Change in Management Following Bronchoscopy in Hematopoietic Stem Cell Transplant Patients With Pulmonary Infiltrates

Role of Fiberoptic Bronchoscopy in Hematopoietic Stem Cell Transplant Patients With Pulmonary Infiltrates in Changing Management Decisions: An Observational Study

Hematopoietic stem cell transplant (HSCT) is a modality that is increasingly utilized to treat various haematological disorders with a varying degree of success. From 2006 to 2019 use of HSCT worldwide has increased from 50,417 to an estimated 1.5 million. Disease relapse, graft versus host disease (GVHD) and infections are the leading causes of morbidity and mortality in patients with HSCT. Pulmonary complications, in particular, are common in patients with HSCT, and the diagnostic approach and management of these complications remain a challenge. FOB is one of the standard and least invasive diagnostic modality for these patients. However, the diagnostic yield and change in clinical decision making in those studies have been variable. Furthermore, all these studies were retrospective, with one exception.

The investigators designed an observational study to understand the rate of change in clinical decision making following Fiberoptic bronchoscopy (FOB). The investigators also looked at the yield of FOB and characteristics associated with a positive diagnostic yield.

Study Overview

• Status: Completed
• Conditions: Pulmonary Complication; Stem Cell Transplant Complications
• Intervention / Treatment: Procedure: Fiberoptic Bronchoscopy

Detailed Description

Hematopoietic stem cell transplant (HSCT) is a modality that is increasingly utilized to treat various hematological disorders with a varying degree of success. From 2006 to 2019 use of HSCT worldwide has increased from 50,417 to an estimated 1.5 million. Disease relapse, graft versus host disease (GVHD) and infections are the leading causes of morbidity and mortality in patients with HSCT. Pulmonary complications, in particular, are common in patients with HSCT, and the diagnostic approach and management of these complications remain a challenge. Reasons for this possibly include a broad spectrum of etiologies, subtle and insidious clinical manifestations, non-specific radiological features, and limited biomarkers. On the other hand, surgical procedures to obtain lung biopsy, which is the ultimate diagnostic tool, are often contraindicated or present high risks to the patients. In this context, less invasive testing such as fiberoptic bronchoscopy (FOB) deserves further consideration. Previous studies showed that the yield of FOB, a low-risk procedure, may provide helpful information in the post HSCT patient with pulmonary infiltrates. However, the diagnostic yield and change in clinical decision making in those studies have been variable. Furthermore, all these studies were retrospective, with one exception.

The stem cell transplant activity in Saudi Arabia has increased exponentially in recent times, with more than 6000 stem cell transplants performed by 2016. Furthermore, the patient population is different regarding specific genetic and immunologic characteristics, underlying disorders and prevalent opportunistic pathogens. Therefore, this study was designed to prospectively evaluate the diagnostic value of FOB in those patients presenting with pulmonary infiltrates.

Study design and Method

This was a retrospective observational study of all patients who had HSCT and pulmonary infiltrates that required bronchoscopy. Data for demographics, clinical presentation, CT scan characteristics, FOB dates and details, microbiology, virology, cytology, histology, change in clinical decision making before and after FOB and 6 months outcome following bronchoscopy were collected.

Primary outcome

Rate of change in clinical decision making following FOB

Secondary outcome

Clinical characteristics associated with a positive yield in FOB CT scan characteristics associated with a positive yield in FOB Six month outcome of patients following FOB.

Statistics

Descriptive statistics for continuous variables were reported as mean ± standard deviation, and categorical variables were summarized as frequencies and percentages. The median and interquartile range (IQR) was used where appropriate.

Continuous variables were compared by independent Student's t-test/ANOVA or non-parametric (Mann Whitney U/Kruskal Wallis) test as appropriate, while categorical variables were compared by Chi-square test. Fisher's exact probability test was applied when examining variables of low incidence. Logistic regression was used to test the association between dependent and independent variables. The level of significance was set at a p-value < 0.05.

• Study Type: Observational
• Enrollment (Actual): 51

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital and Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population was those who had HSCT and suffered from GVHD presenting with pulmonary infiltrates.

Description

Inclusion Criteria:

• All patients who suffered from GVHD following Hematopoietic Stem Cell Transplant and had Pulmonary Infiltrate's requiring Fiberoptic Bronchoscopy.

Exclusion Criteria:

• Any patients aged less than 14 years.
• Unable to consent
• Those patients who the primary physician decided not have Fiberoptic Bronchoscopy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stem cell transplant with Graft versus host disease; Patients who following hematopoietic stem cell transplant suffered from graft versus host disease and presented with pulmonary infiltrates.	Procedure: Fiberoptic Bronchoscopy; Fiberoptic bronchoscopy done under conscious sedation; Other Names: Broncho-alveolar lavage; Transbronchial biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in clinical decision making following FOB	number of patients whose clinical management changed directly as a consequence of fiberoptic bronchoscopy	within 1 months of FOB

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical characteristics associated with a positive yield in Fiberoptic Bronchoscopy	clinical characteristics associated with a positive microbiology, virology or cytological yield.	Within 2 weeks of presentation to FOB
CT scan patterns associated with a positive yield in Fiberoptic Bronchoscopy	clinical characteristics associated with a positive microbiology, virology or cytological yield.	CT within one month before the FOB
Six month outcome of patients following FOB	Mortality in the six months following FOB.	six months

Collaborators and Investigators

• Sponsor: King Faisal Specialist Hospital and Research Centre Madinah

Publications and helpful links

General Publications

• Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, Gratwohl M, Bouzas LF, Confer D, Frauendorfer K, Gluckman E, Greinix H, Horowitz M, Iida M, Lipton J, Madrigal A, Mohty M, Noel L, Novitzky N, Nunez J, Oudshoorn M, Passweg J, van Rood J, Szer J, Blume K, Appelbaum FR, Kodera Y, Niederwieser D; Worldwide Network for Blood and Marrow Transplantation (WBMT). One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015 Mar;2(3):e91-100. doi: 10.1016/S2352-3026(15)00028-9. Epub 2015 Feb 27. Erratum In: Lancet Haematol. 2015 May;2(5):e184.
• Styczynski J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S, Mikulska M, Gil L, Cordonnier C, Ljungman P, Averbuch D, Cesaro S, de la Camara R, Baldomero H, Bader P, Basak G, Bonini C, Duarte R, Dufour C, Kuball J, Lankester A, Montoto S, Nagler A, Snowden JA, Kroger N, Mohty M, Gratwohl A; Infectious Diseases Working Party EBMT. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020 Jan;55(1):126-136. doi: 10.1038/s41409-019-0624-z. Epub 2019 Aug 27.
• Harris B, Geyer AI. Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation. Clin Chest Med. 2017 Jun;38(2):317-331. doi: 10.1016/j.ccm.2016.12.008.
• Lim DH, Lee J, Lee HG, Park BB, Peck KR, Oh WS, Ji SH, Lee SH, Park JO, Kim K, Kim WS, Jung CW, Park YS, Im YH, Kang WK, Park K. Pulmonary complications after hematopoietic stem cell transplantation. J Korean Med Sci. 2006 Jun;21(3):406-11. doi: 10.3346/jkms.2006.21.3.406.
• Lucena CM, Torres A, Rovira M, Marcos MA, de la Bellacasa JP, Sanchez M, Domingo R, Gabarrus A, Mensa J, Agusti C. Pulmonary complications in hematopoietic SCT: a prospective study. Bone Marrow Transplant. 2014 Oct;49(10):1293-9. doi: 10.1038/bmt.2014.151. Epub 2014 Jul 21.

Helpful Links

• Incidence, Risk Factors, Treatment and Long Term Outcome of Refractory and First Relapse AML Patients in the OSHO Studies

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): February 27, 2020

Study Registration Dates

• First Submitted: August 1, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Stem cell transplant; Hematopoietic Stem Cell; Fiberoptic bronchoscopy; Pulmonary infiltrates
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Dimercaprol
• Other Study ID Numbers: 2141128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized data of individual participant will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No