Table 2.
Characteristics of allogeneic HSCT cohort, cases of human herpesvirus-6-associated post-transplantation acute limbic encephalitis (HHV-6-PALE), and crude incidence rates and incidence rate ratios within 100 days of transplantation (DFCI/BWH March 2003–March 2010)
| Characteristics | No. | HHV-6- PALE‡‡ |
% | P | Days at Risk§§ | IR (95% CI)*** | IRR (95% CI)††† |
|---|---|---|---|---|---|---|---|
| Cohort | 1344 | 19 | 1.4 | — | 125288 | 0.15 (0.09–0.2) | — |
| Recipient age, quartiles, y | 0.89 | ||||||
| 18–40 | 338 | 6 | 1.8 | 31405 | 0.19 (0.07–0.4) | 1 | |
| 40–51 | 339 | 4 | 1.2 | 31469 | 0.13 (0.03–0.3) | 0.67 (0.2–2.4) | |
| 51–58 | 330 | 5 | 1.5 | 30793 | 0.16 (0.05–0.4) | 0.85 (0.3–2.8) | |
| 58–74 | 337 | 4 | 1.2 | 31621 | 0.13 (0.03–0.3) | 0.66 (0.2–2.3) | |
| Recipient race | 0.04 | ||||||
| Nonwhite | 54 | 3 | 5.6 | 4964 | 0.60 (0.1–1.8) | 4.55 (1.3–15.6) | |
| White | 1290 | 16 | 1.2 | 120324 | 0.13 (0.08–0.2) | — | |
| Primary disease | 0.95 | ||||||
| AML | 490 | 5 | 1.0 | 45282 | 0.11 (0.04–0.3) | 1 | |
| NHL | 210 | 4 | 1.9 | 19823 | 0.20 (0.05–0.5) | 1.83 (0.5–6.8) | |
| MDS | 156 | 3 | 1.9 | 14331 | 0.21 (0.04–0.6) | 1.90 (0.5–7.9) | |
| ALL | 113 | 2 | 1.8 | 10476 | 0.19 (0.002–0.7) | 1.73 (0.3–8.9) | |
| CLL | 107 | 2 | 1.9 | 10204 | 0.20 (0.02–0.7) | 1.78 (0.3–9.1) | |
| CML | 87 | 1 | 1.2 | 8037 | 0.12 (0.002–0.7) | 1.13 (0.1–9.6) | |
| HD | 62 | 1 | 1.6 | 5915 | 0.17 (0.002–0.9) | 1.53 (0.2–13.1) | |
| AA | 45 | 0 | 0 | 4137 | — | — | |
| MM | 41 | 0 | 0 | 3945 | — | — | |
| MPD | 33 | 1 | 3.0 | 3138 | 0.32 (0.004–1.8) | 2.89 (0.3–24.7) | |
| Conditioning regimen | 0.33 | ||||||
| Myeloablative | 629 | 11 | 1.8 | 57353 | 0.19 (0.1–0.3) | 1.63 (0.7–4.05) | |
| Reduced-intensity | 715 | 8 | 1.1 | 67935 | 0.12 (0.05–0.2) | — | |
| Stem cell source | <0.001 | ||||||
| UCBT | 101 | 10 | 9.9 | 8406 | 1.20 (0.6–2.2) | 15.5 (6.3–38.0) | |
| Adult-donor HSCT | 1243 | 9 | 0.7 | 116882 | 0.08 (0.04–0.2) | — | |
| HLA match, adult cells‡‡‡ | 0.03 | ||||||
| Mismatched donor | 102 | 3 | 2.9 | 9070 | 0.33 (0.07–1.0) | 5.94 (1.5–23.8) | |
| Matched donor | 1141 | 6 | 0.5 | 107812 | 0.06 (0.02–0.1) | — | |
| Donor relatedness, adult cells§§§ | 0.09 | ||||||
| Unrelated donor | 725 | 8 | 1.1 | 67601 | 0.12 (0.05–0.2) | 5.83 (0.7–46.6) | |
| Related donor | 518 | 1 | 0.2 | 49281 | 0.02 (0.0003–0.1) | — | |
| Conditioning agents | |||||||
| Fludarabine | 712 | 10 | 1.4 | 0.98 | 67132 | 0.15 (0.07–0.3) | 1 |
| IV Busulfan | 653 | 2 | 0.3 | <0.001 | 62726 | 0.03 (0.004–0.1) | 0.21 (0.05–1.0) |
| Cyclophosphamide | 639 | 11 | 1.7 | 0.36 | 58169 | 0.19 (0.09–0.3) | 1.27 (0.5–3.0) |
| Total body irradiation | 574 | 11 | 1.9 | 0.18 | 52079 | 0.21 (0.1–0.4) | 1.42 (0.6–3.3) |
| ATG | 150 | 7 | 4.7 | 0.003 | 13852 | 0.51 (0.2–1.04) | 3.39 (1.3–8.9) |
| Melphalan | 75 | 6 | 8.0 | <0.001 | 6340 | 0.95 (0.4–2.06) | 6.35 (2.3–17.5) |
| Thiotepa | 17 | 0 | 0 | 1 | 1660 | — | — |
| Etoposide | 6 | 0 | 0 | 1 | 600 | — | — |
| BCNU | 6 | 0 | 0 | 1 | 600 | — | — |
| CMV recipient seropositivity | 0.82 | ||||||
| CMV seropositive | 652 | 10 | 1.5 | 60742 | 1.65 (0.79–3.03) | 1.17 (0.47–2.89) | |
| CMV seronegative | 685 | 9 | 1.3 | 64091 | 1.40 (0.64–2.67) | — | |
| Acute GVHD | 0.05 | ||||||
| Grades II–IV | 296 | 8 | 2.7 | 27039 | 0.30 (0.1–0.6) | 2.64 (1.06–6.6) | |
| None-grade I | 1048 | 11 | 1.1 | 98249 | 0.11 (0.06–0.2) | — |
HHV-6-PALE indicates HHV-6-associated post-transplantation acute limbic encephalitis; IR, incidence rate; IRR, incidence rate ratio; CI, confidence interval; ---, not applicable.
HHV-6-PALE was defined as a positive CSF PCR for HHV-6 DNA in addition to characteristic clinical findings within 100 days of transplantation.
Days at risk were censored at day of HHV-6-PALE symptom onset, death, or 100 days after transplantation.
IR indicates crude incidence rate of cases per 1,000 patient-days after HSCT. IR and CI were calculated using the Taylor series.
IRR indicates crude incidence rate ratio, when compared with other levels of the covariate. IRR and CI were calculated using the Byar method.
Only patients undergoing adult-donor HSCT are included given that all patients undergoing UCBT received mismatched-unrelated cells.
Only patients undergoing adult-donor HSCT are included given that all patients undergoing UCBT received mismatched-unrelated cells.