Prompt Treatment of Respiratory Syncytial Virus with Inhaled Ribavirin and IVIG in High Risk Allogeneic Stem Cell Transplant Recipients Significantly Diminishes Mortality

Background: Respiratory syncytial virus (RSV) is a potentially life threatening infection in allogeneic stem cell transplant (Allo) recipients. Viral respiratory tract infections have also been implicated in bronchiolitis obliterans (BO) and other post Allo non-infectious pulmonary complications (NIPCs). Since 2000, we have treated RSV infections in Allo patients (pts) in a standardized manner with pre-established criteria. We sought to determine survival of such uniformly treated pts and to ascertain their risk of subsequent NIPCs.

Methods: Allo pts were systematically tested for RSV if they presented with evidence of lower respiratory tract infection or upper respiratory tract symptoms and predefined risk factors for RSV pneumonia. Pts received inhaled ribavirin 2 g q8h × 15 doses and standard IVIG 500 mg/kg/day × 4 days (d) if they exhibited any of the following features: 1) neutropenia, 2) pneumonia, 3) active treatment for GVHD.  Data from 1/00 to 6/12 were collected retrospectively and analysed on an “intent-to-treat” basis.

Results: We present the first 32 pts; their characteristics are shown in Table 1. Of those with RSV pneumonia, one died 17 d after diagnosis (case fatality rate 6.3%; 95%CI: 0.2-30.2%) after receiving partial treatment in the context of palliative care for relapsed leukemia. In total, 13 pts died (40.6%; 95%CI: 23.7-59.4%).  Causes of death other than RSV included GVHD (n=4), relapse (n=5), fungal and bacterial pneumonia (n=2), ARDS (n=1) and other (n=1).  Median OS from RSV infection was 53 months (m) (95%CI: 22 m-not reached). Four pts had been diagnosed with BO 9 to 251 d prior to RSV. Among the 28 at risk for developing BO, the incidence was 0% (95%CI: 0-12.3%). One was diagnosed with cryptogenic organizing pneumonia 36 d after RSV (3.4%; 95%CI: 0-18.3%). 

Conclusion: We observed an extremely low RSV pneumonia fatality rate in contrast to that reported in the literature. Perhaps due to strict control of nosocomial transmission, our cohort tended to contract RSV late, which might account for better outcomes. Our low incidence of NIPCs is intriguing, and could be biased by the fact that 66% of our cohort was on ≥ 2 immunosuppressors. Our findings support prompt treatment of high-risk patients with inhaled ribavirin/IVIG to diminish early RSV-related mortality and morbidity.

Table 1. Patient Characteristics (n=32)
Characteristic	N (%)
Median age (range)	48 (20-62)
Diagnosis
AML/ALL/MDS/CML	3/5/7/3
CLL/NHL/Myeloma	2/6/4
Other	2
Donor source
Matched sibling	15 (47)
Matched unrelated	13 (41)
Mismatched unrelated / haploidentical / cord  blood	4 (12)
Conditioning regimen
Myeloablative	19 (59)
Reduced intensity	13 (41)
Acute GVHD	14 (44)
Chronic GVHD	27 (84)
Patients on ≥2 immunosuppressors at RSV diagnosis	21 (66)
Clinical syndrome
Upper tract infection	16 (50)
Pneumonia	16 (50)
Median days from transplant to RSV infection (interquartile range)	382 (241 to 1049)