Questions 113-120 will be answered for all recipients.

Questions 121– 127 to be completed for malignant hematologic disorders and solid tumor indications ONLY.

Question 113: Has the patient been infected with COVID-19 (SARS-CoV-2) based on a positive test result at any time prior to the start systemic therapy?

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 systemic therapy (e.g., lymphodepleting therapy) or infusion (if no systemic therapy was given).

If the recipient has had a documented COVID-19 (SARS-CoV-2) infection, report Yes.

If the recipient has not had a documented COVID-19 (SARS-CoV-2) infection, report No and continue with question 116.

If this is a subsequent infusion and the documented COVID-19 (SARS-CoV-2) infection was already reported on previous forms, report No and continue with question 116.

Possible Reporting Scenarios:

An infection should not be reported if:

  • A recipient has a positive antibody result. The recipient does not have a history of positive COVID-19 results (PCR or antigen).
  • The recipient was symptomatic and treated, but COVID-19 diagnostic testing as not performed and / or COVID-19 diagnostic testing was performed and negative.

An infection should be reported if:
*A recipient has a positive COVID-19 diagnostic result (PCR or antigen). No treatment was given and / or recipient was symptomatic.

Question 114: 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 116.

Question 115: Was mechanical ventilation used 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.

Question 116: Was a vaccine for COVID-19 (SARS-CoV-2) received at anytime prior to the start of systemic therapy?

Indicate if the recipient received a vaccine for COVID-19 (one dose without a planned second dose, first dose with planned second dose, second dose, third dose and / or booster) at any time prior to the start of the systemic therapy (e.g., lymphodepleting therapy) / infusion.

If the recipient did not receive a vaccine for COVID-19 or it is not known if the recipient received a vaccine, select No *or *Unknown, respectively, and continue with question 121.

If this is a subsequent infusion and all vaccine doses have already been reported on previous forms, select No and continue with question 121.

If this is a subsequent infusion and some, but not all vaccine doses have already been reported on previous forms, select Yes and only report the vaccine doses not previously reported.

Question 117-118: Specify vaccine brand:

For the vaccine dose being reported, specify the brand of vaccine the recipient received. If the vaccine brand is not listed, select Other type and specify.

If the vaccine brand is unknown, leave the data field blank and override the error as ‘unknown.’

Question 120: Select dose received:

For the vaccine dose being reported, select the vaccine dose(s) the recipient received prior to the start of the systemic therapy / infusion and report the date when the vaccine was received. If the exact date is not known, use the process described in the General Instructions, Guidelines for Completing Forms and select Date estimated.

Question 121: Prior viral exposure/infection: (check all that apply)

Indicate if the recipient was positive for any of the viral exposure or infections listed below. Do not select the viral exposure or infection if the test was performed and the results were negative.

If testing for evidence of prior viral exposure / infection was not performed, select Not done.

Select Not applicable if testing for evidence of prior viral exposure / infection was performed and all of the results were negative.

HTLV1 antibody: Human T-Lymphotropic virus I/II (HTLV I/II) is a retrovirus in the same class as HIV. HTLV I/II is associated with certain leukemias and lymphomas, as well as demyelinating diseases such as multiple sclerosis.

Anti-EBV (Epstein-Barr virus antibody): Epstein-Barr Virus (EBV) is a common virus of the herpes family. It can cause infectious mononucleosis, but in most cases is asymptomatic. EBV establishes a lifelong dormant infection in some cells of the body’s immune system. Serious post-transplant complications related to EBV include EBV viremia (reactivation) and post-transplant lymphoproliferative disease (PTLD).

Hepatitis B surface antibody:
Hepatitis B is caused by the hepatitis B virus (HBV). Infection with this virus can cause scarring of the liver, liver failure, liver cancer, and even death. Hepatitis B is spread through infected blood and other body fluids. Acute hepatitis B infection does not usually require treatment because most adults clear the infection. Treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer.

The hepatitis B surface antibody test reveals the presence of hepatitis B antibodies, indicating previous exposure to HBV (or successful vaccination), but the virus is no longer present, and the person cannot pass on the virus.

Anti-HBc (hepatitis B core antibody): The enzyme-linked immunosorbent assay (ELISA) technique tests for the antibody directed against the hepatitis B virus core proteins. The hepatitis B core antibody test can indicate previous HBV infection. Currently there is no licensed confirmatory test for Anti-HBc. If the screening test is reactive, a second Anti-HBc test is performed using a different manufacturer’s test kit.

HBsAg (hepatitis B surface antigen): The ELISA or enzyme immunoassay (EIA) techniques test for the presence of proteins produced by the hepatitis B virus. Confirmatory testing is done using a neutralization test. The first marker appears approximately three weeks following infection, and disappears approximately six months later.

Hepatitis B – NAAT: The HBV NAAT test is more sensitive than regular serologic tests and is often used in conjunction with those tests to monitor patients with chronic HBV infections. If Hepatitis B – NAAT testing was done, report the results in this section.

Anti-HCV (hepatitis C antibody): Hepatitis C is a serious infection caused by the hepatitis C virus (HCV), which attacks the liver and may cause life-long infection. HCV is considered the most serious hepatitis infection because of its significant long-term health consequences. The infection is often asymptomatic, but once established, chronic infection can cause inflammation of the liver. This condition can progress to fibrosis and cirrhosis. In some cases, those with cirrhosis will go on to develop liver failure or liver cancer. Presence of the antibody in the blood represents exposure to HCV, which is most often spread by blood-to-blood contact. No vaccine against HCV is available.

The ELISA technique tests for antibodies to the HCV. Confirmatory testing is done using the recombinant immunoblot assay (RIBA) test. These tests can determine past exposure to HCV, but not current viral load.

Hepatitis C – NAAT: Nucleic acid testing (NAAT) is a combination PCR test that detects the presence of viral genes (HCV RNA) rather than antigens or antibodies. This test allows earlier detection and provides more sensitivity than previously used tests.

HIV antibody: HIV infection is caused by exposure to one of two viruses: HIV-1 or HIV-2. HIV-2 is less virulent and has a longer incubation period than HIV-1. Both types of HIV progressively destroy lymphocytes, which are an important part of the body’s immune defense. HIV can lead to acquired immunodeficiency syndrome (AIDS), a condition in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of bodily fluids and is present as both free virus particles and virus within infected immune cells.

HIV antibody testing is done using combination ELISA which detects antibodies to the HIV-1 and HIV-2 viruses. HIV-1 is confirmed by Western Blot, which detects specific proteins using gel electrophoresis. There is currently no licensed confirmatory test for HIV-2. If the screening test is reactive, HIV-2 is confirmed by specific ELISA.

The results of HIV assessments are often kept in confidence and may not be reportable to anyone other than the patient and their physician. If HIV testing was done, but the results are not available, do not select this option.

If the result is “positive,” an HIV insert (Form 2048) is also required.

HIVNAAT: Nucleic acid testing (NAAT) is a PCR test that detects the presence of viral genes rather than antigens or antibodies. This test allows earlier detection and provides more sensitivity than previously used tests.

The results of HIV assessments are often kept in confidence and may not be reportable to anyone other than the patient and their physician. If HIV testing was done, but the results are not available, do not select this option.

If the result is “positive,” an HIV insert (Form 2048) is also required.

Toxoplasmosis antibody: Toxoplasmosis is caused by the parasitic protozoan Toxoplasma gondii, or T. gondii. Toxoplasmosis is spread through ingestion of contaminated food or water or contact with infected cat feces. T. gondii infection is usually subclinical in healthy individuals, but infection can cause serious symptoms in pregnant women and immunocompromised individuals. Chronic, dormant T. gondii infection may follow initial exposure, and can then reoccur. Severe toxoplasmosis can affect the brain, eyes, and other organs and can cause permanent organ damage.

Testing for antibodies to T. gondii is generally done by enzyme-linked immunosorbent assay (ELISA) or chemiluminescent immunoassay (CIA). These immunoassays can be used to detect IgM and / or IgG antibodies to T. gondii. The presence of IgM antibodies indicates a recent or current infection, usually within the past four to six months. The presence of IgG antibodies indicates a previous infection and confers a long-term immune response to the virus. Results may be expressed as quantified antibody titer; in this case, the laboratory or test kit manufacturer will provide reference ranges to determine if the result is considered positive, indeterminate, or negative. Confirmatory testing is available to verify a positive serological result; this is done by Toxoplasma Serological Profile (TSP), which is a panel of multiple antibody ELISAs and agglutination testing.

Question 122: Were there any co-existing diseases or organ impairment present according to the HCT comorbidity index (HCT-CI)?

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

Report Yes if the recipient has a documented history and / or current diagnosis of any of the following:

Documented Medical History

  • Arrhythmia that has required specific antiarrhythmic treatment
  • Cardiac2
  • Cerebrovascular disease
  • Inflammatory bowel disease
  • Peptic ulcer
  • Rheumatologic
  • Prior malignancy, requiring treatment

Current Diagnosis at the Time of Pre-Infusion Evaluation

  • Diabetes
  • Heart valve disease3
  • Hepatic, mild4
  • Hepatic, moderate/severe
  • Infection
  • Obesity
  • Psychiatric disturbance
  • Pulmonary, moderate5
  • Pulmonary, severe5
  • Renal, moderate/severe6

2Ejection fraction (EF) ≤ 50% should be reported only if present on most recent test
3Excluding asymptomatic mitral valve prolapse
4Including any history of hepatitis B or hepatitis C infection
5If the PFT lists both a “control” FEV1 and a “post-dilator” FEV1, the “control” FEV1 should be used to determine if a pulmonary comorbidity is present.
6Including 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 systemic therapy. 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 123: 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.^7^]

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 requiring treatment.

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 122.

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 122.

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. Do not report a psychiatric comorbidity if therapy was given “as needed” for any mood, anxiety, or other psychiatric disorder.

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 122.

If renal (moderate / severe) comorbidity is selected, complete question 124.

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 125.

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 124: 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 125-127: Specify prior malignancy (check all that apply)

Specify the recipient’s prior solid tumor(s) and / or hematologic malignancy(ies). If Other hematologic malignancy is selected, specify the prior hematologic malignancy in question 126. If Other solid tumor is selected, specify the prior solid tumor in question 127.

7Sorror, M. L. (2013). How I assess comorbidities before hematopoietic cell transplantation. Blood, 121(15), 2854-2863.

Section Updates:

Question Number Date of Change Add/Remove/Modify Description Reasoning (If applicable)
122 9/29/2022 Add Added blue note box above question 122: Prior to answering Were there any co-existing diseases or organ impairment present according to the HCT comorbidity index (HCT-CI) question, review the list of co-existing disease(s) and/or organ impairments listed below. Added text box to match Pre-TED 2400 form manual
122 9/29/2022 Modify Updated text in red: Current Diagnosis at the Time of Pre- Infusion Evaluation Original text was ‘HCT’, which does not apply in the cell therapy manuals
122 9/29/2022 Modify Moved ‘Rheumatologic’ and ‘Prior malignancy, requiring treatment’ to the Documented medical history list. Added ‘heart value disease’ under Current Diagnosis at the Time of Pre-Infusion Evaluation First two options were mislabeled, third option was missing
122 9/29/2022 Modify Removed text from the blue note box: Hepatic and Renal Comorbidities Report all comorbidities including those that are considered complications of the primary disease for infusion. See examples below. This blue note applies to all comorbidities, not just hepatic and renal comorbidities
Last modified: Sep 29, 2022

Need more help with this?
Don’t hesitate to contact us here.

Was this helpful?

Yes No
You indicated this topic was not helpful to you ...
Could you please leave a comment telling us why? Thank you!
Thanks for your feedback.