Table 3.
Multivariable analysis of non-infectious pulmonary toxicity (NPT) after allogeneic transplantation
| Variable | N | HR | 95% CI | P-value |
|---|---|---|---|---|
| 1. Non-infectious Pulmonary Toxicity | ||||
| TBI and Conditioning Intensity | ||||
| MA TBI | 4216 | 1 | <.0001 | |
| NMA TBI | 4010 | 0.566 | 0.442–0.725 | <.0001 |
| No TBI | 12937 | 0.596 | 0.455–0.78 | 0.0002 |
| HCT-CI (minus pulmonary) | ||||
| 0 | 8514 | 1 | <.0001 | |
| 1 | 5193 | 1.262 | 1.09–1.461 | 0.0019 |
| 2 | 2287 | 1.527 | 1.261–1.849 | <.0001 |
| 3 | 2300 | 1.568 | 1.307–1.882 | <.0001 |
| ≥4 | 2385 | 1.484 | 1.231–1.788 | <.0001 |
| Donor type | ||||
| HLA-identical sibling | 5492 | 1 | 0.0089 | |
| Haploidentical /Other relative | 2612 | 1.288 | 0.929–1.786 | 0.1288 |
| Well matched unrelated | 8161 | 1.169 | 0.988–1.383 | 0.0694 |
| Mismatched unrelated | 1867 | 1.33 | 1.092–1.621 | 0.0046 |
| Cord Blood | 2845 | 1.342 | 1.005–1.792 | 0.0465 |
| Year of transplant | ||||
| 2008 to 2010 | 6318 | 1 | 0.0003 | |
| 2011 to 2013 | 4413 | 0.777 | 0.615–0.982 | 0.0346 |
| ≥2014 | 10432 | 0.702 | 0.592–0.833 | <.0001 |
| Pulmonary comorbidity | ||||
| None | 12443 | 1 | 0.0071 | |
| Severe | 3171 | 1.352 | 1.132–1.615 | 0.0009 |
| Moderate | 5081 | 1.105 | 0.944–1.294 | 0.2127 |
| Disease group | ||||
| AML | 7889 | 1 | 0.0021 | |
| ALL | 2469 | 1.061 | 0.887–1.27 | 0.5145 |
| CML/MDS/MPN | 6646 | 1.245 | 1.099–1.41 | 0.0006 |
| Lymphomas/CLL/PCDs | 3073 | 1.239 | 1.049–1.462 | 0.0114 |
| Non-malignant disease | 1086 | 1.36 | 0.971–1.903 | 0.0734 |
| Platelet recovery | ||||
| No | 2325 | 1 | <.0001 | |
| Yes | 18838 | 0.286 | 0.252–0.325 | <.0001 |
| Grade II-IV acute GVHD | ||||
| No | 12480 | 1 | <.0001 | |
| Yes | 8683 | 1.434 | 1.276–1.611 | <.0001 |
| 2. Idiopathic pneumonia syndrome | ||||
| HCT-CI (minus pulmonary) | ||||
| 0 | 8508 | 1 | <.0001 | |
| 1 | 5188 | 1.26 | 1.075–1.477 | 0.0044 |
| 2 | 2281 | 1.437 | 1.173–1.761 | 0.0005 |
| 3 | 2301 | 1.595 | 1.308–1.944 | <.0001 |
| ≥4 | 2381 | 1.489 | 1.211–1.83 | 0.0002 |
| TBI and Conditioning Intensity, Acute GVHD | ||||
| MA TBI+ no acute GVHD | 2264 | 1 | 0.0018 | |
| NMA TBI+ no acute GVHD | 2460 | 0.478 | 0.3788–0.6031 | <.0001 |
| No TBI+ no acute GVHD | 7740 | 0.5149 | 0.4335–0.6117 | <.0001 |
| MA TBI+ acute GVHD | 1947 | 1.0066 | 0.7878–1.2862 | 0.9579 |
| NMA TBI+ acute GVHD | 1547 | 0.7469 | 0.5494–1.0153 | 0.0625 |
| No TBI+ acute GVHD | 5186 | 0.8785 | 0.7157–1.0784 | 0.2156 |
| Year of transplant | ||||
| 2008 to 2010 | 6315 | 1 | 0.0081 | |
| 2011 to 2013 | 4411 | 0.848 | 0.716–1.004 | 0.0561 |
| ≥2014 | 10418 | 0.801 | 0.695–0.923 | 0.0022 |
| Platelet recovery | ||||
| No | 2311 | 1 | <.0001 | |
| Yes | 18833 | 0.338 | 0.281–0.407 | <.0001 |
| 3. Diffuse alveolar hemorrhage | ||||
| Disease group | ||||
| AML | 7892 | 1 | 0.0076 | |
| ALL | 2468 | 0.992 | 0.724–1.36 | 0.9622 |
| CML/MDS/MPN | 6655 | 1.517 | 1.197–1.922 | 0.0006 |
| Lymphomas/CLL/PCDs | 3074 | 1.292 | 0.959–1.741 | 0.0915 |
| Non-malignant disease | 1088 | 1.373 | 0.867–2.174 | 0.1769 |
| Pulmonary comorbidity | ||||
| None | 12449 | 1 | 0.0003 | |
| Severe | 3172 | 1.665 | 1.3–2.132 | <.0001 |
| Moderate | 5085 | 1.373 | 1.093–1.725 | 0.0064 |
| TBI and Conditioning Intensity | ||||
| MA TBI | 4220 | 1 | <.0001 | |
| NMA TBI | 4012 | 0.598 | 0.449–0.797 | 0.0004 |
| No TBI | 12945 | 0.542 | 0.426–0.69 | <.0001 |
| GVHD prophylaxis | ||||
| Ex-vivo T-cell depletion/CD34+ selection | 669 | 1 | <.0001 | |
| PtCy +/− other(s) | 2198 | 1.031 | 0.535–1.987 | 0.9269 |
| CNI + MMF | 5936 | 1.559 | 0.867–2.8 | 0.1377 |
| CNI + MTX | 9668 | 0.828 | 0.457–1.501 | 0.535 |
| CNI + other | 2109 | 1.049 | 0.548–2.008 | 0.8858 |
| Year of transplant | ||||
| 2008 to 2010 | 6319 | 1 | <.0001 | |
| 2011 to 2013 | 4419 | 0.644 | 0.497–0.833 | 0.0008 |
| ≥2014 | 10439 | 0.582 | 0.462–0.733 | <.0001 |
| Grade II-IV Acute GVHD | ||||
| No | 12490 | 1 | 0.0006 | |
| Yes | 8687 | 1.486 | 1.185–1.864 | 0.0006 |
| Platelet recovery | ||||
| No | 2327 | 1 | <.0001 | |
| Yes | 18850 | 0.15 | 0.116–0.194 | <.0001 |
| 4. Cryptogenic organizing pneumonia | ||||
| TBI and Conditioning Intensity | ||||
| MA TBI | 4218 | 1 | 0.007 | |
| NMA TBI | 4013 | 0.753 | 0.423–1.338 | 0.333 |
| No TBI | 12947 | 0.471 | 0.29–0.765 | 0.002 |
| Grade II-IV Acute GVHD | ||||
| No | 12490 | 1 | 0.001 | |
| Yes | 8688 | 1.815 | 1.26–2.613 | 0.001 |
| Platelet recovery | ||||
| No | 2327 | 1 | ||
| Yes | 18851 | 0.502 | 0.329–0.765 | 0.001 |
Abbreviations: NPT = non-infectious pulmonary toxicity; alloHCT = allogeneic hematopoietic cell transplantation; HLA = human leukocyte antigen; haplo-related = haploidentical related donor; HCT-CI = Hematopoietic Cell Transplantation-Comorbidity Index; KPS = Karnofsky Performance Score; AML = acute myeloid leukemia; ALL = acute lymphoid leukemia; CML = chronic myeloid leukemia; MDS = myelodysplastic syndrome; MPN = myeloproliferative neoplasm; CLL = chronic lymphocytic leukemia; PCD = plasma cell disorders; PB = peripheral blood stem cell graft, BM = bone marrow graft; ptCy = posttransplant cyclophosphamide; CNI = calcineurin inhibitor; MMF= mycophenolate mofetil; MTX = methotrexate.