The purpose of this study is to determine whether a lung transplantation prior to bone marrow transplantation (BMT) would allow for restoration of pulmonary function prior to BMT, allowing to proceed to BMT, to restore hematologic function.
The primary purpose of the study is to evaluate the safety and efficacy of performing lung transplantation followed by cadaveric, partially HLA-matched (≥1/6 HLA-match with an identical ABO blood type) CD3+/CD19+ depleted bone marrow transplantation in bone marrow failure and end-stage lung disease. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease for which lung transplantation is the only therapy shown to prolong survival. Given the association of IPF with hematologic cytopenias and bone marrow failure, it is proposed that a tandem lung transplantation and bone marrow transplantation from a single cadaveric donor could be successful. This protocol focuses on performing combined transplantation for candidates that are unable to undergo standard lung transplantation. Lung transplantation prior to bone marrow transplantation (BMT) would allow for restoration of pulmonary function prior to BMT, and to restore hematologic function post BMT transplantation. The secondary objectives are to evaluate the feasibility and long-term complications associated with combined solid organ and BMT including the ability to initiate and successfully withdraw from immunosuppression following BMT and to attain independence from growth factors, red blood cell or platelet transfusions.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Negative selection for CD3/CD19 will be performed on CliniMACS® depletion device and given at time no less than 8 weeks post lung transplantation
Transplantation Conditioning
Transplantation Conditioning
UPMC Presbyterian
Pittsburgh, Pennsylvania, United States
RECRUITINGChildren's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
RECRUITINGDeath
How many, if any, patients die
Time frame: Up to 2 years post stem cell transplant
Engraftment failure
How many, if any, develop engraftment failure
Time frame: Up to 2 years post stem cell transplant
Non-hematologic events
Any Grade 4 event that happens at any time points
Time frame: Up to 2 years post stem cell transplant
Hematological events
Any Grade 4 hematological events
Time frame: after 30 days post stem cell transplant
BOS Score
Bronchiolitis Obliterans Syndrome (BOS) score based off patient pulmonary function testing. Graded on scale (BOS0 to BOS3), BOS0 having a better outcome then BOS3
Time frame: at 1 year post lung transplant
T-cell Chimerism
The number of patients who have ≥25% donor T-cell chimerism
Time frame: at 12 months post stem cell transplant
Myeloid chimerism
The number of patients with myeloid disorders who attain ≥ 10% myeloid chimerism
Time frame: at 12 months post stem cell transplant
Restoration of blood cell count (in absence of growth factors)
Absolute neutrophil count (ANC)≥1000 per microliter of blood, platelets ≥50000 per microliter of blood and hematocrit ≥8 grams per deciliter of blood
Time frame: at 12 months post stem cell transplant
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Transplantation Conditioning
Transplantation Conditioning
Transplantation conditioning
Transplantation Conditioning
Feasibility of patients able to proceed to BMT within 6 months following lung transplantation
The number of patients who are able to proceed to BMT within 6 months following lung transplantation
Time frame: Up to 2 years post stem cell transplant
Independence
The number of patients who are able to be independent from transfusions and growth factors for at least 7 days
Time frame: up to 2 years post stem cell transplant
Independence
The number of patients who are able to be independent from transfusions and growth factors for at least 1 month
Time frame: Up to 2 years post stem cell transplant
Tolerance development to both host and pulmonary grafting
Development of tolerance to both the host and pulmonary graft
Time frame: Up to 2 years post stem cell transplant
Long-term complications
Long-term complications of combined solid organ and BMT
Time frame: Up to 2 years post stem cell transplant
Acute cellular rejection
The number of patients who develop acute cellular rejection
Time frame: Up to 2 years post stem cell transplant
Acute graft-versus-host-disease (GVHD)
The number of patients who develop acute graft-versus-host-disease (GVHD)
Time frame: Up to 2 years post stem cell transplant
Chronic graft-versus-host-disease (GVHD)
The number of patients who develop chronic graft-versus-host-disease (GVHD)
Time frame: Up to 2 years post stem cell transplant
Ability to withdrawal immunosuppression
The number of patients who are able to start immunosuppression withdrawal.
Time frame: By 1 year post stem cell transplant
Time to withdraw immunosuppression
Time from BMT to withdrawal of immunosuppression
Time frame: Up to 2 years post stem cell transplant
Prophylactic antimicrobial drugs
Time from BMT to independence for prophylactic antimicrobial drugs
Time frame: Up to 2 years post stem cell transplant
Treatment antimicrobial drugs
Time from BMT to independence from treatment antimicrobial drugs
Time frame: up to 2 years post stem cell transplant
Chronic lung allograft dysfunction
The number of patients who develop chronic lung allograft dysfunction post lung transplant for all subjects, lung only and lung +stem cell transplant.
Time frame: 1 year post lung transplant