15.2 mos. The MST is not mature enough to estimate as only 15 deaths have occurred. ARM B- Closed early due to 3 (13%) Gr 5 pulmonary events. Overall RR to all therapy was 66.6%. Gr 3–4 toxicities during Con therapy were anemia (13%), fatigue (35%), esophagitis (35%), hemoptysis (4%), pulmonary (26% plus the 3 Gr 5 events). With med follow-up of 22 mos, the med PFS is 7.7 mos and the MST is 13.9 mos. There was a correlation between Gr 3–5 pulmonary toxicity and V20 ≥ 38% (p<0.05). Conclusions: 1) High dose 3-D TRT is feasible within CALGB, 2) the details of TRT (V20) are important with regard to toxicity, 3) the survival of pts on Arm A appears promising. [Table: see text]

Progressive Quadriparesis and Cancer

2021 ◽  
pp. 122-124
Author(s):  
Elia Sechi ◽  
Eoin P. Flanagan
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuropathic Pain ◽  
Intravenous Immunoglobulin ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Oral Corticosteroids ◽  
Bowel And Bladder Dysfunction ◽  
Dose Oral

A 67-year-old man with a history of cigarette smoking sought care at the emergency department for nonspecific dizziness and fatigue. During evaluation, chest radiography showed a right upper lobe mass, and he subsequently underwent right upper lobectomy. Histologic analysis of resected tissue showed the mass to be small cell lung carcinoma. Progressive myelopathy developed. Adjuvant chemotherapy with carboplatin and etoposide was begun. His neurologic symptoms continued to worsen, with gait imbalance, along with numbness and dysesthesias of the 4 limbs and trunk, with a sensory level at C3-C4. He also reported severe bowel and bladder dysfunction. At his neurologic nadir, he had severe quadriparesis and was wheelchair dependent. Cerebrospinal fluid analysis showed lymphocytic pleocytosis of 9 lymphocytes/µL, erythrocyte count of 2/µL, and normal protein and glucose values. Serum neural autoantibody screening revealed the presence of collapsin-response mediator protein 5–immunoglobulin G antibodies on both tissue-based indirect immunofluorescence assay and Western blot. The patient was diagnosed with paraneoplastic myelopathy. The patient was initially treated acutely with a combination of high-dose oral prednisone and plasmapheresis, without improvement. Subsequently, a combination of intravenous immunoglobulin and rituximab resulted in partial improvement. Soon after treatment discontinuation, his symptoms returned with worsening weakness, numbness, and neuropathic pain. Monthly intravenous immunoglobulin and rituximab were reinitiated, with improvement again noted. Oral corticosteroids, methadone, and high-dose gabapentin were also administered, with mild benefit for neuropathic pain. Follow-up spine magnetic resonance imaging 3 years after symptom onset showed evidence of spinal cord atrophy. At 5-year follow-up he remained in remission from small cell lung cancer but was wheelchair dependent. Paraneoplastic myelopathy is a rare and underrecognized neurologic disorder that most often manifests before cancer detection, Clinical presentation is generally subacute or slowly progressive over months, but acute onset is possible. Cerebrospinal fluid typically shows lymphocytic pleocytosis, as in this case patient.

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