Fluoroquinolone Prophylaxis in Autologous Hematopoietic Stem Cell Transplant Recipients

Fluoroquinolone Prophylaxis in Autologous Hematopoietic Stem Cell Transplant Recipients

S128 Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481 Disease Subtype HR for Log Time to AuHCT Lower 95% CI Limit Upper 95% CI Limit ...

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S128

Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481

Disease Subtype

HR for Log Time to AuHCT

Lower 95% CI Limit

Upper 95% CI Limit

P Value

Hodgkin Lymphoma Diffuse Large B Cell Mantle Cell Non-Hodgkin’s Lymphoma T Cell

0.875 1.798 0.324 0.219

0.372 1.085 0.023 0.039

2.06 2.98 4.52 1.229

0.7603 0.0228 0.4019 0.0844

in first complete remission (CR1), if there was no evidence of relapsed, disease or if initial hematopoietic cell transplant was allogeneic. Two hundred and forty one patients were identified for inclusion. Patients with HL had a lower median time to AuHCT as compared to DLBCL (p¼0.0017) and had a higher probability of survival (p¼0.3902). DLBCL patients with longer times to AuHCT had worse overall survival (p¼0.0228). Age was a significant factor in the length of time from diagnosis of relapse to referral to a transplant center (Pearson’s correlation 0.21, p¼0.03) and to AuHCT in DLBCL (Pearson’s correlation¼0.19, p¼0.0402). In all lymphoma subtypes evaluated, age was associated with an increase in the risk of death following AuHCT (HR for a 5 year increase in age¼1.15, 95% CI: 1.054-1.0256, p¼0.0018). Our data suggest that in relapsed DLBCL delayed referral to a transplant center may influence outcomes and should be further evaluated.

148 Evaluation of BEAM Versus Beac High-Dose Chemotherapy in Autologous Stem Cell Transplantation: A Single Center Experience Zahra Mahmoudjafari 1, Sunil Abhyankar 2, Tara L. Lin 2, Anurag K. Singh 2, Leyla Shune 2, Joseph P. McGuirk 2, Omar Aljitawi 2. 1 Department of Pharmacy, University of Kansas Medical Center, Westwood, KS; 2 Blood and Marrow Transplant, University of Kansas Medical Center, Westwood, KS High dose chemotherapy followed by autologous stem cell transplant remains standard of care for patients with lymphoma. BEAM and BEAC preparative regimens have been used; however limited data is available on the comparability of these two regimens. Herein, we report our single center experience using these regimens and compare the two focusing on their efficacy and toxicity. Between January 2007 and December 2014, 275 patients received BEAM (n¼157) or BEAC (n¼118) followed by SCT were retrospectively studied. Table 1 describes patient characteristics. Time to neutrophil engraftment was 10.6 days (range 7-20) in BEAM versus 10.8 days in BEAC (range 8-18), p¼0.302. Total amount of RBC transfusions was 2.1 units versus 1.6 units, p¼0.024. Time to Table 1 Patient Characteristics

Age e years, mean Gender- count (%) Male Histology e count (%) Hodgkins DLBCL Mantle cell Follicular T cell Burkitts Primary CNS Other Disease Status e count (%) CR1 CR 2/3 PR Refractory

BEAC (n¼118)

BEAM (n¼157)

P value

55.5 74 (63)

51.8 99 (63)

0.03 0.95

19 40 17 16 15 3 5 3

(16) (34) (14) (14) (13) (3) (4) (3)

34 51 18 22 13 3 2 14

(22) (33) (12) (14) (8) (2) (1) (9)

43 32 33 10

(36) (27) (30) (9)

50 52 33 22

(32) (33) (21) (14)

0.2

0.1

platelet engraftment was 13.2 days (5-56) in the BEAM group and 13 days (8-46) in the BEAC group, p¼0.726. Total amount of platelet transfusions was lower in the BEAM group than in the BEAC group, 3.4 units versus 3.1 units, p¼0.041. Toxicities between groups were comparable. A higher rate of mucositis, nausea/vomiting and diarrhea was noted in the BEAM group but these results were not statistically significant. Other toxicities included reports of atrial fibrillation, 7 in the BEAM group versus 8 in the BEAC group, and rash, 2 in the BEAM group and 6 in the BEAC group, respectively. Fifty-eight patients (37%) in the BEAM group relapsed compared to 49 patients (42%) in the BEAC group (p¼0.440). Twenty four BEAM patients (15%) proceeded toward an allogeneic stem cell transplant as compared to 14 BEAC patients (12%), p¼0.416. In the BEAM arm, 2 patients expired prior to day 100 as compared to 5 patients in the BEAC arm (p¼0.123). Cause of early death at day 100 was relapse or progression in 2 patients in both groups, and 3 cardiovascular related events in the BEAC arm. At day 365, 12 patients expired in the BEAM arm versus 11 patients in the BEAC arm (p¼0.619). Cause of death by day 365 was relapse/ progression in 11 BEAM versus 8 BEAC patients, other causes included 1 patient in each group from pulmonary causes and 2 patients in the BEAC group from cardiovascular causes. Three year OS rate was 67.6 months from BEAM versus 51.7 months for BEAC, respectively, p¼0.366. The three years EFS rate was 25.4 months versus 24.3 months (p¼0.431). BEAM and BEAC appear to lead to similar OS and EFS, however, less transfusion requirements and less cardiovascular-related deaths are noted in the BEAM group. Randomized prospective trials are needed in this setting.

149 Fluoroquinolone Prophylaxis in Autologous Hematopoietic Stem Cell Transplant Recipients Dipenkumar Modi 1, Abhinav Deol 2, Lois Jeanne Ayash 2, Voravit Ratanatharathorn 2, Seongho Kim 3, Hyejeong Jang 3, Divaya Bhutani 2, Lawrence Lum 2, Kamya Sankar 4, Malini Surapaneni 1, Pranatharthi Chandrasekar 5, Joseph Uberti 2. 1 Department of Internal Medicine, Wayne State University/Detroit Medical Center, Detroit, MI; 2 Division of Oncology, Karmanos Cancer Institute/ Wayne State University School of Medicine, Detroit, MI; 3 Biostatistics Core/ Department of Oncology, Karmanos Cancer Institute/ Wayne State University, Detroit, MI; 4 Wayne State University School of Medicine, Detroit, MI; 5 Department of Infectious Diseases, Karmanos Cancer Institute/Wayne State University School of Medicine, Detroit, MI Introduction: Although fluoroquinolone prophylaxis is frequently utilized in autologous hematopoietic stem cell transplant (AHSCT), there is a concern of increased risk of resistant organisms and C. difficile infection. This study investigates the effect of prophylactic norfloxacin 400mg BID on the incidence of bacteremia, C. difficile infection, intensive care unit (ICU) admissions, antibiotic use, engraftment and 100 day mortality. Methods: We conducted a retrospective study of 291 consecutive adult patients who underwent AHSCT for

Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481

malignant disorders, between June 2013 and January 2015. Outcomes were compared between patients who did and did not receive norfloxacin prophylaxis. The primary end points were incidence and type of bacteremia, ICU admissions and 100 day mortality. Chi-squared(Fisher’s exact) and Kruskal Wallis(log rank) tests were used for categorical and continuous/time-to-event variables. Results: Of 291 patients, 252 patients received norfloxacin prophylaxis. Patients who received prophylaxis were more likely to have multiple myeloma(76%) and receive melphalan as a preparative regimen. In the group of patients who did not receive prophylaxis, more had NHL(46%) and received R-BEAM as a preparative regimen. The median day to engraftment was similar in both groups (12 days). Patients without prophylaxis had significantly higher rate(97%) of neutropenic fever(p¼0.005) and bacteremia(p¼0.04) compared to patients with prophylaxis. Patients without prophylaxis had an increased occurrence of gram negative bacteremia(31% vs.8%) and less gram positive infections. No difference in rate of C. difficile infection was noted between the two groups. As expected, antibiotic use was higher and of longer duration among patients without prophylaxis [97%; median 9(5-24) days] compared to patients with prophylaxis [79%; median 7(3-36) days, p¼0.04]. No differences were noted in the ICU admissions, and duration of ICU stay. The majority of the patients were transferred to ICU for infection(61%), however, no difference in the incidence of septic shock was noted(40% vs. 43%). The median days of hospitalization following AHSCT as well as mortality at day 100 were similar between both groups. Conclusion: Fluoroquinolone prophylaxis during preengraftment period in AHSCT setting is associated with reduced frequency of neutropenic fever, gram negative bacteremia and antibiotic use. There is a tendency for higher rate of staphylococcus bacteremia observed. However, no differences were noted in several important outcomes including ICU care, days in ICU and 100 day mortality. Although these data suggest autologous PBSCT may be done safely without the use of fluoroquinolone prophylaxis, additional follow up will be needed to further confirm the observation. Table 1 Overall results All (n¼291) 12 (2-31) Median day of engraftment (range)& Neutropenic fever 231 (79) (%) Blood stream 70 (24) infection (%) Gram-positive 49 (17) bacteria (%) Gram-negative 33 (11) bacteria (%) C. difficile infection 24 (8) (%) ICU admission 28 (10) (post-transplant) (%) Duration of ICU 7 (1-60) stay (range)d,* Readmission (%) 259 (89) *

Withoutprophylaxis (n¼39)

Withprophylaxis (n¼252)

P value

12 (10-18)

12 (2-31)

0.70$

38 (97)

193 (77)

0.005*

15 (38)

55 (22)

0.04*

150 A Single Center Retrospective Analysis of Busulfan/ Melphalan Conditioning Compared to Carboplatin/ Melphalan/Etoposide in Autologous Transplant for High Risk Neuroblastoma Jerelyn R. Moffet 1, Erika D. Summers 1, Heather B. Allewelt 2, Timothy A. Driscoll 2. 1 Pediatric BMT Program, Duke University Medical Center, Durham, NC; 2 Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, NC This retrospective analysis compares the toxicity and efficacy of two myeloablative regimens, carboplatin/etoposide/ melphalan (CEM) and busulfan/melphalan (bu/mel) in high risk neuroblastoma patients receiving autologous peripheral blood stem cell (autoPBSCT) transplants. Beginning 2006 to 2012, 22 patients received CEM with autoPBSC rescue while fifteen patients received bu/mel with autoPBSCT between October 2012 and June 2015. Neither cohort received MIBG therapy or radiation pre-transplant. Induction chemotherapy and timing of peripheral blood stem cell collection varied within each group. Children were excluded from this analysis if they were > 21 years, received an alternative regimen or an allogeneic transplant. Busulfan was dosed 1 mg/kg IV every 6 hours in 11 patients and 4 mg/kg every 24 hours in 4 patients. Busulfan pharmacokinetics was performed in all patients with dosing incremented in 8 patients. As previously reported, the bu/mel cohort developed more veno-occlusive disease (VOD). Three children in the Bu/Mel group and 1 child in the CEM group developed significant VOD that required defibrotide treatment. There were no deaths due to VOD. Unexpectedly, the bu/mel cohort had delayed neutrophil and platelet engraftment. The median neutrophil engraftment was 13 days for bu/mel and 11 days for CEM, p¼0.01. Median platelet engraftment was 94 days (range 21-490) and 34 days (range 17-102) for the bu/mel and the CEM groups, respectively. Two children in both groups died prior to platelet engraftment. Platelet engraftment has not yet occurred in 2 children > 100 days posttransplant following bu/mel. Seven bu/mel recipients including 3 of the 4 recipients of once daily busulfan dosing received autoPBSC boosts for poor graft function while none in the CEM cohort received an autoPBSC boost. Incidence of relapse is difficult to compare at this time as many children in the bu/mel group are less than 2 years posttransplant.

Gender Race

Age at transplant (years) 6 (15)

43 (17)

0.58*

12 (31)

21 (8)

0.69*

5 (13)

19 (8)

0.34*

5 (13)

23 (9)

0.56z

4 (1-24) 36 (92)

7 (1-60) 223 (88)

0.73z 0.59*

Chi-square test; zFisher’s exact test; *Kruskal-Wallis test; $Log-rank test; Days; dData are not available for 1 with-prophylaxis patient

&

S129

Days to Neutrophil Engraftment (>500 cells/uL) Days to Platelet engraftment (>50,000 cells/uL) Cell Dose (CD34 cells/kg) CFU-GM (colonies/100,000 cells) CFU-GEMM (colonies/100,000 cells) Veno-occlusive Disease Required stem cell boost Relapse

Carbo/Etop/Mel (N ¼ 22)

Bu/Mel (N ¼ 15)

36.4% female 68.2% Caucasian 31.8% African American

11 (10-43)

53.3% female 53.4% Caucasian 40% African American 6.6% Hispanic Median (range) 3.64 (1.5911.66) 13 (11-43)

34 (17-102)

94 (21-490)

6.43 x 10e6 (1.9513.89) 102.5 (0-135) 0 (0-7.5)

4.98 x 10e6 (0.69-7.24) 50 (0-240) 0 (0-27.5)

n (%) 1 (4.5) 0 (0) 10 (45.5)

n (%) 3 (20) 7 (46.7) 2 (13.3)

Median (range) 2.7 (1.3-10.6)