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Diffuse Infiltrates Following Hematopoietic Stem Cell Transplantation

Case Editor - Judd Flesch

Reviewed By Allergy, Immunology & Inflammation Assembly

Submitted by

Karen Wood, MD

Assistant Professor of Medicine

Pulmonary/Critical Care Medicine

The Ohio State University

Columbus, OH

Kiran Devulapally, MD

Clinical Instructor and Fellow, Pulmonary/Critical Care Medicine

The Ohio State University

Columbus, OH

Submit your comments to the author(s).


A 23 year old white man with refractory Hodgkin's disease and a history of hematopoietic stem cell transplantation was admitted with nausea, vomiting, abdominal pain and weight loss.  Of note, he also complained of a chronic non-productive cough and mild new onset dyspnea. His past medical history was significant for relapsed refractory Hodgkin's disease initially diagnosed 8 years prior to transplantation. He had multiple chemotherapy regimens and both autologous and allogeneic stem cell transplants. He developed gemcitabine induced pneumonitis one year ago with clinical and radiological resolution after discontinuation of gemcitabine.  His autologous hematopoietic stem cell transplantation was six years prior to presentation, and he had a nonmyeloablative, matched, unrelated, allogenic hematopoietic stem cell transplantation 267 days prior to presentation.  He had been maintained on tacrolimus and mycophenolate for graft-versus-host disease prophylaxis.  However, because of recurrence of his disease, he was taken off the immunosuppression to induce graft versus tumor effect. He had 2 cycles of ifosfamide, etoposide, and carboplatin 2-3 months prior, and additionally had a donor lymphocytic infusion 42 days prior to admission for recurrent disease. He had no evidence of graft-versus-host disease prior to donor lymphocyte infusion.   In the first 2 hospital days, he developed increasing dyspnea despite aggressive therapy with empiric antibiotics and steroids.

Physical Exam

On admission, he was afebrile with stable vital signs. Oxygen saturation was 98% on room air.  His sclerae were icteric.  Lung exam revealed fine dry crackles in both bases.  Abdomen was benign without any hepatosplenomegaly.  Hospital Course:  The patient rapidly worsened and progressed to respiratory failure requiring intubation with severe hypoxemia.   A surgical open lung biopsy was undertaken and showed diffuse alveolar damage with type II pneumocyte hyperplasia, infiltration of alveolar cells with macrophages, plasma cells, lymphocytes and hyaline membrane formation. There was no evidence of infection.


His white blood cell count (WBC) was 4.8K/µl, hemoglobin (Hb) was 12.2g/dl, and platelet count was 83K/µl. The differential was neutrophilic predominant. Basic metabolic profile was within normal limits. Total bilirubin was 2.0 mg/dL and the liver transaminases were elevated at four times normal.  Alkaline phosphatase was elevated at 584 U/L and lactate dehydrogenase was 265 U/L .Biopsies of the skin, stomach, duodenum, and liver revealed acute graft-versus-host disease.


Figure 1) Computed tomography (CT) of the chest demonstrated bilateral extensive ground glass densities involving all lobes.

Figure 2) A photograph showing the pathology seen in diffuse alveolar damage. Many alveoli contain dense proteinaceous debris, desquamated cells, and hyaline membranes (arrows).

Question 1

The most likely diagnosis in this patient is:


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