Incidence Of Neutropenic Fever Research Articles

Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( −) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( −) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

On-demand plerixafor added to high-dose cyclophosphamide and pegylated recombinant human granulocyte colony-stimulating factor in the mobilization of patients with multiple myeloma: a treatment with high effectiveness, convenient, and affordable cost.

The combination of high-dose cyclophosphamide (HD-Cy) (3g/m2) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor (PXF) has been considered an effective mobilization regimen of patients with multiple myeloma(MM). However, the daily multi-injection regimen of G-CSF poses challenges. This study delves into the efficiency and cost implications of a novel approach, using HD-Cy alongside pegylated G-CSF (PEG G-CSF) and on-demand PXF. Unlike G-CSF, which necessitates daily injections, the half-life of PEG G-CSF extended allows for a single injection. A retrospective analysis was conducted on 350 MM patients, which were categorized based on their mobilization regimens: Cy+PEG G-CSF+/-PXF (n=66), Cy+PEG G-CSF (n=91), Cy+ G-CSF (n=169), and G-CSF+PXF (n=24). Mobilization with Cy+PEG G-CSF+/-PXF(8.79)yielded a notably higher median CD34+ cell count compared to the other regimens: Cy+PEG G-CSF(4.96), Cy+G-CSF (4.65), and G-CSF+PXF (2.99) (P<0.001). The percentage of patients who achieved >6×106/kg CD34+ cells was significantly higher in the Cy+PEG G-CSF+/-PXF group (77.3%) than in the other mobilization regimens: Cy+PEG G-CSF (41.8%), Cy+ G-CSF (37.3%), and G-CSF+PXF (8.3%) (P<0.001). From a cost perspective, the Cy+PEG G-CSF+/-PXF approach was more economical than the G-CSF+PXF strategy but was marginally costlier than the other two methods. A multivariate assessment highlighted that the combination of Cy+PEG G-CSF with on-demand PXF had a superior potential to achieve the desired harvest (6×106/kg) compared to the Cy+PEG G-CSF protocol without PXF. The incremental cost-effectiveness ratio for each 1% increase in the probability of achieving a successful optimal harvest was $ 97.02 per patient. The incidence of neutropenic fever was 3.0% in the Cy+PEG G-CSF+/-PXF group. The combination of on-demand PXF with HD-Cy and PEG G-CSF offers a cost-effective approach with a high mobilization success rate, manageable side effects, and the convenience of fewer injections. It stands as a promising mobilization strategy for MM patients.

When a Number Is Just a Number: Duffy-Null Blood Group Phenotype, Absolute Neutrophil Count, and Incidence of Neutropenic Fever and Chemotherapy Dose Reductions in Patients Treated for Plasma Cell Dyscrasias

Introduction: A single nucleotide polymorphism in the promoter region of the Duffy antigen/chemokine receptor (DARC) gene results in the red blood cell (RBC) Duffy-null phenotype, which is present in up to 80% of individuals of Sub-Saharan ancestry. Duffy-null phenotype is associated with lower peripheral absolute neutrophil counts (ANC) with preserved myeloid maturation and neutrophil function. The impact of Duffy-null phenotype on patients with hematologic malignancies is largely unknown; however, lower ANC (both at baseline and during treatment) may lead to the receipt of less intense treatment (with lower upfront dosing as well as more treatment interruptions/dose reductions). Lower ANC also pose challenges in enrollment in clinical trials due to ANC cutoffs for eligibility criteria. Herein, we evaluated the impact of Duffy phenotype status on the incidence of neutropenic fever and chemotherapy dose reductions in a cohort of patients treated for multiple myeloma (MM) or light chain (AL) amyloidosis at the largest safety net hospital in New England, USA. Methods: In this retrospective study, we identified patients treated for MM or AL amyloidosis at Boston University Medical Center (BMC) who underwent phenotyping for the RBC Duffy antigen. Patients were categorized as Duffy-null phenotype, i.e., Fy (a-b-) or non-Duffy-null phenotype including Duffy heterozygous, i.e., Fy (a-b+ or a+b-) or Duffy positive, i.e., Fy (a+b+). We collected data from medical charts including patient demographics; clinical characteristics (including malignancy and treatment regimens); incidence of neutropenia (defined as ANC &amp;lt;1,800/µL); incidence of neutropenic fever (excluding peri-stem cell transplantation [SCT] neutropenia); and chemotherapy dose adjustments. This research was approved by the BMC Institutional Review Board. Results: Between 06/2020 and 06/2023, 136 patients had a Duffy phenotype evaluation; mean age at the time of first chemotherapy was 65 (± 11.3) years and 62/136 (46%) were female. The most common self-identified race/ethnicity was non-Hispanic Black (74/136, 54%), followed by non-Hispanic White (34/136, 25%), Hispanic (18/136, 13%), and other (10/36, 7%), and other (10/136, 6%). Plasma cell dyscrasias included MM (94/136, 69%), AL amyloidosis (34/136, 25%) (Table 1). Duffy-null Fy (a-b-) phenotype was seen in 52/136 (38%) patients, while 84/136 (62%) were non-Duffy-null, including 73/136 (54%) with Duffy heterozygosity Fy (a-b+ or a+b-) and 11/136 (8%) with Duffy positivity Fy (a+ b+). Number of lines of treatment did not differ by Duffy status (Table 1): 35/136 (26%) received 2 lines of treatment; 56/136 (41%) received ≥ 3 lines; and 28/136 (21%) received high-dose chemotherapy and autologous SCT. Among those with known baseline ANC, we observed a higher frequency of neutropenia before receipt of any chemotherapy in patients with Duffy-null status (17/50, 34%) compared to those with non-Duffy-null status (8/79, 10%), p= 0.0009. Similarly, the incidence of treatment-related neutropenia (excluding the peri-SCT period) was higher in Duffy-null patients (44/52, 85%) compared to non-Duffy-null (39/82, 48%) patients, p&amp;lt;0.0001. Overall, the incidence of febrile neutropenia in our cohort was low; all 7 patients who experienced a febrile neutropenic event were non-Duffy-null (7/84, 8%). None of the patients in the Duffy-null cohort (0/52, 0%) had febrile neutropenia, despite higher incidences of both baseline and treatment-related neutropenia. Treatment interruptions/delays or dose reductions due to any cause were observed in 95/136 (70%) of all patients and did not differ by Duffy phenotype status (Table 1). The proportion of patients initiated on upfront reduced-dose pomalidomide or lenalidomide was 62/106 (59%) and also did not differ by Duffy phenotype status. Conclusion: In this retrospective study, we found that compared to patients with non-Duffy-null phenotype, patients with Duffy-null phenotype treated for plasma cell dyscrasias did not have a higher incidence of neutropenic fever, treatment interruptions or dose reductions, despite having higher frequencies of both baseline and treatment-related neutropenia. Prospective validation of our results could help to inform the creation and implementation of guidelines for the management of patients with lower ANC related to Duffy-null phenotype who undergo treatment for plasma cell dyscrasias.

Phase 2 Study of Dasatinib with and without Venetoclax in Patients with Early Chronic Phase Chronic Myeloid Leukemia (ECP-CML)

Background Treatment-free remission (TFR) is a therapeutic goal for patients with ECP-CML once patients maintain a deep molecular remission (DMR) on tyrosine kinase inhibitors (TKIs). Only a fraction of patients (pts) achieved sustained (3+ years) molecular remission with 4.0- to 4.5-log reduction (MR4.5). Preclinical studies showed that BCL-2 is a key survival factor for CML stem/progenitor cells. Therefore, the combination of TKIs and venetoclax, targeting BCR::ABL1 and BCL-2, has the potential to significantly improve DMR and subsequently the rates of TFR. The aim of this study is to evaluate the safety and efficacy of the combination. Methods Patients with ECP-CML or accelerated phase (AP; defined by clonal evolution only) were eligible; pts with &amp;lt; 1 month of prior TKI therapy were eligible. Pts received single-agent dasatinib 50 mg/d for the first 3 months. From Month 4 and onwards, venetoclax was administered from Days 1 to 14 each month concomitantly with dasatinib for a total of 3 years. The first 16 patients received venetoclax 200 mg/d, with a rapid ramp-up starting 50 mg on Day 1, then 100 mg on Day 2, then 200 mg daily on Day 3 and onwards. Due to neutropenia observed with continuous dose of venetoclax 200 mg/d, the protocol was ameded: from patient #17 and onwards, venetoclax was administered at 200 mg/d for 14 days per month and upon achievement of MR4.5, venetoclax was reduced to 100 mg/d for 7 days per month. After 3 years of combination, patients received single-agent dasatinib. TFR was offered after ≥ 3 years of DMR. The primary endpoint was the rate of major molecular response (MMR) by 12 months of the combination. The secondary endpoints were the 12-month rate of MR4.5 and the cumulative overall rate of MR4.5; the rates of MR4.5 at 6-, 12-, 18-, 24, and 36-months of the combination; the proportion of patients with sustained MR4.5 of 3 years and more; the TFR rate; overall survival; and the safety of the combination. Cumulative response rates were calculated with treatment failure as a competing event. Failure-free survival (FFS) was calculated from the initiation of therapy to loss of major cytogenetic response (MCyR), transformation to AP or blast phase, discontinuation of therapy for any reason except of TFR, or death. Results Sixty-five pts were enrolled and treated between April 2018 and August 2021. The median age at treatment initation was 46 years (range, 23-73) and 57% of the pts were females. Twenty-one (32%) pts had splenomegaly, 46 (71%) had low Sokal risk disease and 3 (5%) had high Sokal risk disease (Table 1). By 12 months of the combination, 85% of the pts had achieved MMR or deeper response. The median time to MMR, MR4, and MR4.5 were 6.2 months, 13 months, and 23.9 months from the time of TKI start, respectively. After a median follow-up of 25.7 months (range, 8.7-48.1), two pts discontinued therapy due to adverse events (GI intolerance, and pleural effusion); the 2 -year FFS was 96%. One pt switched TKI therapy due to the lack of 18-month complete cytogenetic response (CCyR); no loss of CCyR, transformation, or death was observed. We then compared the outcomes with the combination to the outcomes of 85 pts treated with single-agent dasatinib. From the start of TKI therapy, the 12-month cumulative MMR rates were 78% and 79% in the dasatinib single-agent and dasatinib + venetoclax groups, respectively. The cumulative 24-month rates of CCyR, MMR, MR4, and MR4.5 are summarized in Table 2. In the dasatinib single-agent group, 3 pts switched TKI therapy due to the lack of 12-month MCyR, 18-month CCyR, and the acquisition of ABL1 mutation (1 each); 3 pts switched TKI therapy due to loss of CCyR; 2 pts died during therapy (deaths unrelated to CML). Within one year of therapy, the incidence of grade 1/2 neutropenia (absolute neutrophil count, below lower range of normal to 1,000 x10 9/L) was 21% and 52% in the dasatinib single agent and dasatinib + venetoclax groups, respectively ( P&amp;lt;0.001); the incidence of grade 3/4 neutropenia (absolute neutrophil count, below 1,000 x10 9/L) was 8% and 17%, respectively ( P&amp;lt;0.001). There was no incidence of neutropenic fever in the dasatinib + venetoclax. Conclusion The combination of dasatinib 50 mg/d and venetoclax is safe and effective in pts with ECP-CML. With a median follow-up of 2 years, the cumulative resposne of dasatinib + venetoclax is similar to that of dasatinib single-agent without adding significant toxicities. Further follow-up is needed for the evaluation of TFR.

On-Demand Plerixafor Added to High-Dose Cyclophosphamide and Pegylated Recombinant Human Granulocyte Colony-Stimulating Factorin the Mobilization of Patients with Multiple Myeloma: High Effectiveness and Affordable Cost

Background Autologous stem cell transplantation(ASCT) still represents an integral part of treatment for patients with eligible newly diagnosed multiple myeloma. It is important to collect enough stem cells for two transplants in the first mobilization.The combination of high-dose cyclophosphamide(Cy) (3g/m 2) plus granulocyte colony-stimulating factor(G-CSF)and on-demand plerixafor has been considered the effective method as mobilization regimen, but G-CSF requires daily, multi-injection administration. Here, we performed a real-world analysis to evaluate the efficacy and cost of high-dose Cy combination pegylated recombinant human granulocyte colony-stimulating factor（PEG-rhG-CSF）and on-demand plerixafor for the first time, allowing for a single injection given the long half-life and slow elimination of PEG-rhG-CSF. Methods We retrospectively compared 343 patients whith MM mobilized between August 2008 and December 2022 using the following mobilization strategies: Cy+PEG-rhG-CSF+/-plerixafor(n=61), Cy+PEG-rhG-CSF(n=89),Cy+ G-CSF( n=169), G-CSF+plerixafor(n=24). Then the stem cell mobilization and collection results of the four groups were compared. Results Mobilization with Cy+PEG-rhG-CSF+/-plerixafor resulted in a significantly higher total CD34+ cells ( ×10 6/kg )collected( 8.81) compared to patients mobilized with other mobilization regimens：Cy+PEG-rhG-CSF(5.47；p＜0.001),Cy+ G-CSF(4.65; p＜0.001), G-CSF+plerixafor( 2.99; p＜0.001). Day1+Day 2 CD34+ cells ( ×10 6/kg ) collected were higher in Cy+PEG-rhG-CSF+/-plerixafor group too (Cy+PEG-rhG-CSF+/-plerixafor, 7.87 vs. Cy+PEG-rhG-CSF, 4.96 vs. Cy+ G-CSF,3.92 vs. G-CSF+plerixafor, 2.43) (p＜0.001).The percentage of patients who achieved＞6×10 6/kg CD34+ cells were significantly higher in Cy+PEG-rhG-CSF+/-plerixafor group group (77.0%) than other mobilization regimens：Cy+PEG-rhG-CSF (42.7% ；p＜0.001),Cy+ G-CSF( 37.3% ;p＜0.001）, G-CSF+plerixafor( 8 % ;p＜0.001). Apheresis sessions were fewer in Cy+PEG-rhG-CSF+/-plerixafor group ( Cy+PEG-rhG-CSF+/-plerixafor, 2 vs. Cy+PEG-rhG-CSF,3 vs. Cy+ G-CSF ,3 vs. G-CSF+plerixafor,4)(p＜0.001). Patients proceeded to ASCT with a mean of 2.94 CD34+cell (×10 6/kg ) infused for PEG-rhG-CSF+/-plerixafor , 2.94 infused for Cy+PEG-rhG-CSF, 2.61infused for G-CSF+plerixafor, 3.17 infused for Cy+ G-CSF (p=0.057) . The median time to neutrophil and platelet engraftment not different in the four groups. The total cost of mobilization and apheresis using Cy+PEG-rhG-CSF+/-plerixafor was significant lower ($5670.64) compared to G-CSF+plerixafor group($11098.61), and significant higher than Cy+PEG-rhG-CSF group ($3842.23)and Cy+ G-CSF group($3727.82)（p＜0.001）. Multivariate analysis showed that patients who received Cy+PEG-rhG-CSF +/-plerixafor treatment had significantly higher likelihoods of successfully achieving the optimal harvest (6×10 6/kg) in respect to Cy+PEG-rhG-CSF group mobilized without any plerixafor. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful optimal harvest, was $62.57 per patient. The incidence of neutropenic fever not different in the Cy+PEG-rhG-CSF+/-plerixafor group(4%), Cy+PEG-rhG-CSF group (10%) and Cy+ G-CSF group(18%)(p=0.051). There was no patients suffered with neutropenic fever in G-CSF+plerixafor group. Conclusion Given higher rates of successful mobilization, affordable cost and toxicity, on-demand plerixafor added to high-dose Cy and PEG-rhG-CSF may be preferable in the mobilization of patients with multiple myeloma.

Safety and Efficacy of Outpatient Myeloablative Busulfan Conditioning in Allogeneic Stem Cell Transplantation

INTRODUCTION: Busulfan-based regimens are the backbone of myeloablative conditioning (MAC) in allogeneic hematopoietic stem cell transplant (allo-HSCT), particularly for patients (pts) with Acute Myelogenous Leukemia (AML). However, literature on busulfan conditioning administered in the outpatient (OP) setting is limited. Here, we investigate the safety and efficacy of OP busulfan as compared to standard inpatient (IP) administration. METHODS: Pts &amp;gt; 18 years of age who received pharmacokinetically dose adjusted IV busulfan (130 mg/m2 x 4 days) conditioning prior to HSCT between January 2019 and April 2023 at our institution were included in this retrospective analysis. Pts who received non-myeloablative conditioning or who underwent a haploidentical HSCT were excluded. All pts undergoing HSCT were classified as having low-, intermediate-, or high-risk disease by the Disease Risk Index. Pts with AML were classified as having favorable, intermediate, or adverse disease by 2022 ELN classification. CIBMTR guidelines were used to determine neutrophil and platelet engraftment. Oral mucositis was graded per the World Health Organization scale. Clinical grading of acute graft-vs-host disease (AGVHD) was assigned per standard criteria. Adverse events (AEs) were reported in accordance with the CTCAE, v.5. Categorical variables were compared using the Fisher's Exact test. Continuous variables were compared using the Wilcoxon Rank-Sum test. Overall survival (OS) was defined as time from HSCT to time of death from all-cause mortality. Relapse-free survival (RFS) was defined as time from HSCT to time of relapse or non-relapse mortality. The Kaplan-Meier method was used to estimate OS and RFS. Survival differences between cohorts were compared using the Log-rank test. All hypothesis testing was two-sided and conducted at a significance level of 0.05. RESULTS: In total, 54 pts met eligibility criteria; 43 IP and 11 OP. The OP cohort was younger than the IP cohort (35 years vs 47 years median age; p=0.0284). All other patient, disease, and transplant characteristics were similar between cohorts. The majority of pts were male (IP: 56%, OP: 55%) and White/Caucasian (IP: 100%, OP: 91%). AML (IP: 88%, OP: 82%) was the most common indication for HSCT. Most pts were in CR1 (IP: 74%, OP: 89%) and had intermediate risk disease by both DRI (IP: 84%, OP: 64%) and 2022 ELN classification (IP: 62%, OP: 67%). PBSCT (IP: 88%, OP: 91%) and 10/10 MUD (IP: 67%, OP: 45%) were the most common types of HSCT. The majority of pts received a conditioning regimen of Flu/Bu4 (IP: 58%, OP: 55%). The use of PTCy was comparable between groups (p=0.6593). Of the 11 pts who received OP busulfan, 1 had to complete their conditioning IP after experiencing a seizure in the setting of prior meningitis. Between the 2 cohorts, there was no significant difference in the incidence of AEs &amp;gt; grade 2 (p=1), grade 2 AEs (p=0.8695), grade 3 AEs (p=0.7592), grade 4 AEs (p=0.2487), and grade 5 AEs (p=0.6457) within 30 days of conditioning. Incidences of transplant-related GI toxicities, including nausea (p=1), vomiting (p=0.4979), diarrhea/enteritis (p=1), and mucositis (oral: p=0.6102, GI: p=0.2821) were similar. There was no difference in time to neutrophil (p=0.1606) or platelet engraftment (p=0.9742). Length of hospitalization was shorter in the OP vs IP cohort (18 vs 24 days; p&amp;lt;0.0001). During hospitalization, there was no difference in the incidences of neutropenic fever (p=1), infection (p=0.5104), ICU transfer (p=1), or engraftment syndrome (p=0.7076). Number of infections per patient during hospitalization were comparable (p=0.3764). D30 chimerism was similar IP vs OP. Within 180 days of HSCT, there was no difference in the incidence of AGVHD (p=0.5152) or Grade II-IV AGVHD (p=1). Differences in 2-year OS (LR=0.2200) and 4-year RFS (LR=0.3144) were not significant. CONCLUSION: In pts undergoing MAC allo-HSCT with IV busulfan,OP administration shortens the length of hospitalization without delaying engraftment or increasing the risk of toxicity, neutropenic fever, infection, or ICU admission. Additionally, D30 chimerism, rates of engraftment syndrome and AGVHD, and survival were not affected. This makes OP busulfan an attractive option for transplant centers and their pts.

Addition of doxycycline to fluoroquinolones for bacterial prophylaxis in autologous stem cell transplantation for multiple myeloma.

e18732 Background: Autologous stem cell transplant (ASCT) is standard therapy for patients (pts) with multiple myeloma (MM), yet the risks of such treatment include neutropenic fever (NF) and bacteremia. Fluoroquinolones (FQs) are a mainstay of bacterial prophylaxis (ppx) of NF in ASCT at many transplant centers and reduce the incidence of bacteremia. Nevertheless, ppx regimens for ASCT are not standardized and variability exists even within single institutions. While antibacterial ppx decreases infections, antibiotic use can also cause toxicity, resistance, and microbiome disturbance. The addition of doxycycline (doxy) to FQs was previously linked to reduced NF and bacteremia when utilized for ppx in MM pts at our institution, leading some providers to incorporate doxy into their ppx regimens. However, our prior study introduced multiple confounders, including differing pre-transplant conditioning regimens between ppx groups. We sought to further compare the incidence of NF and bacteremia in MM pts receiving ppx with FQ alone and FQ-doxy during a time when ppx strategies varied but transplant conditioning was consistent between groups. Methods: This is a single institution retrospective review. We analyzed all medical charts in the ASCT database of MM pts treated at our institution between Jan 2016 and Dec 2021. The primary objective was to determine the effect of bacterial ppx on the rate of NF and bacteremia within 30 days of ASCT. Data was also collected on several pt characteristics. Results: Out of 341 pts with MM who underwent ASCT following melphalan (mel) conditioning, 121 received FQ (ciprofloxacin or levofloxacin) ppx and 220 received FQ-doxy ppx. Pt characteristics and outcomes of interest are shown in Table 1. NF developed in 71 (58.7%) and 103 (46.8%) pts in the FQ and FQ-doxy groups, respectively (p = 0.042). The odds of NF in FQ-doxy compared to FQ is 0.62 (95% CI 0.4, 0.97). Bacteremia developed in 7 (5.8%) and 6 (2.7%) pts of the FQ and FQ-doxy groups (p = 0.235). The odds of bacteremia in FQ-doxy compared to FQ is 0.46 (95% CI 0.15, 1.39). Documented bacteremia was infrequent, yet resistance profiles demonstrated FQ-resistant E. coli strains in the 7 total Gram-negative bacteremia cases and 5 extended-spectrum beta-lactamases. Conclusions: Overall, there were fewer cases of NF in the FQ-doxy ppx group than FQ, however there was no significant difference in the cases of bacteremia. This finding does not support the addition of doxy to FQ ppx at our institution and a future randomized controlled trial investigating appropriate ppx for ASCT is warranted. [Table: see text]

Prophylactic Trimethoprim-Sulfamethoxazole for Allogeneic Hematopoietic Stem Cell Transplant Recipients During the Pre-engraftment Period

BackgroundOur institution has used trimethoprim-sulfamethoxazole (TMP-SMX) as the antibacterial agent of choice for infection prophylaxis during the pre-engraftment period in the allogeneic transplant (allo-HCT) population.MethodsThis retrospective, single center study was developed to compare the safety of that antibacterial prophylaxis to fluoroquinolones in allo-HCT. The primary endpoint was time to neutrophil engraftment.ResultsA total of 366 patients were reviewed (TMP-SMX n = 332, fluoroquinolone n = 34). No difference in days to neutrophil engraftment was found (median 15 versus 16 days, p = 0.62). Hyperkalemia was more common in the TMP-SMX cohort (32.2% versus 14.7%, p = 0.035); this did not contribute to a higher rate of agent discontinuation or arrhythmia. There was no significant difference in the incidence of neutropenic fever; however, those in the TMP-SMX cohort were more likely to have microbiologically confirmed bacteremia (24.1% versus 8.8% respectively, p = 0.043). There was no significant difference in infections. No long-term implication of prophylactic antibacterial agent selection was observed in terms of graft-versus-host-disease, underlying disease relapse, or mortality.ConclusionThe use of TMP-SMX was associated with a higher likelihood of bacteremia and hyperkalemia; however, this did not result in increased hospital stay, escalation of care, or mortality. The use of TMP-SMX for prophylaxis during the pre-engraftment period for allo-HCT recipients is safe and effective.

Updated analysis: Effect of biweekly dosing schedule of trifluridine-tipiracil (TAS-102) on rates of myelosuppression and maintenance of therapeutic efficacy in patients (pts) with previously treated metastatic colorectal cancer (mCRC).

95 Background: For surgically unresectable metastatic colorectal cancer pts, a continuum of treatment is required to improve the OS of our pts. Oral trifluridine-tipiracil (TAS-102) is FDA approved in refractory mCRC per the RECOURSE trial. As per the FDA insert, the recommended dose is 35 mg/m2 twice daily (maximum = 80 mg/day) on Days 1-5 and Days 8-12 of 28-day cycles commonly resulting in Grade 3-4 neutropenia (38%), dose delays (53%), dose reductions (14%) and requiring G-CSF support (9%). To maintain efficacy and to potentially reduce toxicity, we analyzed an alternative biweekly dosing (Days 1-5 and Days 15-19 q28 days). Methods: A retrospective analysis was completed (2019-2022) at Vanderbilt-Ingram Cancer Center in pts with refractory mCRC and appendiceal cancer (CA) who completed ≥ 12 days of TAS-102 therapy and underwent surveillance imaging every 8-12 weeks. Patient data was assessed for ECOG performance status (PS), prior lines of therapy, the use of bevacizumab and CTCAE grade of treatment-related myelotoxicity. Evaluation of progression-free survival (PFS) was completed in mCRC pts. Results: Forty-three patients met the inclusion criteria, with a mCRC:appendiceal CA ratio of 39:4. The median age = 50 y/o (range 30-80); male:female 23:20; median ECOG PS = 1; median number of prior therapies = 3; and median duration of therapy = 97 days (range: 12-396). Associated grade 3/4 hematologic toxicities included: Neutropenia 39% [Grade 3 (12.2%), Grade 4 (2.4%)]; anemia 36.5% [Grade 3 (12.2%)]. No pts required G-CSF. No incidences of neutropenic fever were reported. Five pts (11.6%) required a dose delay and 3 pts (7%) required a dose reduction due to myelosuppression. In mCRC pts, the median PFS was 2.53 months. To date, 6 pts remain on treatment (range: 97-331). Conclusions: In our updated analysis, biweekly dosing of TAS-102 (35 mg/m2 twice daily; Days 1-5 and Days 15-19 of 28-day cycles) for pts with refractory mCRC and appendiceal CA demonstrated tolerable myelosuppression, while preserving PFS in pts with mCRC. With an improved toxicity profile, this alternative TAS -102 dosing schedule may potentially broaden utilization of TAS-102 in patients with borderline PS and may be a more favorable option for future combination studies. Additional prospective data are needed to validate these findings. To our knowledge, this remains the first analysis of biweekly TAS-102 in a US patient population.

Pediatrik sarkom hastalarında profilaktik beta-glukan kullanımının nötropenik ateş sıklığı ve sağkalım üzerine etkisi

Purpose: Some patients with cancer use herbal therapy as an adjunct while receiving conventional cancer treatments. Beta-glucans have direct cytotoxic effects on cancer cells as well as stimulatory effects on the immune system. In this study, a nutritional supplement containing 1,3-1,6 beta-glucan obtained from baker's yeast (Saccharomyces cerevisiae) was used by patients diagnosed with sarcoma, and this study aimed to retrospectively evaluate the effect of beta-glucan use on the incidence of neutropenic fever (NF) and survival rates. &#x0D; Materials and Methods: Among the patients diagnosed with sarcoma between 2014 and 2017, 27 patients who used beta-glucan were included in the beta-glucan group, and 31 patients who did not use beta-glucan were included in the control group. The clinical records of patients were retrospectively analyzed.&#x0D; Results: The number of patients who had NF and the mean length of hospital stay due to NF were higher in the beta-glucan group than those in the control group, but the results were not statistically significant. The overall survival rates at 5 years were 83.3% and 52.9% and event-free survival rates at 5 years were 48.1% and 71% in the beta-glucan and control groups, respectively. &#x0D; Conclusion: The effect of prophylactic beta-glucan use on the incidence of NF and survival rates in pediatric patients with sarcoma should be evaluated more reliably in further prospective studies on a large patient group.

Loss of microbiota-derived protective metabolites after neutropenic fever

Neutropenic fever (NF) is a common complication of chemotherapy in patients with cancer which often prolongs hospitalization and worsens the quality of life. Although an empiric antimicrobial approach is used to prevent and treat NF, a clear etiology cannot be found in most cases. Emerging data suggest an altered microbiota-host crosstalk leading to NF. We profiled the serum metabolome and gut microbiome in longitudinal samples before and after NF in patients with acute myeloid leukemia, a prototype setting with a high incidence of NF. We identified a circulating metabolomic shift after NF, with a minimal signature containing 18 metabolites, 13 of which were associated with the gut microbiota. Among these metabolites were markers of intestinal epithelial health and bacterial metabolites of dietary tryptophan with known anti-inflammatory and gut-protective effects. The level of these metabolites decreased after NF, in parallel with biologically consistent changes in the abundance of mucolytic and butyrogenic bacteria with known effects on the intestinal epithelium. Together, our findings indicate a metabolomic shift with NF which is primarily characterized by a loss of microbiota-derived protective metabolites rather than an increase in detrimental metabolites. This analysis suggests that the current antimicrobial approach to NF may need a revision to protect the commensal microbiota.

Safety of Autologous Hematopoietic Stem Cell Transplantation in Patients over 75 Years Old. Single Center Experience Serving a Minority Population

Background:Autologous hematopoietic stem cell transplant (auto-HSCT) is a commonly used treatment for multiple myeloma (MM) and for relapsed/refractory non-Hodgkin lymphomas (NHL) for patients who are <65 years old. However, the majority of new diagnoses of MM and NHL are in patients >65 years old, and nearly half of those are in patients >75 years old. While some studies have evaluated the use of auto-HSCT in older patients 65-75 years of age, there are few studies evaluating the relative safety of this treatment in patients above the age of 75 years. Such patients and their providers require outcome data of auto-HSCT in the elderly in order to help guide informed decision-making.Methods:We conducted a retrospective cohort study comparing short-term outcomes for auto-HSCT in patients >75 years old and 55-65 years old for the diagnosis of MM or NHL, who were conditioned with either melphalan or BEAM (carmustine, etoposide, cytarabine, melphalan) respectively.To identify patients, we used an internal database of auto-HSCT performed between 2005 - 2021. The study group included patients >75 years old. The control group included patients 55-65 years old that were matched to the study group patients by sex and time of transplant. Medical records were reviewed to gather data on demographics, pre-transplant functional status, transplant indication and conditioning regimen, length of stay, admission mortality, 30-day rehospitalization rate, ICU admission, neutropenic fever and infectious workup results, and time to WBC and platelet engraftment.The primary outcomes of the study were admission mortality, length of stay, time to WBC and platelet engraftment incidence, incidence of neutropenic fever, positive blood culture, ICU admission, and 30-day rehospitalization rate.Averages were calculated using medians and IQR. Admission mortality was evaluated using log rank test. P values were calculated using Fisher's test for categorical data and Wilcoxon rank sum test for continuous data. Significance was denoted by α =0.05.Results:We identified 43 patients aged >75 years old who underwent autologous stem cell transplant for multiple myeloma or lymphoma with melphalan or BEAM conditioning at Montefiore Medical Center between 2005-2021.Patient characteristics (Table 1) The earliest transplant in out cohort was in 12/2005 and the latest was in 3/2021. The median time between transplants of patients in the study and cohort groups was 14 [7.5, 24] days. 24 (55.8%) patients were female. The median age in the study group was 77.1 [76.2, 77.9] years old and 61.9 [57.4, 63.0] years old in the control group. Both groups predominantly included patients from minority populations: 55.8 and 46.5% were Spanish/Hispanic/Latino and 25.6% and 14.0% were African American, in study and control groups respectively. Multiple myeloma was the most common indication for auto-HSCT.Primary outcomes (Table 2) Admission mortality did not differ significantly between the groups, with only one death in the control group (p = 0.083). The length of stay was comparable at 18 [17, 22] days and 19 [16, 20] days (p = 0.2) for study and control groups, respectively.Time to WBC engraftment in the study group was 12 [11, 12] days and 11 [11, 12] days in the control group (p = 0.032). Time to platelet engraftment in the study group was 14 [12, 15] days and 12 [11, 14] days in the control group (p = 0.014). Although both time to WBC and platelet engraftment was significantly longer in the study group, the clinical significance of this finding is questionable, especially as it did not seem to prolong length of stay.There was no significant difference between incidence of neutropenic fever, or between incidence of positive blood cultures in patients with neutropenic fever. There was a non-statistically significant increase in the rate of ICU admissions in the study group vs control group 4/43 and 0/43 respectively (p=0.12). 30-day rehospitalization rate was comparable between the two groups.Conclusion:We did not find a statistically significant increase in morbidity or mortality for patients 75-80 years of age undergoing auto-HSCT compared with patients 55-65 years old. To our knowledge this is the largest cohort to date demonstrating the safety of auto-HSCT in this elderly population. [Display omitted] DisclosuresGritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy. Verma: Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; BMS: Research Funding.

Safety and Short-Term Efficacy of Venetoclax Combined with Azacitidine in Acute Myeloid Leukemia: A Single Institution Experience

IntroductionThe oral anti-apoptotic B-cell lymphoma 2 protein inhibitor (venetoclax) combined with hypomethylating agents (azacitidine) has shown promising activity in patients with acute myeloid leukemia (AML). However, there are no single center real-world research results with relatively large sample size in China. The purpose of this study is to explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven + AZA) in previously untreated patients who were ineligible for standard chemotherapy and patients with relapsed/refractory (R/R) AML in China.MethodsA retrospective study was conducted on 60 previously untreated patients who were ineligible for standard chemotherapy and patients with R/R AML who received Ven + AZA (venetoclax，100mg D1、200mg D2、400mg D3-28；azacitidine, 75mg/m2 D1-7) in the Peking University Institute of Hematology from March 15, 2019 to May 20, 2021. The incidence of adverse events (AE), complete remission (CR)/CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) and minimal residual disease (MRD) status in patients with different risk stratification and different gene subtypes were analyzed.ResultsPatient CharacteristicsThe median age was 54 (18-77) years, 33 males (55.0%), and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients who were ineligible for standard chemotherapy and 36 (60.0%) were R/R patients. The median cycles of Ven + AZA in the two groups were both 1 (1-5). The median follow-up time of them were 2.9 (1.5-13.2) and 118 (1.4-26.3) months, respectively.In the previously untreated patients who were ineligible for standard chemotherapy, 2 were over 75 years old, 16 cases were diagnosed with active infection, 6 had organ dysfunction. According to the risk stratification of NCCN, it was divided into 8 cases of favorable-risk, 2 cases of intermediate-risk and 14 cases of poor-risk. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 cases in the poor-risk group (CR to hematological recurrence <18 months, no remission after 1 cycle of therapy, no remission after ≥2 cycles of therapy).EfficacyIn the previously untreated patients who were ineligible for standard chemotherapy, after the first cycle of Ven + AZA treatment, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) cases achieved partial remission (PR), and the ORR was 83.3%. Among the CR/CRi patients, 8/17 (47.1%) achieved MRD negative after 2 cycles of therapy. Four patients achieved CR/CRi after the first cycle of Ven + AZA, ineligible factors (active infection) were eliminated, followed by chemotherapy, and MRD achieved negative after 1-2 cycles of consolidation therapy.The median duration of induction therapy in R/R group was 28 (14-28) days, and the total CR/CRi rate was 58.3%. 11/24 (45.8%) cases achieved CR/CRi after one cycle of Ven + AZA in the poor-risk R/R group, and 10/12 (83.3%) cases achieved CR/CRi in the favorable-risk R/R group, which was significantly superior than that in the poor-risk group (P = 0.031). The efficacy in patients with different risk stratification and gene subtypes are displayed in Table.SafetyThe incidence of hematological AEs was 100%, and the incidence of neutropenic fever was 40.0% (24/60). The incidence of grade 3-4 leukopenia was 86.7% (52/60), of which 60.0% (36/60) occurred before therapy, and the incidence of grade 3-4 leukopenia caused by therapy was 26.7% (16/60). The incidence of grade 3-4 anemia was 71.7% (43/60), of which 51.7% (31/60) occurred before therapy, and the incidence of grade 3-4 anemia caused by therapy was 20.0% (12/60). The incidence of grade 3-4 thrombocytopenia was 76.7% (46/60), of which 60.0% (36/60) occurred before therapy, and the incidence of grade 3-4 thrombocytopenia caused by therapy was 16.7%. The most common non hematological AE was infection, followed by gastrointestinal AE. Infection mainly included pneumonia (13.3%) and soft tissue infection (6.7%), both of which were grade 3-4.ConclusionVen + AZA has acceptable safety in previously untreated patients who were ineligible for standard chemotherapy and patients with R/R AML, can achieve a high response rate, and some patients can achieve MRD negative in China. It is effective in patients with NPM1, IDH1/IDH2 and TP53 positive. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risk factors for neutropenic fever in non-Hodgkin's lymphoma patients with primary granulocyte colony-stimulating factor prophylaxis.

Background/AimsFebrile neutropenia (FN) interferes with the proper chemotherapy dose density or intensity in non-Hodgkin’s lymphoma (NHL) patients. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab has an intermediate FN risk. Prophylactic granulocyte colony-stimulating factor (G-CSF) support is recommended for patients with other host-related risk factors.MethodsWe evaluated the risk factors for FN-related admission in NHL patients who have received primary G-CSF (lenograstim) prophylaxis.ResultsData from 148 patients were analyzed. The incidence of neutropenic fever was 96 events (12.2%), and the median period was 3.85 days (range, 0 to 5.9); the median duration of neutropenia was 4.21 days (range, 3.3 to 5.07). Eighty-three FN-related admissions were reported. Advanced age (> 60 years), female sex, a low albumin level, and prednisone use were associated with FN-related admission in multivariable analysis (p = 0.010, p < 0.001, and p = 0.010, respectively). A comparison between diffuse large B-cell lymphoma patients treated with R-CHOP and pegylated G-CSF and those treated with R-CHOP and lenograstim did not reveal significant differences in the FN-related admission rate between the two groups, although the lenograstim-treated group had a higher incidence of severe neutropenia.ConclusionsElderly patients, female patients, and patients with low albumin levels need to be actively followed-up for FN even when primary prophylaxis with G-CSF has been used.

Low-Dose Cytarabine versus Best Supportive Care for Patients with Acute Myeloid Leukaemia Unfit for the Standard of Care: Egyptian Centre Experience

Background: Acute myeloid leukaemia (AML) in the elderly is not strong enough to tolerate aggressive chemotherapy. We conducted the present study to compare the efficacy and safety of low-dose cytarabine (LDAC) with best supportive care (BSC) in Egyptian patients. Method: A prospective randomized study included 60 eligible patients aged over 60 years with newly diagnosed AML. They were randomized to receive LDAC or BSC. The overall survival (OS) was the primary endpoint, while the secondary endpoint was to compare the quality of life in the form of a length of hospital stays (LOHS), mode and frequency of admission in the two studied groups. Results: Herein, 30 patients received LDAC and 30 patients received BSC. The mean survival time was 7.5 months in the BSC group compared with 10.2 months in the LDAC group. Even though the median OS was 8.4 months in the BSC group, it did not reach in the LDAC group; HR= 2.047, CI 95% (0.541-7.743) (P=0.2). There was a statistically significant association with LDAC and the frequency of hospital admission through the emergency department (ED) due to neutropenic fever and prolonged LOHS (P<0.001, P<0.002, and P<0.001, respectively). Meanwhile, the admission through the outpatient clinic (OPC) and for transfusion support were statistically insignificant in the two groups (P< 0.12 and P< 0.6, respectively). Conclusion: Despite, there were no OS statistically significant benefits of the use of LDAC over BSC in our patients, poor quality of life in the form of frequent admission through the ED, more incidence of neutropenic fever, and prolonged LOHS were reported more to patients received LDAC.

Rifaximin use favoured micafungin-resistant Candida spp. infections in recipients of allogeneic hematopoietic cell transplantation

Damage to gut mucosa following conditioning regimens may favour bacterial infections that can trigger graft versus host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Rifaximin, an oral and non-absorbable antibiotic, has been recently proposed as effective prophylaxis to reduce bacterial infections in the gut and consequently acute GvHD in this setting. The present study evaluated safety and outcomes of HSCT patients that were treated with rifaximin prophylaxis at Perugia University Hospital. Rifaximin prophylaxis was introduced as standard of care in HSCT patients in May 2018. We retrieved data from 118 consecutive transplants, and we compared the outcomes of rifaximin-treated patients with historical controls that did not receive antibiotic prophylaxis. While incidences of neutropenic fever, documented bacterial infections, and aGvHD were similar in the two groups, we found an increased frequency of invasive candidiasis and clinically relevant Candida spp. infections in rifaximin-treated patients (5 patients vs 1 patient, 25% [± 0.99%] vs 1% [± 0.01%], p < .0001). Three rifaximin-treated patients experienced life-threating candidemia (2 C. krusei, 1 C. orthopsilosis). Rifaximin was the only factor that increased the risk of Candida spp. infections. Rifaximin could have contributed to microbiome disruption which favoured an outbreak of life-threatening Candida infections. This important complication forced us to halt its use. Larger, prospective studies are needed to assess the impact of rifaximin prophylaxis on incidence of bacterial infections, aGvHD, and survival of HSCT patients.

A Randomized Placebo-Controlled Trial of Recombinant Human Interleukin-11 in Cancer Patients With Severe Thrombocytopenia Due To Chemotherapy

Thrombocytopenia is a complication of cancer treatment that can limit dose intensity. Interleukin-11 (IL-11) is a growth factor that increases platelet production. We conducted a multicenter, randomized, placebo-controlled trial of recombinant human IL-11 (rhIL-11) in 93 patients with cancer who had already been transfused platelets for severe thrombocytopenia resulting from chemotherapy. The patients had received platelet transfusions for nadir platelet counts of < or = 20,000/microL during the chemotherapy cycle immediately preceding study entry. Chemotherapy was continued during the study without dose reduction. Patients were randomized to receive placebo or rhIL-11 at 50 or 25 micrograms/kg subcutaneously once daily for 14 to 21 days beginning 1 day after chemotherapy. Eight of 27 (30%) evaluable patients treated with rhIL-11 at a dose of 50 micrograms/kg did not require platelet transfusions versus 1 of 27 (4%) patients who received placebo (P < .05). Five of 23 (18%) patients treated with rhIL-11 at 25 micrograms/kg avoided platelet transfusions (P = .23). Side effects were fatigue and cardiovascular symptoms, including a low incidence of atrial arrhythmias and syncope. There were no differences among treatment groups in the incidence of neutropenic fever, days of hospitalization, or number of red blood cell transfusions. This study shows that rhIL-11 treatment of a dose of 50 micrograms/kg significantly increases the likelihood that patients who have already been transfused platelets for severe chemotherapy-induced thrombocytopenia will not require platelet transfusions during a subsequent chemotherapy cycle.

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever.

BackgroundAutologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT.MethodsBetween January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT.ResultsThe incidence of NF among the groups was reduced (64%, 44%, and 24%; P<0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI >2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age ≥60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05).ConclusionsG-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial.

Primary peg-filgrastim prophylaxis versus filgrastim given “on demand” for neutropenia during therapy with cladribine for hairy cell leukemia

BackgroundMajor advances in the treatment of patients with hairy cell leukemia (HCL) have been made following the introduction of purine analogues. The major significant short-term toxicity of cladribine therapy are neutropenia and neutropenic fever (NF) which may be life-threatening. AimIn this retrospective study, we compared the incidence and duration of neutropenia and hospitalization in patients with HCL treated with cladribine followed by peg-filgrastim as primary prophylaxis versus daily filgrastim given “on demand” according to absolute neutrophil count (ANC). MethodsMedical records of patients with HCL diagnosed and followed in 12 medical centers in Israel during 1985–2015 were examined for details of disease at diagnosis. The efficacy of peg-filgrastim and filgrastim was assessed by evaluating the incidence of neutropenia (ANC < 1.0 × 10 [9]/L), number and length of hospitalizations, and number of days from the last day of therapy to recovery of ANC to >1.0 × 10 [9]/L. ResultsThe study population included 202 patients with HCL, 159 of whom (80.7%) were treated with cladribine; 78 patients (49%) required hospitalization for the administration of broad-spectrum antibiotics due to NF. Twenty-eight (19%) patients were treated with peg-filgrastim as primary prophylaxis, while 74 (64%) received filgrastim “on demand” due to neutropenia. Median length of hospitalization, and nadir duration were 8 and 18 days respectively (p = 0.71, p = 0.44). ConclusionsInfectious complications post-cladribine treatment remain high. No difference was found in terms of incidence of NF, number of febrile days, and nadir duration in patients receiving primary peg-filgrastim prophylaxis compared to filgrastim given on demand. Both approaches are justifiable, and the choice remains at the physician’s discretion.

Primary Prophylaxis with Piperacillin/Tazobactam in Lymphoma Patients Managed at Home after Autologous Stem Cell Transplantation

Background: Neutropenic fever (NF) is the most frequent cause of hospital readmission in ambulatory care programs for patients treated with autologous stem cell transplantation (ASCT). Methods: Analyze the impact of intensifying primary antibiotic prophylaxis with piperacillin/tazobactam (PT) in the incidence of NF and in the need for hospital readmission in a home care ASCT model. Between January 2002 and June 2017, 143 consecutive lymphoma patients, conditioned with BEAM, were managed at home since +1day of ASCT. Sixty-one patients (42*7%) received prophylactic ceftriaxone (Ct) and 82 (57*3%) PT. Due to the presence of differences in the baseline characteristics, we performed a propensity score matching. The final study population was 86 patients (43 in each group). Findings: NF occurred in 39*5% of patients in the prophylactic PT group compared with 86% in Ct group (P<0*0001). Blood culture positive was documented in 11*8% and 18*9% febrile episodes in the PT and Ct group, respectively; being coagulase-negative Staphylococcus the most frequently isolated bacteria in Ct group. In the multivariate analysis, PT retained its independent protective factor for NF (OR 0*11; P<0*001). Hospital readmission was required in 6 (14%) patients in the Ct group and 1 (2*3%) patient in the PT group (P=0*1). In the multivariate analysis, only PT retained its independent protective factor for hospital readmission (OR 0*11; P=0*05). Interpretation: This study suggests that in at home ASCT, the use of PT prophylaxis significantly reduces the incidence of NF in lymphoma patients. Funding: The authors do not have any funding sources. Declaration of Interest: The authors declare no disclosures. Ethical Approval: The Ethics Committee of the Hospital Clinic of Barcelona approved the study and was in accordance with the Declaration of Helsinki. All patients signed a written informed consent.