Q41 – 66: Disease Assessment at the Time of Best Response to Infusion - Forms Instruction Manual

!Malignant Diseases Only
Only complete Disease Assessment at the Time of Best Response to Infusion questions if the infusion being reported was given to treat a malignant disease. If the infusion being reported was given to treat a non-malignant disease, leave these questions blank. FormsNet3^SM should enable / disable this section based on the primary disease reported on the Pre-TED Disease Classification (2402) Form. Contact the CIBMTR Customer Support if you believe FormsNet3^SM is incorrectly enabling / disabling these fields.

This section collects the data known as ‘best response to infusion.’ The purpose of this section is to report the recipient’s best response to the planned course of the infusion. This includes response to any therapy given for post-infusion maintenance, prior to progression (if applicable), but does not include response to treatment given for decreased / loss of chimerism, consolidation, measurable residual disease (MRD), persistent disease, or progressive / relapsed disease.

If the recipient receives consolidation therapy or therapy for MRD, decreased / loss of chimerism, persistent disease, or progressive / relapsed disease, the response to that additional therapy should not be reported in this section. The best response prior to the therapy should be reported. For subsequent reporting periods where the best response prior to the start of unplanned therapy was reported, if a CR was achieved prior to relapse / progression, the date of best response will be reported as Previously reported. If a CR was not achieved prior to the administration of therapy, the best response will be reported as Not evaluated. Refer to the best response to infusion questions below for more information.

Tandem Transplants
For recipients receiving a tandem transplant, the best response to the prior infusion (i.e., HCT #1 of the tandem) depends on the pre-infusion disease status.

If the recipient was in complete remission at the time of HCT #1, report the best response to transplant as Continued complete remission (CCR).
If the recipient was not in complete remission at the time of HCT #1, and no disease assessments (including labs and / or physician’s exams) occurred in the reporting period, between HCT #1 and HCT #2 of their tandem transplant, report Not evaluated. However, ensure the best response to infusion and the current disease status are reported consistently.
If the recipient was not in complete remission at the time of HCT #1, and achieved complete remission after HCT #2 of their tandem transplant, report Complete remission and the date which complete remission was achieved.
If the recipient was not in complete remission at the time of HCT #1 and did not achieve complete remission in response to HCT #1 and prior to HCT #2 of their tandem transplant, report Not in complete remission (NCR)

Review the example below for additional information regarding tandem transplants:

Example 1: A recipient with neuroblastoma is not in complete remission prior to transplant, in the Day 100 reporting period the recipient receives a tandem transplant. Between HCT #1 and HCT #2 the only disease assessment performed was a clinical evaluation. In this case either option would be appropriate to answer for the best response: Not evaluated or Not in complete remission (NCR) and No disease detected but incomplete evaluation to establish CR.

Question 41: Compared to the disease status prior to the preparative regimen, what was the best response to infusion? (Include response to any therapy given for post-infusion maintenance, but exclude any therapy given for relapsed, persistent, or progressive disease)

Report the best response to infusion, using the following guidelines:

Continued complete remission (CCR): The recipient was already in CR at the start of the preparative regimen.
Complete remission (CR): The recipient achieved CR post-infusion, excluding unplanned therapy (i.e., therapy given for relapsed, persistent, progressive, decreased / loss of chimerism or consolidation therapy for MRD,).
Not in complete remission: The recipient has not achieved a post-infusion CR.
Not evaluated: This option should be used in two scenarios:
- The recipient’s disease was not evaluated post-infusion
  - This option is rarely used as this would indicate no tests, including radiological, laboratory, or clinical assessments, were performed at any time in the reporting period.
- The recipient never achieved a post-infusion CR and started unplanned therapy (including treatment given for decreased / loss of chimerism. consolidation therapy, or treatment for MRD), in a previous reporting period).

Question 42: Specify disease status if not in complete remission

For recipients Not in complete remission, indicate whether clinical evidence of disease persisted on disease-specific assessments within the reporting period, using the guidelines below:

No disease detected but incomplete evaluation to establish CR: A post-infusion CR was not achieved, and the most recent assessments have shown resolution of disease, but not all assessments required to report CR have been completed or disease assessments were not performed within the reporting period.
Disease detected: The most recent radiological or clinical / hematological assessment detects disease
- Persistence of abnormalities by molecular, cytogenetic, or flow cytometry assessments does not constitute ‘disease detected’ and should not be reported as disease detected for this question.

Review the examples below for additional information:

Example 2: A recipient with multiple myeloma goes to transplant in VGPR, without a bone marrow showing < 5% plasma cells completed prior to transplant. Post-transplant serum and urine electrophoreses and immunofixations are negative. However, no bone marrow biopsy is performed within the 100-day reporting period. In this case, Not in complete remission should be selected for the best response, and No disease detected but incomplete evaluation to evaluation to establish CR for specifying the disease status if not in complete remission data field.
Example 3: A recipient with AML goes to transplant in Primary induction failure. Post-transplant, they recover their blood counts but had circulating blasts noted on peripheral blood differential. They expire due to persistent disease with their last CBC performed on their date of death showing circulating blasts. In this case, Not in complete remission should be selected for the best response to infusion, and Disease detected for specifying the disease status if not in complete remission data field.
Example 4: Like the example above, a recipient with AML goes to transplant in Primary induction failure. They expire on D+11 due to infection and were not engrafted as of that date. Their last CBC showed a WBC of 0.5 × 10⁹/L with no blasts detected on their differential. A bone marrow biopsy was not performed between transplant and the date of death. In this case, Not in complete remission should be selected for the best response to infusion, and No disease detected by incomplete evaluation to establish CR for specifying the disease status if not in complete remission data field.

Question 43: Was the date of best response previously reported?

Indicate whether complete remission was reported in a previous reporting period.

Question 44: Date of best response

Report the date complete remission was achieved in the reporting period. This date should fall after the infusion date but before or on the date of contact for the current reporting period. This should reflect the date of specimen collection or imaging for the latest assessment required to fulfill the clinical / hematologic complete remission criteria for the recipient’s primary disease for infusion.

Disease Assessment at Time of Best Response

The disease assessment questions (i.e., molecular, clonoSEQ®, flow cytometry, cytogenetic, radiologic and clinical / hematologic assessments) refer to disease assessments performed at the time of best response (Date assessed). The following guidelines should be used to determine whether testing was performed at the time of best response:

If the recipient’s best response is Not in complete remission, report the latest assessments performed during the reporting period. If the recipient never achieved a CR and progressed or started treatment for decreased / loss of chimerism, relapse, progression, persistent disease, MRD. or consolidation therapy, report the most recent assessments prior to progression or the start of therapy. Review examples 9 and 10 below.
If the recipient’s best response is Complete remission, report testing performed closest to the date of best response (Date assessed) and within the time windows in the Table 1. Disease Assessment Time Windows table listed below.

Table 1. Disease Assessment Time Windows

Follow-Up Form	Approximate Range
Day 100	+/- 15 days of date of best response (Date assessed)
Six-months	+/- 15 days of date of best response (Date assessed)
Annual	+/- 30 days of date of best response (Date assessed)

Disease Assessment Reporting Scenarios:

Example 5: A recipient receives a transplant on 1/1/2015 for multiple myeloma in Partial remission. Prior to infusion, FISH testing detects an IGH rearrangement associated with the recipient’s primary disease. During the 100-day reporting period, the recipient achieves a Very good partial remission. FISH testing is only performed on 2/1/2015, which is positive for the previously detected IGH rearrangement. The 100-day date of contact is 4/15/2015. In this case, report the recipient was Not in complete remission on the Day 100 Post-TED (2450) Form and report FISH testing was performed on 2/1/2015. When the best response is Not in complete remission report the most recent testing performed during the reporting period (assuming treatment was not started for decreased / loss of chimerism, measurable residual disease, persistent disease, progressive / relapsed, disease during the reporting period – see example 6).
Example 6: A recipient receives a transplant on 1/1/2015 for multiple myeloma in Partial remission. Prior to infusion, FISH testing detects an IGH rearrangement associated with the recipient’s primary disease. During the Day 100 reporting period, the recipient has disease progression and starts treatment on 3/1/2015. FISH testing is performed on 2/1/2015 and 3/15/2015. Both tests are positive for the previously detected IGH rearrangement. The Day 100 date of contact is 4/15/2015. In this case, report the recipient was Not in complete remission on the Day 100 Post-TED (2450) Form and report FISH testing was performed on 2/1/2015. When the best response is Not in complete remission report the most recent testing performed during the reporting period and prior to any unplanned therapy.
- For all subsequent reporting periods, report Not evaluated for the best response to infusion. If unplanned treatment was started in a prior reporting period, the recipient’s best response to the infusion can no longer be assessed.
Example 7: A recipient receives a transplant on 1/1/2015 for AML in Primary induction failure. Prior to infusion, molecular testing confirms the recipient’s disease is FLT3 positive. On 2/1/2015, the recipient achieves a morphologic remission, but FLT3 is not tested at that time. Later, on 2/10/2015, molecular testing is performed and confirms the recipient is FLT3 negative. In this case, the report the recipient achieved a Complete remission on 2/1/2015 on the Day 100 Post-TED (2450) Form and report molecular testing was performed at the time of best response as testing was done within 15 days of 2/1/2015.
Example 8: A recipient receives a transplant on 1/1/2015 for AML in Primary induction failure. Prior to infusion, molecular testing confirms the recipient’s disease is FLT3 positive. On 2/1/2015, the recipient achieves a hematologic remission, but FLT3 is not tested at that time. Later, on 3/1/2015, molecular testing is performed and confirms the recipient is FLT3 negative. In this case, the report the recipient achieved a Complete remission on 2/1/2015 on the Day 100 Post-TED (2450) Form and report no molecular testing was performed at the time of best response as testing was not done within 15 days of 2/1/2015.
Example 9: A recipient receives a transplant on 1/1/2015 for NHL in Stable disease. During the 100 Day reporting period, a PET / CT was performed on Day 60, confirming stable disease but then on Day 95, another PET / CT was performed and showed progression. As a result, therapy for progression began on Day 100. The best response to infusion for the Day 100 reporting period would be reported as Not in complete remission – disease detected and report Yes, radiologic assessments were performed with the Day 60 PET / CT, as this is the most recent scan prior to disease progression.
Example 10: A recipient receives a transplant on 1/1/2020 for IgA Kappa Multiple Myeloma in Stable disease. During the Day 100 reporting period, the first set of myeloma labs on Day 29, 1/30/2020, show Progressive disease. Myeloma labs repeated on Day 60 and Day 100 also showed disease progression. As a result, therapy is planned to be given, starting in the six-month reporting period, on Day 110. The best response to infusion for the Day 100 reporting period would be reported as Not in complete remission – disease detected and report Yes, clinical / hematologic assessments were performed with the Day 100 myeloma labs, as this is the most recent testing in the reporting period. In cases where the first assessment post-infusion shows progression, report the last assessment prior to the start of treatment. If treatment doesn’t start until the next reporting period, report the last assessment in the current reporting period.

Question 45: Was the disease status assessed via molecular markers? (e.g. PCR, NGS)

Molecular assessment involves determining whether a molecular marker for the disease exists in the blood or bone marrow. Molecular assessment is the most sensitive method of detection and can indicate known genetic abnormalities associated with the disease for which the HCT was performed. Molecular assessments include polymerase chain reaction (PCR) amplification to detect single specific disease markers; however, molecular methods are evolving and now include Sanger sequencing and next generation sequencing (e.g., Illumina, Roche 454, Proton / PGM, SOLiD). Molecular marker results identified by FISH or chromosomal microarray assessments should not be reported as molecular testing.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for persistent disease, decreased / loss of chimerism, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy.
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 71: Date assessed

If the best response is Not in complete remission, report the date of the most recent testing performed during the reporting period and prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy, if applicable.

If the best response is Complete remission, report the date of testing performed nearest to the date of best response (within the time windows listed in the Table 1. Disease Assessments Time Windows above) and prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy, if applicable.

Report the date of specimen collection for molecular disease assessment. If the exact date is not known, refer to General Instructions, General Guidelines for Completing Forms for information about reporting partial or unknown dates.

Question 47: Was disease detected?

Report whether the recipient’s primary disease was detected via molecular testing on the reported date. Yes may be reported even when the best response is Not in complete remission – no disease detected but incomplete evaluation to establish CR. For the molecular assessment to be considered positive for disease, the assay must detect several copies of the molecular marker exceeding the threshold for sensitivity of the assay, for a quantitative study. However, the presence of only a single marker among numerous tested is sufficient to indicate disease was detected.

Question 48: Was the disease status assessed via ClonoSEQ®?

ClonoSEQ® assessments measure minimal residual disease (MRD) at the molecular level through proprietary bioinformatics and advancements in next-generation sequencing (NGS). These assessments can be used to identify a recipient’s tumor-associated DNA sequences, predict long term outcomes, assess treatment response, detect early relapse, inform changes to treatment, and monitor a recipient’s disease burden over time.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 49: Date assessed

Report the date of specimen collection for ClonoSEQ® evaluation. If exact date is not known, refer to General Instructions, General Guidelines for Completing Forms for information about reporting partial or unknown dates.

Question 50: Was disease detected?

Report whether the recipient’s primary disease was detected by ClonoSEQ® on the date reported. Yes may be reported even when the best response is Not in complete remission – no disease detected but incomplete evaluation to establish CR.

Question 51: Was the disease status assessed via flow cytometry?

Flow cytometry is a technique that can be performed on blood, bone marrow, or tissue preparations where cell surface markers can be quantified on cellular material. This allows for the detection of abnormal cell populations for some diseases.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 52: Date assessed

Report the date of specimen collection for flow cytometry. If exact date is not known, refer to General Instructions, General Guidelines for Completing Forms for information about reporting partial or unknown dates.

Question 53: Was disease detected?

Report whether the recipient’s primary disease was detected by flow cytometry on the reported date. Report Yes if an abnormal cell population associated with the recipient’s primary disease was detected regardless of the sensitivity of the flow cytometry panel performed; this means an abnormal cell population detected by MRD flow cytometry would be reported in the same way as an abnormal cell population detected by a standard flow cytometry assay.

Yes may be reported even when the best response is Not in complete remission – no disease detected but incomplete evaluation to establish CR.

Question 54: Was the disease status assessed by cytogenetic testing? (karyotyping or FISH)

Cytogenetic studies involve the study of chromosomes, typically through one of two methods: karyotyping or fluorescence in situ hybridization (FISH). Blood, bone marrow, or tissue preparations may be tested by either of these two methods. Karyotyping is both less sensitive and less specific than FISH testing; FISH studies identify only abnormalities detectable by the employed probe set and cannot provide information about the presence or absence of chromosomal abnormalities or markers outside the specific probe set utilized.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 55: Was the disease status assessed via FISH?

FISH XX/XY probe sets are not considered relevant to disease assessment and should not be reported in the disease assessment section. Chromosomal microarrays / chromosomal genomic arrays should be reported as FISH assessments.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 56: Date assessed

Report the date of specimen collection for FISH testing. If exact date is not known, refer to General Instructions, General Guidelines for Completing Forms for information about reporting partial or unknown dates.

Question 57: Was disease detected?

Report whether the recipient’s primary disease was detected by FISH testing on the date reported. Yes may be reported even when the best response is Not in complete remission – no disease detected but incomplete evaluation to establish CR.

Question 58: Was the disease status assessed via karyotyping?

Karyotyping, also referred to as conventional cytogenetics, is performed by culturing cells (growing cells under controlled conditions) until they reach the dividing phase.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 59: Date assessed

Report the date of specimen collection for karyotyping. If exact date is not known, refer to General Instructions, General Guidelines for Completing Forms for information about reporting partial or unknown dates.

Question 60: Was disease detected

Report whether the recipient’s primary disease was detected by karyotyping on the date reported. Do not include clinically insignificant polymorphism, non-clonal and constitutional abnormalities, or chromosomal abnormalities of no known significance as disease detected; this includes anomalies such as age-dependent loss of the chromosome Y.

Yes may be reported even when the best response is Not in complete remission – no disease detected but incomplete evaluation to establish CR.

Question 61: Was the disease status assessed by radiological assessment? (e.g. PET, MRI, CT)

Radiologic assessments are imaging techniques used to assess disease response to transplant, typically for lymphomas or solid tumors, though valuable in some less common presentations of disease, such as leukemia cutis. Imaging techniques used to evaluate disease response typically include PET, CT, or MIBG, but may include x-ray, skeletal survey, or ultrasound in some cases.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 62: Date assessed

If the best response is Not in complete remission – no disease detected but incomplete evaluation to establish CR, report the last assessment performed in the reporting period and prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy, if applicable.

If the best response is Not in complete remission – disease detected, report the most recent radiological testing performed in the reporting period that detects disease and prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy, if applicable. If disease was not detected by this method report the date of the most recent radiological testing performed and prior to progression or any unplanned therapy.

If the best response is Complete remission, report the date of the assessment performed nearest the date of best response (within the time windows listed in the Table 1. Disease Assessments Time Windows above) and prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy, if applicable.

For recipients with lymphomas, solid tumors, or other diseases with imaging criteria for reporting CR, this date may match the date CR was achieved reported in Date assessed for the best response.

If exact date is not known, refer to General Instructions, General Guidelines for Completing Forms for information about reporting partial or unknown dates.

Question 63: Was disease detected?

Report whether the recipient’s primary disease was detected by radiologic assessment on the reported date.

Question 64: Was the disease status assessed by clinical / hematologic assessment?

Clinical / hematologic disease assessments are the least sensitive method of disease detection. Examples include circulating blasts in the bloodstream for AML, and enlargement of a malignant mass for lymphoma or a solid tumor on physical examination. Every recipient who has an evaluation by a physician has a “clinical” assessment. Do not include radiologic or imaging assessments when answering this question.

If the recipient’s best response is Not in complete remission, report Yes if assessments were performed, prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy. Report No if assessments were not performed prior to progression or any unplanned therapy
If the recipient’s best response is Complete remission, report Yes if disease assessments were performed within the time windows listed in the Table 1. Disease Assessments Time Windows above. If testing was not performed within the applicable time window, report No.

Question 65: Date assessed

If the best response is Not in complete remission – disease detected, report the most recent assessment performed in the reporting period that detects disease and prior to progression or treatment for decreased / loss of chimerism, persistent disease, progression, relapse, MRD, or consolidation therapy, if applicable.

This date will likely match the date CR reported in Date assessed for the best response, since complete remission criteria generally requires a clinical or hematologic assessment to confirm.