Predictive Value of Pulmonary Function Tests before Marrow Transplantation

doi:10.1378/chest.101.5.1257

Chest

Volume 101, Issue 5, May 1992, Pages 1257-1264

https://doi.org/10.1378/chest.101.5.1257 Get rights and content

Objective

To evaluate association between pulmonary function tests (PFT) performed before marrow transplantation and mortality after transplant.

Setting

A single marrow transplantation research center.

Design

Case-series review.

Patients

All patients between January 1986 and July 1990 who performed PFT before a first marrow transplant for the treatment of malignancy (n = 1297) were included in study. Six hundred twenty-eight (48 percent) patients had morphologically or cytologically active malignant neoplasms at the time of transplant. Allogeneic marrow transplants were performed in 1,056 (82 percent) and autologous transplants were performed in 235 (18 percent). Three hundred seventy-two (29 percent) patients received HLA-nonidentical donor marrow. Graft-vs-host disease prophylaxis was methotrexate and cyclosporine in 901 (85 percent) of the allogeneic recipients. Most patients were prepared for transplant with total body irradiation in addition to cyclophosphamide (n = 1,059, 82 percent), while 230 (18 percent) were conditioned with busulfan and cyclophosphamide.

Measurements and Main Results

The overall mortality during the first six months of follow-up was 44 percent. Respiratory failure requiring assisted mechanical ventilation occurred in 23 percent (n = 298) of patients. A proportional hazards regression analysis was used to evaluate the predictive value of PFT results: (1) FEV₁/FVC; (2) P(A-a)O₂ gradient; (3) TLC; and (4) Dco_sb (the latter two presented a percent of predicted). Abnormalities in TLC, Dco_sb, and P(A-a)O₂ were found to be significantly associated with death in univariate analysis. Next, the value of PFT for prediction above and beyond other baseline covariates was evaluated by first using the step-up stepwise proportional hazards model to select predictive variables other than the PFT variables. Then each of the PFT variables was tested in the presence of these other variables. The factors of age, primary diagnosis, relapse status, and donor-recipient HLA nonidentity were found to be risks for death and were entered as covariates. Each of the variables of PFT were entered stepwise into the model. Dco_sb (RR = 1.43 for a value 80 percent of predicted) and P(A-a)O₂ (RR = 1.28 for a value of 20 mm Hg) were found to be independent risk factors for death. The use of assisted mechanical ventilation appeared to increase proportionately with the increase in mortality among patients with abnormal Dco_sb or P(A-a)O₂.

Conclusions

Decreased Dco_sb and increased P(A-a)O₂ gradient before marrow transplant carry significantly increased risk of death after marrow transplant. The risk associated with abnormal PFT is less than that associated with other recognized risk factors, such as relapse status and donor-recipient HLA nonidentity. Respiratory failure does not appear to account entirely for the increased mortality associated with abnormal pretransplant PFT. PFT should be used in assessing fully the risks to recipients of marrow transplants for malignancy, but should not be used as absolute exclusion criteria for transplantation.

Section snippets

Subjects and PFT Methods

All marrow recipients who performed PFT before a first marrow transplantation for malignant neoplasms between January 1986 and July 1990 were included in the study (n = 1,297). This represented 87 percent of marrow transplants performed at the center during this interval. Testing was done using American Thoracic Society guidelines.⁸ A pulmonary function analyzer (Gould 1000 IV, Gould, Inc, Dayton, Ohio) was used with nitrogen washout to determine lung volumes. The diffusing capacity for carbon

Patient Characteristics

Between January 1986 and July 1990, 1,297 marrow recipients with malignant neoplasms performed PFT within two weeks before transplantation (Table 1). The patients ranged in age from 4 to 63 years (mean and median = 31 years). Most (82 percent) received allogeneic transplants. Eight-one percent of the donor marrows were phenotypically HLA identical with the recipient. Almost half (48 percent) of all patients had active malignant disease (morphologic or cytogenetic relapse of leukemia or

DISCUSSION

This analysis of 1,297 marrow transplant recipients for treatment of malignant disease demonstrates predictive value of PFT abnormalities for death after transplant. The study was limited to patients who had undergone transplants for malignant neoplasms because of the lower complication and mortality rates among patients who had undergone transplants for aplastic anemia. The strengths of the analysis lie, in part, in the large numbers of assessable patients, the prospective collection of all

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Adjusting diffusing capacity for anemia in patients undergoing allogeneic HCT: a comparison of two methodologies
2024, Current Research in Translational Medicine
Diffusing capacity (DLCO) measurements are affected by hemoglobin. Two adjustment equations are used: Cotes (recommended by ATS/ERS) and Dinakara (used in the hematopoietic stem cell transplantation comorbidity index [HCT-CI]). It is unknown how these methods compare, and which is better from a prognostication standpoint.
This is a retrospective cohort of 1273 adult patients who underwent allogeneic HCT, completed a pre-transplant DLCO and had a concurrent hemoglobin measurement. Non-relapse mortality was measured using competing risk analysis.
Patients had normal spirometry (FEV₁ 99.7% [IQR: 89.4–109.8%; FVC 100.1% [IQR: 91.0-109.6%] predicted), left ventricular ejection fraction (57.2[6.7]%) and right ventricular systolic pressure (30.1[7.0] mmHg). Cotes-DLCO was 85.6% (IQR: 76.5-95.7%) and Dinakara-DLCO was 103.6% (IQR: 90.7-117.2%) predicted. For anemic patients (Hb<10g/dL), Cotes-DLCO was 84.2% (IQR: 73.9–94.1%) while Dinakara-DLCO 111.0% (97.3–124.7%) predicted. Cotes-DLCO increased HCT-CI score for 323 (25.4%) and decreased for 4 (0.3%) patients. Cotes-DLCO was superior for predicting non-relapse mortality: for both mild (66-80% predicted, HR 1.55 [95%CI: 1.26-1.92, p < 0.001]) and moderate (<65% predicted, HR 2.11 [95%CI: 1.55-2.87, p<0.001]) impairment. In contrast, for Dinakara-DLCO, only mild impairment (HR 1.69 [95%CI 1.26-2.27, p < 0.001]) was associated with lower survival while moderate impairment was not (HR 1.44 [95%CI: 0.64-3.21, p = 0.4]). In multivariable analyses, after adjusting for demographics, hematologic variables, cardiac function and FEV₁, Cotes-DLCO was predictive of overall survival at 1-year (OR 0.98 [95%CI: 0.97-1.00], p = 0.01), but Dinakara-DLCO was not (OR 1.00 [95%CI: 0.98-1.00], p = 0.20).
The ERS/ATS recommended Cotes method likely underestimates DLCO in patients with anemia, whereas the Dinakara (used in the HCT-CI score) overestimates DLCO. The Cotes method is superior to the Dinakara method score in predicting overall survival and relapse-free survival in patients undergoing allogeneic HCT.
Screening Chest CT Prior to Allogenic Hematopoietic Stem Cell Transplantation
2023, Transplantation and Cellular Therapy
Pulmonary complications constitute a major cause of morbidity and mortality in the post-allogenic hematopoietic stem cell transplantation (alloHSCT) period. Although chest X-ray (CXR) is customarily used for screening, we have used chest computed tomography (CT) scans. To characterize the prevalence of abnormalities and explore their impact on alloHSCT eligibility and outcomes post-transplantation, we conducted a retrospective analysis using real-world data collected at our center for adult patients who were evaluated for alloHSCT between January 2013 and December 2020 and identified 511 eligible patients. The most common primary disease was acute myeloid leukemia, in 49% of patients, followed by myelodysplastic syndrome (23%), lymphoma (11%), and acute lymphocytic leukemia (10%). Abnormal screening chest CT results were found in 199 patients (39%). The most frequent detected abnormality was pulmonary nodule, in 78 patients (35%), followed by consolidation in 42 (19%), ground-glass opacification in 33 (15%), bronchitis and bronchiolitis in 25 (11%), pleural effusions in 14 (6%), and new primary cancer in 7 (2%). CXR detected abnormalities in only approximately one-half of the patients (48%) with an abnormal chest CT scan. Among the 199 patients with an abnormal chest CT scan, 98 (49%) underwent further assessment and/or intervention before transplantation. The most common workup was pulmonary consultation in 32%, followed by infectious diseases consultation in 24%. Lung biopsy was obtained in 20%, and antimicrobial therapy was initiated after confirming an infection diagnosis in 20%. Patients with an abnormal chest CT scan demonstrated worse overall survival (P = .032), nonrelapse mortality (P = .015), and pulmonary-related mortality (P < .001) compared to those with a normal chest CT scan. Our study suggests that pretransplantation screening chest CT is beneficial in uncovering invasive infections and underlying malignancies and allows for appropriate interventions before alloHSCT to prevent potentially serious post-transplantation complications without causing a delay in alloHSCT. Nevertheless, abnormal CT findings prior to transplantation may be associated with overall worse prognosis.
Miscellaneous Complications of Hematopoietic Cellular Transplantation
2023, Manual of Hematopoietic Cell Transplantation and Cellular Therapies
Advancements in hematopoietic cell transplantation (HCT) have been associated with expanding indications and eligibility, alternative donor options, and improvement in overall survival. Yet, HCT for hematologic malignancies are still associated with the potential for significant toxicities that may be influenced by the primary diagnosis, prior treatment history, comorbid conditions and/or preparative regimen, and/or donor source. Candidates for HCT undergo comprehensive medical evaluations to confirm eligibility and inform ultimate preparative regimen and donor selection. Acute toxicities associated with HCT can generally be classified as infectious or noninfectious. Infectious complications of HCT are outside the scope of this chapter. Toxicities of HCT may occur during administration of the preparative regimen, around HCT infusion, and/or following HCT. Early toxicities are usually related to the specific agents used as part of the preparative regimen. These agents and/or prior toxic injuries to the endothelium may also contribute to post-HCT endotheliopathies such as preengraftment or engraftment syndrome, venoocclusive disease now more commonly referred to as sinusoidal obstructive syndrome, transplant-associated thrombotic microangiopathy, and/or diffuse alveolar hemorrhage. Poor immune reconstitution post-HCT may be associated with clinical sequelae such as posttransplant lymphoproliferative disease, which historically was associated with very poor outcomes. Patients undergoing HCT may also develop endocrinopathies, acute fluid overload, acute kidney injury, acute respiratory failure, and/or neurologic sequelae. A significant number of patients undergoing HCT may develop multiorgan dysfunction syndrome and/or require critical care support. High vigilance and/or early initiation of specific therapies when available and/or appropriate supportive care may significantly mitigate toxicities.
Addressing Race in Pulmonary Function Testing by Aligning Intent and Evidence With Practice and Perception
2022, Chest
The practice of using race or ethnicity in medicine to explain differences between individuals is being called into question because it may contribute to biased medical care and research that perpetuates health disparities and structural racism. A commonly cited example is the use of race or ethnicity in the interpretation of pulmonary function test (PFT) results, yet the perspectives of practicing pulmonologists and physiologists are missing from this discussion. This discussion has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain. We review the underlying sources of differences in lung function, including those that may be captured by race or ethnicity, and demonstrate how the current practice of PFT measurement and interpretation is imperfect in its ability to describe accurately the relationship between function and health outcomes. We summarize the arguments against using race-specific equations as well as address concerns about removing race from the interpretation of PFT results. Further, we outline knowledge gaps and critical questions that need to be answered to change the current approach of including race or ethnicity in PFT results interpretation thoughtfully. Finally, we propose changes in interpretation strategies and future research to reduce health disparities.
Impact of Lung Function on Bronchiolitis Obliterans Syndrome and Outcome after Allogeneic Hematopoietic Cell Transplantation with Reduced-Intensity Conditioning
2018, Biology of Blood and Marrow Transplantation
Citation Excerpt :
Of note, patients with small airway disease defined as FEF25-75 <60% of predicted before allo-HCT had also higher risk of death (HR, 1.57; 95% CI, 1.13 to 2.19; P = .007) due mainly to NRM (subhazard ratio, 1.97; 95% CI, 1.72 to 3.31; P = .01) (Supplementary Table 9). In addition, CO-diffusion abnormalities before allo-HCT has previously been shown to be associated with increased mortality, although the threshold of DLCOcSB increasing NRM varies among studies probably due to patient characteristics, conditioning regimen, and GVHD prophylaxis [13,46,47]. Previous studies have associated the decrease of DLCOcSB and FEV1 with NRM due to pulmonary toxicity, GVHD, and infections [13].
Lung function deterioration contributes to treatment-related morbidity and mortality in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Better understanding of impaired lung function including bronchiolitis obliterans syndrome (BOS) as chronic manifestation of graft-versus-host disease (GVHD) might improve outcomes of patients after allo-HCT.
To detect early pulmonary function test abnormalities associated with BOS incidence and outcome after allo-HCT, we performed a retrospective analysis of homogenous-treated 445 patients (median age, 61.9 years; range, 19 to 76 years) with a reduced intensity/toxicity conditioning protocol. The cumulative incidence of BOS was 4.1% (95% confidence interval [CI], 2.6 to 6.4) at 1 year and 8.6% (95% CI, 6.3 to 11.6) at 5 years after allo-HCT with a median follow-up of 43.2 months (range, 3.3 to 209 months). In multivariate analysis, pre-existence of moderate small airway disease reflected by decreased midexpiratory flows before allo-HCT was associated with increased risk for BOS development. In addition, severe small airway disease before allo-HCT and combined restrictive/obstructive lung disease at day +100 after allo-HCT were associated with higher risk for nonrelapse mortality (NRM) due mainly to pulmonary cause of death.
In summary, we identified novel pulmonary function test abnormalities prior and after allo-HCT associated with BOS development and NRM. These findings might help to identify a risk population and result in personalized GVHD prophylaxis and preventive or early therapeutic interventions.
Pulmonary Function and Pretransplant Evaluation of the Hematopoietic Cell Transplant Candidate
2017, Clinics in Chest Medicine
Citation Excerpt :
Studies from the 1980s and 1990s showed that a reduced FEV1 was associated with early complications; however, the association with mortality remained controversial, perhaps owing to the relatively small numbers of patients and fatal respiratory events.17–19 Notably, Crawford and Fisher19 analyzed 1297 predominantly allogeneic HCT recipients (82%) during an early era of transplantation (1986–1990) and showed that gas exchange abnormalities, and not spirometric parameters or lung volumes, were associated with increased mortality. In a larger, more contemporary cohort of 2852 allogeneic HCT recipients from the same center, Parimon and colleagues20 showed that progressively more abnormal pretransplant FEV1 was associated independently with stepwise increased risk of early respiratory failure, with an HR of 2.7 to 2.9 (95% confidence interval [CI], 1.7–4.2), and that a pretransplant FEV1 of less than 70% predicted was associated with a 1.7- to 2.2-fold increase in mortality.

View all citing articles on Scopus

: This investigation was supported by Public Health Service grants CA-18029 and CA-47748 from the National Cancer Institute and grant HL-36444 from the National Heart, Lung, Blood Institute.

View full text

Chest

Predictive Value of Pulmonary Function Tests before Marrow Transplantation

Objective

Setting

Design

Patients

Measurements and Main Results

Conclusions

Section snippets

Subjects and PFT Methods

Patient Characteristics

DISCUSSION

Chest

Chest

Blood

Blood

Blood

Risk factors for airflow obstruction in recipients of bone marrow transplants

Ann Intern Med

Small-airways disease in recipients of allogeneic bone marrow transplants

Medicine

Pulmonary function of marrow transplant patients, I: effects of marrow infusion, acute graft-versus-host-disease, and interstitial pneumonitis

Exp Hematol

Lung function changes after allogeneic bone marrow transplantation

Thorax

Pulmonary function changes in long-term survivors of allogeneic marrow transplantation

ATS statement-Snowbird workshop in standardization of spirometry

Am J Respir Dis

Respiratory function tests: normal values at median altitudes and the prediction of normal results

Am Rev Tuberculosis