Transplant_Samples_-__Contractor_Requirements.pdf

NHLBI HEART/LUNG TRANSPLANT SAMPLE COLLECTION

1. CONTRACTOR REQUIREMENTS

Independently and not as an agent of the Government, the Contractor shall provide the NHLBI with clinical samples according to the following guidelines:

1.1. SAMPLE PROCESSING:

The Contractor shall use the NHLBI’s collection/processing kit to process each sample within two (2) hours of collection as follows:

1) Collect RNA-Later. Add 5 mL of total blood to a solution to preserve RNA-Later for later RNA purification at NIH.

2) Centrifuge to collect Plasma. Spin the remaining whole blood twice (1500G followed by 15,000 G) to isolate plasma.

3) Collect Peripheral Blood Mononuclear Cells (PBMNC). Use the cell pellet to purify mononuclear cells on a Ficoll gradient. (Only technicians who have undergone CHI standard operating procedure training at NIH shall perform this step).

4) Scan pathology slides into NHLBI’s online repository.

5) Enter data into NHLBI’s clinical database. (See Section 3.3, “Data

Collection”).

6) Freeze Sample. Once all the necessary data has been recorded, freeze the sample and prepare the sample for shipment. (See Section 3.2.3, “Sample Shipment”).

1.2. DATA ENTRY:

The Contractor shall upload the following information onto the NHLBI’s online database for each sample processed:

1.2.1. LUNG-TRANSPLANT PATIENT SAMPLES:

1.2.1.1. Pre-Transplantation Data Collection (Demographics of Recipient):

Study-specific identification number Date enrolled (date when consent form signed), UNOS status at enrollment, UNOS status at transplantation Transplant center Gender, race, ethnicity Date of birth, weight at enrollment, height, body mass index Primary diagnosis for transplantation Co-morbid conditions pre-transplant [diseases, hospitalization, ventilator, inotropes, ECMO, VAD, IABP, HD, creatinine, smoker status, NO, inhaled prostacyclin, prostaglandins, supplemental oxygen (also dose), infection requiring antibiotics, other medications]

Pre-transplant spirogram: FEV1. FVC, FEV1/FVC. TLC, RV/TLC, DLCO, DLCO/VA

Pre-transplant echocardiogram Pre-transplant medications Blood type HLA type IgG cPRA, C1q cPRA, Transplant listing date CMV status Physical capacity pre-transplant measured by 6 minute-walk test

1.2.1.2. Pre-Transplantation Data Collection (Demographics of Donor):

OPO

Age, weight, height, Gender, race, ethnicity Blood type, HLA type Graft PaO2, FIO2 Pulmonary artery catheter measurements Donor bronchoscopy results Donor cultures from BAL Donor CXR results: abnormalities (mass, infiltrates,) and location CMV status Comorbidities (diseases, CAD status, smoking, chest trauma, EtOH use, IVDU).

High risk status per CDC guidelines Ex-vivo lung perfusion Cause of death Donor sample collected for DNA isolation: where-blood, spleenocytes, etc

1.2.1.3. Peri-Transplantation Data Collection:

Ischemic time per lung for double lung transplant Induction regimen Duration of mechanical ventilation Primary Graft Dysfunction: diagnosis, grade and duration of symptoms 6mwt, oxygen requirement at discharge Spirogram prior to discharge Echocardiogram prior to discharge Discharge medication (dose, levels) Blood sample collected twice a week during hospitalization

1.2.1.4. Post-Transplantation Data Collection (Routine follow-up clinical data collection):

Last hospitalization: diagnosis, treatment, bronchoscopy report, imaging data, pathology report, microbiology results, immunosuppression drug levels) Symptoms (cough, sputum, sputum color, sob, chest pain) Imaging (CXR or CT chest): indication, findings and location of findings

Spirogram data Echocardiogram data Baseline oxygen requirement, SpO2 6mwt, ABG Post-transplant complications: diabetes, bronchial stenosis, renal failure, depression, etc Prior history of acute rejection: date of diagnosis, symptoms, biopsy-grade, treatment CMV/RSV, respiratory virus status BOS status: diagnosis and severity DSA status and titer Medications: dose and levels

1.2.1.5. Post-Transplantation Data Collection (Biopsy visit and sample collections):

Time point (weeks/months after transplant) Biopsy visit: routine or emergent/urgent Procedures performed (BAL, TBBx, stent placement) BAL cell count and differential, immunocompromised viral panel, culture results Biopsy results: infection, rejection type: antibody vs. cellular rejection Biopsy grade: 2004 ISHLT classification Amount of excess BAL collected Blood sample collected.

Blood product isolated: plasma, PBMNC, RNA-later Sample shipping date

1.2.1.6. Post-Transplantation Data Collection (Rejection/infection Event Data Collection):

Date of diagnosis Specific symptoms: cough, sputum (color, blood), chest pain, sob CT chest data/CXR data: indication, findings and location of findings Echo performed Spirometry, 6mwt (admission and discharge) Medications on admissions and levels Bronchoscopy: BAL, biopsy, stent Biopsy results (infection, ACR, AMR) and grade Microbiology (sputum/BAL/biopsy culture results, respiratory virus immunocompromised panel results) Rejection treatment: steroid (dose), ATG, IVIg, Plasmapheresis, Rituximab, other Antibiotic treatment Medication changes at discharge, drug levels Hospitalization data: duration, supplemental oxygen, discharge oxygen requirement and FEV1

Outcome: resolved, no sequel, improving, death, etc…

1.2.1.7. Post-Transplantation Data Collection (Spirogram Data Collection):

Scheduled or urgent

FEV1, FEV1/FVC, FVC, TLC, TLC/RV, DLCO, DLCO

1.2.2. HEART-TRANSPLANT PATIENTS:

1.2.2.1. Pre-Transplantation Data Collection (Demographics of Recipient):

Study specific identification number Date enrolled (date when consent form signed), UNOS status at enrollment, UNOS status at transplantation Transplant center Gender, race, ethnicity DOB, weight at enrollment, height, BMI Primary diagnosis for transplantation Prior sternotomy Co-morbid conditions pre-transplant (disease, ICU stay, in-hospital, ventilator, inotropes, ECMO, VAD (LVAD, LVAD Type, BiVADs, TAH), IABP, HD, creatinine, GFR, smoker status)

Pre-transplant echocardiogram, pre-transplant spirogram Pre-transplant medications Blood type HLA type IgG cPRA, C1q cPRA Transplant listing date CMV status

1.2.2.2. Pre-Transplantation Data Collection (Demographics of Donor):

OPO

Age, weight, height, Gender, race, ethnicity ECHO: EF, LVEDD, IVSd, PWd Pa catheter measurements Inotropes / Vasopressors Blood type, HLA type CMV status Comorbidities (diseases, CAD status, smoking, chest trauma, EtOH use, IVDU).

High risk status per CDC guidelines Cause of death Donor sample collected for DNA isolation (?) from where-blood, spleen?)

1.2.2.3. Peri-Transplantation Data Collection:

Ischemic time Induction regimen Duration of mechanical ventilation PGD: diagnosis, grade, duration 6 mwt, oxygen requirement at discharge Spirogram prior to discharge Echocardiogram at discharge: EF, LVEDD, IVSd, PWd Discharge medication (dose, levels) Blood samples collected twice weekly

1.2.2.4. Post-Transplantation Data Collection (Routine Follow-Up Clinical Data

Collection):

Last hospitalization diagnosis, treatment, bronchoscopy report, imaging data, pathology Symptoms (cough, sob, chest pain) Hemodynamics (vital signs) CXR/CT chest: indication, findings and location of findings Echocardiogram: EF, LVEDD, IVSd, PWd Spirogram data Baseline oxygen requirement, SpO2 6mwt, ABG Post-transplant complications: diabetes, bronchial stenosis, renal failure, depression, etc Prior history of acute rejection: date of diagnosis, symptoms, biopsy-grade, treatment CMV status CAV status DSA status and titer Drug and dose, drug levels where applicable, dose change

1.2.2.5. Post-Transplantation Data Collection (Biopsy visit and sample data collection):

Time point (weeks/months after transplant) Biopsy visit: routine or emergent/urgent Biopsy grade: 2004 ISHLT classification Rejection type: antibody vs. cellular rejection Allomap score Amount of blood sample collected Blood product isolated: plasma, PBMNC, RNA-later Sample shipping date

1.2.2.6. Post-Transplantation Data Collection (Rejection event data collection):

Date of diagnosis

Specific symptoms: None, chest pain, sob, etc Admission drugs and levels Echocardiogram: EF, LVEDD, IVSd, PWd Spirometry Imaging data (CXR, CT chest) CMV status, viral load Biopsy performed Biopsy grade: 2004 ISHLT classification Echocardiogram: EF, LVEDD, IVSd, PWd Rejection treatment: steroid (dose), ATG, IVIg, Plasmapheresis, Rituximab, Bortezomib, other Medication changes and levels Hospitalization data: duration, supplemental oxygen, mechanical ventilation, diuresis, CVVH, iHD, discharge oxygen requirement, Outcome: resolved, no sequel, improving, death, etc

1.2.2.7. Post-Transplantation Data Collection (Angiography data collection):

Scheduled or urgent Angiography CAV grade IVUS CAV grade if performed

1.3. SAMPLE SHIPMENT:

After ensuring the sample has been properly frozen, the Contractor shall complete a Sample Collection Form provided by the NHLBI and place it along with the sample into a pre-stamped envelope also provided by the NHLBI. The Contractor shall then schedule the pick-up/delivery of the sample to the address listed on the pre-stamped envelope.