Hematopoietic Stem Cell Transplant Recipients Research Articles

A Multiplex Fluorescence of Loop Primer Upon Self-Dequenching Loop-Mediated Isothermal Amplification Assay for the Detection of Epstein-Barr Virus and Human Parvovirus B19 in Clinical Transplant Samples.

Viral infections are major causes of mortality in solid-organ and hematopoietic stem cell transplant recipients. Epstein-Barr virus (EBV) and Parvovirus B19 (B19V) are among the common viral infections after transplantation and were recommended for increased screening in relevant guidelines. Therefore, the development of rapid, specific, and cost-effective diagnostic methods for EBV and B19V is of paramount importance. We applied Fluorescence of Loop Primer Upon Self-Dequenching Loop-mediated Isothermal Amplification (FLOS-LAMP) for the first time to develop a novel multiplex assay for the detection of EBV and B19V; the fluorophore attached to the probe are self-quenched in unbound state. After binding to the dumbbell-shaped DNA target, the fluorophore is dequenched, resulting in fluorescence development. The novel multiplex FLOS-LAMP assay was optimized by testing various ratios of primer sets. This novel assay, with great specificity, did not cross-react with the common virus. For the detection of EBV and B19V, the limits of detection could reach 969 and 798 copies/μL, respectively, and the assay could be completed within 25 min. Applying this novel assay to detect 200 clinical transplant individuals indicated that the novel assay had high specificity and good sensitivity. We developed multiplex FLOS-LAMP assay for the detection of EBV and B19V, which has the potential to become an important tool for clinical transplant patient screening.

Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center

Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were Fusarium spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by Scedosporium spp. (respectively 14.5% and 26.1%) and Alternaria spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for Fusarium spp., Scedosporium spp. or multiple pathogens IMD compared with Alternaria or other pathogens (51.7% vs. 17.6%, p < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, p = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.

T1 Mapping in Cardiovascular Magnetic Resonance—A Marker of Diffuse Myocardial Fibrosis in Patients Undergoing Hematopoietic Stem Cell Transplantation

Introduction: Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular diseases. In our study, we aimed to find subclinical changes in myocardial tissue after HSCT with the help of cardiovascular magnetic resonance (CMR) tissue imaging techniques. Methods: The data of 44 patients undergoing autologous and allogeneic HSCT in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from October 2021 to February 2023 were analyzed. Bioethics approval for the prospective study was obtained (No BE-2-96). CMR was performed two times: before enrolling for the HSCT procedure (before starting mobilization chemotherapy for autologous HSCT and before starting the conditioning regimen for allogeneic HSCT) and 12 ± 1 months after HSCT. LV end-diastolic volume, LV end-systolic volume, LV mass and values indexed to body surface area (BSA), and LV ejection fraction were calculated. T1 and T2 mapping values were measured. Results: There was a statistically significant change in T1 mapping values. Before HSCT, mean T1 mapping was 1226.13 ± 39.74 ms, and after HSCT, it was 1248.70 ± 41.07 ms (p = 0.01). The other parameters did not differ significantly. Conclusions: Increases in T1 mapping values following HSCT can show the progress of diffuse myocardial fibrosis and may reflect subclinical injury. T2 mapping values remain the same and do not show edema and active inflammation processes at 12 months after HSCT.

A retrospective study of intravenous pentamidine for PCP prophylaxis in adult patients with hematological malignancies – its utility during respiratory virus pandemics

BackgroundIn Haematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematological malignancies. Trimethoprim–sulfamethoxazole (TMP-SMX) is the recommended first-line agent, but its use is not straightforward. Inhaled pentamidine is the recommended second-line agent but aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. AimWe evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic HSCT recipients and patients with hematological malignancies during COVID-19. FindingsA total of 202 unique patients who received 239 courses of IV pentamidine, with a median of 3 doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The commonest reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients develop an infusion reaction or suffer adverse effects from IV pentamidine Conclusion: Pentamidine administered IV monthly is safe and effective.

Severe acute respiratory syndrome coronavirus 2 infection in hematopoietic stem cell transplant recipients in Mexico City.

Hematopoietic stem cell transplant (HSCT) recipients are among patients with highest risk of adverse coronavirus disease 2019 (COVID-19) outcomes. We compared clinical outcomes in post-HSCT patients with COVID-19 before and during the Omicron period. This was a retrospective study including patients post-HSCT with severe acute respiratory syndrome coronavirus 2 infection from April 2020 to March 2023 at Instituto Nacional de Cancerología, Mexico City. We describe their clinical characteristics and report the variables associated with severe clinical disease, hospitalization, and death. Fifty-three patients were included; 31 (58.5%) from the pre-Omicron period and 22 (41.5%) from the Omicron period. Median age was 42-years old (interquartile range 26-53), and 31 patients (59%) were men. Only four patients (16%) had received a vaccine prior to COVID-19 diagnosis in the pre-Omicron period versus 20 (91%) in the Omicron period (p<0.001). COVID-19 severe cases were more common before Omicron: seven patients (23%) versus two patients (9%). Only one patient (3%) received an antiviral in the pre-Omicron period compared to 11 patients (50%) during the Omicron period (p<0.01). COVID-19-associated mortality was almost double in the pre-Omicron period (16%vs. 9%, p=0.6). This study reports patients with a high proportion of severe outcomes during the first 2 years of the pandemic. Outcomes improved during Omicron with better access to vaccines and antivirals and no in-hospital cases. Variables associated with worse outcomes were similar to other reports. Strengthening infection control measures in the hospital and better access to preventive strategies and therapeutic options are mandatory in these high-risk patients.

IMPROVE-BMT: A Pilot Randomized Controlled Trial of Prehabilitation Exercise for Adult Hematopoietic Stem Cell Transplant Recipients.

Background: There is limited evidence on the effects of aerobic and resistance training exercise interventions to improve physical function and patient-reported outcomes prior to autologous and allogeneic hematopoietic stem cell transplant (HSCT). IMPROVE-BMT was a single-site, pilot randomized controlled trial investigating the feasibility, acceptability, and safety of a pragmatic resistance training exercise program prior to HSCT compared to usual HSCT care. Secondary aims included differences in physical function between the exercise group (EX) and usual care control group (UC). Methods: Outcome measurements were assessed: prior to HSCT, on/around day of HSCT admission, +30 days post-HSCT, and +100 days post-HSCT. The exercise intervention was a home-based exercise program that incorporated resistance-band and bodyweight exercises. Results: Acceptability among participants was 83%; exercise adherence averaged at 92%; and there were zero exercise-related adverse or serious adverse events. The average pre-transplant exercise phase was 6.28 weeks (2.71-18.29 weeks). EX (n = 36) demonstrated larger increases in the six-minute walk test distance, short physical performance battery scores, and 30-s chair stands compared to UC (n = 38) and demonstrated significant within-group improvements for the six-minute walk test, the short physical performance battery, the 30-s chair stands, and the timed up-and-go test. Conclusions: IMPROVE-BMT demonstrates that pragmatic exercise is highly feasible for HSCT recipients and can potentially lead to enhanced recovery that may not be achievable in non-exercisers.

Evaluation of colonization and infection profile in allogeneic hematopoietic stem cell transplantation recipients

Evaluation of colonization and infection profile in allogeneic hematopoietic stem cell transplantation recipients

Efficacy and safety of mRNA1273 SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Single center experience

BackgroundCOVID-19 represents a worldwide pandemic and vaccination remains the most effective preventive strategy. Among hematological patients, COVID-19 has been associated with a high mortality rate. Vaccination against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalization and deaths related to severe COVID-19 disease. However, patients with impaired immunity may have lower sero-responsiveness to vaccination. MethodsThis study focuses on hematopoietic stem cell transplantation (HSCT) recipients. We performed a unicenter, prospective, observational study of a cohort of 31 allogeneic and 56 autologous-HSCT recipients monitored between March 2021 and May 2021 for serological response after COVID-19 vaccination with two doses of mRNA1273 vaccine (Moderna). In order to determine seroconversion, serological status before vaccination was studied. ResultsAt a median range of 75 days after the second vaccine dose, seroconversion rates were 84% and 85% for the autologous and allogeneic-HSCT groups, respectively. We confirmed some potential risk factors for a negative serological response, such as receiving anti-CD20 therapy in the previous year before vaccination, a low B-lymphocyte count and hypogammaglobulinemia. Neutralizing antibodies were quantified in 44 patients, with a good correlation with serological tests. Adverse events were minimal. ConclusionmRNA1273 vaccination is safe and effective in HSCT recipients, especially in those presenting recovered immunity.

Patient-Reported Outcomes in Hematopoietic Stem Cell Transplant Recipients: Design, Implementation, and Pilot Results

Background: Patient-reported outcome measures (PROMs) offer a collaborative opportunity between the patient and the care team to improve the quality of care. Objectives: To define PROMs in patients receiving hematopoietic stem cell transplant (HSCT), a pre-visit questionnaire (PVQ) was developed, which included a single agenda-setting question, the PROMIS-29 survey, and the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT). Study Design: Patients completed the PVQ 1 month prior to transplant (baseline) and at 1, 3, 6, and 12 months following transplant. Results: Sixty-five patients (n = 27 allogenic; n = 38 autologous) participated. Survey completion rates were 95% at 1 month post-transplant, 74% at 6 months, and 65% at one year. One month following transplant, patients’ fatigue (P &lt; .001) increased, while physical (P &lt; .001) and social (P &lt; .001) functions decreased. Each returned to baseline at 3 months (P &lt; .001). Fatigue was more pronounced in allogeneic recipients (P = .017) and autologous recipients recovered physical function much sooner (P = .021). Conclusions: This study confirms the feasibility of capturing PROMs longitudinally in patients receiving HSCT and demonstrates significant changes in fatigue and physical and social functioning following transplant.

Listeria monocytogenes infections in hematopoietic cell transplant recipients: clinical manifestations and risk factors: A multinational retrospective case control study of the Infectious Diseases Working Party (IDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

BackgroundListeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. ObjectivesTo describe listeriosis following HCT and assess risk factors for listeriosis. Study designIn this retrospective international case control study, we described 41 listeriosis episodes during 2000-2021 in HCT recipients (111 transplant centers; 30 countries) and assessed risk factors for listeriosis by comparing to matched controls. ResultsForty-one listeriosis episodes (all due to Listeria monocytogenes, LM) in 30 allo- and 11 auto-HCT recipients occurred at a median of 6.2 (interquartile range [1Q-3Q] 1.6-19.3) months post-HCT. The estimated incidence was 49.8/100,000 in allo-HCT, and 13.7/100,000 population in auto-HCT. The most common manifestations were fever (39; 95%), headache (9; 22%), diarrhea, and impaired consciousness (8 each; 20%); 4 (10%) presented with septic shock; 19/38 (50%) were severely lymphocytopenic. Thirty-seven (90%) patients had LM bacteremia. Eleven (27%) patients had neurolisteriosis; 4/11 presented with non-specific signs, and 5/11 had normal brain imaging. Cerebrospinal fluid (CSF) analysis revealed high protein and, mainly neutrophilic, pleocytosis. Three-months mortality was 7/41 (17%): 3/11 (27%) among neurolisteriosis, and 4/30 (13%) among non-neurolisteriosis cases. In the multivariate analysis comparing to 74 controls, ≥2 HCT (OR [95%CI] 5.84 [1.10-30.82], p=0.038); and lymphocytopenia<500 cells/mm3 (OR [95%CI] 7.54 [1.50-37.83], p=0.014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. ConclusionsHCT patients have an increased risk for listeriosis compared to general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with non-specific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with increased risk of listeriosis; cotrimoxazole was not protective.

Trajectory of Sleep, Depression, and Quality of Life in Pediatric HSCT Recipients

Disrupted sleep is commonly reported during hematopoietic stem cell transplant. In this study, we use actigraphy to measure sleep parameters, and qualitative measures of quality of life, depression, and sleep in pediatric and young adult transplant recipients to describe their time course through transplant. Eight patients had evaluable actigraphy data, and 10 patients completed the surveys. The median age of the 6 male and 7 female participants was 13.94 years old. Sleep duration and efficiency measured by actigraphy were suboptimal prior to transplant, then declined to a nadir between Day +7 to +14. Self-reported sleep quality, depression, and quality of life were worst at Day +14 to +30 but improved by Day +100. Findings support efforts to improve sleep, which may improve recovery, mental health and quality of life.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P=.002) compared with the control group. Additionally, the time duration of CMV reactivation (P=.001) and bacterial infection rate (P=.013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P=.006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. To document endocrine sequelae and other late effects of all HSCT recipients. Retrospective review. Royal Children's Hospital Melbourne. 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. None. Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

High rates of intestinal colonization with carbapenemase producing Enterobacteriaceae inhematopoietic stem cell transplant recipients.

Carbapenem resistant Enterobacteriaceae (CRE) are major human pathogens because, these cause high number of difficult-to-treat infections. Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are highly exposed to these type of bacteria. The aim of our study was to investigate prevalence of CRE colonization in AHSCT patients and to determine genes encoding carbapenem resistance. Aretrospective study conducted between January 2015 and December 2019, involved 55 patients colonized with CRE strains. We determined the rate of antibiotic resistance according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the carbapenem resistance genes by PCR assays for genes encoding most frequent β-lactamases namely, blaGES, blaKPC, blaIMI, blaNDM, blaVIM, blaIMP and blaOXA-48. Eighty-one episodes of CRE colonization were recorded in 55 patients, mainly suffering from acute leukaemia (30%) and aplastic anemia (26%). History of hospitalization was noted in 80 episodes. Prior antibiotic treatment, severe neutropenia and corticosteroid therapy were respectively found in 94%, 76% and 58% of cases. Among the 55 patients, six patients (11%) developed a CRE infection. The CRE responsible for colonization were carbapenemase producers in 90% of cases. They belonged mostly to Klebsiella pneumoniae (61/81) and Escherichia coli species (10/81). Antibiotic resistance rates were 100% for ertapenem, 53% for imipenem, 42% for amikacin, 88% for ciprofloxacin and 27% for fosfomycin. Molecular study showed that blaOXA-48 gene was the most frequent (60.5%), followed by blaNDM (58%). Thirty-five (43%) strains were co-producers of carbapenemases. In our study, we report a high rate of CRE intestinal colonization in AHSCT recipients of our center.

Presentation, anagement, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study.

Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients.  Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients. A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated. A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis. In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment.

Surveillance over cytomegalovirus (CMV) reactivation following hematopoietic stem cell transplantation: a single-center experience

Cytomegalovirus (CMV) infection is widespread and usually asymptomatic in immunocompetent individuals. However, during immune suppression, especially after hematopoietic stem cell transplantation (HSCT), viral reactivation may result in symptomatic infection and end-organ disease. Because there is high incidence of CMV seropositivity in Bulgaria, CMV infection/reactivation is an expected common complication in HSCT recipients which requires frequent monitoring. CMV reactivation monitoring via qRT PCR has a significant role in terms of the moment of initiating pre-emptive therapy in these high-risk patients in order to avoid the development of CMV disease and better clinical management. The aim of this study was to determine and analyze the incidence of CMV reactivation in HSCT recipients in a new transplant center in Bulgaria. The incidence of early CMV reactivation after HSCT in our center is very high (76.7%) most likely related to the high-risk donor/recipient (D/R) profile of our recipients. The mean period from HSCT to the first positive PCR result was quite short, 21.5 days on average. The highest-risk group donor-/recipient+ (D-/R+) experienced the longest and the highest levels of viremia, as well as the highest number of reactivations. The nature of the D/R status most significantly affected the degree of viral load. Our data demonstrate the essential role of monitoring of CMV with reliable and sensitive laboratory methods, such as qRT-PCR to avoid development of CMV disease in high-risk patients.

What Are the Perceptions of Recipients of Allogeneic Hematopoietic Stem Cell Transplant About Medication Adherence?: A Synthesis of Qualitative Studies.

Recipients of allogeneic hematopoietic stem cell transplant (HSCT) may encounter difficulties in adhering to their post-transplant medication as prescribed to avoid complications. Despite the relevance of patients' perspectives to inform the clinical practice, to date, no summary regarding their lived experience of oral medication adherence (MA) has been produced. To summarize the lived experience of MA by recipients of allogeneic HSCT as documented in qualitative studies. A systematic review and meta-synthesis of qualitative research was performed. Six databases were searched up to June 27, 2023. Four qualitative studies met eligibility and were included: those designed and conducted with scientifically sound methodologies and those regarding adult patients who had undergone allogeneic HSCT and required an oral medication regimen in the post-transplant phase. Data were extracted and synthesized using thematic analysis. Four analytical themes were identified: "The initiation is a challenge," "Time as a new issue," "Internal and external obstacles threaten medication adherence," and "Different strategies are the answer to medication non-adherence." Medication adherence in patients after HSCT is a complex phenomenon wherein different factors play a role. When designing targeted interventions to improve MA, it is imperative to start with patients' experiences and perspectives. Patients developed different strategies to deal with obstacles to MA that may inform daily practice. Before discharge, healthcare professionals should emphasize to both patients and carers the importance of MA.

'Lesion on the back of the hand in a hematopoietic stem cell transplant recipient'.

'Lesion on the back of the hand in a hematopoietic stem cell transplant recipient'.

Nature-based virtual reality intervention to manage stress in family caregivers of allogeneic hematopoietic stem cell transplant recipients: a two-phase pilot study protocol.

ClinicalTrials.gov, identifier NCT05909202.

Atypical pneumonia testing in transplant recipients.

The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.