Clinical Characteristics of Adeno-Associated Virus (AAV) Viremia in Hematopoietic Cell Transplant Recipients
| Case Patient | Age, y (Sex) | Underlying Malignancy (Transplant Type) | PTD of AAV-Positive Specimen (Viral Load, Copies/mL) | Duration of Viral Detection, d | Clinical Events in Week Before or After AAV Detection | Abnormal Radiographic or Laboratory Findings | GVHD, Grade (Location) | Copathogens Detected in Real Time | Copathogens Detected Retrospectively by PCR (Copies/mL) | Clinical Outcome and Autopsy Findings |
| 1 | 48 (M) | CML (allo-MUR) | 64 (1043); 71 (none detected); 79 (none detected); 87 (<50) | Up to 23 | Admitted to the hospital with shortness of breath and hypoxemia | LLL infiltrate, pancytopenia, hypocellular bone marrow specimen | 3 (skin, GI tract, liver) | BAL specimen showed budding yeast forms and gram-positive cocci; C. glabrata cultured from sputum | BAL specimen positive for C. glabrata; BK virus viremia (360 000) and adenovirus viremia (10 032) on d 64 | Died on d 111 of pulmonary failure; DAD reported as cause of death at autopsy |
| 2 | 48 (F) | MDSRA (allo-MUR) | 21 (52.5) | <7 | None | None | 2 (skin, GI tract) | None | Low-level HHV-6 viremia (230) on d 21 | Died on d 1517 of recurrent refractory anemia with excess blasts; no autopsy report available |
| 3 | 40 (F) | AML (autologous) | 77 (<50) | <7 | Admitted to the hospital with dyspnea | Multiple patchy LUL and RLL infiltrates | None | BAL and lung biopsy specimens negative for infectious organisms; blood culture positive for Stenotrophomonas | Low-level HHV-6 viremia (23)a on d 63 | Died on d 95 of pulmonary failure; autopsy findings included nonspecific destruction of small bronchioles, DAD, and leukemic relapse |
| 4 | 18 (M) | ALL (allo-MR, second transplant) | 28 (2571) | <7 | Reported nausea and diarrhea as an outpatient; endoscopy positive for GVHD | Bilirubin peaked at 9.8 mg/dL with normal transaminase levels | 3 (skin, GI tract, liver) | None | Low-level HHV-6 viremia (23) on d 28 | Died on d 297 from P. jiroveci pneumonia and respiratory failure; family declined autopsy |
| Case Patient | Age, y (Sex) | Underlying Malignancy (Transplant Type) | PTD of AAV-Positive Specimen (Viral Load, Copies/mL) | Duration of Viral Detection, d | Clinical Events in Week Before or After AAV Detection | Abnormal Radiographic or Laboratory Findings | GVHD, Grade (Location) | Copathogens Detected in Real Time | Copathogens Detected Retrospectively by PCR (Copies/mL) | Clinical Outcome and Autopsy Findings |
| 1 | 48 (M) | CML (allo-MUR) | 64 (1043); 71 (none detected); 79 (none detected); 87 (<50) | Up to 23 | Admitted to the hospital with shortness of breath and hypoxemia | LLL infiltrate, pancytopenia, hypocellular bone marrow specimen | 3 (skin, GI tract, liver) | BAL specimen showed budding yeast forms and gram-positive cocci; C. glabrata cultured from sputum | BAL specimen positive for C. glabrata; BK virus viremia (360 000) and adenovirus viremia (10 032) on d 64 | Died on d 111 of pulmonary failure; DAD reported as cause of death at autopsy |
| 2 | 48 (F) | MDSRA (allo-MUR) | 21 (52.5) | <7 | None | None | 2 (skin, GI tract) | None | Low-level HHV-6 viremia (230) on d 21 | Died on d 1517 of recurrent refractory anemia with excess blasts; no autopsy report available |
| 3 | 40 (F) | AML (autologous) | 77 (<50) | <7 | Admitted to the hospital with dyspnea | Multiple patchy LUL and RLL infiltrates | None | BAL and lung biopsy specimens negative for infectious organisms; blood culture positive for Stenotrophomonas | Low-level HHV-6 viremia (23)a on d 63 | Died on d 95 of pulmonary failure; autopsy findings included nonspecific destruction of small bronchioles, DAD, and leukemic relapse |
| 4 | 18 (M) | ALL (allo-MR, second transplant) | 28 (2571) | <7 | Reported nausea and diarrhea as an outpatient; endoscopy positive for GVHD | Bilirubin peaked at 9.8 mg/dL with normal transaminase levels | 3 (skin, GI tract, liver) | None | Low-level HHV-6 viremia (23) on d 28 | Died on d 297 from P. jiroveci pneumonia and respiratory failure; family declined autopsy |
Abbreviations: ALL, acute lymphocytic leukemia; allo, allogeneic; AML, acute myelogenous leukemia; BAL, bronchoalveolar lavage; C. glabrata, Candida glabrata; CML, chronic myelogenous leukemia; DAD, diffuse alveolar damage; GI, gastrointestinal tract; GVHD, graft versus host disease; HHV-6, human herpesvirus 6; LLL, left lower lobe; LUL, left upper lobe; MDSRA, myelodysplastic syndrome with refractory anemia; MR, matched related; MUR, matched unrelated; PCR, polymerase chain reaction; P. jiroveci, Pneumocystis jiroveci; PTD, posttransplantation day.
Limit of detection of the assay is 23 copies/mL [5].
Clinical Characteristics of Adeno-Associated Virus (AAV) Viremia in Hematopoietic Cell Transplant Recipients
| Case Patient | Age, y (Sex) | Underlying Malignancy (Transplant Type) | PTD of AAV-Positive Specimen (Viral Load, Copies/mL) | Duration of Viral Detection, d | Clinical Events in Week Before or After AAV Detection | Abnormal Radiographic or Laboratory Findings | GVHD, Grade (Location) | Copathogens Detected in Real Time | Copathogens Detected Retrospectively by PCR (Copies/mL) | Clinical Outcome and Autopsy Findings |
| 1 | 48 (M) | CML (allo-MUR) | 64 (1043); 71 (none detected); 79 (none detected); 87 (<50) | Up to 23 | Admitted to the hospital with shortness of breath and hypoxemia | LLL infiltrate, pancytopenia, hypocellular bone marrow specimen | 3 (skin, GI tract, liver) | BAL specimen showed budding yeast forms and gram-positive cocci; C. glabrata cultured from sputum | BAL specimen positive for C. glabrata; BK virus viremia (360 000) and adenovirus viremia (10 032) on d 64 | Died on d 111 of pulmonary failure; DAD reported as cause of death at autopsy |
| 2 | 48 (F) | MDSRA (allo-MUR) | 21 (52.5) | <7 | None | None | 2 (skin, GI tract) | None | Low-level HHV-6 viremia (230) on d 21 | Died on d 1517 of recurrent refractory anemia with excess blasts; no autopsy report available |
| 3 | 40 (F) | AML (autologous) | 77 (<50) | <7 | Admitted to the hospital with dyspnea | Multiple patchy LUL and RLL infiltrates | None | BAL and lung biopsy specimens negative for infectious organisms; blood culture positive for Stenotrophomonas | Low-level HHV-6 viremia (23)a on d 63 | Died on d 95 of pulmonary failure; autopsy findings included nonspecific destruction of small bronchioles, DAD, and leukemic relapse |
| 4 | 18 (M) | ALL (allo-MR, second transplant) | 28 (2571) | <7 | Reported nausea and diarrhea as an outpatient; endoscopy positive for GVHD | Bilirubin peaked at 9.8 mg/dL with normal transaminase levels | 3 (skin, GI tract, liver) | None | Low-level HHV-6 viremia (23) on d 28 | Died on d 297 from P. jiroveci pneumonia and respiratory failure; family declined autopsy |
| Case Patient | Age, y (Sex) | Underlying Malignancy (Transplant Type) | PTD of AAV-Positive Specimen (Viral Load, Copies/mL) | Duration of Viral Detection, d | Clinical Events in Week Before or After AAV Detection | Abnormal Radiographic or Laboratory Findings | GVHD, Grade (Location) | Copathogens Detected in Real Time | Copathogens Detected Retrospectively by PCR (Copies/mL) | Clinical Outcome and Autopsy Findings |
| 1 | 48 (M) | CML (allo-MUR) | 64 (1043); 71 (none detected); 79 (none detected); 87 (<50) | Up to 23 | Admitted to the hospital with shortness of breath and hypoxemia | LLL infiltrate, pancytopenia, hypocellular bone marrow specimen | 3 (skin, GI tract, liver) | BAL specimen showed budding yeast forms and gram-positive cocci; C. glabrata cultured from sputum | BAL specimen positive for C. glabrata; BK virus viremia (360 000) and adenovirus viremia (10 032) on d 64 | Died on d 111 of pulmonary failure; DAD reported as cause of death at autopsy |
| 2 | 48 (F) | MDSRA (allo-MUR) | 21 (52.5) | <7 | None | None | 2 (skin, GI tract) | None | Low-level HHV-6 viremia (230) on d 21 | Died on d 1517 of recurrent refractory anemia with excess blasts; no autopsy report available |
| 3 | 40 (F) | AML (autologous) | 77 (<50) | <7 | Admitted to the hospital with dyspnea | Multiple patchy LUL and RLL infiltrates | None | BAL and lung biopsy specimens negative for infectious organisms; blood culture positive for Stenotrophomonas | Low-level HHV-6 viremia (23)a on d 63 | Died on d 95 of pulmonary failure; autopsy findings included nonspecific destruction of small bronchioles, DAD, and leukemic relapse |
| 4 | 18 (M) | ALL (allo-MR, second transplant) | 28 (2571) | <7 | Reported nausea and diarrhea as an outpatient; endoscopy positive for GVHD | Bilirubin peaked at 9.8 mg/dL with normal transaminase levels | 3 (skin, GI tract, liver) | None | Low-level HHV-6 viremia (23) on d 28 | Died on d 297 from P. jiroveci pneumonia and respiratory failure; family declined autopsy |
Abbreviations: ALL, acute lymphocytic leukemia; allo, allogeneic; AML, acute myelogenous leukemia; BAL, bronchoalveolar lavage; C. glabrata, Candida glabrata; CML, chronic myelogenous leukemia; DAD, diffuse alveolar damage; GI, gastrointestinal tract; GVHD, graft versus host disease; HHV-6, human herpesvirus 6; LLL, left lower lobe; LUL, left upper lobe; MDSRA, myelodysplastic syndrome with refractory anemia; MR, matched related; MUR, matched unrelated; PCR, polymerase chain reaction; P. jiroveci, Pneumocystis jiroveci; PTD, posttransplantation day.
Limit of detection of the assay is 23 copies/mL [5].
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