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F. Khawaja et al.
ly small.28,35,36 In a recent study, 181 HM patients with RSV infections were identified over 13 years.37 Of these, 65% and 35% presented with URTI and LRTI, respectively. Among the HM patients with URTI, 13% progressed to develop a LRTI (73% were patients with leukemia, 27% with multiple myeloma, and none with lymphoma).37 In a recent study from our institution focusing on RSV LRTI in HM patients who had or had not undergone HCT, we found that most HM patients who had not undergone HCT were defined as having possible RSV LRTI as bron- choscopy had not been performed in most of these patients at the time of diagnosis.38
Few data are available with regards to RSV infections in pediatric HCT recipients. The estimated incidence of RSV infections among this population is 3% to 7%,39,40 with 22%-37%39,41 developing LRTI.
Risk factors for the progression of upper to lower respiratory tract infection
The most significant complication of RSV infection in HM patients and HCT recipients is progression to LRTI, which is associated with a higher mortality rate.5,20,22,24,25,42-51 Many risk factors for progression have been identified in the hopes that target populations that could benefit from early therapy could be identified. These risk factors prima- rily consist of host factors, as previous studies on RSV serotypes A and B found no differences in outcomes.35,52
hand, there are well-described risk factors that are associ- ated with progression to LRTI in HM patients; these include lymphopenia and neutropenia,4,28,37,54,55,57 which are generally defined as ≤200 lymphocytes/mL37,54,57 and ≤500 neutrophils/mL, respectively .In multiple retrospective analyses of HCT recipients, lymphocytopenia4,37,54,57 and neutropenia4,37,54,57 at the time of the diagnosis of RSV were independent predictors of progression to LRTI.
In a cohort of 237 allogeneic HCT recipients with RSV infection, the hazard ratio (HR) of experiencing progres- sion from RSV URTI to LRTI was 4.1 for an absolute neu- trophil count of <500 cells/mL and 2.6 for an absolute lymphocyte count of <200 cells/mL,53 making them the most predictive factors for progression.53 Among leukemia patients, post-induction chemotherapy neutropenia and leukopenia have also been shown to increase the risk of progression to LRTI.22,24 In a recent retrospective study, neutropenia and lymphopenia were not independently associated with progression of disease in HM patients, but the combination of the two factors was associated with a higher risk of progression.37 However, time from last chemotherapy was not shown to play a role in progres- sion to LRTI in HM patients.37 On the other hand, lack of ribavirin therapy was associated with progression of dis-
Table 2. Risk factors for progression to respiratory syncytial virus lower respiratory tract infections among hematopoietic cell transplant recip- ients and patients with hematologic malignancies.
To assist with the identification of HCT recipients who are at risk of progression to LRTI and a fatal outcome, an Immunodeficiency Scoring Index (ISI) for RSV was devel- oped based on a combination of multiple host risk factors,53 which means it is applicable to other respiratory viruses. Six factors were included in the scoring index: neutropenia of less than 500 neutrophils/mL, lymphope- nia of less than 200 lymphocytes/mL, age greater than 40 years, graft-versus-host disease, steroid use, myeloablative chemotherapy, and time from HCT.53 On the basis of the total score, the ISI stratifies HCT recipients with RSV URTI into low-risk (score of 0-2), medium-risk (score of 3- 6), and high-risk (score of 7-12) categories.53 Other risk fac- tors that were identified in other studies and were not included in the ISI were smoking status,54 hypoxia,28 noso- comial infection,28,37 matched unrelated donor/mis- matched donor status,25,42,55 prior autologous HCT, and stem cell source25,28 (Table 2). The ISI for RSV has been val- idated by other authors12,56 (Table 3). Wang et al. found that allogenic HCT recipients with high ISI scores experienced progression to pneumonia after being diagnosed with RSV, influenza, coronavirus, or adenovirus.12
There is currently no predictive scoring index for the progression of respiratory viruses in patients with leukemia, lymphoma, or multiple myeloma. On the other
HCT recipients
Risk factors for progression to RSV LRTI
Patients with hematologic
malignancies
Neutropenia ≤ 500 cells/mL Lymphopenia ≤ 200 cells/mL
Neutropenia ≤ 500 cells/mL
Lymphopenia ≤ 200 cells/mL
Age ≥ 40 years
HCT within 1 year of infection
Myeloablative chemotherapy within 1 year of infection
Presence of GvHD
Use of steroids within 2 weeks of infection
History of smoking Nosocomial infection Hypoxia
Matched unrelated donor transplant/mismatched donor source
Prior autologous HCT Cord blood as transplant
cell source
Table 3. Outcome data stratified by respiratory syncytial virus-Immunodeficiency Scoring Index from three different cohorts.
Shah et al. 201453
ISI risk stratification Low Medium High n=69 n=147 n=21
Wang et al. 201612 Low Medium High n=17 n=20 n=7
Damlaj et al. 201556 Low Medium High n=11 n=28 n=6
RSV: respiratory syncytial virus; LRTI: lower respiratory tract infection; HCT: hematopoi- etic cell transplant; GvHD: graft versus host disease.
Mortalityrate,% 0 3 29 0 20 14 0 4 50
RateofprogressiontoLRTI,% 7 15 42 6 15 29 NA NA NA
ISI: Immunodeficiency Scoring Index; LRTI: lower respiratory tract infection.
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haematologica | 2019; 104(7)