Late-onset cytomegalovirus pneumonia after autologous stem cell transplantation for angioimmunoblastic T-cell lymphoma: a case report

Abstract

This case report illustrates a diagnostic and therapeutic challenge in a highly immunocompromised host: severe pneumonia occurring late after autologous hematopoietic stem cell transplantation (auto-HSCT). A 57-year-old male with angioimmunoblastic T-cell lymphoma (AITL) presented with hypoxemic respiratory failure 1 year post-auto-HSCT, a timeline extending beyond the typical high-risk period for opportunistic infections. A profoundly low CD4+ T-cell count (172/µL) was identified as the key predisposing factor. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) enabled rapid, unbiased pathogen detection, confirming cytomegalovirus (CMV) pneumonia (viral load: 3.0 × 10⁴ copies/mL) with Klebsiella pneumoniae coinfection. An integrated management strategy was instituted, comprising early empiric coverage for Pneumocystis jirovecii pneumonia, targeted therapy with ganciclovir and levofloxacin, and adjunctive immunomodulation using intravenous immunoglobulin and corticosteroids. This comprehensive approach resulted in full recovery, highlighting that the severity of immune suppression—rather than time since transplantation alone—determines infection risk. This case challenges the conventional time-based risk paradigm and supports immune-guided surveillance. It underscores the transformative role of mNGS in diagnosing complex infections in immunocompromised patients and advocates for a management paradigm that concurrently addresses pathogen eradication and host immune dysfunction.

Plain language summary

A late and severe lung infection after stem cell transplant: How advanced testing and combined treatment led to recovery

Patients with blood cancers like AITL often undergo a stem cell transplant using their own cells. This can weaken the immune system for a long time. While doctors watch for infections in the first months after transplant, this case shows danger can appear much later if the immune system remains very weak. We describe a 57-year-old man with AITL. He received his own stem cell transplant and was doing well, but one year later, he suddenly developed severe breathing problems and pneumonia. Tests showed he lacked a key immune cell (CD4+ T-cells), making him vulnerable to infections that rarely affect healthy people. The challenge was quickly identifying the cause of pneumonia. Using an advanced genetic test (mNGS) on fluid from his lungs, doctors identified two culprits: cytomegalovirus (CMV) and Klebsiella pneumoniae. This test screened for many germs at once, speeding diagnosis. His treatment involved a combined strategy: 1) starting immediately with medicines to cover the most common deadly infections; 2) switching to targeted treatments—an antiviral for CMV and an antibiotic for the bacteria—once mNGS results came in; and 3) adding immune-supporting therapy to help fight infection and control inflammation.

This approach worked. His breathing improved within days, and follow-up scans showed healing. He was discharged and remained well. He received long-term preventive medication.

Keywords

angioimmunoblastic T-cell lymphoma autologous stem cell transplantation case management cytomegalovirus pneumonia immunocompromised host metagenomic next-generation sequencing

Introduction

Patients with lymphoma, particularly those with T-cell malignancies such as angioimmunoblastic T-cell lymphoma (AITL), experience profound immune compromise due to both the underlying disease and the effects of intensive therapy. This state renders them exceptionally vulnerable to severe and frequently polymicrobial pulmonary infections.^1,2 Among these, cytomegalovirus (CMV) pneumonia is a well-recognized and life-threatening complication following hematopoietic stem cell transplantation (HSCT). While the epidemiology, risk factors, and management of CMV infection are clearly established for allogeneic HSCT recipients—typically occurring within the first 100 days—its clinical profile in autologous HSCT (auto-HSCT) recipients is less distinct. Notably, late-onset CMV pneumonia, presenting beyond 1 year post-transplant, is an uncommon but critically important scenario that is often under-recognized in clinical practice, potentially leading to detrimental delays in diagnosis and treatment. In this high-stakes context, the rapid and precise identification of the causative pathogen(s) is paramount for patient survival. This article details the case of a 57-year-old male with AITL who developed severe hypoxemic respiratory failure caused by coinfection with CMV and Klebsiella pneumoniae 1 year after auto-HSCT.³ We present this case to highlight that risk in auto-HSCT recipients extends with persistent immunodeficiency, to demonstrate the decisive diagnostic utility of metagenomic next-generation sequencing (mNGS), and to elucidate an effective management strategy that integrates targeted antimicrobials with adjunctive immunomodulation.

Case presentation

A 57-year-old male was admitted to our department in July 2025 with a one-month history of progressive dyspnea and a 2-day history of fever. He reported a cough. A chest CT scan performed at a local hospital prior to transfer revealed diffuse bilateral patchy opacities (Figure 1). His past medical history was significant for AITL, stage IIA, diagnosed in January 2024 via right cervical lymph node biopsy. He received six cycles of CHOP-based induction chemotherapy, achieving a partial metabolic response. Notably, following the fourth cycle, he developed interstitial pneumonia, managed as a suspected immune-mediated lung injury with methylprednisolone and sulfonamides. He subsequently achieved a complete metabolic response and underwent autologous hematopoietic stem cell transplantation (auto-HSCT) in July 2024. Regular follow-up confirmed sustained remission without evidence of lymphoma recurrence. His comorbidities included type 2 diabetes mellitus of 15 years’ duration, well-controlled with basal insulin therapy. This case report was prepared and reported in accordance with the CARE (CAse REport) guidelines.⁴ The CARE checklist is provided as Supplemental Material.

Figure 1.

Chest CT scan at local hospital (1 day before admission). Axial images show diffuse bilateral patchy opacities and ground-glass shadows, indicative of a severe interstitial-alveolar inflammatory process.

Regarding immune reconstitution after auto-HSCT, the patient’s CD4+ T-cell count was not routinely measured during the first 6 months post-transplant. However, he did not experience any opportunistic infections during that period, suggesting partial immune recovery. Nevertheless, the subsequent decline to 172/µL at 1 year post-transplant indicates late and persistent immune dysfunction, likely attributable to both the residual effects of intensive chemotherapy and the inherent immune dysregulation associated with AITL.

Physical examination and preliminary investigations on admission

On examination, the patient was tachycardic (100 beats/min), tachypneic (20 breaths/min), and hypoxic with a peripheral oxygen saturation of 90% on room air. He appeared cyanotic with a wheezing posture. Auscultation of the chest revealed coarse breath sounds and diffuse moist rales bilaterally.

Initial laboratory investigations confirmed type I respiratory failure (arterial blood gas on FiO₂ 29%: pH 7.433, PaO₂ 67.6 mmHg, PaCO₂ 34.9 mmHg). Critically, lymphocyte subset analysis demonstrated profound CD4+ T-cell lymphopenia. Key findings are summarized in Table 1.

Table 1.

Selected laboratory findings on admission.

Parameter	Result	Reference range/note
White Blood Cell Count	8.06 × 10⁹/L
Lymphocyte Count	3.3 × 10⁹/L
CD4+ T-cell Count	172/µL	Markedly decreased
CD8+ T-cell Count	875/µL
Lactate Dehydrogenase	266.6 U/L
Serum IgG	8.4 g/L	Mildly decreased

Diagnosis and treatment process

Initial Empirical Management: Given the presentation of severe hypoxemic pneumonia in the context of profound immunosuppression (CD4+ count < 200/µL), the leading differential diagnoses were Pneumocystis jirovecii pneumonia (PJP) and viral pneumonitis. Immediate high-flow oxygen therapy was initiated. Empirical treatment with intravenous methylprednisolone (40 mg daily) and high-dose oral trimethoprim-sulfamethoxazole (TMP-SMX, 1.44 g every 8 h) was commenced.

Etiological Diagnosis: Due to persistent hypoxia, bedside bronchoscopy with bronchoalveolar lavage (BAL) was performed on hospital day 2. BAL fluid analysis showed aneutrophilic predominance (73%). Metagenomic next-generation sequencing (mNGS) of the BAL fluid was sent for analysis and identified 281 CMV-specific sequence reads. Confirmatory quantitative PCR returned a high CMV DNA load of 3.0 × 10⁴ copies/mL in BAL fluid, while plasma CMV DNA was negative. This confirmed the diagnosis of CMV pneumonia with suspected bacterial coinfection.

It is important to acknowledge that while mNGS offers high sensitivity, it also carries the risk of false-positive results, particularly when BALF samples are contaminated with oral or pharyngeal flora during the procedure. In this case, however, the high CMV read count and subsequent confirmatory PCR supported true infection rather than contamination or colonization.

Targeted Treatment and Clinical Course: Upon receipt of the mNGS result, targeted therapy was started: intravenous ganciclovir (5 mg/kg every 12 h, adjusted for renal function) for CMV and intravenous levofloxacin for bacterial coverage. Adjunctive therapy with intravenous immunoglobulin (IVIG, 10 g daily for 4 days) was administered. The patient’s respiratory status and oxygenation showed marked improvement within 72 h. Methylprednisolone was tapered, and a follow-up bedside chest radiograph showed evolving interstitial changes (Figure 2).

Figure 2.

Bedside chest radiograph during treatment. The image, obtained after the initiation of targeted therapy, shows evolving bilateral grid-like interstitial changes accompanied by multiple patchy opacities.

Subsequent confirmation, discharge, and final diagnoses

Subsequent diagnostic confirmation and clinical evolution: The initial sputum culture later confirmed growth of Klebsiella pneumoniae (2+), validating the concurrent bacterial infection for which levofloxacin provided appropriate coverage. A follow-up chest CT scan on August 11 (Figure 3) demonstrated residual but improving bilateral ground-glass opacities and consolidations, with minimal bilateral pleural effusion. Clinically, the patient showed remarkable improvement, mobilizing independently with resolution of dyspnea, which permitted a reduction in high-flow oxygen support.

Figure 3.

Serial chest CT imaging showing therapeutic response. (a) (2025-08-11): CT scan after 1 week of targeted therapy shows bilateral patchy ground-glass opacities and consolidations, with minimal pleural effusion. (b) (2025-09-02): Follow-up CT scan at 6 weeks demonstrates significant resolution of the parenchymal opacities and complete absorption of the pleural effusion.

Discharge planning and follow-up: By August 15, with sustained clinical recovery, targeted antimicrobial therapy (ganciclovir and levofloxacin) was discontinued, and oxygen supplementation was stepped down to a nasal cannula. The patient was discharged on August 18. Discharge medications and diagnoses are summarized in Table 2.

Table 2.

Discharge medications and diagnoses.

Category	Details
Discharge medications	• Prednisone: 20 mg daily, to taper over 2 weeks.• Pneumocystis Prophylaxis: Trimethoprim-sulfamethoxazole (TMP-SMX), initial high dose (1.44 g every 8 h) until August 20, then reduced to long-term maintenance (0.48 g daily).• Supportive Care: Omeprazole (20 mg daily), Calcium Carbonate D3 (600 mg daily).
Final diagnoses	1. Cytomegalovirus (CMV) Pneumonia2. Klebsiella pneumoniae Pneumonia3. Prophylaxis for Pneumocystis jirovecii Pneumonia (PJP)4. Angioimmunoblastic T-cell Lymphoma (Post-auto-HSCT, in remission)5. Type 2 Diabetes Mellitus

Regarding antimicrobial prophylaxis, our institutional practice for auto-HSCT recipients includes primary PJP prophylaxis with TMP-SMX (0.48 g daily) for at least 6 months post-transplant, or longer if CD4+ counts remain below 200/µL. Antifungal prophylaxis (e.g., fluconazole) and anti-VZV prophylaxis (e.g., acyclovir) are not routinely administered unless clinically indicated. In this patient, primary prophylaxis had been discontinued after 6 months due to apparent immune recovery, which may have contributed to his susceptibility to late-onset infection. This case underscores the need for individualized, immune-based prophylaxis strategies.

Follow-up

The patient returned for a follow-up evaluation on September 2, 2025. A repeat chest CT scan (Figure 3(b)) demonstrated significant resolution of the pulmonary infiltrates and complete absorption of the bilateral pleural effusion. He reported complete resolution of respiratory symptoms.

Long-term management instructions were reinforced. The oral prednisone dose was to be tapered by 5 mg every 5 days until discontinuation. Long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX, 0.48 g daily) was prescribed due to his persistent immunocompromised state. Figure 4 provides a chronological summary of the key diagnostic and therapeutic decision points throughout his hospitalization and recovery.

Figure 4.

Clinical timeline of diagnosis and treatment. The figure visualizes the concurrence of diagnostic milestones (diamonds) and therapeutic phases (colored bars), highlighting the rapid shift to targeted therapy post-mNGS.

Discussion

The successful management of this critical case provides salient insights that challenge the conventional timeline for post-transplant surveillance, exemplify the pivotal role of modern diagnostics, and underscore the necessity of an integrated therapeutic approach. The following sections will elaborate on: the extended vulnerability period defined by immune status rather than time alone, the decisive contribution of metagenomic next-generation sequencing (mNGS) to rapid diagnosis, and the principles of a combined management strategy that addresses both pathogen eradication and host immunomodulation.

Late-onset CMV pneumonia after Auto-HSCT: Redefining the window of vulnerability

This case highlights a life-threatening presentation of cytomegalovirus (CMV) pneumonia occurring approximately 1 year following autologous hematopoietic stem cell transplantation (auto-HSCT) for AITL. CMV disease is a classic opportunistic infection post-transplant, yet its epidemiology is predominantly defined in the context of allogeneic HSCT, typically occurring within the first 100 days.⁵ The occurrence of symptomatic CMV pneumonia in an auto-HSCT recipient at this late stage is clinically significant and underscores a potential gap in routine long-term surveillance. The pivotal predisposing factor was the profound and persistent CD4+ T-cell lymphopenia (172/µL). The failure of immune reconstitution in this patient likely stems from two interconnected factors: first, the intensive chemotherapy and conditioning regimens prior to auto-HSCT can deplete T-cell reserves; second, AITL itself is associated with intrinsic immune dysregulation, including defects in T-cell function and cytokine signaling, which may persist even after achieving disease remission.⁶ This aligns with data indicating that CMV reactivation is not uncommon after auto-HSCT, occurring in up to 41% of seropositive patients.⁶ The pathogenesis of CMV in the immunocompromised host involves complex viral–host interactions that contribute to both direct end-organ disease and indirect immunomodulatory effects.^7,8 This case compellingly argues that the risk for severe opportunistic infections in transplant recipients is governed primarily by the depth and duration of cellular immunodeficiency, rather than a fixed post-transplant timeline. Consequently, long-term management of patients with AITL and similar conditions should incorporate functional immune monitoring to identify those requiring extended vigilance.

The diagnostic pivot: The decisive role of mNGS in complex pneumonia

The etiological diagnosis of pneumonia in profoundly immunocompromised hosts is challenging due to the broad differential, which includes usual and opportunistic pathogens. While the detection of CMV DNA in bronchoalveolar lavage fluid (BALF) is a cornerstone for diagnosing CMV pneumonia, distinguishing disease from latency or shedding requires quantitative assessment, with a viral load >500 IU/mL being highly suggestive of active infection.^9,10 In this patient, conventional diagnostics were non-revealing. The application of metagenomic next-generation sequencing (mNGS) on BALF provided a critical, unbiased pathogen survey, rapidly and definitively identifying CMV as the lead pathogen. This was corroborated by a high CMV DNA load (3.0 × 10⁴ copies/mL) in BALF, while plasma PCR remained negative, confirming localized pulmonary disease rather than disseminated infection.¹⁰ The principal advantage of mNGS in this setting is its ability to detect a vast array of potential pathogens—viral, bacterial, fungal, and parasitic—without a priori clinical suspicion, dramatically accelerating time to targeted therapy.¹¹ However, it is also important to recognize the limitations of mNGS, including the potential for false-positive results due to sample contamination (e.g., from oral flora during bronchoscopy) or the detection of colonizing organisms that are not truly pathogenic. Additionally, the high cost and variable availability of mNGS may limit its routine use in resource-limited settings. Therefore, mNGS results should always be interpreted in conjunction with clinical context and confirmatory testing.¹¹ This case strongly supports the integration of mNGS into the early diagnostic workflow for severe pneumonia in immunocompromised patients, where diagnostic speed and breadth are paramount for survival.

Integrated management: A multi-targeted strategy for success

The favorable outcome in this critically ill patient underscores the necessity of a multi-modal management strategy that extends beyond antiviral monotherapy. First, prompt empirical therapy with corticosteroids and trimethoprim-sulfamethoxazole (TMP-SMX) addressed the most imminent threats—severe inflammatory lung injury and Pneumocystis jirovecii pneumonia (PJP)—which are common and lethal in this patient population.^12
–14 Second, upon definitive diagnosis via mNGS, therapy was seamlessly escalated to precision-targeted antimicrobials: intravenous ganciclovir (first-line for CMV) and levofloxacin (for the concurrently identified Klebsiella pneumoniae).^7,15 Third, and of paramount importance, was the adjunctive use of immunomodulation. Intravenous immunoglobulin (IVIG) was administered based on evidence supporting its role in improving outcomes for severe CMV pneumonitis, likely through pathogen neutralization and modulation of the dysregulated host inflammatory response.⁷ This triad of “empiric coverage, targeted pathogen eradication, and host-directed immunomodulation” represents a comprehensive therapeutic paradigm essential for managing complex infections in the setting of significant immune dysfunction.⁶

Coinfections and secondary prophylaxis: Foundational to long-term care

The presence of Klebsiella pneumoniae coinfection reiterates that CMV pneumonia often occurs within a polymicrobial context.⁶ Furthermore, the patient’s profound immunosuppression mandated long-term secondary prophylaxis against PJP with TMP-SMX, a standard and life-saving intervention in such scenarios.^14,16 Notably, this case also raises the question of whether primary prophylaxis should have been extended beyond 6 months, given the patient’s persistently low CD4+ count. Current guidelines do not provide a clear consensus on the duration of primary prophylaxis after auto-HSCT, but this case suggests that immune-based prolongation may be beneficial in selected high-risk patients. This aspect of management is not ancillary but fundamental to securing the patient’s recovery and protecting the gains achieved by curing the acute infection, thereby preserving the opportunity for continued long-term management of the underlying lymphoma.

Conclusion

This case of late-onset CMV pneumonia following auto-HSCT for AITL provides several critical insights for clinical practice: (1) Vigilance for opportunistic infections must be guided by ongoing assessments of immune function rather than elapsed time since transplant; (2) Advanced diagnostic tools like mNGS can be pivotal in rapidly deciphering the etiology of complex pneumonias, enabling a shift from empiric to precision medicine, though their limitations must be carefully considered; (3) Effective management requires an integrated strategy that concurrently addresses the identified pathogens, modulates detrimental host responses, and provides long-term prophylactic support. Adopting this comprehensive approach is essential for improving outcomes in immunocompromised hosts facing severe infectious complications.

Supplemental Material

sj-docx-1-tai-10.1177_20499361261450721 – Supplemental material for Late-onset cytomegalovirus pneumonia after autologous stem cell transplantation for angioimmunoblastic T-cell lymphoma: a case report

Supplemental material, sj-docx-1-tai-10.1177_20499361261450721 for Late-onset cytomegalovirus pneumonia after autologous stem cell transplantation for angioimmunoblastic T-cell lymphoma: a case report by Zhe Zhang, Zihan Jia, Xinjun Zhang, Wailong Zou and Jichao Chen in Therapeutic Advances in Infectious Disease

Footnotes

Acknowledgements

We thank the clinical care team and the departments of Clinical Laboratory and Radiology for their support. We are especially grateful to the metagenomic next-generation sequencing team for their pivotal diagnostic contribution. We also thank the patient for providing consent for publication.

Declarations

ORCID iD

Wailong Zou

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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