Table 1:
Characteristics of the study cohort at baseline and at BOS diagnosis according to azithromycin exposure after BOS diagnosis
| Total (n=316) | Azithromycin exposure | ||
|---|---|---|---|
| No (n=89) | Yes (n=227) | ||
| Baseline characteristics at HCT | |||
| Women, n (%) | 129 (40.8%) | 31 (34.8%) | 98 (43.1%) |
| Age, median (IQR), y | 48.6 [33.6–58.6] | 47.9 [36–59] | 48.7 [33–57.6] |
| Diagnosis, n (%) | |||
| Acute leukemia | 140 (44.3%) | 35 (39.3%) | 105 (33.5%) |
| Chronic myeloid leukemia | 32 (10.1%) | 12 (13.5%) | 20 (8.8%) |
| Other myeloproliferative disorders | 8 (2.5%) | 3 (3.4%) | 5 (2.2%) |
| Myelodysplastic disorders | |||
| Lymphoid malignancies | 52 (16.4%) | 20 (22.5%) | 32 (36.6%) |
| Others | 73 (23.1%) | 16 (18%) | 57 (25.11%) |
| 11 (3.5%) | 3 (3.4%) | 8 (3.5%) | |
| Disease risk index at HCT, n (%) | |||
| Low | 47 (14.9%) | 18 (21.7%) | 29 (13.3%) |
| Intermediate | 176 (55.7%) | 43 (51.8%) | 133 (61%) |
| High | 68 (21.5%) | 19 (22.9%) | 49 (22.5%) |
| NA | 25 (7.9%) | 9 (10.1%) | 16 (7%) |
| History of smoking, n (%) | 122 (38.6%) | 45 (51.1%) | 77 (33.9%) |
| History of solid cancer prior to HCT, n (%) | 31 (9.8%) | 4 (4.5%) | 27 (11.9%) |
| Prior autologous HCT, n (%) | 96 (30.4%) | 19 (21.3%) | 77 (33.9%) |
| Donor type, n (%) | |||
| Related | 138 (43.7%) | 42 (47.2%) | 96 (42.3%) |
| Haploidentical | 5 (1.6%) | 2 (2.2%) | 3 (1.3%) |
| Unrelated HLA-match# | 130 (41.1%) | 32 (36%) | 98 (43%) |
| Unrelated HLA-mismatch## | 36 (11.4%) | 9 (10.1%) | 27 (11.9%) |
| Donor/recipient sex, n, (%)* | |||
| Male/male | 91 (29.5%) | 28 (32.9%) | 63 (28.3%) |
| Male/female | 57 (18.5%) | 16 (18.8%) | 41 (18.4%) |
| Female/male | 92 (29.9%) | 27 (31.8%) | 65 (29.1%) |
| Female/female | 68 (22.1%) | 14 (16.5%) | 54 (24.2%) |
| Source of stem cells graft, n (%) | |||
| Peripheral blood | 273 (86.4%) | 74 (83.1%) | 199 (87.7%) |
| Bone marrow | 36 (11.4%) | 11 (12.4%) | 25 (11%) |
| Cord blood | 7 (2.2%) | 4 (4.5%) | 3 (1.3%) |
| Conditioning regimen, n (%) | |||
| Myeloablative | 180 (57%) | 47 (52.8%) | 133 (58.6%) |
| Nonmyeloablative | 136 (43%) | 42 (47.2%) | 94 (41.4%) |
| TBI | 159 (50.3%) | 33 (37.1%) | 126 (55.5%) |
| Dose, median (IQR), Grays | 2(2–12) | 2 (2–12) | 2(2–12) |
| Antithymocyte globulin### | 39 (12.3%) | 14 (15.7%) | 25 (11.0%) |
| Lung function | |||
| FEV1 (% predicted), median (IQR), | 92.8 [82.8–100.2] | 91.1 [83.1–97.9] | 92.9 [82.7–100.7] |
| FVC (% predicted), median (IQR) | 95.1 [85.9–105.6] | 92.0 [83.9–103.7] | 96.2 [86.5–106.0] |
| Characteristics at BOS diagnosis | |||
| Months from HCT, median (IQR), | 16.8 [10.8–30.6] | 13.9 [10.7–24.5] | 18.1 [11–33.5] |
| Chronic GVHD | |||
| Before BOS | 273 (86.4%) | 76 (85.4%) | 197 (86.8%) |
| At or after BOS, n (%) | 33 (10%) | 10 (11%) | 23 (10%) |
| Grade max | |||
| Mild | 25 (7.9%) | 13 (14.8%) | 12 (5.4%) |
| Moderate | 117 (37%) | 33 (37.5%) | 84 (37.8%) |
| Severe | 161 (50.9%) | 39 (44.3%) | 122 (54.9%) |
| Death free of chronic GVHD | 5 (1.6%) | 2 (2.2%) | 3 (1.3%) |
| Absence of chronic GVHD | 5 (1.6%) | 1 (1.1%) | 4 (1.8%) |
| Lung function | |||
| FEV1 (% predicted), median (IQR), | 55.9 [42.9–65.5] | 60.4 [51.1–68.8] | 53.2 [40.4–63.7] |
| FVC (% predicted), median (IQR) | 71.9 [64.0–83.5] | 72.9 [65.5–83.6] | 71.3 [63–83.5] |
| FEV1/FVC, median (IQR) | |||
| RV (% predicted), median (IQR) | 0.63 [0.51–0.69] | 0.67 [0.60–0.73] | 0.61 [0.48–0.67] |
| 131.7 [103.0–161.3] | 134.8 [113.9–161.1] | 130.8 [100.8–161.3] | |
| Treatments for BOS†, n (%) | |||
| Azithromycin | 197 (62%) | 0 (0%) | 197 (87%)‡ |
| Systemic steroids | 105 (33%) | 16 (18%) | 89 (39%) |
| ICS/LABA | 153 (48%) | 44 (49%) | 109 (48%) |
| ICS without LABA | 154 (49%) | 18 (20%) | 98 (43%) |
| Montelukast | 146 (46%) | 7 (8%) | 139 (62%) |
Excluding cord blood recipients, and 1 missing value for a recipient of a peripheral blood stem cell graft
Treatments administered for BOS at the time of diagnosis or thereafter; of the 227 patients who received azithromycin after the diagnosis of BOS, 197 received it specifically for the treatment of BOS and 30 for another indication (antimicrobial prophylaxis or treatment of an infection)
A total of 95 patients (30%) received the azithromycin in the FAM regimen (fluticasone, azithromycin, montelukast).
74 patients minimal 8/8 HLA-match and 56 patients 10/10 HLA-match
34 patients 7/8 HLA-match and 2 patients 9/10 HLA-match
no patients had HCT with ex vivo depletion of donor T-cells
IQR: interquartile range; HCT: hematopoietic cell transplant; FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; GVHD: graft-versus-host disease; ICS/LABA: inhaled corticosteroids/long-acting beta-agonist; ICS: inhaled corticosteroids; HLA: human leukocyte antigen; NA: not available