Characteristics of allogeneic HSCT cohort, cumulative CMV reactivation, and crude incidence rates to day +100, DFCI/BWH April 2000-June 2004
| Characteristic . | No. . | CMV reactivation* . | % . | P . | Days after HSCT† . | IR (95% CI)‡ . | IRR (95% CI)§ . |
|---|---|---|---|---|---|---|---|
| Cohort | 606 | 225 | 37.1 | — | 45064 | 0.499 (0.438-0.569) | — |
| CMV serostatus‖ | < .001 | ||||||
| CMV D−/R− | 246 | 45 | 18.3 | 20982 | 0.215 (0.160-0.287) | 1 | |
| CMV D+/R− | 115 | 36 | 31.3 | 8881 | 0.405 (0.292-0.562) | 1.89 (1.19-3.00) | |
| CMV D+/R+ | 110 | 55 | 50.0 | 7289 | 0.755 (0.579-0.983) | 3.52 (2.33-5.34) | |
| CMV D−/R+ | 135 | 89 | 65.9 | 7912 | 1.130 (0.914-1.390) | 5.25 (3.63-7.68) | |
| Recipient age, quartiles, y | .50 | ||||||
| 18 to 35 | 152 | 66 | 43.4 | 11089 | 0.595 (0.468-0.758) | 1 | |
| 36 to 45 | 154 | 48 | 31.2 | 11873 | 0.404 (0.305-0.537) | 0.679 (0.458-1.00) | |
| 46 to 53 | 152 | 55 | 36.2 | 10938 | 0.503 (0.386-0.655) | 0.845 (0.580-1.23) | |
| 54 to 70 | 148 | 56 | 37.8 | 11164 | 0.502 (0.386-0.652) | 0.843 (0.580-1.22) | |
| Recipient sex | .55 | ||||||
| Female | 249 | 96 | 38.6 | 18586 | 0.517 (0.423-0.631) | 1.06 (0.813-1.38) | |
| Male | 357 | 129 | 36.1 | 26478 | 0.487 (0.410-0.579) | — | |
| Recipient race | < .001 | ||||||
| Nonwhite | 42 | 30 | 71.4 | 2384 | 1.260 (0.880-1.800) | 2.75 (1.85-4.00) | |
| White | 564 | 195 | 34.6 | 42680 | 0.457 (0.397-0.526) | — | |
| Primary disease | .25 | ||||||
| AML | 177 | 68 | 38.4 | 12713 | 0.535 (0.422-0.678) | 1 | |
| CML | 90 | 35 | 38.9 | 6605 | 0.530 (0.381-0.738) | 0.991 (0.639-1.51) | |
| MDS | 86 | 36 | 41.9 | 5859 | 0.614 (0.443-0.852) | 1.150 (0.745-1.75) | |
| NHL | 84 | 27 | 32.1 | 6935 | 0.389 (0.267-0.568) | 0.728 (0.448-1.15) | |
| Other | 61 | 16 | 26.2 | 4881 | 0.328 (0.201-0.535) | 0.613 (0.332-1.07) | |
| ALL | 58 | 27 | 46.6 | 4163 | 0.649 (0.445-0.946) | 1.210 (0.746-1.92) | |
| CLL | 50 | 16 | 32.0 | 3908 | 0.409 (0.251-0.668) | 0.765 (0.414-1.33) | |
| Conditioning regimen | .17 | ||||||
| Reduced-intensity | 238 | 80 | 33.6 | 18573 | 0.431 (0.346-0.536) | 0.787 (0.597-1.03) | |
| Myeloablative | 368 | 145 | 39.4 | 26491 | 0.547 (0.465-0.644) | — | |
| HLA match¶ | .08 | ||||||
| Mismatched donor | 65 | 31 | 47.7 | 4097 | 0.757 (0.532-1.760) | 1.60 (1.06-2.34) | |
| Matched donor | 541 | 194 | 35.9 | 40967 | 0.474 (0.411-0.545) | — | |
| Donor relatedness | .02 | ||||||
| Unrelated donor | 315 | 131 | 41.6 | 22395 | 0.585 (0.493-0.694) | 1.41 (1.07-1.86) | |
| Related donor | 291 | 94 | 32.3 | 22669 | 0.415 (0.339-0.508) | — | |
| Stem cell source | .002 | ||||||
| Peripheral blood | 415 | 136 | 32.8 | 31764 | 0.428 (0.362-0.507) | 0.640 (0.490-0.838) | |
| Bone marrow | 191 | 89 | 46.6 | 13300 | 0.669 (0.544-0.824) | — | |
| BMT disease risk group** | .61 | ||||||
| Low | 177 | 71 | 40.1 | 12727 | 0.558 (0.442-0.704) | 1 | |
| Intermediate | 324 | 116 | 35.8 | 24431 | 0.475 (0.396-0.570) | 0.851 (0.628-1.16) | |
| High | 105 | 38 | 36.2 | 7906 | 0.481 (0.350-0.661) | 0.862 (0.565-1.30) | |
| Acute GVHD | .002 | ||||||
| Grades II-IV | 196 | 90 | 45.9 | 13572 | 0.663 (0.539-0.815) | 1.55 (1.17-2.04) | |
| None–grade I | 410 | 135 | 32.9 | 31492 | 0.429 (0.362-0.507) | — | |
| GVHD prophylaxis regimen†† | |||||||
| Cyclosporine | 127 | 55 | 43.3 | .12 | 9172 | 0.600 (0.460-0.781) | 1.27 (0.919-1.73) |
| No cyclosporine | 479 | 170 | 35.5 | 35892 | 0.473 (0.407-0.549) | — | |
| Tacrolimus‡‡ | 199 | 80 | 40.2 | .28 | 14087 | 0.568 (0.456-0.707) | 1.21 (0.912-1.61) |
| No tacrolimus | 407 | 145 | 35.6 | 30977 | 0.468 (0.398-0.551) | — | |
| Sirolimus + tacrolimus | 252 | 78 | 31 | .008 | 19789 | 0.394 (0.316-0.492) | 0.678 (0.508-0.898) |
| No sirolimus + tacrolimus | 354 | 147 | 41.5 | 25275 | 0.582 (0.495-0.684) | — | |
| Prednisone | 110 | 45 | 40.9 | .38 | 8155 | 0.552 (0.412-0.739) | 1.13 (0.797-1.58) |
| No prednisone | 496 | 180 | 36.3 | 36909 | 0.488 (0.421-0.564) | — | |
| Methotrexate | 382 | 150 | 39.3 | .16 | 27559 | 0.544 (0.464-0.639) | 1.27 (0.957-1.70) |
| No methotrexate | 224 | 75 | 33.5 | 17505 | 0.428 (0.342-0.537) | — | |
| Mycophenolate mofetil | 48 | 20 | 41.7 | .53 | 3455 | 0.579 (0.374-0.897) | 1.18 (0.703-1.86) |
| No mycophenolate mofetil | 558 | 205 | 36.7 | 41609 | 0.493 (0.430-0.565) | — | |
| T-cell depletion§§ | 75 | 29 | 38.7 | .80 | 5513 | 0.526 (0.366-0.757) | 1.06 (0.693-1.57) |
| No T-cell depletion | 531 | 196 | 36.9 | 39551 | 0.496 (0.431-0.570) | — | |
| Transplantation period | .03 | ||||||
| 4/2000-6/2001 | 157 | 73 | 46.5 | 10653 | 0.685 (0.545-0.862) | 1 | |
| 7/2001-6/2002 | 144 | 51 | 35.4 | 10717 | 0.476 (0.362-0.626) | 0.695 (0.476-1.010) | |
| 7/2002-6/2003 | 150 | 46 | 30.7 | 11919 | 0.386 (0.289-0.515) | 0.563 (0.381-0.826) | |
| 7/2003-6/2004 | 155 | 55 | 35.5 | 11775 | 0.467 (0.359-0.608) | 0.682 (0.471-0.981) |
| Characteristic . | No. . | CMV reactivation* . | % . | P . | Days after HSCT† . | IR (95% CI)‡ . | IRR (95% CI)§ . |
|---|---|---|---|---|---|---|---|
| Cohort | 606 | 225 | 37.1 | — | 45064 | 0.499 (0.438-0.569) | — |
| CMV serostatus‖ | < .001 | ||||||
| CMV D−/R− | 246 | 45 | 18.3 | 20982 | 0.215 (0.160-0.287) | 1 | |
| CMV D+/R− | 115 | 36 | 31.3 | 8881 | 0.405 (0.292-0.562) | 1.89 (1.19-3.00) | |
| CMV D+/R+ | 110 | 55 | 50.0 | 7289 | 0.755 (0.579-0.983) | 3.52 (2.33-5.34) | |
| CMV D−/R+ | 135 | 89 | 65.9 | 7912 | 1.130 (0.914-1.390) | 5.25 (3.63-7.68) | |
| Recipient age, quartiles, y | .50 | ||||||
| 18 to 35 | 152 | 66 | 43.4 | 11089 | 0.595 (0.468-0.758) | 1 | |
| 36 to 45 | 154 | 48 | 31.2 | 11873 | 0.404 (0.305-0.537) | 0.679 (0.458-1.00) | |
| 46 to 53 | 152 | 55 | 36.2 | 10938 | 0.503 (0.386-0.655) | 0.845 (0.580-1.23) | |
| 54 to 70 | 148 | 56 | 37.8 | 11164 | 0.502 (0.386-0.652) | 0.843 (0.580-1.22) | |
| Recipient sex | .55 | ||||||
| Female | 249 | 96 | 38.6 | 18586 | 0.517 (0.423-0.631) | 1.06 (0.813-1.38) | |
| Male | 357 | 129 | 36.1 | 26478 | 0.487 (0.410-0.579) | — | |
| Recipient race | < .001 | ||||||
| Nonwhite | 42 | 30 | 71.4 | 2384 | 1.260 (0.880-1.800) | 2.75 (1.85-4.00) | |
| White | 564 | 195 | 34.6 | 42680 | 0.457 (0.397-0.526) | — | |
| Primary disease | .25 | ||||||
| AML | 177 | 68 | 38.4 | 12713 | 0.535 (0.422-0.678) | 1 | |
| CML | 90 | 35 | 38.9 | 6605 | 0.530 (0.381-0.738) | 0.991 (0.639-1.51) | |
| MDS | 86 | 36 | 41.9 | 5859 | 0.614 (0.443-0.852) | 1.150 (0.745-1.75) | |
| NHL | 84 | 27 | 32.1 | 6935 | 0.389 (0.267-0.568) | 0.728 (0.448-1.15) | |
| Other | 61 | 16 | 26.2 | 4881 | 0.328 (0.201-0.535) | 0.613 (0.332-1.07) | |
| ALL | 58 | 27 | 46.6 | 4163 | 0.649 (0.445-0.946) | 1.210 (0.746-1.92) | |
| CLL | 50 | 16 | 32.0 | 3908 | 0.409 (0.251-0.668) | 0.765 (0.414-1.33) | |
| Conditioning regimen | .17 | ||||||
| Reduced-intensity | 238 | 80 | 33.6 | 18573 | 0.431 (0.346-0.536) | 0.787 (0.597-1.03) | |
| Myeloablative | 368 | 145 | 39.4 | 26491 | 0.547 (0.465-0.644) | — | |
| HLA match¶ | .08 | ||||||
| Mismatched donor | 65 | 31 | 47.7 | 4097 | 0.757 (0.532-1.760) | 1.60 (1.06-2.34) | |
| Matched donor | 541 | 194 | 35.9 | 40967 | 0.474 (0.411-0.545) | — | |
| Donor relatedness | .02 | ||||||
| Unrelated donor | 315 | 131 | 41.6 | 22395 | 0.585 (0.493-0.694) | 1.41 (1.07-1.86) | |
| Related donor | 291 | 94 | 32.3 | 22669 | 0.415 (0.339-0.508) | — | |
| Stem cell source | .002 | ||||||
| Peripheral blood | 415 | 136 | 32.8 | 31764 | 0.428 (0.362-0.507) | 0.640 (0.490-0.838) | |
| Bone marrow | 191 | 89 | 46.6 | 13300 | 0.669 (0.544-0.824) | — | |
| BMT disease risk group** | .61 | ||||||
| Low | 177 | 71 | 40.1 | 12727 | 0.558 (0.442-0.704) | 1 | |
| Intermediate | 324 | 116 | 35.8 | 24431 | 0.475 (0.396-0.570) | 0.851 (0.628-1.16) | |
| High | 105 | 38 | 36.2 | 7906 | 0.481 (0.350-0.661) | 0.862 (0.565-1.30) | |
| Acute GVHD | .002 | ||||||
| Grades II-IV | 196 | 90 | 45.9 | 13572 | 0.663 (0.539-0.815) | 1.55 (1.17-2.04) | |
| None–grade I | 410 | 135 | 32.9 | 31492 | 0.429 (0.362-0.507) | — | |
| GVHD prophylaxis regimen†† | |||||||
| Cyclosporine | 127 | 55 | 43.3 | .12 | 9172 | 0.600 (0.460-0.781) | 1.27 (0.919-1.73) |
| No cyclosporine | 479 | 170 | 35.5 | 35892 | 0.473 (0.407-0.549) | — | |
| Tacrolimus‡‡ | 199 | 80 | 40.2 | .28 | 14087 | 0.568 (0.456-0.707) | 1.21 (0.912-1.61) |
| No tacrolimus | 407 | 145 | 35.6 | 30977 | 0.468 (0.398-0.551) | — | |
| Sirolimus + tacrolimus | 252 | 78 | 31 | .008 | 19789 | 0.394 (0.316-0.492) | 0.678 (0.508-0.898) |
| No sirolimus + tacrolimus | 354 | 147 | 41.5 | 25275 | 0.582 (0.495-0.684) | — | |
| Prednisone | 110 | 45 | 40.9 | .38 | 8155 | 0.552 (0.412-0.739) | 1.13 (0.797-1.58) |
| No prednisone | 496 | 180 | 36.3 | 36909 | 0.488 (0.421-0.564) | — | |
| Methotrexate | 382 | 150 | 39.3 | .16 | 27559 | 0.544 (0.464-0.639) | 1.27 (0.957-1.70) |
| No methotrexate | 224 | 75 | 33.5 | 17505 | 0.428 (0.342-0.537) | — | |
| Mycophenolate mofetil | 48 | 20 | 41.7 | .53 | 3455 | 0.579 (0.374-0.897) | 1.18 (0.703-1.86) |
| No mycophenolate mofetil | 558 | 205 | 36.7 | 41609 | 0.493 (0.430-0.565) | — | |
| T-cell depletion§§ | 75 | 29 | 38.7 | .80 | 5513 | 0.526 (0.366-0.757) | 1.06 (0.693-1.57) |
| No T-cell depletion | 531 | 196 | 36.9 | 39551 | 0.496 (0.431-0.570) | — | |
| Transplantation period | .03 | ||||||
| 4/2000-6/2001 | 157 | 73 | 46.5 | 10653 | 0.685 (0.545-0.862) | 1 | |
| 7/2001-6/2002 | 144 | 51 | 35.4 | 10717 | 0.476 (0.362-0.626) | 0.695 (0.476-1.010) | |
| 7/2002-6/2003 | 150 | 46 | 30.7 | 11919 | 0.386 (0.289-0.515) | 0.563 (0.381-0.826) | |
| 7/2003-6/2004 | 155 | 55 | 35.5 | 11775 | 0.467 (0.359-0.608) | 0.682 (0.471-0.981) |
AML indicates acute myelogenous leukemia; CML, chronic myelogenous leukemia; MDS, myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; and Other, other hematologic malignancies (myeloproliferative syndromes, Hodgkin disease, multiple myeloma, etc); ALL, acute lymphocytic leukemia; and CLL, chronic lymphocytic leukemia.
Positive CMV-HCA, whole blood CMV DNA hybrid capture assay, within the first 100 days after HSCT.
Censored at day of positive CMV reactivation, death, or day +100.
IR indicates crude incidence rate. Cases/100 patient-days after HSCT. Confidence intervals were calculated using the Rothman-Greenland method.
IRR indicates crude incidence rate ratio, when compared with other levels of the covariate. Confidence intervals were calculated using the Fisher Exact method.
D indicates donor; R, recipient; +, CMV IgG positive; and −, CMV IgG negative.
Patients were considered HLA-matched if all 6/6 HLA A, B, and DR were identical.
Diseases considered low risk were AML or ALL in first complete remission, CML in first chronic phase, aplastic anemia, MDS in patients with refractory anemia or refractory anemia with ringed sideroblasts. Patients with relapsed or refractory disease were considered high risk. Patients not meeting either criterion were considered intermediate risk.
Most regimens included more than one agent or procedure.
Patients who received tacrolimus prophylaxis without concomitant sirolimus.
Includes CD6– or CD8–depletion or CD34+ selection.