Symbolic illustration of lung transplant complications.

When Immunosuppression Backfires: A Lung Transplant Cautionary Tale

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"Could cladribine, a drug used to treat Langerhans cell histiocytosis (LCH), increase the risk of graft-versus-host disease (GVHD) after lung transplantation? A recent case raises important questions."

Organ transplantation offers a lifeline for individuals with severe, life-threatening conditions. However, the journey isn't without risks. Graft-versus-host disease (GVHD), a rare but devastating complication where the donor's immune cells attack the recipient's tissues, can occur after solid organ transplants.

A recent case highlights the complexities of managing immunosuppression in patients undergoing lung transplantation. This article examines the case of a young female with pulmonary Langerhans cell histiocytosis (LCH) who developed GVHD following a lung transplant, potentially linked to prior treatment with cladribine, an immunosuppressive drug.

By exploring this case, we aim to shed light on the delicate balance between suppressing the immune system to treat LCH and the potential for increasing the risk of GVHD after transplantation. Understanding this balance is crucial for optimizing treatment strategies and improving outcomes for patients with rare conditions like LCH.

The Case: LCH, Cladribine, and a Post-Transplant Complication

Symbolic illustration of lung transplant complications.

The patient, a 5-year-old female, presented with severe respiratory distress due to pulmonary LCH. Her condition was so critical that she required respiratory assistance from the start. Initial blood tests revealed a normal lymphocyte count but a concerningly low T CD3 count, suggesting immune system compromise potentially related to lung and thymus involvement.

To combat the LCH, she received four courses of cladribine, a potent immunosuppressant. While cladribine is often effective against LCH, it further reduced her already low lymphocyte count. Despite the treatment, her dependence on mechanical respiratory assistance persisted, leading to a lung transplant on day 173.

Cladribine: An immunosuppressant.
Lymphopenia: Low lymphocyte count.
GVHD: Graft-versus-host disease.
LCH: Langerhans cell histiocytosis.

Initially, the transplant was successful, with her lung function fully recovering within a week. However, 30 days post-transplant, while on a regimen of steroids and cyclosporine A (both immunosuppressants), she developed a fever, followed by cholestasis, intractable diarrhea, and a skin rash. Biopsies confirmed acute GVHD, and despite treatment, she succumbed to multi-organ failure on day 44 post-transplant.

A Delicate Balance: Immunosuppression and Transplant Risk

GVHD after solid organ transplantation is rare, occurring in less than 1% of cases, and is particularly uncommon after lung transplants. The fact that it proved fatal in this case, underscores the severity of this complication.

This case suggests that the severe lymphopenia, potentially worsened by cladribine, created a favorable environment for GVHD to develop. It raises concerns about using cladribine, and other similar drugs like clofarabine, in LCH patients who may eventually need organ transplants.

While a single case report, it serves as a crucial reminder of the need for cautious use of immunosuppressive drugs and careful consideration of transplant timing in patients with conditions like LCH. Further research is needed to fully understand the interplay between immunosuppression, LCH, and the risk of GVHD after transplantation.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1002/pbc.27477, Alternate LINK

Title: Cladribine-Related Immunosuppression May Have Fostered Graft-Versus-Host Disease After Lung Transplant For Pulmonary Langerhans Cell Histiocytosis

Subject: Oncology

Journal: Pediatric Blood & Cancer

Publisher: Wiley

Authors: Claire Galambrun, Florentine Garaix, Fabrice Ughetto, Christophe Picard, Philippe Petit, Emmanuelle Bosdure, Pascale Poullin, Nathalie Stremler, Loic Mace, Jean Donadieu

Published: 2018-09-30

Everything You Need To Know

What is Langerhans cell histiocytosis (LCH) and why is it relevant here?

Langerhans cell histiocytosis (LCH) is a rare disease characterized by an overproduction of Langerhans cells, which can damage various organs, including the lungs. In the context of this case, the young patient had severe pulmonary LCH, which led to respiratory distress and the need for a lung transplant.

What is cladribine and how was it used in this situation?

Cladribine is an immunosuppressant drug used to treat conditions like Langerhans cell histiocytosis (LCH). It works by suppressing the immune system, which can be beneficial in controlling diseases where the immune system is overactive. In this instance, Cladribine was used to treat pulmonary LCH, but its use prior to a lung transplant may have contributed to the development of graft-versus-host disease (GVHD).

What is graft-versus-host disease (GVHD) and what happened to the patient?

Graft-versus-host disease (GVHD) is a serious complication that can occur after solid organ transplants, including lung transplants. It happens when the donor's immune cells (in this case, the donor lung) recognize the recipient's body as foreign and attack the recipient's tissues. In this instance, the patient developed GVHD 30 days post-transplant, leading to multi-organ failure and ultimately, death.

Why is immunosuppression important, and how does it relate to the transplant and complications?

Immunosuppression is the act of reducing the activity of the immune system. In the context of organ transplantation, it's crucial to prevent the recipient's body from rejecting the new organ. However, excessive or poorly timed immunosuppression, as suggested by the use of cladribine before the lung transplant, can increase the risk of complications like graft-versus-host disease (GVHD). The article emphasizes the importance of carefully balancing immunosuppression to treat the underlying disease (like LCH) while minimizing transplant risks.

What does lymphopenia mean and what was its significance in this case?

Lymphopenia refers to a low lymphocyte count in the blood. Lymphocytes are a type of white blood cell that plays a key role in the immune system. In the case presented, the patient had a low lymphocyte count, potentially due to the pulmonary Langerhans cell histiocytosis (LCH) and the treatment with Cladribine. This pre-existing lymphopenia might have further complicated the immune response after the lung transplant, potentially making the patient more susceptible to GVHD.