Infectious Complications in the Outpatient and Inpatient Autologous Stem Cell Transplantation Setting for Patients with Multiple Myeloma. Princess Margaret Cancer Center Experience
Authors: Nikonova Anna , Zeglinski Christina , Husain Shahid , So Miranda , Atenafu Eshetu G , Reece Donna E , Trudel Suzanne , Kukreti Vishal , Tiedemann Rodger E. , Prica Anca , Franke Norman Anthony , Huynh Jane , Tao Leeping , Chen Christine I 
Published: October 2019

Abstract
Background: Autologous stem cell transplant (ASCT) for multiple myeloma (MM) can be feasible and safe in the outpatient setting and has become standard of care at many centers. Limited literature, however, exists on the types of infectious complications, including specific pathogenic isolates and resistance patterns in the outpatient (OP) setting and whether these differ from the inpatient (IP) setting. This creates uncertainty and variation among local treatment guidelines on antibiotic prophylaxis and treatment of infections in the outpatient population.
Methods:
In this retrospective study, at total of 240 patients who underwent ASCT at our institution from 2015 to 2016 were reviewed. Study objectives included: 1) to describe the types of infections and pathogenic isolates in MM patients during the acute transplant period and 2) compare isolate results between patients undergoing OP vs IP ASCT. We also aimed to assess 30-day post-ASCT all-cause mortality, readmission rates, and incidence of multidrug resistant bacterial infections in each cohort. As per standard transplant protocol at our institution, all patients received ciprofloxacin and fluconazole prophylaxis and standardized initial therapy for febrile neutropenia with piperacillin-tazocin. Daily GCSF support was routinely used starting day +7 for IPs, and on demand only for OPs.
Results:
Patient, disease and transplant characteristics:
Baseline demographics of both OP and IP cohorts are shown in Table 1 (total n=240; 109 OP, 131 IP). As expected, IPs had poorer performance status (KPS<90), more comorbidities (HCT-CI ≥3), more advanced stage MM, had worse pre-transplant renal function, and were more likely to receive Melphalan dose reductions. Median time to engraftment was similar between groups - 12 days for IP and 13 days for OP (range 9-25), with duration of neutropenia <0.5x10^9/L exceeding 7 days in 46% of the cohort. Median length of stay in hospital was 17 days (12-55) for the inpatients. In the OP cohort, 63.9% of patients required readmission to hospital, with median 3-day hospital stay. In total, only 4 (1.7%) patients required ICU admission.
Infections in total cohort (OP and IP):
Overall, 121 of 240 patients (50.4%) developed febrile neutropenia, with most common causes including: blood stream infection (BSI) (n=35, 29%), pneumonia (n=18, 14.8%) and respiratory virus infections (n=16, 13.2%). Opportunistic infections were uncommon (n=6, 2.5%) with 1 case of invasive aspergillosis and 5 cases of CMV infection.
Of the 43 cases of BSI, 33 (76%) were identified as central line associated blood stream infections (CLABSI), 20 (46.5%) due to gram positive and 20 (46.5%) due to gram negative organisms. Multi-drug resistant gram negative organism isolates were observed in 22 patients (51%), including 5 cases of extended spectrum beta lactamase producing bacteria (ESBL; 11.6%), 9 cases of gram negative bacteria carrying inducible AmpC gene (SPICE; 20.1%), and 10 (23%) cases of quinolone resistant gram negative BSI.
Comparison of IP vs OP infections:
Although the OP cohort were less frail with fewer comorbidities than the IP cohort, they had more episodes of febrile neutropenia (64% vs 51%; p=0.042), worse mucositis (22.0% vs 10.8%, p= 0.021), and more BSI (24.7% vs 12.9% p=0.019). In the multivariable analysis, only OP status (OR 2.4, p=0.03) and baseline ANC<1.5 pre ASCT (OR 6.3, p=0.003) predicted for BSI occurrence.
At 18 months, OS was 98.5% and PFS was 68% for all patients, with no difference between IP and OP (p=0.772). PFS was worse in patients with BSI (p=0.0031, HR 8.7), with gram positive infections in particular (p=0.0264, HR 4.9)
Conclusions:
In our autotransplant experience, blood stream and lung infections are common, with multi-drug resistance a concern. We were surprised to report that patients undergoing outpatient-based transplant had more BSI, presumably central line-related, and that this may impact disease outcomes (PFS). We hypothesize that outpatients may undergo additional line manipulation or inferior line hygiene, suggesting that enhanced patient/staff education on infection control measures should be a focus. In general, though, outpatient ASCT patients had excellent outcomes, with similar engraftment rates, short readmission rates, low ICU usage, as the entire cohort.

Disclosures
Tiedemann: Novartis: Consultancy; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Merck: Consultancy; Roche: Consultancy. Chen:Amgen: Honoraria.