Table 1.
Presumptive EV-D68 cases in patients with hematologic malignancy and HCT recipients
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 8 | |
|---|---|---|---|---|---|---|---|---|
| Patient info | 62-y-old F with AML | 22-yo M with ALL | 61-y-old M with MDS, RAEB | 29-y-old F with ALL | 37-y-old F with AML | 54-y-old M with ALL | 69-y-old M with diffuse large B-cell lymphoma | 34-y-old M with cutaneous T-cell lymphoma |
| Therapy | Myeloablative MURD PBSCT with relapse (6 mo prior); decitabine (day −5); MEC (day +7) | Myeloablative MURD BMT with persistent minimal residual disease (1 y prior); imatinib (start 8 mo prior) | Autologous HCT for glioblastoma (5 y prior); G-CLAM (days −48 and −13) | Hyper-CVAD × 5 cycles IT, chemotherapy × 4 (5 mo prior); cylcophosphamide (day +12); CAR T-cell infusion (day +15) | Myeloablative MURD PBSCT (2 y prior), in remission | Nonmyeloablative MURD PBSCT (day −51); dasatinib daily (start day −10); IT methotrexate (days −10, +11) | R-CHOP cycle 5 (day −7) | Myeloablative MURD PBSCT (1.5 y prior); corticosteroids, sirolimus, imatinib, rituxan (5 mo prior); prednisone and IL-2 (start 2 mo prior) |
| Setting | Outpatient/inpatient | Inpatient/ICU | Inpatient/ICU | Outpatient | Outpatient | Outpatient/inpatient | Inpatient/ICU | Inpatient |
| Symptoms | Malaise, productive cough, nasal congestion, clear rhinorrhea, dyspnea, cough | Parasternal chest pain, dyspnea, cough, fever | Productive cough, sputum, fever, altered mental status | Sore throat, cough, headache, malaise, mild rhinorrhea | Sore throat, malaise, cough | Sore throat, rhinorrhea, nonproductive cough, fever (day +23) | Fever, dry cough, fatigue, malaise, chest tightness, syncope, altered mental status | Fever, productive cough, fatigue, diarrhea |
| Chest exam at diagnosis | Respirations regular and clear, productive cough | Clear lungs | Clear lungs | Diminished breath sounds, normal effort | Lungs clear | Respirations regular, cough, rhinorrhea | Decreased breath sounds L base, cough | Lungs clear |
| Maximum oxygen requirement | 3 L via nasal cannula | Mechanical ventilation | None | None | None | None | Mechanical ventilation | 2 L via nasal cannula |
| Radiologic findings | CXR (day +8): new consolidation L base, R pleural effusion | CXR (day +3): diffuse L lung disease and patchy R lung disease; possible bilateral pleural effusion; CT chest (day +18): worsening ground-glass L upper lobe, patchy ground-glass R right upper and middle lobes (see Figure 2) | CXR (day −3): bibasilar consolidation; CT chest (day −1): patchy consolidation R lower lobe, nodules in both lower lobes; mild interlobular septal thickening (see Figure 2) | CXR (day +8): lungs clear | NA | CXR (day +12): bronchial wall thickening in upper lungs | CXR (day +1): large L pleural effusion, L lower lobe atelectasis; CT chest (day +4): interval increase R pleural effusion; large L pleural effusion; new patchy consolidation R middle lobe; bilateral lower lobe consolidation (see Figure 2) | CXR (day 0): right basilar consolidation |
| Day posttransplant EV-D68 positive | 192 | 374 | 1833 | NA | 666 | 51 | NA | 596 |
| Day postchemotherapy EV-D68 positive | 5 | NA | 13 | 150 | NA | NA | 7 | NA |
| Coinfections | Coagulase-negative Staphylococcus bacteremia (second admission) | Mycobacterium fortuitum on prior BAL; Candida albicans, Aspergillus niger, and Enterobacter cloacae from BAL (day +21) | Streptococcus mitis septicemia | None | None | CMV viremia (day −4); admitted for fever and neutropenia day +24-26, no etiology identified | Clostridium difficile colitis | None |
| ANC at diagnosis (109 cells/L) | 0.58 | 11.3 | 0 | 3.68 | 7.42 | 6.33 | 0.01 | 5.19 |
| ALC at diagnosis (109 cells/L) | 0.42 | 0.41 | 0 | 0.43 | 0.84 | 1.54 | 0.12 | 0.67 |
| Duration of symptoms | 55 d | >52 d | 6 d | 11 d | 3 d | 33 d | 15 d | 7 d |
| Duration of initial hospitalization | 4 d | >54 d, ICU 13 d | 27 d, ICU 2 d | NA | NA | 3 d | 14 d, ICU 3 d | 3 d |
| Outcome | Death at day +55 due to respiratory failure in setting of CHF, fluid overload and paraplegia due to compression fracture | Remains admitted on nasal cannula, persistent respiratory symptoms in setting of pneumonia and bronchiolitis obliterans | In remission, being evaluated for HCT; respiratory symptoms resolved | Successful CAR T-cell therapy with planned non-myeloablative matched related HCT; respiratory symptoms resolved | In remission, remains on therapy for chronic GVHD; respiratory symptoms resolved | In remission, developed mild gut GVHD; respiratory symptoms resolved | Discharged to skilled nursing facility; respiratory symptoms resolved | Respiratory symptoms resolved |
| Select relevant medications at time of diagnosis | Sirolimus, prednisone, budesonide, triamcinolone cream | Budesonide, cyclosporine, prednisone, imatinib, albuterol, fluticasone-salmeterol, montelukast | Prednisone, budesonide | Cyclosporine, dasatinib, mycophenolate mofetil, prednisone | Prednisone, IL-2 (subcutaneous), fluticasone, montelukast | |||
| Other relevant medical history | Chronic GVHD (skin and gut) | Acute GVHD (gut), chronic GVHD (mouth), bronchiolitis obliterans | Glioblastoma multiforme s/p resection, radiotherapy and chemotherapy (5 y prior) | Asthma | Chronic GVHD (skin and gut) | Allergic rhinitis, hypertension, type 2 diabetes mellitus | Chronic left pleural effusion, coronary artery disease, history of tobacco use | Chronic GVHD (skin, eyes, mouth), restrictive pulmonary disease, osteoblastoma cervical spine, superficial melanoma, pediatric T-cell NHL of the large intestine |
AML, acute myeloid leukemia; ANC, absolute neutrophil count; ALC, absolute lymphocyte count; ALL, acute lymphoblastic leukemia; BAL, bronchoalveolar lavage; BMT, bone marrow transplant; CAR, chimeric antigen receptor; CHF, congestive heart failure; CMV, cytomegalovirus; CXR, chest radiograph; F, female; G-CLAM, granulocyte colony-stimulating factor/cladribine/cytarabine/dose-escalated mitoxantrone; GVHD, graft-versus-host disease; hyper-CVAD, cyclophosphamide/vincristine/doxorubicin/dexamethasone with methotrexate and cytarabine; IL-2, interleukin-2; IT, intrathecal; M, male; MDS, myelodysplastic syndrome; MEC, mitoxantrone/etoposide/cytarabine; MURD, matched unrelated donor; NHL, non-Hodgkins lymphoma; PBSCT, peripheral blood stem cell transplant; RAEB, refractory anemia with excessive blasts; R-CHOP, rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone.