Pulmonary Complications Following Stem Cell Transplant

Thanks to Dr. Ellis for a great presentation today of a patient with a history of allogeneic bone marrow transplantation who developed diffuse alveolar hemorrhage (DAH).

When approaching a patient with a history of bone marrow transplantation and pulmonary symptoms it is important to keep in mind several transplant specific factors such as what type of transplant (allogeneic vs. autologous), how long ago was the transplant (ie. early post-engraftment period vs. late post engraftment period), and the conditioning chemotherapy regimen the patient received, as this will help differentiate the list of potential causes of pulmonary pathology. A Chest article from 2013 included a nice table of the list below

Pulmonary complications post HSCT.PNG

For patients in the pre- engraftment period (day 0-30)

  • Pulmonary infections
  • Pulmonary edema
  • Engraftment syndrome (typically within 10 days, more common with autologous transplant)
  • Diffuse alveolar hemorrhage (more common in allogenic than autologous)
  • Idiopathic pneumonia syndrome (more common in allo than auto)
  • Hyperacute/acute GVHD predominate.
  • TRALI/TACO due to transfusion support

For patients in the early post- engraftment period (Engraftment day-100 days post engraftment)

  • Infectious more likely (viral- influenza, CMV, adenovirus, bacterial- pneumococcus, legionella, nocardia,actinomyces,mycobacteria, and fungal- PCP, aspergillus)
  • Idiopathic pneumonia syndrome
  • Drug toxicity/Radiation pneumonitis

For patients in the post-engraftment period (day 100 onward)

  • Bronchiolitis obliterans
  • Organizing pneumonia
  • Malignancy
  • Pulmonary alveolar proteinosis/pulmonary cytolytic thrombi
  • Radiation pneumonitis
  • Autoimmune connective tissue disorders

Outcomes in patients who develop DAH following are poor, as noted in this paper from Bone Marrow Transplantation [http://www.nature.com/articles/1705695][1]

If more reading is desired, the complete review of the chest article can be found here: [https://www-sciencedirect-com.liboff.ohsu.edu/science/article/pii/S0012369215487033][2]

Want more? Keep reading…

We often have trouble deciphering the language surrounding transplantation. As such, I have included a list of the most common terms used below:

1.MURD: Matched Unrelated Donor

2.MRD: Matched related Donor

3.Matched: HLA alleles (2 alleles for each) from donor and recipient are the same down to a certain degree

  • 10/10 match: HLA-A,B,C (MHC class I). HLA- DR, DQ (MHC Class II)
  • 12/12 match: HLA A,B,C, DR, DQ, DP

4.Mismatched: Some of the alleles do not match, usually just one (ie. 9/10= mismatched).

5.Haploidentical (Haplo) donor: Donor where half of the alleles are a match (usually a sibling or parent)

6.Conditioning Regimen: Chemotherapy used to ablate the bone marrow (see chart below)

  • Myeloablative: Regimen will ablate all marrow hematopoiesis- patient will not recover without new stem cell infusion (ie. hematopoietic stem cell transplant).

    • Common chemotherapy used: Busulfan, Melphalan, Cyclophosphamide, Fludarabine
    • Total body irradiation (TBI)
  • Non-myeloablative: Regimen will cause cytopenias, but patient hematopoiesis can recover without transplant.
  • Reduced Intensity Conditioning: A “lighter” version of myeloablative conditioning. Uses ~ 30% dose reduction compared to myeloablative, but patient will still need transplant to survive.

DAH in Bone Marrow Transplant

Non-Infectious Pulmonary Complications in Transplant

BMT conditioning regimen intensity.PNG

DAH can be classified by histopathological findings into 3 categories. These categories can be useful when thinking about the most common clinical etiologies, which can demonstrate overlap. The clinical presentation and history are very helpful in eliciting an etiology (of note, there are numerous causes- some of the more common ones are listed below).

1.Bland Hemorrhage:
     a.Thrombocytopenia, coagulopathy, connective tissue diseases, drugs. 
2.Diffuse alveolar damage
    a.Infection (including opportunistic infections), Rheumatological diseases, drugs/toxins, ARDS, organizing pneumonia. 
    a.Vasculitis, Rheumatological diseases (other than vasculitis), Drugs, Stem cell transplant.