Factors associated with bronchiolitis obliterans syndrome and chronic graft‐versus‐host disease after allogeneic hematopoietic cell transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) is a form of chronic graft vs. host disease (cGVHD) and a highly morbid pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). We assessed the prevalence and risk factors for BOS and cGVHD in a cohort of HSCT recipients, including those who received reduced intensity conditioning (RIC) HSCT. Between January 1, 2000 and June 30, 2010, all patients who underwent allogeneic HSCT at our institution (n = 1854) were retrospectively screened for the development of BOS by PFT criteria. We matched the BOS cases with two groups of control patients: (1) patients who had concurrent cGVHD without BOS and (2) those who developed neither cGVHD nor BOS. Comparisons between BOS patients and controls were conducted using t-test or Fisher’s exact tests. Multivariate regression analysis was performed to examine factors associated with BOS diagnosis. All statistical analyses were performed using SAS 9.2. We identified 89 patients (4.8%) meeting diagnostic criteria for BOS at a median time of 491 days (range: 48–2067) after HSCT. Eighty-six (97%) of our BOS cohort had extra-pulmonary cGVHD. In multivariate analysis compared to patients without cGVHD, patients who received busulfan-based conditioning, had unrelated donors, and had female donors were significantly more likely to develop BOS, while ATG administration was associated with a lower risk of BOS. Our novel results suggest that busulfan conditioning, even in RIC transplantation, could be an important risk factor for BOS and cGVHD.

The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

“…In addition, Nakasone et al [14] have reported that female recipients, ABO mismatch HCT, a busulfan + cyclophosphamide-based conditioning regimen, and acute GVHD involving the skin were significant risk factors for the development of BOS. Recently, busulfan-based conditioning, an unrelated donor, and female donor were also reported as risk factors for BOS development [15]. In our present study, a busulfan-based conditioning regimen was found to be the only independent predictor of BOS development, which was consistent with previous studies [6,14,15].…”

“…Recently, busulfan-based conditioning, an unrelated donor, and female donor were also reported as risk factors for BOS development [15]. In our present study, a busulfan-based conditioning regimen was found to be the only independent predictor of BOS development, which was consistent with previous studies [6,14,15]. It has been suggested that busulfan may cause direct toxicity to the epithelial lining cells of the lung, which can result in donor alloreactivity that contributes to the development of BOS [3,15].…”

“…Hazard ratios (HRs) and Cox regression analysis were used to calculate the adjusted risk. In addition to the prophylactic use of azithromycin, independent variables for multivariate analysis were selected on the basis of their statistical significance in univariate analysis, and clinical significance in previous studies [3,6,14,15]. All tests of significance were two sided, and P < 0.05 was considered to indicate statistical significance.…”

Late non-infectious lung damage in children after allogeneic hematopoietic stem cells transplantation

“…Показано также, что при использовании режимов кондиционирования со сниженной токсичностью LONIPC развиваются реже [21,22]. Однако применение бусульфана даже в режи-мах со сниженной токсичностью достоверно повыша-ет риск развития LONIPC [23]. Также доказанными факторами риска можно считать наличие хронической РТПХ (у 97 % пациентов с LONIPC), отсутствие анти-тимоцитарного глобулина в кондиционировании, не-родственные ТГСК, женский пол донора у реципиен-та мужского пола [23].…”

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“…A busulfan-based regimen even in the setting of reduced intensity conditioning, use of an unrelated donor or female donor, pretransplant lung disease, acute GVHD, Cytomegalovirus (CMV)-positive status, and high-risk transplant were associated with increased risk of BOS. 24 On the other hand, antithymocyte globulin (ATG) was protective against GVHD and BOS. The study highlights the importance of busulfan as a risk factor for chronic GVHD and BOS.…”