A High Angiopoietin-2/Angiopoietin-1 Ratio Independently Predicts Septic Shock Development in Patients with Chemotherapy-Associated Febrile Neutropenia and Hematological Malignancies.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2154-2154
Author(s):  
Maiara Marx Luz Fiusa ◽  
Carolina Costa-Lima ◽  
Gleice Regina Souza ◽  
Afonso Celso Vigorito ◽  
Francisco J P Aranha ◽  
...  
Keyword(s):  
Septic Shock ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Hematological Malignancies ◽  
Hematologic Malignancies ◽  
Endothelial Barrier ◽  
Prognostic Impact ◽  
Independent Population ◽  
Significant Difference ◽  
Risk Patients

Abstract Abstract 2154 Introduction: Febrile neutropenia (FN) patients with hematologic malignancies present a high risk of septic shock. Clinical scores such as MASCC can identify low-risk patients with FN, mainly in the outpatient setting, but are not very informative for high-risk patients (MASCC<21), which is the category that most patients with hematologic malignancies fit in. Endothelial barrier breakdown is a key element in septic shock, so that proteins involved in this process are currently considered among the most promising biomarkers and therapeutic targets in sepsis. Notably, angiopoietins (Ang) 1 and 2 are key elements of embryonic vascular development, with vessel-stabilizing and -destabilizing properties respectively. In an exploratory study, we previously demonstrated that levels of these proteins are increased in neutropenic patients with septic shock. Materials and Methods: here we prospectively evaluated the significance of VEGF-A, sFlt-1, Ang-1 and Ang-2 levels as biomarkers of septic shock progression in an independent population of patients with chemotherapy-associated FN and hematological malignancies. The study was deliberately designed to mimic real-life conditions in which a sepsis biomarker would be ordered. All patients admitted to the Hematology or BMT wards of our Institution for the treatment of FN between April 2011 and March 2012 were invited to participate. Blood samples were collected in the morning after enrollment, along with the routine blood work-up, by non-study staff. Biomarker levels were obtained by commercially-available ELISA. Primary clinical endpoints were septic shock development or mortality from infection, in 30 days from fever onset. Results: Of the 99 patients that fulfilled the inclusion criteria, 20 (19.8%) developed septic shock and 17 (16.8%) died from infection. Of these, 78 (78.8%) were classified as high-risk according to the MASCC score, a distribution characteristic of hematological malignancies. There were no significant clinical and demographic differences between patients with non-complicated FN and septic shock. No significant difference could be detected in VEGF-A or sFlt-1 levels between outcome groups either. In contrast, Ang-2 concentrations were increased in patients with septic shock (6,494 pg/ml, range 1,730–49,611 pg/ml) compared to non-complicated FN (4,467 pg/ml, range 1,289–37,318 pg/ml; P=0.02), whereas an inverse finding was observed for Ang-1 concentrations, which were lower in patients that developed septic shock (898.8 pg/ml, range 77.87–5,420 pg/ml) than in patients with non-complicated FN (1,220 pg/ml, range 32.55–47,924 pg/ml; P=0.07). Because imbalances between Ang-1 and Ang-2 could be more informative than each isolated biomarker, we calculated the Ang-2/Ang-1 ratio, which was much higher in patients with septic shock (5.29, range 0.58–57.14) than in non-complicated FN (1.99, range 0.06–64.62; P = 0.01). When analyzed as a continuous variable, the Ang-2/Ang-1 ratio proved to be an independent factor for shock septic development. The presence of a threshold level of Ang-2/Ang-1 ratio for an increase in the risk of shock septic could be demonstrated by dichotomizing the ratio by the median and by the optimal cut-off value identified using a ROC procedure (Ang-2/Ang-1=5.0). After adjustment for confounding factors, the multivariate risk for septic shock development was RR=5.47 (CI95% 1.93–15.53) for values above 5.0 and RR=2.99 (CI95%1.02–8.42) for values above the median. Similar results were obtained for 30-day mortality from infection. Conclusion: the prognostic impact of a high Ang-2/Ang-1 ratio as a biomarker for septic shock development was demonstrated in an independent and representative population of high-risk FN patients. The persistence of statistical significance of this association in a much less controlled context than in exploratory studies of biomarker research highlights the strength of the association between this important modulator of endothelial barrier integrity and progression to septic shock. This information has important implications for the clinical management of patients with FN and hematological malignancies, for whom no validated sepsis biomarkers are used in clinical practice, as well as for the development of new therapeutic strategies for the treatment of septic shock. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological Profile and Outcome in High Risk Patients

2015 ◽  
Vol 7 (02) ◽  
pp. 116-120 ◽  
Author(s):  
Kuntegowdanahalli C Lakshmaiah ◽  
Abhayakumar S Malabagi ◽  
Rachan Shetty ◽  
Mahua Sinha ◽  
Rudrapatna S Jayashree ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Hematological Malignancies ◽  
Hematologic Malignancies ◽  
First Line ◽  
Gram Negative ◽  
Microbiological Profile ◽  
Satisfactory Outcome ◽  
Sensitivity Pattern ◽  
Empiric Antibiotic

ABSTRACT Background and Objectives: Febrile neutropenia (FN) is considered a medical emergency. Patients with hematological malignancies (HM) commonly experience FN. Broad spectrum antibiotics have to be started empirically to prevent complications. This study depicts the clinical profile, microbiological profile, antibiotic sensitivity pattern, and outcome in high risk HM. Materials and Methods: In this prospective study, 72 patients with hematologic malignancies, diagnosed and treated for 108 high risk febrile neutropenic episodes from August 2011 to January 2013 at a Regional Cancer Center, in South India were analyzed. Cefoperazone-sulbactum was used as a first-line empiric antibiotic. Results: Majority of the patients with FN episodes had acute myeloid leukemia. Overall culture positivity was 29.62%. The most common organisms isolated were Gram-negative bacilli (63.64%), with Escherichia coli being the most frequent pathogen. All Gram-negative organisms were sensitive to imipenem, whereas sensitivity pattern to other antibiotics were as follows: 85.71%, 78.26%, 69.52%, 63.64%, 41.66% and 47.05% for pipercillin-tazoactum, meropenem, cefoperazone-sulbactum, amikacin, ceftazidime, ciprofloxacin respectively. Overall mortality was 13.5%. Most of the patients responded to empiric antibiotic cefoperazone-sulbactum. Conclusions: In the hematologic malignancies particularly in acute leukemia, there is high risk of developing FN. Empiric therapy with cefoperazone-sulbactum as a first line leads to satisfactory outcome in high risk FN and therapy should be tailored to the most appropriate antibiotics according to the bacterial culture results.

scholarly journals Reduced Mortality From KPC-K.Pneumoniae Bloodstream Infection in High-Risk Patients With Hematological Malignancies Colonized by KPC-K.Pneumoniae

2020 ◽  
Author(s):  
Alessandra Micozzi ◽  
Giuseppe Gentile ◽  
Stefania Santilli ◽  
Clara Minotti ◽  
Saveria Capria ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Bloodstream Infection ◽  
Active Treatment ◽  
Hematological Malignancies ◽  
Hematological Malignancy ◽  
High Risk Patients ◽  
Period 2 ◽  
Risk Patients ◽  
Related Mortality

Abstract Background. KPC-K.pneumoniae bloodstream infection (KPC-KpBSI) mortality rate in patients with hematological malignancies is reported about 60%. The initial treatment active against KPC-K.pneumoniae is crucial for survival and KPC-K.pneumoniae rectal colonization usually precedes KPC-KpBSI. We evaluated the impact on KPC-KpBSI mortality of the preemptive use of antibiotics active against KPC-K.pneumoniae, as opposed to inactive or standard empiric antibiotics, for the empiric treatment of febrile neutropenia episodes in patients with hematological malignancy identified as KPC-K.pneumoniae intestinal carriers. Methods. We compared the outcomes of KPC-KpBSIs occurring in high-risk patients with hematological malignancy known to be colonized with KPC-K.pneumoniae, during two time periods: March 2012-December 2013 (Period 1, initial approach to KPC-K.pneumoniae spread) and January 2017-October 2018 (Period 2, full application of the preemptive strategy). The relative importance of the various prognostic factors that could influence death rates were assessed by forward stepwise logistic regression models.Results. KPC-KpBSI-related mortality in patients with hematological malignancies identified as KPC-K.pneumoniae carriers dropped from 50% in Period 1 to 6% in Period 2 (p<0.01), from 58% to 9% in acute myeloid leukemia carriers (p<0.01). KPC-KpBSIs developed in patients identified as KPC-K.pneumoniae carriers were treated with initial active therapy in 56% and 100% of cases in Period 1 and Period 2, respectively (p<0.01), consisting in active antibiotic combinations in 39% and 94% of cases, respectively (p<0.01). In Period 1, the 61% of KPC-KpBSI were breakthrough (fatal in the 73% of cases) while no breakthrough KPC-KpBSI was observed in Period 2 (p<0.01). Overall, KPC-KpBSI-related mortality was 88% with no initial active treatment, 11.5% with at least one initial active antibiotic (p<0.01), 9% with initial active combination. Only the initial active treatment resulted independently associated with survival. Conclusions. In high-risk patients with hematological malignancies colonized by KPC-K.pneumoniae, the empiric treatment of febrile neutropenia active against KPC-K.pneumoniae reduced KPC-KpBSI-related mortality to 6% and prevented fatal breakthrough KPC-KpBSI.

scholarly journals A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons

2021 ◽  
Author(s):  
Nobu Akiyama ◽  
Takuho Okamura ◽  
Minoru Yoshida ◽  
Shun-ichi Kimura ◽  
Shingo Yano ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Supportive Care ◽  
Questionnaire Survey ◽  
Primary Treatment ◽  
Beta Lactam ◽  
Clinical Practices ◽  
High Risk Patients ◽  
Mascc Score ◽  
Risk Patients

Abstract Purpose The Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study’s purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics. Result A total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score “always” or “more than half.” Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10–20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency < 10% regimen. The medians of complete and complete plus partial compliance rates were 46.4% (range 7.0–92.8) and 77.8% (range 35.4–98.7). The complete compliance rates were less than 30% in seven recommendations, including the MASCC score assessment. Conclusion GL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

P–671 Dual Trigger(low adjuvant HCG4h after GnRHagonist trigger)have positive impact of overall embryo’s quality, implantation ,clinical pregnancy and live birth rates in high-risk patients for OHSS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Petanovsk. Kostova
Keyword(s):  
High Risk ◽  
Live Birth ◽  
Clinical Pregnancy ◽  
Birth Rates ◽  
High Risk Patients ◽  
Live Birth Rates ◽  
Significant Difference ◽  
Risk Patients ◽  
Group A ◽  
Group B

Abstract Study question Study aim is to compare implantation,clinical pregnancy and livebirth rates between giving1500IU of hCG4hours after GnRHagonist,on trigger day or GnRHagonist as alone trigger with luteal support withHCG1500IU.35h later on OPUday. Summary answer Adjuvant doze of1500IUhCG4h after bolus of GnRHagonist on trigger day significantly improve quality of blastocyst,implantation,clinical pregnancy and live birth rates without increasing the risk ofOHSS. What is known already The use of GnRHagonist for final oocyte maturation in antagonist cycle significantly decrease the incidence of OHSS,but there have been studies showing lower pregnancy rates in patients triggered with GnRHagonist compared with hCG in autologous cycles,attributed to a defective luteal phase, especially in high–risk patients despite intensive luteal phase support.To improve the results of IVF,an alternative approach is adding a small bolus dose of hCG(1500IU)35h later,on the OPU day after GnRHagonist trigger which provides more sustained support for the corpus luteum.The question is does low doses of hCGgiven on the same day with GnRHagonist trigger is making better quality oocytes. Study design, size, duration Single center prospective longitudinal cohort study fromJanuary2017 to Decembar2019.The initial inclusion criteria were:women age≥18and≤39years,AMH≥3,3ng/ml and ≥12 antral follicles on basal ultrasound.Patients with history of OHSS and PCO are also included in the study.Patients with applied “freeze-all” technique with peak estradiol≥4000pg/ml on trigger day&gt;18oocytes on the OPU day,and recognized significant risk for developing OHSS were also included.The cumulative implantation,clinical pregnancy and live birth rates were analyzed,only in embryos from the same COS protocol in every patient. Participants/materials, setting, methods A total of 231 patients were entered for final analysis,who underwent a flexible antagonist protocol,ICSI and fresh or thawed ET on 3th(38.53%) or 5th( 61.47%)day in women’s autologous cycles.Patients were randomized in one of two groups: GroupA-Dual trigger group 1500IUof hCG 4h after GnRH agonist application on trigger day and GroupB –1500IU of HCG 35h later,on the OPU day.We used nonparametric and parametric statistical tests.Significant differences were considered all values ​​of p &lt; 0.05 Main results and the role of chance Both groups are homogenous regarding several variables:age,BMI,type of sterility,smoking status,AMH,PCO, spermogram.There is no significant difference between the two(AvsB)groups according to average number of retrieved oocytes(13.6 vs 14.6 p &gt; 0,05),M II oocytes(11.03 vs 11.99 p &gt; 0.05).The dual trigger group(A)had a higher fertility rate(69.99% vs 64.11% p &lt; 0,05)compared with GnRHagonist trigger group(B).There are no significant difference between groups(AvsB)according to cumulative average number of:transferred embryos(2.4vs2.5 p &gt; 0.05)TQE transfered on 3th day(1.5.vs 1.3.p&gt;0.05);transferred blastocyst(2.6 vs2.7 &gt;0.05);cryo embryos(2.5vs1.9 p &gt; 0.05),but there are significant difference according to cumulative implantation rate of transferred blastocyst in favor of group A(48.18% vs 33.89%p&lt;0.05).Analyzes of morphological characteristics of transferred blastocyst depicted in the order of degree of blastocyst expansion,inner cellular mass(ICM)and trofoectoderm(TE) and ranking overall blastocysts quality from“excellent”,“good”,“average” and “pore” ,shows that there are significantly more percentage of patient with embryo transfer of “excellent” or even one “excellent” blastocyst in group A (30.56%,31.94% vs 21.54%,23.08% p &lt; 0.05) in opposite of percentage of patients with embryo transfer with “poore “” blastocyst in group B (37.5% vs 46.15.%p&lt;0.05). Clinical pregnanacy rate (71.68% vs 50.84% p &lt; 0.05) , and live birth rate (60,18% vs 42,58% ), were significantly higher in group A. There were no cases of moderate or severe OHSS in both groups. Limitations, reasons for caution Dual trigger in GnRH antagonist protocols should be advocated as a safe approach but undetected high risk patients are reasons for caution for developing clinically significant OHSS. Wider implications of the findings: Adjuvant low dose of hCG on GnRHagonist trigger day improve clinical pregnancy and live birth rates without increasing the risk of clinically significant OHSS.Protocol of dual trigger and freezing all oocytes or embryos in patients with high risk of developing OHSS is promising technique in everyday practice. Trial registration number 8698

scholarly journals Preoperative Score to Stratify Recurrence Risk After Curative Resection of Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Yu Jiang ◽  
SIYI Zou ◽  
Weishen Wang ◽  
Haoda Chen ◽  
Qian Zhan ◽  
...  
Keyword(s):  
High Risk ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Score ◽  
Multidisciplinary Treatment ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Final Model ◽  
Significant Difference ◽  
Risk Patients

Abstract Background: Oncological survival after operation of resectable pancreatic ductal adenocarcinoma (R-PDAC) is variable depending on various factors. Preoperative risk stratification could guide decision-making in multidisciplinary treatment concepts. We develop and validate a prognostic score for disease-free survival (DFS) in R-PDAC to solve this issue.Methods: 421 R-PDAC patients between January 2012 and December 2015 were enrolled. Performance of the final model was evaluated with respect to discrimination, calibration and clinical usefulness. A prognostic score based on the final model was developed, and external validated in 290 patients.Results: On multivariable analysis, age, tumor size, carbohydrate antigen (CA)19-9, CA125, lymphocyte-monocyte ratio, and systemic-immune-inflammation index were independently associated with DFS. Final model had acceptable calibration, discrimination and internal validity. The prognostic score could delineate low- and high-risk groups with median DFS of 19.6 and 10.1 months (P<0.0001). Tumors in high-risk group exhibited more aggressive pathobiological behaviors. Additionally, at 1-year follow-up, the restricted mean survival time was longer with adjuvant chemotherapy than those without in low-risk patients. However, no significant difference was detected in high-risk patients.Discussion: The prognostic score could accurately predict DFS preoperatively in R-PDAC patients and provide reference for risk-adapted strategies formulation for R-PDAC management in the future.

Aggressive intravenous hydration with lactated Ringer’s solution for prevention of post-ERCP pancreatitis: a prospective randomized multicenter clinical trial

Endoscopy ◽  
2017 ◽  
Vol 50 (04) ◽  
pp. 378-385 ◽  
Author(s):  
Chang-Hwan Park ◽  
Woo Paik ◽  
Eun Park ◽  
Chan Shim ◽  
Tae Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Multicenter Trial ◽  
High Risk Patients ◽  
Intention To Treat ◽  
Ringer’S Solution ◽  
Significant Difference ◽  
Risk Patients ◽  
Intravenous Hydration ◽  
Lactated Ringer's Solution ◽  
First Time

Abstract Background and study aims The present study aimed to determine the type of intravenous hydration that is best suited to reducing the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Patients and methods In a prospective randomized multicenter trial, average-to-high risk patients who underwent first-time ERCP were randomly assigned to three groups (1:1:1) who received: aggressive intravenous hydration (3 mL/kg/h during ERCP, a 20-mL/kg bolus and 3 mL/kg/h for 8 hours after ERCP) with either lactated Ringer’s solution (LRS) or normal saline solution (NSS), or standard intravenous hydration with LRS (1.5 mL/kg/h during and for 8 hours after ERCP). The primary end point was post-ERCP pancreatitis (PEP). Results 395 patients were enrolled, and 385 completed the protocols. The three groups showed no significant differences in demographic characteristics. There was a significant difference in the intention-to-treat (ITT) PEP rate between the aggressive LRS group (3.0 %, 95 % confidence interval [CI] 0.1 % – 5.9 %; 4 /132), the aggressive NSS group (6.7 %, 95 %CI 2.5 % – 10.9 %; 9 /134) and the standard LRS group (11.6 %, 95 %CI 6.1 % – 17.2 %; 15 /129; P = 0.03). In the two-group comparisons, the ITT PEP rate was significantly lower for the aggressive LRS group than for the standard LRS group (relative risk [RR] 0.26, 95 %CI 0.08 – 0.76; P = 0.008). There was no significant difference in the ITT PEP rate between the aggressive NSS group and the standard LRS group (RR 0.57, 95 %CI 0.26 – 1.27; P = 0.17). Conclusion Aggressive hydration with LRS is the best approach to intravenous hydration for the prevention of PEP in average-to-high risk patients.

scholarly journals Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2139-2149 ◽  
Author(s):  
JH Antin ◽  
BE Bierer ◽  
BR Smith ◽  
J Ferrara ◽  
EC Guinan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Graft Failure ◽  
Hematologic Malignancies ◽  
Host Disease ◽  
Graft Versus Host ◽  
High Risk Patients ◽  
Risk Patients

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti- CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC- mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC- mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.

Oxycodone-induced neurotoxicity secondary, to concurrent voriconazole use in a patient with cancer

2017 ◽  
Vol 13 (3) ◽  
pp. 141 ◽  
Author(s):  
Lana Alghothani, MD ◽  
Jillian Gustin, MD
Keyword(s):  
Chronic Pain ◽  
High Risk ◽  
Adverse Effects ◽  
Advanced Disease ◽  
Hematologic Malignancies ◽  
Patients With Cancer ◽  
Concurrent Use ◽  
Underlying Malignancy ◽  
Risk Patients ◽  
Active Disease

Chronic pain is common in patients with underlying malignancy with prevalence of up to 70 percent in those with advanced disease. Opioids are often used for those with both active disease and chronic cancer-related pain. In high-risk patients with hematologic malignancies and pneumonia, the Infectious Diseases Society of America recommends empiric antifungal therapy, often with voriconazole or another similar azole agent. Thus, patients with cancer are commonly on medications, such as antifungals, that have the potential to interact with opioids, causing adverse effects. Our case demonstrates severe neurotoxicity due to the concurrent use of voriconazole and oxycodone.

Intensified Conditioning for Children Undergoing BMT for First Bone Marrow Relapse of Acute Lymphoblastic Leukaemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5169-5169
Author(s):  
John Moppett ◽  
Jerry Hancock ◽  
Christopher J.C. Knechtli ◽  
Anthony Oakhill ◽  
Nicholas J. Goulden
Keyword(s):  
High Risk ◽  
Treatment Failure ◽  
Risk Group ◽  
Control Group ◽  
Childhood All ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients ◽  
High Level ◽  
Risk Of Treatment

Abstract BMT remains the treatment of choice for early BM relapse of childhood ALL. We reasoned that further intensification of cytoreductive therapy pre-BMT may further improve survival amongst those with the highest risk of treatment failure, early BM relapse (BFM groups S3/4) and high level MRD pre-BMT. A cohort of 32 patients transplanted at a single institution (1996–1999) provided an historical control. 8 high risk patients transplanted 1999–2000 received additional fludarabine cytoreduction therapy at the time of transplant (FLA group). MRD analysis and time to relapse were used in a subsequent cohort of 22 patients (BMT 2000–2002) to allocate those at highest risk of treatment failure to receive a further cytoreductive block, FLX, pre-BMT. Method. All patients were conditioned with cyclophosphamide (60mg/m2 x2) and TBI (14.4 Gy). UD and haplo-BMT were T-cell depleted with Campth-1M in vitro and Campath-1G day -9 to -5 (Control and FLA group), and by Miltenyi CD34+ cell depletion (FLX group). GvHD prophylaxis - CSA + MTX for matched related, CSA for Campath treated grafts and none for Miltenyi grafts. The FLA group received fludarabine 25mg/m2 from d −12 to d −10. Patients with on treatment relapse (S4) or high level MRD pre-BMT (MRD++) in the FLX group received DaunoXome 100mg/m2, fludarabine 30mg/m2 x 5d and cytosine 2g/m2 x 5d 3 weeks prior to BMT. Patients and donors. Control group: 28 precursor-B ALL 4 T-ALL; donors - 7 matched related, 13 matched unrelated (MUD) and 12 mismatched unrelated (MMUD); 14 S2, 18 S3/4. FLA group: 5 presursor-B ALL and 3 T-ALL; donors - 2 SIB, 4 MUD, 1 MMUD and 2 haplo; all S4. FLX group: 21 precursor-B and 1 T-ALL; donors - 6 SIB, 7 MUD, 5 MMUD and 4 haplo;13 S2, 9 S4. 7 patients received FLX intensified conditioning (6 S4, 5 high level MRD ++). 3 high risk patients violated protocol and did not receive FLX (1 age &lt;1yr on treatment relapse, 2 S2 MRD ++). Results. Considering those in the high-risk S3/4 group, there was no significant difference in OS between the 3 groups. Survival by study and risk group Study S2 S3/4 Overall Control 10/14 (71%) 3/18 (17%) 13/32 (41%) FLA 2/8 (25%) 2/8 (25%) FLX 11/13 (85%) 3/9 (33%) 14/22 (64%) No excess cardiac events were seen. The TRM is higher in the FLX group than in the control. Outcome data Study TRM Relapse Alive Total Control 3 16 13 32 S2 2 2 10 14 S3/4 1 14 3 18 FLA 3 3 6 12 S2 - - - - S3/4 3 3 3 9 FLX 6 2 14 22 S2 2 0 11 13 S3/4 4 2 3 9 Total 12 21 33 66 2 of 7 patients treated with FLX are in CCR, 2 relapsed and 3 died of TRM. The 3 high risk patients in the FLX study, but who did not receive FLX, are also in CCR. Survival in those in the S2 group (late BM relapse) has been good throughout the study period. Conclusion. In this study the addition of intensive pre-BMT conditioning has not improved survival amongst high risk (S3/4 or MRD ++ pre-BMT) relapses. The number of post-BMT relapses has fallen but this is not clearly related to the use of FLX. The use of more haploidentical donors, more immunosupressive BMT regimes and additional cytoreductive chemotherapy may have contributed to the increased TRM seen. Time and site of relapse remain the clearest predictor of outcome. Further novel strategies are required to improve survival for the S4 risk group. The good OS for children receiving BMT in the S2 group should be noted.

Therapeutic CSF Primed Donor Lymphocyte Infusion Using Cells Reserved at the Time of Transplantation for Patients with Relapsed Hematologic Malignancies after allo-PBSCT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5285-5285
Author(s):  
Sang Kyun Sohn ◽  
YoonYoung Cho ◽  
JongGwang Kim ◽  
YeeSoo Chae
Keyword(s):  
High Risk ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Donor Lymphocyte Infusion ◽  
Cd34 Cells ◽  
New Development ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Intent To Treat ◽  
Relapsed Disease

Abstract Background Reharvesting leukocytes from donors for a donor lymphocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. The effect of a growth factor-primed DLI is known to be comparable to that of nonprimed DLI for patients with relapsed disease. We reserved some portion of PBSCs harvested at the time of transplantation for the purpose of future DLI for relaping disease. Method In total, ninety nine patients (43 high risk, 46 standard disease) with hematologic malignancies who were treated by allo-PBSCT were allocated on an intent-to-treat basis. The dose of CD34+ cells with a range of 2–6*106/kg was transplanted, and additional PBSCs were cryopreserved. Result PBSC harvest for transplantation allowed to reserve extra cells in 35 (67.3%) high risk patients and in low risk 25 (55.6%) patients. Among 29 patients (29.9%) who relapsed after allogeneic PBSCT, 19 (65.5%) patients were treated with mainly cytarabine-based chemotherapy followed by cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLI was 1.43*108/kg and 4.75*106/kg, respectively. Six (24.9%) out of 19 relapsed patients exhibited a complete response after the primed DLI, and their 1-year survival rate was 36%. The new development or progression of graft-versus-host disease after the primed DLI was observed in 16 (82%) patients. Overall, the survival at 1 year after the primed DLI was 21%. Conclusion The induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the time of transplantation, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach seem to be more convenient for donors.

Sign in / Sign up

Export Citation Format

Share Document