Questions 111-113 will be answered for all recipients.

Question 111: Has the patient been infected with COVID-19 (SARS-CoV-2) based on a positive test result at any time prior to the start of the preparative regimen / infusion

SARS-CoV-2 is a novel virus belonging to the coronavirus (CoV) family that emerged in December 2019. The disease caused by this new CoV is known as COVID-19 (coronavirus disease 2019). The new virus is highly contagious and was officially declared a pandemic in March 2020. Transmission is believed to be from person to person through respiratory droplets from coughing and sneezing . Testing for COVID-19 is generally performed on specimens collected from a nasal swab or sputum sample .

Indicate whether or not the recipient has ever had a known COVID-19 (SARS-CoV-2) infection, based on a positive test result, at any time prior to the start of the preparative regimen or infusion (if no preparative regimen was given).

If the recipient has had a documented COVID-19 (SARS-CoV-2) infection, report “yes” and continue with question 112.

If the recipient has not had a documented COVID-19 (SARS-CoV-2) infection, report “no” and continue with question 114.

Question 112: Did the patient require hospitalization for management of COVID-19 (SARS-CoV-2) infection?

Report “yes” if the recipient was admitted to the hospital for management of their COVID-19 (SARS-CoV-2) infection. This includes any regular hospital or intensive care unit (ICU) admissions. Otherwise, report “no” and continue with question 114.

Question 113: Was mechanical ventilation given for COVID-19 (SARS-CoV-2) infection?

The clinical spectrum of COVID-19 varies from asymptomatic or paucisymptomatic forms to clinical conditions characterized by respiratory failure that necessitates mechanical ventilation and support in an intensive care unit (ICU)1. Mechanical ventilation may impact the recipient’s pulmonary function post-infusion. Report “yes” if the recipient was placed on mechanical ventilation for COVID-19 and continue with question 114.

Questions 114-120 will be answered for malignant hematologic disorders and solid tumor indications only

Question 114: Were there clinically significant co-existing disease or organ impairment at the time of patient assessment prior to preparative regimen?

Report “yes” to question 114 if the recipient has a documented history and/or current diagnosis of any of the following:

Documented Medical History
Arrythmia
Cardiac2
Cerebrovascular disease
Heart valve disease3
Inflammatory bowel disease
Peptic ulcer
Current Diagnosis at the Time of Pre-HCT Evaluation
Rheumatologic
Solid tumor, prior4
Diabetes
Hepatic, mild5
Hepatic, moderate/severe
Infection
Obesity
Psychiatric disturbance
Pulmonary, moderate
Pulmonary, severe
Renal, moderate/severe6

2 Ejection fraction (EF) ≤ 50% should be reported only if present on most recent test

3 Excluding asymptomatic mitral valve prolapse

4 Excluding non-melanoma skin cancer, leukemia, lymphoma, or multiple myeloma

5 Including any history of hepatitis B or hepatitis C infection

6 Including renal transplantation at any time in the patient’s history

Examples of complications of the primary disease for infusion that should be reported as comorbidities.

  • A patient with sickle cell had a stroke prior to infusion, the comorbidity to report would be “cerebrovascular disease”.
  • A toddler with Hurler Syndrome has cardiomyopathy, cardiac valvular disease and an ejection fraction of 45%, the comorbidities to report would be “cardiac” & “heart valve disease”.

The intent of this question is to identify serious pre-existing conditions that may have an effect on the outcome of the cellular therapy. For the purposes of this manual, the term “clinically significant” refers to conditions that are being treated at the time of pre-infusion evaluation, or are in the recipient’s medical history and could cause complications post-infusion. Conditions listed in the recipient’s medical history that have been resolved (e.g., appendectomy), and/or that would not pose a concern during or after the infusion should not be reported.

Additionally, for the purposes of this manual, the term “at the time of patient assessment” is defined as the pre-infusion evaluation period performed within 6 months prior to the start of the lympho-depleting or preparative regimen. If the recipient does not have a documented history of clinically significant disease(s) or organ impairment(s), check “no” and submit the form.

For information regarding reporting clinically significant co-existing disease or organ impairment, see Appendix J.

Question 115: Co-existing diseases or organ impairments

Indicate if the recipient had any of the co-existing diseases or organ impairments listed below. The definitions for each of the categories below are taken from Sorror, M. L. (2013). How I assess comorbidities before hematopoietic cell transplantation. Blood, 121(15), 2854-2863.

Arrhythmia: Any history of any type of arrhythmia that has necessitated the delivery of a specific antiarrhythmic agent. Examples include, but are not limited to, atrial fibrillation or flutter, sick sinus syndrome, and ventricular arrhythmias.

Cardiac: Any history of coronary artery disease (one or more vessel coronary artery stenosis requiring medical treatment, stent, or bypass graft), congestive heart failure, myocardial infarction, and / or ejection fraction ≤ 50% (shortening fraction < 26% for pediatric recipients) on the most recent test.

Cerebrovascular disease: Any history of transient ischemic attack, subarachnoid hemorrhage, and / or cerebral thrombosis embolism, or hemorrhage.

Diabetes: Diabetes or steroid-induced hyperglycemia requiring continuous treatment with insulin or oral hypoglycemics in the last 4 weeks.

Heart valve disease: Moderate or severe valve stenosis or insufficiency (mitral, aortic, tricuspid, or pulmonary) as determined by the most recent heart evaluation by an echocardiogram, prosthetic mitral or aortic valve, and / or symptomatic mitral valve prolapse. This does not include a documented medical history of heart valve disease.

Hepatic (mild): Chronic hepatitis, bilirubin > upper limit of normal to 1.5x upper limit of normal, or AST/ALT > upper limit of normal to 2.5x upper limit of normal, or any history of hepatitis B or hepatitis C infection. See note in question 114.

Hepatic (moderate/severe): Liver cirrhosis, bilirubin > 1.5x upper limit of normal, or AST/ALT > 2.5x upper limit of normal. See note in question 114.

Infection: Documented infection, fever of unknown origin, or pulmonary nodules requiring continuation of antimicrobial treatment after day 0.

Inflammatory bowel disease: Any history of Crohn’s disease or ulcerative colitis requiring treatment.

Obesity: Patients with a body mass index > 35 kg/m2 or BMI-for-age ≥ 95% (pediatric recipients only) during pre-transplant work-up period.

Peptic ulcer: Any history of peptic ulcer confirmed by endoscopy and requiring treatment.

Psychiatric disturbance: The presence of any mood, anxiety, or other psychiatric disorder requiring continuous treatment during the last four weeks. Examples include, but are not limited to, depression, anxiety, Attention-Deficit Disorder (ADD), Attention-Deficit Hyperactivity Disorder (ADHD), bipolar disorder, and schizophrenia requiring psychiatric consult or treatment in the last 4 weeks.

Pulmonary (moderate): Corrected diffusion capacity of carbon monoxide (e.g., DLCOc, DLCOcorr, DLCO) and/or FEV1 66-80% or dyspnea on slight activity at transplant. Use the Dinakara equation below to determine the DLCOc if only an uncorrected value is provided. For recipients assessed by a post- bronchodilator test, only the pre-bronchodilator FEV1 values are considered for evaluation of pulmonary comorbidity.

Dinakara Equation: DLCOc = {uncorrected DLCO} / [0.06965 x {hemoglobin g/dL}]

Pulmonary (severe): Corrected diffusion capacity of carbon monoxide (e.g., DLCOc, DLCOcorr, DLCO) and/or FEV1 ≤ 65% or dyspnea at rest or
requiring oxygen at transplant. Use the Dinakara equation above to determine the DLCOc if only an uncorrected value is provided. For recipients assessed by a post-bronchodilator test, only the pre-bronchodilator FEV1 values are considered for evaluation of pulmonary comorbidity.

Renal (moderate / severe): Serum creatinine > 2 mg/dL or > 176.8 μmol/L, or on any form of dialysis at transplant, or prior renal transplantation. See note in question 114.

If renal (moderate / severe) comorbidity is selected, complete question 116.

Rheumatologic: Any history of systemic lupus erythematosus, rheumatoid arthritis, polymyositis, mixed connective tissue disease, or polymyalgia rheumatica requiring treatment (do NOT include degenerative joint disease, osteoarthritis)

Prior malignancy, specify: Any solid tumor(s) and / or hematologic malignancy(ies) that have been treated at any time point in the patient’s past history. A history of any benign tumor(s) should not be reported.

If the recipient is receiving a cellular therapy for a disease that has transformed from one disease to another, the original malignancy should not be reported in this section. Details regarding disease transformation will be captured on the Pre- TED Disease Classification Form (Form 2402). For more information regarding disease combinations and transformations, refer to the Common Disease Combinations and Common Disease Transformations tables in the Primary Disease for HCT / Cellular Therapy section of the Disease Classification Form (Form 2402).
If prior malignancy is selected, complete question 117.

The physician performing the recipient’s pre-infusion evaluation may use the HCT Co- Morbidity Index (HCT-CI) to document co-morbid conditions (see Appendix J).

Question 116: Was the recipient on dialysis immediately prior to start of lymphodepleting therapy?

Indicate if the recipient was dialysis, hemodialysis, or peritoneal dialysis dependent within approximately one month prior to the start of the lymphodepleting therapy.

Question 117-120: Specify prior malignancy (check all that apply)

Specify the recipient’s prior solid tumor(s) and / or hematologic malignancy(ies). If “Other skin malignancy (basal cell, squamous” is selected, specify the skin malignancy in question 118. If “Other hematologic malignancy” is selected, specify the prior hematologic malignancy in question 119. If “Other solid tumor” is selected, specify the prior solid tumor in question 120.

1 Sorror, M. L. (2013). How I assess comorbidities before hematopoietic cell transplantation. Blood, 121(15), 2854-2863.

Last modified: Nov 13, 2020

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