Predictive Value of Rothman Index in Patients That Develop Febrile Neutropenia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2107-2107 ◽  
Author(s):  
Luis Alberto Rubio ◽  
David Banach ◽  
Alfred I Lee
Keyword(s):  
Respiratory Failure ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Renal Disease ◽  
Primary Outcome ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Short Term ◽  
Clinical Variables

Abstract Background: Febrile Neutropenia (FN) in cancer patients is associated with a high mortality rate yet identifying patients with FN at highest risk for short term morbidity and mortality remains challenging. The Rothman Index (RI) is a real-time composite measurement of a patient's condition using 26 clinical variables sensitive to signs of patient clinical decline. RI has been shown to predict intensive care unit (ICU) admission, hospital readmission and short term mortality among inpatients. A prior study from our institution demonstrated that hospitalized patients with hematological malignancies and RI < 60 have a greater likelihood of readmission or discharge to hospice rather than those with higher RI scores. The aim of this study was to explore RI as a predictor of adverse outcomes in patients with hematological malignancies who have FN. Methods: Chart records of all patients with hematological malignancies and FN who were hospitalized at Yale Cancer Center between February of 2013 and July of 2014 were reviewed. Clinical variables collected included demographics, malignancy type, comorbidities, admission condition and microbiological data related to the FN episode. The primary outcome measure was a composite of in-hospital mortality and discharge to hospice care. Variables associated with the primary outcome in univariate analysis were entered into a multivariate logistic regression model for analysis. Results: Of 308 patients with hematological malignancies, 180 (58.4%) developed FN during their admission and 38 (12.3%) died during the admission or were discharged to hospice. A total of 85 (27.6%) patients had a RI < 60, 155 (50.3%) had a RI between 60-80, and 71 (23.1%) had a RI > 80. Controlling for malignancy type, major medical comorbidities and microbiologically confirmed bacterial infection, RI < 60 was independently associated with this outcome (Odds ratio 3.02, 95% Confidence Interval 1.25-7.34). Baseline renal disease, pneumonia, respiratory failure and sepsis were also associated with the primary outcome. Conclusion: RI is an objective measure that can independently predict poor outcomes among inpatients with FN. RI can guide clinicians caring for patients with FN in both prognostication and identifying high risk patients with an RI < 60 who are at higher risk for mortality, discharge to hospice, or high risk of readmission. The utility of this scoring system should be compared to existing risk stratification systems used in Oncology to identify its optimal use in the clinical setting. Table 1. Factors associated with inpatient mortality or hospice discharge among hematologic malignancy inpatients with febrile neutropenia Variable OR 95% CI for OR p RI < 60 3.02 1.25-7.34 .015 Respiratory Failure 3.51 1.07-11.56 .039 Renal Disease 4.97 1.38-17.9 .014 Sepsis 8.18 1.63-41.2 .011 Pneumonia 8.01 1.42-45.1 .018 Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set

Blood ◽  
2020 ◽  
Vol 136 (26) ◽  
pp. 3033-3040 ◽  
Author(s):  
Ajai Chari ◽  
Mehmet Kemal Samur ◽  
Joaquin Martinez-Lopez ◽  
Gordon Cook ◽  
Noa Biran ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Renal Disease ◽  
Univariate Analysis ◽  
Staging System ◽  
Outcome Data ◽  
Careful Consideration ◽  
Hospitalized Patients ◽  
Related Factors ◽  
Data Set

Abstract The primary cause of morbidity and mortality in patients with multiple myeloma (MM) is an infection. Therefore, there is great concern about susceptibility to the outcome of COVID-19–infected patients with MM. This retrospective study describes the baseline characteristics and outcome data of COVID-19 infection in 650 patients with plasma cell disorders, collected by the International Myeloma Society to understand the initial challenges faced by myeloma patients during the COVID-19 pandemic. Analyses were performed for hospitalized MM patients. Among hospitalized patients, the median age was 69 years, and nearly all patients (96%) had MM. Approximately 36% were recently diagnosed (2019-2020), and 54% of patients were receiving first-line therapy. Thirty-three percent of patients have died, with significant geographic variability, ranging from 27% to 57% of hospitalized patients. Univariate analysis identified age, International Staging System stage 3 (ISS3), high-risk disease, renal disease, suboptimal myeloma control (active or progressive disease), and 1 or more comorbidities as risk factors for higher rates of death. Neither history of transplant, including within a year of COVID-19 diagnosis, nor other anti-MM treatments were associated with outcomes. Multivariate analysis found that only age, high-risk MM, renal disease, and suboptimal MM control remained independent predictors of adverse outcome with COVID-19 infection. The management of MM in the era of COVID-19 requires careful consideration of patient- and disease-related factors to decrease the risk of acquiring COVID-19 infection, while not compromising disease control through appropriate MM treatment. This study provides initial data to develop recommendations for the management of MM patients with COVID-19 infection.

A Predictive Model for Chemotherapy-Associated Thrombosis Based on Findings from a Prospective Outpatient Registry.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2586-2586
Author(s):  
Alok A. Khorana ◽  
Charles W. Francis ◽  
Eva Culakova ◽  
Rami Komrokji ◽  
Nikhil Uppal ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Model ◽  
Cancer Patients ◽  
Risk Score ◽  
Univariate Analysis ◽  
Fold Increase ◽  
Hematologic Malignancies ◽  
Multivariate Model ◽  
Risk Scores ◽  
Clinical Variables

Abstract Background: Venous thromboembolism (VTE) is a significant complication of cancer and particularly of newer anti-cancer therapies. The risk of VTE is estimated to be 0.04%/month (0.5%/year) in cancer patients. We conducted a prospective analysis to determine the frequency and risk factors for symptomatic VTE in cancer patients actively receiving chemotherapy. Methods: The Awareness of Neutropenia in Cancer (ANC) Study Group is currently enrolling patients with breast, lung, colon, ovary and other cancers, at 137 sites nationwide, with an accrual goal of 4,500 patients. Patients are registered at the time of initiation of a new chemotherapy regimen, and followed for the duration of 4 cycles. The association of VTE with clinical variables was studied in univariate analysis and in a multiple logistic regression model. No significant first-order interactions were observed between the variables in this model. A risk score for VTE was estimated for each subject from the weighted sum of model predictor variables from the multivariate model. Results: A total of 2,151 patients treated with at least one cycle of chemotherapy were available for analysis. Pulmonary embolism occurred in 11, and deep venous thrombosis in 35, for a VTE incidence of 2.14 % over median follow-up of 2.5 months (0.85%/month). Incidence of first VTE event was greatest in cycles 1 (0.93%/cycle) and 2 (0.88%/cycle), and declined in cycle 3 (0.53%/cycle). Incidence varied significantly by site of disease (p=0.01) with highest rates in patients with upper gastrointestinal (2.4%/month) and lung cancers (1.2%/month), and lymphomas (1.2%/month). Other clinical variables associated with development of VTE in univariate analysis included baseline platelet count ≥350,000, an ECOG PS ≥ 2, and baseline use of erythropoietin or colony-stimulating factors. Patients with VTE reported a chemotherapy delay of ≥ 7 days in 40% compared to 23.6% in patients without VTE (OR 2.15, p=0.01). Based on the results of the multivariate model (c statistic=0.73[.65,.81]) the population was divided into low, intermediate and high-risk based on tertiles of risk scores. Patients deemed high-risk had a VTE risk of 1.5%/month, which was a six-fold increase compared to those deemed low-risk (see Table). Conclusion: Symptomatic VTE is much more frequent in cancer patients on chemotherapy than previously estimated, even in patients with hematologic malignancies. VTE is associated with a nearly two-fold risk of significant delay in chemotherapy, which could impact on cancer outcomes. This is the first prospectively generated predictive model for chemotherapy-associated thrombosis, and can be used to define a high-risk study population for trials of thromboprophylaxis. Incidence of Chemotherapy-Associated VTE By Risk Categories Risk Score N VTE events Observed VTE Incidence(%) Predicted VTE Incidence(%) Low 648 4 0.62(0.24/month) 0.58(0.23/month) Intermediate 702 10 1.42(0.56/month) 1.48(0.59/month) High 799 30 3.75(1.5/month) 3.73(1.49/month)

Double-Unit Cord Blood Transplantation (DCBT) for Acute Leukemia: High Disease-Free Survival in Adults and Children with Comparable Survival in European and Minority Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3080-3080
Author(s):  
Juliet N Barker ◽  
Doris M Ponce ◽  
Anne Marie R Gonzales ◽  
Marissa N Lubin ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
European Ancestry ◽  
High Dose ◽  
Free Survival ◽  
Disease Free

Abstract Abstract 3080 As compared to single-unit CBT, DCBT may improve engraftment and protect against relapse. Therefore, we have adopted DCBT for both children and adults with acute leukemia, myelodysplasia (MDS), and myeloproliferative diseases (MPD). However, determinants of disease-free survival (DFS) have yet to be fully established. Furthermore, whether DFS after DCBT is comparable in patients of European and non-European ancestry is of special interest. Therefore, we analyzed the DFS of 75 DCBT recipients with acute leukemia in morphologic remission or aplasia (n = 69), and MDS/MPD with ≤ 5% blasts (n = 6) transplanted from 10/2005-4/2011. Nearly all patients had high-risk disease. Children 0–15 years (n = 23) had the following characteristics: median age 9 years (range 0.9–15); median weight 37 kg (range 7–72); 30% European; and 26% CMV sero-positive. Diagnoses were 43% AML (or biphenotypic), 52% ALL, and 4% MDS/MPD, and all received high-dose conditioning. The children received grafts with a median infused TNC × 107/kg of 3.3 (larger unit) and 2.6 (smaller unit), and 2% of units were 6/6 HLA-A, -B antigen, -DRB1 allele matched, 63% 5/6, and 35% 4/6. Adults ≥ 16 years (n = 52) had the following characteristics: median age 41 years (range 16–69); median weight 69 kg (range 47–105); 48% European; 69% CMV sero-positive; and diagnoses were 63% AML (or biphenotypic), 27% ALL, and 10% MDS/MPD. Fifty percent received high-dose and 50% reduced intensity conditioning. Their units had a median infused TNC/kg of 2.7 and 1.9, and 3% were 6/6 HLA-matched, 47% 5/6, and 50% 4/6. All patients (pediatric and adult) received calcineurin-inhibitor/ mycophenolate mofetil immunosuppression, and none received anti-thymocyte globulin. Sustained donor neutrophil engraftment was seen in 91% of children and 94% of adults at medians of 20 and 26 days, respectively. The incidence of grade II-IV acute GVHD by day 180 was 44% in children and 58% in adults. Day 100 transplant-related mortality (TRM) was 9% in children and 19% in adults. The 2-year relapse incidence was 9% in children and 6% in adults. With a median follow-up of survivors of 26 months (range 4–70), 2-year Kaplan-Meier estimate of DFS was 78% in children and 64% in adults (Figure). Differences in survival by age did not reach significance. Univariate analysis of variables potentially influencing 2-year DFS (with log rank estimates of significance) in all patients is shown in the Table. There were no differences in 2-year DFS according to ancestry, remission status, and conditioning intensity. There was also no difference in 2-year DFS according to engrafting unit-recipient HLA-match (4-6/6 or 10 allele), or engrafting unit infused TNC dose/kg. However, patients who were CMV seronegative had a higher 2-year DFS (85% vs 55%, p = 0.018). Multivariate analysis revealed recipient CMV serostatus was a predictor of DFS independent of patient age, and its effect was mediated by an influence on TRM. We have previously shown that DCBT extends transplant access to minority patients. We now demonstrate that DCBT can achieve high and comparable DFS in both European and non-European pediatric and adult patients with acute leukemia and MDS/MPD. While these are very encouraging results further investigation in racial/ethnic sub-groups is needed. Nonetheless, our findings support DCBT as an immediate alternative therapy for high-risk acute leukemia in patients without suitable unrelated volunteer donors, especially given the very low incidence of relapse. Disclosures: No relevant conflicts of interest to declare.

A Phase I/II Study Of Cytarabine Or Azacitidine In Combination With Tosedostat In Older Patients With AML Or High-Risk MDS

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2698-2698 ◽  
Author(s):  
Courtney D. DiNardo ◽  
Hagop M Kantarjian ◽  
Farhad Ravandi ◽  
Marina Konopleva ◽  
Tapan M. Kadia ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Dose Escalation ◽  
Older Patients ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Study Drug ◽  
Starting Dose ◽  
Wbc Count

Abstract Background The aminopeptidase inhibitor tosedostat is an orally bioavailable novel chemotherapeutic, functioning through enzymatic blockade of intracellular protein degradation and re-synthesis. Encouraging results have been observed with tosedostat monotherapy in Phase I and II trials of relapsed and refractory elderly AML patients. Aims This Phase I/II trial explores the safety, tolerability and activity of tosedostat in combination with cytarabine or azacitidine in older patients with AML or high-risk MDS. Methods Eligibility includes age >60 years, performance status of 0-2, with relapsed/refractory AML or high-risk MDS having failed prior hypomethylating agent (HMA) and/or lenalidomide therapy. All subjects received tosedostat 120mg orally once daily for 28 day cycles, with either subcutaneous (SQ) cytarabine at starting dose of 7.5mg twice daily for 10 days, or azacitidine (AZA) IV/SQ at starting dose of 50mg/m2 daily for 7 days, per investigator’s choice. A modified 3+3 dose escalation design was used in the Phase I portion to identify the maximum tolerated dose independently for both arms. Escalation to the predefined target dose levels of 10mg SQ cytarabine twice daily for 10 days, or azacitidine 75mg/m² IV/SQ daily for 7 days per 28 day cycle was achieved. Dose escalation to 180mg daily tosedostat was allowable for patients not achieving a CR after 4 weeks on therapy. Results From November 2012 to April 2013, the Phase I portion completed enrollment with a total of 18 patients (10 with AZA, 8 cytarabine). Six patients discontinued prior to completion of cycle 1 for reasons other than study-drug related toxicity or progressive disease and were replaced; they are considered as non-responders in the primary efficacy analysis. Median age was 73 (range 60-81), and 56% were male. 13 patients (72%) had secondary or therapy-related AML, of which 11 (61%) had prior MDS. The median number of prior treatments for MDS and/or AML was 2 (range 1-6), and 11 (61%) had received prior HMA therapy. Median white blood cell (WBC) count at study start was 5x10⁹/L (range 0.3 – 44.2), with median peripheral blood blasts of 27% (range 0-95%), and bone marrow blasts 57% (range 6-90%). The majority (61%) of patients had complex cytogenetics or abnormal cytogenetics involving chromosome 5 and/or 7; six patients (33%) had diploid cytogenetics. Molecular analysis identified 1 FLT3-ITD, 3 DNMT3A, 2 JAK2 V617F, 2 NRAS, 2 KRAS, and 1 IDH1 mutation. Median duration on study was 49 days (range 13 – 254), with median overall survival (OS) of 3.1 months (range 0.4-8.5) and an overall response rate (ORR) of 33% (CR/CRp/MLFS 17%, PR 17%). ORR was 50% (CR/CRp/MLFS 25%, PR 25%) in fully evaluable patients remaining on study for >28 days. Median OS for patients with CR/CRp/MLFS and PR was 7.3 and 3.5 months, respectively, while OS for unevaluable patients or those with progressive disease was 29 days. On univariate analysis, the presence of a diploid karyotype (p=0.001) or WBC count <4x10⁹/L (p=0.036) associated with an improved ORR. The most common non-hematologic toxicities regardless of attribution (all %; grade >3) included pleural and pericardial effusions (72%; 0%), dyspnea (67%; 0%), peripheral edema (61%; 6%), pneumonia (56%; 50%), fatigue (50%; 0%), diarrhea (50%; 0%), and cough (39%; 0%). Additional cardiac toxicities included systolic dysfunction (17%; 6%), QTc prolongation (50%; 6%) and myocardial infarction (MI) (11%; 11%). One fatal acute coronary event on cycle 2, day 2 of tosedostat 180mg and AZA 75mg/m² was considered possibly related to study drug. Conclusions The combination of tosedostat with low-dose cytarabine or azacitidine appears effective in a population with an overall very poor prognosis. Additional safety and efficacy evaluations are ongoing. Updated results and follow-up will be presented at the annual meeting. Disclosures: No relevant conflicts of interest to declare.

Absence of High-Dose Consolidation Courses and Low Numbers of Allogeneic HSCTs Did Not Affect Overall Optimistic Results in B-Cell Precursor Ph-Negative Adult ALL Patients Treated By Non-Intensive but Non-Interruptive ALL-2009 Protocol: Data of the Russian ALL Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2497-2497
Author(s):  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey Sokolov ◽  
Galina Kliasova ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Risk Groups ◽  
High Dose ◽  
Late Response ◽  
Allogeneic Hsct ◽  
Blast Cells

Abstract Introduction It is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Patients and Methods The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L>100). No central MRD monitoring was performed. Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC <30, EGIL BII-III, LDH < 2N; no late CR; t(4;11)-negative), 56,5% (n=95) - in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis. Results CR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%). Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d, PRD resistance) age (>30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant. Conclusions Our data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Interactions Between Total Nucleated and CD34 Cell Dose and Their Impact on Outcomes After Single and Double Unrelated Cord Blood Transplantation for Patients with Hematological Malignancies. An Analysis on Behalf of Societe' Française De Greffe De Moelle Et Therapie Cellulaire (SFGM-TC) and Eurocord

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 361-361 ◽  
Author(s):  
Mauricette Michallet ◽  
Renato L.G. Cunha ◽  
Gérard Michel ◽  
Gérard Socié ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Median Time ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Small Series ◽  
The Impact

Abstract Abstract 361 Pre-freezing (pf) and post-thawing (pt) total nucleated cells (TNC) is one of the most important factor for outcomes after UCBT. Its impact has been demonstrated after single UCBT (sUCBT); a minimum cell dose has been established as pfTNC of 2.5 ×107/kg, but its impact on outcomes after double UCBT (dUCBT) has not been shown. Also number of pfCD34 cells/kg is associated with outcomes after sUCBT, but only small series of patients have been analyzed. In order to evaluate the interactions between pf and pt TNC and CD34 and their impact on outcomes, we have studied separately 600 patients with hematological malignancies receiving a first sUCBT and 397 a first dUCBT in France (Table1). Methods: for all prognostic analysis pf and pt TNC and CD34 were divided into 4 categories at 25th, 50th and 75th percentiles. Results: Single UCBT: there was a highly statistical significant correlation between pf and pt TNC and CD34 (p<0.001, respectively). Median time to ANC recovery was 26 days (6-84). Cumulative incidence (CI) of ANC recovery at day 60 was 83%. In univariate analysis, the best cutoff point (associated with greater ANC recovery) of pfTNC and pfCD34 were ≥3.6 ×107/kg and ’1.6 ×105/kg and ptTNC and ptCD34 were ≥3.3 ×107/kg and ≥1.3 ×105/kg. In multivariate analysis pf or pt TNC or CD34 were independently associated with ANC recovery (pfTNC HR=1.4, p=0.005; pfCD34 HR=1.3, p=0.01; ptTNC HR=1.4, p=0.01, ptCD34 HR=1.4, p<0.0001). We have not found any association of number of HLA disparities and ANC recovery. When analyzing only adults, patients receiving <2.0 ×107/kg, CI of ANC recovery was only 70% compared to 81% for ≥2.0 ×107/kg (p=0.02). CI of aGVHD at day 100 was 36% and was not associated with TNC or CD34. Estimated 2 year (y) OS was 47%, 2 y DFS was 40%. Interestingly, in a multivariate analysis, pfTNC, pfCD34 or ptCD34 were not associated with OS or DFS, but only higher ptTNC (≥3.3 ×107/kg) was associated with OS (51%vs43%, HR: 0.78, p=0.05) but not with DFS. Double UCBT: there was a highly correlation between pf and pt TNC and CD34 (p<0.001, respectively). CI of ANC recovery at day 60 was 81% in a median time of 23 days (5-64). In univariate analysis, pfTNC, pfCD34 and ptTNC were not associated with ANC recovery. However, there was an association of ptCD34 cell dose (Figure1) and ANC recovery. Chimerism data was available for 75% of the patients (n=298) during the first 100 days: 76% were full donor, 14% were mixed and 11% of the patients had autologous recovery. Autologous recovery was also associated with lower CD34 cell dose, it was 49% in patients receiving (<0.9×105/kg), and 25% for remainders (p<0.001). In multivariate analysis, ptCD34 >0.9x ×105/kg was the only independent factor associated with ANC recovery (HR=1.6, p=0.001). CI of acute GVHD at day 100 was 42% and was not associated with TNC or CD34 cell dose. At 1 y NRM was 22% and relapse incidence 26%. Estimate 1 y DFS was 50±3%. TNC or CD34 cell dose were not associated with any of the above outcomes. Only disease status at transplant impacts outcomes (64% early phase, 49% intermediate phase and 37% for more advanced disease). In conclusion, our study confirms the impact of cell dose measured by pf and ptTNC and CD34 on neutrophil recovery after sUCBT and the minimum cell dose recommended should be pfTNC≥2.5 ×107/kg and ptTNC≥2×107/kg, however only ptTNC is associated with survival in sUCBT. This is the first time that an impact of ptCD34 cell dose on neutrophil recovery after dUCBT is demonstrated and may be used to choose the best CB units. The different associations of cell dose in sUCBT and dUCBT can be explained by biological and immunological properties of other CB cells in the graft. Disclosures: No relevant conflicts of interest to declare.

The Role of PET-CT for the Diagnosis of Infections in Hemato-Oncological Patients with Persistent Febrile Neutropenia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4289-4289
Author(s):  
Anat Gafter-Gvili ◽  
Mical Paul ◽  
Hanna Bernstine ◽  
Liat Vidal ◽  
Ron Ram ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Primary Analysis ◽  
Abdominal Ct ◽  
Pet Ct ◽  
Total Body

Abstract Abstract 4289 Background and aims: Patients with hematological malignancies and prolonged febrile neutropenia are at high risk for bacterial and invasive fungal infections (IFIs). We aimed to evaluate the role of PET-CT for detection of such infections among these patients. Methods: Prospective cohort study of patients with hematological malignancies given intensive conventional chemotherapy and hematopoietic-cell transplantation (HCT) at our center. All consecutive, consenting patients with neutropenia (<500/mm3) and persistent or breakthrough fever despite broad spectrum antibiotics (>5days) had a PET-CT examination. The CT component of the PET-CT was a contrast-enhanced diagnostic CT. Results were available to clinicians in real time. Blinded evaluation of chest and sinus CT and the full PET-CT scan (i.e.chest, sinus CT, abdominal CT, and FDG uptake) were compared with the final clinical diagnosis 30 days after neutropenia resolution, as determined by an expert panel consisting of a hematologist and an infectious diseases expert. Patients were included more than once in the study for different episodes of persistent febrile neutropenia and each episode could receive more than one diagnosis at 30 days. Episodes concluding in no documented infection or other pathological process were classified as fever of unknown origin (FUO). Results: Between January 2008 and January 2011, 91 PET-CT examinations were performed in 79 patients. Median age was 56 (range: 21–85) years. PET-CT was performed after a median of 10 days from last chemotherapy (range: 0–255). Patients were neutropenic for a median of 11 (range:1–100) days. Most patients had acute leukemia (71 episodes), 7 patients underwent allogeneic HCT and 6 patients with lymphoma underwent autologous HCT. The types and number of individual diagnoses are listed in the table. Of the 91 PET-CT examinations, 23 episodes had two or more diagnoses, most commonly a combination of bacterial and fungal infection. Of 28 microbiologically documented infections (MDIs), bacteremia was the diagnosis in 20 episodes, most commonly without a focal source. In the primary analysis we considered FUO as “no disease” and all else as “disease”. The sensitivity to detect any infection or non-infectious pathology in chest/sinus CT, was 58.8% (60 /102 diagnoses). The respective sensitivity for PET- CT was 85.3% (87/102). The difference in sensitivity was 26.5% (95% confidence interval 21.4% to 31.6%), matched sample p<0.001. The specificities of CT and PET-CT were not significantly different, 66.7% (10/15 episodes of FUO) and 60% (9/15), respectively. Of note, all 7 proven or probable fungal infections were FDG- positive. In 28 cases, PET-CT demonstrated findings which were not detected on chest/sinus CT (27.5% of diagnoses).These were mainly abdominal infections (as appendicitis, diverticulitis, etc.) and abscesses (perianal, splenic, etc.). When we compared PET-CT to total body (chest, sinus and abdominal) CT, we found that 7 of these cases were found only on PETCT. The sensitivity of total body CT to detect disease was 78.4% (80/102). PET-CT resulted in modifications of patients’ management in 46 (55%) cases. These included change in antibiotics (14 cases), change in antifungals (14), change in both (5), an invasive diagnostic procedure (7), a surgical procedure (appendectomy, 3) and abscess drainage (4). Conclusions: PET-CT has a higher sensitivity with no loss of specificity compared to chest/sinus CT in patients with persistent febrile neutropenia. The increase in sensitivity afforded by PET-CT was mainly due to the addition of abdominal CT. Thus, PET-CT has a potential role for the diagnosis of infections in neutropenic patients with persistent fever. Disclosures: No relevant conflicts of interest to declare.

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 Identification of a Predictive Pre-Chemotherapy Score for Febrile Neutropenia - the Fnipi INDEX

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Marco Sanna ◽  
Giovanni Caocci ◽  
Antonio Ledda ◽  
Elisabetta Belardinelli ◽  
Pietro Garau ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Univariate Analysis ◽  
Central Line ◽  
Assessment Tools ◽  
Predictive Score ◽  
Chronic Obstructive Pulmonary Disorder ◽  
Increased Risk ◽  
Active Disease

Introduction Febrile neutropenia (FN) is a leading cause of morbidity and mortality in hematology; typically, patients considered at high risk of FN are those who experience chemotherapy-induced neutropenia longer than 7 days. Other potential risk factors have been reported to impact on mortality but evidence is scarce. Also, clinicians still lack valid prediction model to identify patients at increased risk of FN. Methods We retrospectively analyzed a cohort of 100 consecutive patients who underwent intensive chemotherapy cycles (ICC) for several hematologic malignancies from October 2019 to February 2020, for a total of 368 chemotherapy courses. All patients were evaluated for age, sex, diagnosis, central line catheter, disease status, chemotherapy regimen, number of previous ICC administered, antibiotic prophylaxis, antimycotic prophylaxis, antiviral prophylaxis, anti-hepatitis B reactivation prophylaxis, G-CSF therapy, pegylated (PEG)-G-CSF therapy, previous appendectomy, diabetes, chronic obstructive pulmonary disorder (COPD), previous FN. A binary logistic regression was used to evaluate the association between independent variables and FN; statistically significant variables were included in a FN predictive score. Results In univariate analysis, an higher incidence of FN was found in patients with active disease (p&lt;0.001, HR=3.98, 95%CI= 2.07-7,66), AML diagnosis (p&lt;0.001, HR=6,6, 95%CI= 2.82-15.6), previous appendectomy (p&lt;0.001, HR=3.45, 95%CI=1.65-7.2), diabetes (p&lt;0.001, HR=4.23, 95%CI= 1.77-10.1), central line catheter in comparison with peripherally inserted central catheter (PICC) or no central line catheter (p&lt;0.001, HR=2.66, 95%CI=1.36-5.1), CHOP like chemotherapy (p&lt;0.001, HR=0.39, 95%CI=1.28-5.3), ICC&lt;3, (p=0.006, HR=2,6, 95%CI=1,28-5,3). In multivariate analysis only 4 variables remained significantly associated with FN incidence: AML diagnosis (p=0.007, HR=4.28, 95%CI=1.48-12.38), active disease (p=0.002, HR=3.11, 95%CI=1.5-6.45), previous appendectomy (p=0.007, HR=3.19, 95%CI=1.36-7.47) and diabetes (p=0.01, HR=3.6, 95%CI=1.34-9.67) (Figure 1). The 4 significant variables were considered in a new score called Febrile Neutropenia Incidence Prognostic Index (FNIPI). A single point was assigned to each variable, for a maximum of 4 points. The incidence of FN was found significantly higher in cycles showing a FNIPI score of 2-4 in comparison with 0-1 (p&lt;0.001, HR=10.1, 95%CI 4.77-21.3). Conclusions We identified several pre-treatment risk factors associated with chemotherapy-induced FN risk. Here we propose a novel score, the FNIPI, based on 4 factors (AML diagnosis, active disease, previous appendicectomy, diabetes) that discriminates patients at risk of FN after ICC. Risk assessment tools could represent a useful instrument for clinicians, to develop adequate strategies in patients at high risk of FN. To note, this observation requires larger prospective cohorts to be confirmed. Disclosures No relevant conflicts of interest to declare.

Effects of Multiple Myeloma (MM) Therapy and Type of Thromboprophylaxis On the Incidence and Timing of Venous Thromboembolism (VTE) and Factors Predictive of VTE.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2244-2244
Author(s):  
Jatin J. Shah ◽  
Aparna Hegde ◽  
Xiao Zhou ◽  
Sheeba K. Thomas ◽  
Michael Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Cancer Center ◽  
Hematopoietic Stem ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Multivariate Proportional Hazard ◽  
The Impact

Abstract Abstract 2244 Background: Patients (pts) with MM are at increased risk for VTE due to various risk factors related to the host, disease, and treatment. Immunomodulatory drugs (IMiDs) such as thalidomide and lenalidomide have further increased the risk of VTE. Several studies have shown the VTE risk can be reduced with the use of low molecular weight heparin (LMWH) or aspirin thromboprophylaxis. Based on these findings, VTE thromboprophylaxis has been recommended in pts receiving IMiDs + Dexamethasone (Dex), but the impact of these guidelines on patient outcomes in clinical practice is unclear. The objective of this observational study was to evaluate the incidence, timing and risk factors of VTE and the impact of different types of thromboprophylaxis on the incidence of VTE. Methods: This was a retrospective cohort study, and included all MM pts newly referred to the M.D. Anderson Cancer Center in 2006. Medical records of these pts were reviewed for the type and site of VTE, the incidence and timing of VTE during the five-year period from the referral date, and the risk factors, including pt demographics, co-morbidities, baseline laboratory values, types of MM and treatment, and types of thromboprophylaxis. Univariate and multivariate proportional hazard models were fitted to find the independent risk factors predictive of VTE. The stepwise selection method was employed to build a multivariate model using variables with p<0.15 in univariate analysis. Results: The cumulative incidence of VTE was 24% (38/159 pts) during the 5-year follow up period. Of the 38 pts with VTE, 25 (66%) had deep vein thrombosis (DVT), 11 (29%) had pulmonary embolus (PE), and 2 had concurrent DVT and PE. Most of the pts (32/38, 84%) had VTE within 1 year from the referral date. The incidence of recurrent VTE among these pts was 27.5% (11/38 pts), for a total of 52 episodes. Since the majority of VTEs and recurrences were within one year, we examined the risk factors for VTE during this period. Treatment with IMiDs + Dex and thromboprophylaxis with LMWH or Coumadin were independent predictive factors as shown below. The incidence of VTE was highest in pts exposed to IMiDs + Dex (30/38 pts), even after discontinuation of treatment, with most episodes (17/30) occurring during the preparation (7/30) or within 30 days (10/30) following hematopoietic stem cell transplantation (HSCT), when most (16/17) pts were not receiving anti-coagulants. Conclusions: These findings suggest that patients treated with IMiDs + Dex are at high risk for VTE, even after discontinuation of this treatment, especially, during and after the HSCT period. Future studies are needed to investigate VTE prevention strategies for this high-risk pt population. Disclosures: No relevant conflicts of interest to declare.

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