Longitudinal Changes in Pulmonary Function Following Bone Marrow Transplantation

Summary:We retrospectively reviewed the results of serial pulmonary function tests (PFT) after allogeneic bone marrow transplantation (BMT) performed in 80 children at a single institution over a 16-year period. We looked for associations linking PFT results to graft-versus-host disease (GVHD), conditioning regimen (total body irradiation (TBI) vs busulphan), and cytomegalovirus immune status. The median follow-up after BMT was 4 years. At 2 years after BMT, significant declines were found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), as compared to baseline. Both FEV1 and the FEV1/FVC ratio showed significantly greater reductions in the group conditioned with busulphan (n ¼ 22) than in the group conditioned with TBI (n ¼ 49) and were significantly lower in the patients with (n ¼ 16) than without (n ¼ 64) chronic GVHD. Busulphan may be associated with greater long-term lung toxicity than TBI. The relevance of this finding to selection of conditioning regimens for BMT should be examined in the light of the overall pattern of side effects. Chronic GVHD was associated with airway obstruction. total body irradiation; busulphan; cytomegalovirus Bone marrow transplantation (BMT) has been used with increasing success in children with malignant and nonmalignant haematological diseases, which cannot be cured with conventional treatment. Major advances made in recent years have sharply increased the rate of long-term relapse-free survival after BMT in children. The corollary of this progress is a need for evaluation of the long-term effects of BMT on organ system function. Chronic pulmonary disease remains a major source of morbidity and mortality in children after BMT. [1][2][3][4][5] We reviewed serial pulmonary function tests (PFT) in children treated with allogeneic BMT at a single institution over a 16-year period. We examined the relationships linking graft-versushost disease (GVHD), conditioning regimen (total body irradiation (TBI) vs busulphan), and cytomegalovirus (CMV) immune status to the development of PFT abnormalities after BMT. Patients and methods Patient characteristicsWe retrospectively reviewed PFT data from children who underwent allogeneic BMT at the Debrousse Hospital between 1984 and 2000. A total of 80 children with at least PFT performed at a year after BMT were studied. The median follow-up was 4 years and minimum follow-up was 1 year. The main patient characteristics are shown in Table 1. Age at BMT, type of pretransplant conditioning regimen, CMV immune status of the recipient, and presence or absence of acute or chronic GVHD were recorded for statistical analyses. TBI consisted of two radiation sessions per day for 3 consecutive days, delivering 12 Gy in all. The lungs were shielded after 9 Gy. GVHD prophylaxis included cyclosporine plus methotrexate 15 mg/m 2 on day 1 after BMT and 10 mg/m 2 on days 3, 6, and 11. All the patients received cotrimoxazole for the first 12 months as Pneumocystis carinii prophylaxis. Whenever possible, PFT were obtained before BMT and...

Section: Discussionmentioning

confidence: 99%

Effects of allogeneic bone marrow transplantation on pulmonary function in 80 children in a single paediatric centre

Bruno

Souillet

Bertrand

et al. 2004

“…[1][2][3][4][5][6][7][8][9] Most studies have focused on measures of airflow (FEV 1 and FVC) as predictors of pneumonia. At this center, D L CO c and P(A-a)O 2 were independently associated with death when entered in a multivariate proportional hazards model controlling for other covariates associated with mortality after transplant, such as age, HLA-nonidentical donor marrow, active malignancy at transplant, and primary diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Association of pulmonary function testing abnormalities and severe veno-occlusive disease of the liver after marrow transplantation

Matute-Bello

Hinds

et al. 1998

Summary:We investigated an association between pulmonary function testing (PFT) before bone marrow transplantation and the development of severe veno-occlusive disease (VOD) of the liver. We previously noted that reductions in diffusing capacity of the lung for carbon monoxide (corrected for hemoglobin) (D L CO c ) were associated with mortality after transplantation, but this was not caused by respiratory failure. We performed a case-series review of prospectively collected data from 307 marrow recipients who underwent PFT within 2 weeks of transplantation. Of these, 170 (56%) developed VOD; 39 (13%) mild, 81 (26%) moderate, and 50 (16%) severe or fatal. Both total lung capacity (TLC) and D L CO c were associated with severe VOD in univariate analysis (P = 0.006 for each). However, D L CO c entered logistic regression models that contained variables for all known risk factors for severe VOD, while TLC did not contribute additional predictive information. The odds ratio (OR) associated with a D L CO c below the lower limits of normal (70% of predicted) was 2.4 (95% CI, 1.0 to 5.4; P = 0.04). We conclude that reduced diffusion capacity of the lung measured before marrow transplantation is an independent risk for severe hepatic VOD. We speculate that the decreased D L CO c indicates pre-existing systemic endothelial cell damage and a susceptibility to severe hepatic injury from chemotherapy. Keywords: bone marrow transplantation; hepatic venoocclusive disease; pulmonary function tests; diffusing capacity; risk factors Pulmonary function testing (PFT) is frequently performed before marrow transplantation.1-3 These results are used as a baseline for comparison with future studies, 4-6 and to predict development of respiratory complications. 7,8 Recent data from this center suggested that decreased diffusion capacity of the lung for carbon monoxide (corrected for hemoglobin) (D L CO c ), and an increased alveolar-arterial oxygen difference (P(A-a)O 2 ) before marrow transplan- tation are associated with an increased risk of death during the first 6 months after transplantation. Surprisingly, the D L CO c and the P(A-a)O 2 acted independently of each other as risk factors, suggesting that they indicate separate mechanisms leading to death.9 Furthermore, the increased incidence of death associated with a reduced D L CO c could not be accounted for by an increase in the incidence of respiratory failure.We therefore hypothesized that a reduced D L CO c may be associated with another common organ failure leading to death after marrow transplantation, such as severe venoocclusive disease (VOD) of the liver. We postulated that a decreased D L CO c measurement, which is influenced by capillary blood volume in the lung, could reflect systemic endothelial damage due to previous chemotherapy or irradiation. Therefore, the increased mortality associated with low D L CO c may be due to non-pulmonary complications related to further endothelial injury during the cytoreductive conditioning chemotherapy.Since VOD of the liver has be...

“…Twenty studies presented PFT results in patients both before and at least 3 months after BMT and were reviewed in full. [3][4][5][6][7]11,16,[22][23][24][25][26][27][28][29][30][31][32][33][34] These reports provided information on up to 1786 allogeneic BMT patients. The exact number is unclear due to overlap in patient samples between studies, and incomplete description of numbers of patients with PFT data and allo-vs autoBMT.…”

Section: Systematic Reviewmentioning

confidence: 99%

“…Twelve studies had fewer than 50 patients, 7,[22][23][24][25][26][27][28][31][32][33][34] four studies had 50-99 patients, 3,11,29,30 three studies had 100 or more patients, 4,5,16 and one study did not clearly state the number of patients with pre-and post-BMT PFTs. 3 Seven studies were limited to adults, 4,7,16,25,26,30,32 six studied only children, 6,24,27,28,31,34 five studied adults and children, 3,5,22,23,33 and the remaining two did not specify patient ages. 11,29 Conditioning regimens commonly included cyclophosphamide, busulfan and total body irradiation (TBI).…”

Section: Systematic Reviewmentioning

confidence: 99%

“…[5][6][7]33 Risk factors for the development of PFT abnormalities were identified in several studies, listed in Table 1. Obstruction was associated with GVHD in 12 studies, [4][5][6][7]11,16,22,26,29,30,32,33 increasing age at transplant in pediatric patients in two studies, 6,31 and increasing HLA mismatch, 6 leukemia, 33 busulfan conditioning 30 and alveolar capillary permeability, 25 in one study each. Restriction was associated with GVHD in four studies, 16,22,23,30 and TBI, 16 single fraction TBI, 11 infection, 23 busulfan conditioning, 30 CMV seropositivity, 24 increasing age among pediatric patients 31 and age less than 18 years overall, 23 in one study each.…”

Section: Systematic Reviewmentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary function abnormalities after allogeneic marrow transplantation: a systematic review and assessment of an existing predictive instrument

Marras

Szalai

Chan

et al. 2002

Summary:Pulmonary function testing (PFT) is used to characterize non-infectious pulmonary complications after allogeneic BMT. Identifying high-risk patients could facilitate preventive or early therapeutic measures. The objectives of the study were first, to review available data on PFT changes after BMT and second, to validate a previously published predictive index for PFT obstruction in patients transplanted at one center. For the systematic review, frequency, severity and time course of PFT changes after BMT and for the validation study, retrospective cohort comparing predicted with observed PFT, and calculation of indices of predictive accuracy were summarized. The validation study involved 434 patients from Princess Margaret Hospital, Toronto, Canada, who received their first BMT between 1980 and 1997, survived for at least 6 months and had adequate PFT follow-up. The systematic review included 20 studies. After BMT, decreased diffusion and total lung capacity were common and partially reversible. Obstruction was less common. The validation study of a previously published index, performed in 434 patients, found a sensitivity and specificity of 48% and 68% for identifying patients who develop obstruction. We concluded that PFT changes after BMT are common. A published predictive index is not sufficiently accurate to identify high-risk patients for potential preventive or early therapeutic strategies. The lung is often a target organ for complications after allogeneic marrow transplantation (BMT), 1,2 with pulmonary complications including infection, neoplasia, and idiopathic and iatrogenic disorders such as pulmonary edema, diffuse alveolar hemorrhage and obliterative bronchiolitis (OB). In the latter process, bronchioles become progressively constricted and obliterated from intramural infiltration, fibrosis and scarring. 1 After BMT, pulmonary function testing (PFT) can be useful to help diagnose complications, and in routine follow-up, as PFT abnormalities correlate with non-relapse mortality. 3 There are three main categories of PFT abnormalities. Obstructive defects occur when there is small airway closure or obstruction on expiration, leading to diminished forced expiratory volumes (one second forced expiratory volume -FEV1), classically with a preserved forced vital capacity (FVC), resulting in a decrease in FEV1/FVC ratio. In the BMT population, the prototypical cause of obstruction is OB. Its occurrence has been linked to chronic graft-versus-host disease (cGVHD), 4-11 and its frequency has been estimated to range from 8 to 33%. 4,[6][7][8][12][13][14] Although defined histologically, the diagnosis is most often presumptive, made based on signs and symptoms, radiographic changes and PFT showing obstruction, hyperinflation and gas trapping.Restriction is a pattern of decreased lung volumes (TLC, best measured by body plethysmography), with a preserved FEV1/FVC ratio. Our group and others have identified a decrease in TLC post BMT which tends to improve over time, 3,11,[15][16][17] with a reported inc...