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S350 Abstracts / Biol Blood Marrow Transplant 25 (2019) S290 S442

It occurs most commonly at 21 to 42 days following HCT. The Infectious Diseases, Infection Control & Employee Health, MD
clinical manifestations of BKPyV-associated hemorrhagic cysti- Anderson Cancer Center, Houston, TX; 2 Department of Infectious
tis after HCT may include cystitis, hematuria with or without Diseases, Infection Control, and Employee Health, The University
clots, renal failure due to obstruction, and rarely, life-threaten- of Texas MD Anderson Cancer Center, Houston, TX; 3 1515
ing bleeding. Holcombe Blvd, MD Anderson Cancer Center, HOUSTON, TX;
4
Objectives: We report in this case series the treatment Division of Pharmacy, The University of Texas MD Anderson
approach in three of our patients who developed symptomatic Cancer Center, Houston, TX
infection as listed below
Introduction: CMV infection remains a leading cause of mor-
bidity and mortality in allogeneic hematopoietic cell transplant
patient Malignancy Conditioning Donor Symptomatic
(allo-HCT) recipients. CMV can cause tissue-invasive disease,
regimen infection
1 Pre B-ALL MA- CY/TBI + rATG MUD D38 especially pneumonitis, with poor outcomes.
2 T-Cell lymphoma RI-BU/FLU MRD Day 35 Methods: We performed a retrospective study in HCT recipi-
3 Mixed RI- BU/FLU MRD Day 31 ents who had CMV pneumonia from January 2014 to August
phenotype AML 2018. The microbiology laboratory records were queried to
identify patients with CMV pneumonia based on CMV viral cul-
ture and CMV real time-PCR in bronchoalveolar lavage (BAL).
Method: Our treatment approach was to initiate aggressive Data on demographics, clinical characteristics, management
hydration, decrease immunosuppressive medications, and and mortality were collected.
start treatment with combination high dose cidofovir, and Results: A total of 35 patients were diagnosed with CMV pneu-
IVIG. Cidofovir has a modest in vitro antiviral activity against monia and 16 (47%) were male, with a median age of 56 years
BKPyV, and has been widely used to treat patients with BKPyV (range: 18-83). The median time from HCT to CMV pneumonia
hemorrhagic cystitis, even though it is not FDA approved for was 141 days (range 25-1579); the majority occurred after day
that indication. On the other hand, immunoglobulin prepara- 100 (60%). All patients except one were CMV seropositive and
tions contain BKPyV neutralizing antibodies against all major 15/31 (48%) had GVHD at time of diagnosis. The median
genotypes of BKPyV. Our patients had low immunoglobulin plasma CMV viral load (VL) at diagnosis was 137 UI/mL (range:
level, and for that reason adding IVIG to their treatment regi- 0-6.586) while the median VL in BAL was 1.700 UI/mL (range
men was considered. All three patients received the first treat- 79-64.800) (Figure). Foscarnet was the most common antiviral
ment with cidofovir (5 mg/kg/dose), and IVIG, immediately agent used (23, 70%) followed by ganciclovir (16, 48%). Twenty
after their symptoms started, and the diagnosis was confirmed. (61%) patients received combination therapy with IVIGs with a
Results: All three patients noticed significant improvement in mean number of doses of 4.35 (range: 1-17). All-cause mortal-
their symptoms after the first treatment. Patients 1, and 2, ity was 80% and CMV-associated mortality was 66%. Systemic
received three treatments with weekly cidofovir, over three steroids (75%), co-infections after diagnosis of CMV pneumonia
weeks, while patient 3 received 2 treatments only, and the (37%) and mechanical ventilation (82%) were associated with
third treatment was held due to complete resolution of the mortality death.
symptoms. As shown in table 2, we can see how the BKPyV Conclusion: CMV pneumonia remains a significant cause of
level was trending down as the patients were receiving their mortality after HCT and most occurred after day 100.
treatment; this also coincided with the improvement in their
macroscopic hematuria, the amount of blood clots in the urine,
urinary frequency and bladder spasms that they presented
with.

BK virus level (copies/mL) initial Week 1 Week 2 Week 3


1 4.00E+08 2.70E+0 1.20E+08 0
2 9.60E+07 1.40E+07 1,700,000 35,800
3 3.50E+08 210,000 0 N/A

Conclusion: BKPyV hemorrhagic cystitis is a significant cause


of morbidity, occurring in up to 20 % of stem cell transplant
recipients. At the present time treating these patients centers
around hydration, reduce immune suppression, and some-
times using cidofovir, which is still not FDA approved for this
indication. In this case series we demonstrated that starting
our three patients on combination treatment with cidofovir, Figure 1. Comparison of median CMV viral load, in plasma and BAL, by Mann-
and IVIG, helped improve their symptoms and reduce their whitney test.
BKPyV level, just after the first treatment, with complete reso-
lution of their symptoms in 2-3 weeks.

524
Human Metapneumovirus or Influenza A Upper Respiratory
523 Tract Infection Associated with Increased Risk of Bacterial
High Mortality of CMV Pneumonia in Hematopietic Cell Superinfection in Allogeneic Hematopoietic Cell Transplant
Transplant Recipients. Recipients
Marjorie V. Batista MD, TID, PhD1, Fareed Khawaja MD2, Chikara Ogimi MD1, Hu Xie MS2, Angela P Campbell MD, MPH3,
Lynn El Haddad PhD3, Samuel L Aitken PharmD, BCPS4, Alpana Waghmare MD4, Jane M Kuypers PhD5,
Farnaz Foolad PharmD, BCPS4, Keith R Jerome MD, PhD3, Jason Chien MD, MS6, Cheryl Callais7,
Roy F. Chemaly MD, MPH, FIDSA, FACP2. 1 Department of Guang-Shing Cheng MD8, Steven A. Pergam MD, MPH9,
Abstracts / Biol Blood Marrow Transplant 25 (2019) S290 S442 S351

Wendy M Leisenring PhD3, Janet A Englund MD1, pre- and post-transplant factors, significant URTI variables for
Michael J Boeckh MD, PhD9. 1 Pediatrics, University of outcomes in both models were (1) Flu A for gram-positive bac-
Washington, Seattle, WA; 2 Clinical Biostatistics, Fred Hutchinson teremia, (2) HMPV for gram-positive pneumonia, and (3)
Cancer Research Center, Seattle, WA; 3 Fred Hutchinson Cancer HMPV for bacteremia or bacterial pneumonia (Figure). The
Research Center, Seattle, WA; 4 Infectious Diseases, Seattle association between PIV URTI and development of bacteremia
Children's Hospital, Seattle, WA; 5 Laboratory Medicine, or pneumonia approached statistical significance.
University of Washington, Seattle, WA; 6 Janssen Biopharma, Inc., Conclusion: In HCT recipients, URTIs due to Flu A and HMPV are
Seattle, WA; 7 Clinical Trial Services, Inc., Covington, WA; significant risk factors for the development of gram-positive bac-
8
Medicine, University of Washington, Seattle, WA; 9 Vaccine and teremia and pneumonia, respectively. Further studies are needed
Infectious Diseases Division, Fred Hutchinson Cancer Research to assess whether prevention or early diagnostic and treatment
Center, Seattle, WA strategies for RVIs can reduce the risk of bacterial infection.

Introduction: Bacterial superinfection following moderate to


severe respiratory viral infections (RVIs), especially influenza
(Flu), is well described in immunocompetent hosts. The clinical 525
impact of preceding RVIs on the development of bacterial Impact of Influenza Vaccination on Outcomes of Influenza
superinfection in hematopoietic cell transplant (HCT) recipi- Infections in Immunocompromised Patients
ents may be significant although data are limited. Furthermore, Lea Sacca MPH1, Roy F. Chemaly MD, MPH, FIDSA, FACP2,
the impact of upper respiratory tract infection (URTI) on this Marjorie V. Batista MD, TID, PhD3, Ying Jiang MS4,
outcome has not been systematically evaluated. Lynn El Haddad PhD2,
Objectives: To investigate whether URTI due to specific respi- Ella J Ariza-Heredia MD2. 1 MPH Health Promotion Behavioral
ratory viruses was associated with increased risk of developing Sciences/Global Health, University of Texas Health Science Center
bacteremia or bacterial pneumonia post-HCT. Houston, Houston, TX; 2 Department of Infectious Diseases,
Methods: In a longitudinal surveillance study of RVIs among Infection Control, and Employee Health, The University of Texas
allogeneic HCT recipients conducted from 2005-10, weekly MD Anderson Cancer Center, Houston, TX; 3 Department of
post-HCT nasal washes were collected through day 100. Nasal Infectious Diseases, Infection Control & Employee Health, MD
and bronchoalveolar lavage samples were tested by multiplex Anderson Cancer Center, Houston, TX; 4 Department of Infectious
PCR for respiratory syncytial virus, parainfluenza viruses (PIV) Diseases, Infection Control & Employee Health, The University of
1 4, Flu A/B, human metapneumovirus (HMPV), adenovirus, Texas MD Anderson Cancer Center, Houston, TX
rhinoviruses and coronaviruses. URTI was defined as having
respiratory virus detected from nasal samples with respiratory Introduction: Patients with cancer are more susceptible to
symptoms. Bacteremia and bacterial pneumonia were defined influenza infections than the general population, Hematopoi-
as growth of significant bacteria (e.g., Coagulase-negative etic Cell Transplant (HCT) recipients in particular. Conflicting
staphylococci was defined as insignificant bacteria) from blood data on influenza vaccine effectiveness and a lack of clear rec-
and lower respiratory tract samples including bronchoalveolar ommendations in complex clinical scenarios make the compli-
lavage, respectively. Separate Cox proportional hazards models ance with immunization suboptimal.
were used to examine associations between first URTI for indi- Methods: We conducted a retrospective study and included
vidual viruses and the subsequent development of first bacter- both HCT and non-HCT recipients with laboratory-confirmed
emia and/or bacterial pneumonia by 100 days post-HCT. influenza infection during the previous flu season (September
Results: We identified 471 HCT recipients (median age: 2017- May 2018). We evaluated 365 patients with hematologic
51 years, range 8 months-75 years). Number of patients for malignancies (85), HCT recipients (138), and patients with var-
each first outcome event by 100 days post-HCT included the ious solid tumors (142). We analyzed the impact of influenza
following: Gram-positive bacteremia (n=64), Gram-negative vaccination on mortality.
bacteremia (n=53), Gram-positive pneumonia (n=46), Gram- Results: Influenza A/H3N2 was the most common type
negative pneumonia (n=8), and either bacteremia or pneumo- detected during the past season with a total of 251 (69%)
nia (n=152). After adjusting for pre-transplant factors only and patients affected and half of the patients were hospitalized.
Amongst the HCT recipients, more patients had an allogeneic
than autologous transplant (56% vs. 44%). When compared to
HCT recipients who were vaccinated, non-vaccinated HCT
recipients had higher mortality rate (21% vs. 6%, p<0.05) and
more died from respiratory failure (17% vs. 5%, p<0.05). When
stratifying HCT recipients with or without lymphopenia

Table 1
Vaccination rates among ST patients, HM patients, and HCT recipients charac-
terized by flu-type groups, administration of oseltamivirtherapy, death, and
cause of death

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