Q195 – 301: Acute Leukemias of Mixed or Ambiguous Lineage

Question 1: Date of diagnosis of primary disease for infusion

Report the date of the first pathological diagnosis (e.g., bone marrow or tissue biopsy) of the disease. Enter the date the sample was collected for examination. If the diagnosis was determined at an outside center, and no documentation of a pathological or laboratory assessment is available, the dictated date of diagnosis within a physician note may be reported. Do not report the date symptoms first appeared.

If the exact diagnosis date is not known, use the process described in General Instructions, Guidelines for Completing Forms

Questions 195: Specify acute leukemias of mixed or ambiguous lineage

CIBMTR captures the classification of ambiguous lineage and other myeloid neoplasms based on the World Health Organization (WHO) 2022. Report the disease classification at diagnosis.

Report the most specific entity that applies to the recipient. If the cytogenetic or molecular abnormalities present are listed on the form, check the sub-type rather than Acute leukemia of ambiguous lineage, NOS.

• Acute undifferentiated leukemia is a type of AML characterized by immature predominating cells that cannot be classified.
• Biphenotypic, bilineage, hybrid, or mixed leukemias have characteristics representative of both myeloid and lymphoid lineages.

In some cases, disease specific cytogenetic and / or molecular abnormalities are not identified at the initial diagnosis but identified at some point prior to the infusion, report the most disease specific entity. Review the example below for further clarification:

• Example 1: A recipient diagnosed with mixed-phenotype acute leukemia had only a bone marrow biopsy and FISH testing for BCR-ABL performed at diagnosis. The bone marrow identified mixed-phenotype acute leukemia and FISH was negative for BCR-ABL. Induction began and additional molecular testing completed after starting treatment which identified KMT2A rearrangement. The disease classification should be reported as Mixed phenotype acute leukemia with KMT2A rearrangement.

!Subsequent Infusion and At Diagnosis Time Point
If this is a subsequent infusion for the same disease, the at diagnosis time point is disable.

*At Diagnosis Assessments
Assessments performed at diagnosis, last evaluation and in between questions ask about testing performed at different time points prior to infusion. For reporting purposes, at diagnosis time point is defined as any testing performed closest to (before or after) the date of diagnosis and prior to the start of any treatment for acute leukemias of mixed or ambiguous lineage.

Question 196: Were cytogenetics tested (conventional or FISH)? (at diagnosis)

Cytogenetics is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of known chromosomal abnormalities that reflect the recipient’s disease.

Testing methods include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C: Cytogenetics.

Indicate if cytogenetic studies were obtained at diagnosis. If no cytogenetic studies were obtained, or it is unknown if chromosome studies were performed, select No or Unknown, respectively.

Question 197: Were cytogenetics tested via FISH? (at diagnosis)

Specify if FISH studies were performed at diagnosis. If FISH studies were not performed at diagnosis or FISH samples were inadequate or the result ‘failed,’ report No.

If it is not known if it was performed, report Unknown.

Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.

Question 198: Results of tests

Specify if FISH abnormalities were identified at diagnosis.

!International System for Human Cytogenetic Nomenclature (ISCN) for FISH
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled for FISH and cannot be answered at this time.

*Submitting FISH Documentation
CIBMTR strongly encourages attaching the FISH report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 199 – 202: Specify FISH abnormalities (at diagnosis)

Report the ISCN compatible string, if the data field is enabled. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select the number of abnormalities detected by FISH at diagnosis and select all abnormalities detected.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

Question 203: Were cytogenetics tested via karyotyping? (at diagnosis)

Specify if karyotyping studies were performed at diagnosis. Report Yes even if there were no evaluable metaphase cells / failed (these results will be specified below).

If karyotyping studies were not performed at diagnosis or it is unknown if performed, report No or Unknown, respectively.

Question 204: Results of tests

Specify if abnormalities were detected by karyotype at diagnosis.

If karyotyping failed or the sample was inadequate, select No evaluable metaphases.

*Submitting Karyotype Documentation
CIBMTR strongly encourages attaching the karyotype report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 205 – 208: Specify karyotype abnormalities (at diagnosis)

Report the ISCN compatible string, if applicable. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select the number of abnormalities detected by karyotype at diagnosis and select all abnormalities detected.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

*Molecular Marker Results
Questions capturing molecular marker results are intended to capture molecular abnormalities identified by molecular methods. Additional testing methods, such as FISH and chromosomal microarray, may identify molecular marker results but should not be reported in the molecular section(s) of the Disease Classification (2402) form. Abnormalities identified by karyotyping, FISH, or chromosomal microarray should only be reported in the cytogenetic section of the Disease Classification (2402) form.

*Submitting Molecular Marker Documentation
CIBMTR strongly encourages attaching the molecular report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 209 – 228: Specify molecular marker results (at diagnosis)

Molecular markers for disease refer to specific genetic sequences which are believed to be associated with the recipient’s primary disease. Testing for these sequences is often performed using PCR based methods. Once a marker has been identified, these methods can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue. 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).

The molecular markers listed below are ELN AML markers and prognostic of leukemia. Due to the importance of these markers, it is necessary to know if the marker was positive, negative, or not assessed.

• ASXL1
• BCOR
• BCR::ABL1
• CEBPA
• DDX41
• EZH2
• FLT3-ITD
• GATA2
• NPM1
• RUNX1
• SF3B1
• SRSF2
• STAG2
• TP53
• U2AF1
• ZRSR2

For each molecular marker, specify if the marker was Positive or Negative at diagnosis and answer and additional questions. If the molecular marker was not assessed at diagnosis, select Not done.

If CEBPA was Positive, specify the CEBPA variant mutation and allelic expression. If the variant mutation is not documented, report the mutation as Unknown. If the allelic expression is not documented, confirm with the lab if this information can be determined prior to reporting Unknown.

If FLT3-ITD was Positive, specify the allelic ratio, if known. If there are multiple allelic ratios available for the at diagnosis time point, report the highest allelic ratio. If the allelic ratio is not documented, confirm with the lab if this information can be determined prior to reporting Unknown.

The allelic ratio data field is intended to capture the ratio of the FLT3-ITD mutation. This data field does not collect the allelic frequency, the allelic frequency is used to calculate the allelic ratio. The FLT-3 ITD allelic ratio (or signal ratio) compares the number of ITD-mutated alleles to the number of wild-type (normal) alleles. If the allele frequency was assessed, the ITD-mutated allele frequency will be documented on the molecular report; however, the wild-type allele frequency will need to be calculated. To determine the wild-type allele frequency, subtract the ITD-mutated allele frequency from 1 (or 100.0%). After determining the wild-type allele frequency, the allelic ratio can be assessed. To calculate the allelic ratio, divide the mutant allele frequency by the wild-type (normal) allele frequency. Review example 2 below for more information:

• Example 2:

• ITD variant allele frequency: 1.14% (0.0114)
  • As documented in the molecular report
• Wild-type allele frequency: 98.86% (0.9886)
  • Determined by subtraction 1.14% from 100.0%
• FLT3-ITD allelic ratio: 0.0114 / 0.9886 = 0.0115

Report the FLT3-ITD allelic ratio as 0.01

*Submitting Molecular Marker Documentation
CIBMTR strongly encourages attaching the molecular report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 229 – 230: Specify any other positive molecular marker(s) identified (check all that apply)

Indicate if any other positive molecular markers (excluding the ELN AML molecular markers listed above), including variance of unknown significant markers, were detected at diagnosis.

If a molecular marker was detected, but not listed as an option, select Other molecular marker and specify the abnormality.

If molecular markers were not detected at diagnosis, the sample failed, testing was not completed or unknown if completed at diagnosis report None. This option should also be selected if other molecular markers were tested and resulted as negative.

*In Between Diagnosis and Last Evaluation Assessments
Assessments performed at diagnosis, last evaluation and in between questions ask about testing performed at different time points prior to infusion. For reporting purposes, the in between time point is defined as any pre-infusion testing which cannot be reported as part of at diagnosis or last evaluation. For subsequent infusions, any testing performed after the prior infusion until the last evaluation for the current infusion should be reported here. For example, if relapse / progression occurred after the previous infusion but prior to last evaluation of the current infusion, report the relapse / progression abnormalities at the in between time point.

Question 231: Were cytogenetics tested (karyotyping or FISH)? (between diagnosis and last evaluation)

Cytogenetics is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of known chromosomal abnormalities that reflect the recipient’s disease.

Testing methods include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C: Cytogenetics.

Indicate if cytogenetic studies were performed between diagnosis and the last evaluation. If cytogenetic studies were not obtained at this time point or it is not known whether chromosome studies were performed, indicate No.

Question 232: Were cytogenetics tested via FISH? (between diagnosis and last evaluation)

Specify if FISH studies were performed between diagnosis and the last evaluation. If FISH studies were not performed at this time point, FISH sample was inadequate, the result ‘failed,’ or it is unknown if performed, report No.

Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.

Question 233: Results of tests

Specify if FISH abnormalities were identified between diagnosis and the last evaluation.

!International System for Human Cytogenetic Nomenclature (ISCN) for FISH
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled for FISH and cannot be answered at this time.

*Submitting FISH Documentation
CIBMTR strongly encourages attaching the FISH report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 234 – 237: Specify FISH abnormalities (between diagnosis and last evaluation)

Report the ISCN compatible string, if the data field is enabled. If reporting the ISCN compatible string and multiple FISH assessments were completed between diagnosis and the last evaluation, add a separate instance of the ISCN compatible string to report each FISH ISCN compatible string.

Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select the number of abnormalities detected by FISH between diagnosis and the last evaluation and select all abnormalities detected.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

Question 238: Were cytogenetics tested via karyotyping? (between diagnosis and last evaluation)

Specify if karyotyping studies were performed between diagnosis and the last evaluation. Report Yes even if there were no evaluable metaphase cells (these results will be specified below).

If karyotyping studies were not performed at this time point or it is unknown if performed, report No.

Question 239: Results of tests

Specify if abnormalities were detected by karyotype between diagnosis and the last evaluation.

If karyotyping failed, select No evaluable metaphases.

*Submitting Karyotype Documentation
CIBMTR strongly encourages attaching the karyotype report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 240 – 243: Specify karyotype abnormalities (between diagnosis and last evaluation)

Report the ISCN compatible string, if applicable. If reporting the ISCN compatible string and multiple karyotype studies were completed between diagnosis and the last evaluation, add a separate instance of the ISCN compatible string to report each karyotype ISCN compatible string.

Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select the number of abnormalities detected by karyotype between diagnosis and the last evaluation and select all abnormalities detected.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

*Molecular Marker Results
Questions capturing molecular marker results are intended to capture molecular abnormalities identified by molecular methods. Additional testing methods, such as FISH and chromosomal microarray, may identify molecular marker results but should not be reported in the molecular section(s) of the Disease Classification (2402) form. Abnormalities identified by karyotyping, FISH, or chromosomal microarray should only be reported in the cytogenetic section of the Disease Classification (2402) form.

*Submitting Molecular Marker Documentation
CIBMTR strongly encourages attaching the molecular report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 244 – 263: Specify molecular marker results (between diagnosis and last evaluation)

Molecular markers for disease refer to specific genetic sequences which are believed to be associated with the recipient’s primary disease. Testing for these sequences is often performed using PCR based methods. Once a marker has been identified, these methods can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue. 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).

The molecular markers listed below are ELN AML markers and prognostic of leukemia. Due to the importance of these markers, it is necessary to know if the marker was positive, negative, or not assessed.

Questions 244 – 263: Specify molecular marker results (between diagnosis and last evaluation)

Molecular markers for disease refer to specific genetic sequences which are believed to be associated with the recipient’s primary disease. Testing for these sequences is often performed using PCR based methods. Once a marker has been identified, these methods can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue. 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).

The molecular markers listed below are ELN AML markers and prognostic of leukemia. Due to the importance of these markers, it is necessary to know if the marker was positive, negative, or not assessed.

• ASXL1
• BCOR
• BCR::ABL1
• CEBPA
• DDX41
• EZH2
• FLT3-ITD
• GATA2
• NPM1
• RUNX1
• SF3B1
• SRSF2
• STAG2
• TP53
• U2AF1
• ZRSR2

For each molecular marker, specify if the marker was Positive or Negative between diagnosis and the last evaluation and answer additional questions. If the molecular marker was not assessed between diagnosis and the last evaluation, select Not done.

If CEBPA was Positive, specify the CEBPA variant mutation and allelic expression. If the variant mutation is not documented, report the mutation as Unknown. If the allelic expression is not documented, confirm with the lab if this information can be determined prior to reporting Unknown.

If FLT3-ITD was Positive, specify the allelic ratio, if known. If there are multiple allelic ratios available for the in between time point, report the lowest allelic ratio. If the allelic ratio is not documented, confirm with the lab if this information can be determined prior to reporting Unknown.

The allelic ratio data field is intended to capture the ratio of the FLT3-ITD mutation. This data field does not collect the allelic frequency; the allelic frequency is used to calculate the allelic ratio. The FLT-3 ITD allelic ratio (or signal ratio) compares the number of ITD-mutated alleles to the number of wild-type (normal) alleles. If the allele frequency was assessed, the ITD-mutated allele frequency will be documented on the molecular report; however, the wild-type allele frequency will need to be calculated. To determine the wild-type allele frequency, subtract the ITD-mutated allele frequency from 1 (or 100.0%). After determining the wild-type allele frequency, the allelic ratio can be assessed. To calculate the allelic ratio, divide the mutant allele frequency by the wild-type (normal) allele frequency. Review example 3 below for more information:

• Example 3:

• ITD variant allele frequency: 1.14% (0.0114)
  • As documented in the molecular report
• Wild-type allele frequency: 98.86% (0.9886)
  • Determined by subtraction 1.14% from 100.0%
• FLT3-ITD allelic ratio: 0.0114 / 0.9886 = 0.0115

Report the FLT3-ITD allelic ratio as 0.01

*Submitting Molecular Marker Documentation
CIBMTR strongly encourages attaching the molecular report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 264 – 265: Specify any other positive molecular marker(s) identified (check all that apply)

Indicate if any other positive molecular markers (excluding the ELN AML molecular markers listed above), including variance of unknown significant markers, were detected between diagnosis and the last evaluation.

If a molecular marker was detected, but not listed as an option, select Other molecular marker and specify the abnormality.

If molecular markers were not detected between diagnosis and the last evaluation, the sample failed, testing was not completed or unknown if completed at diagnosis report None. This option should also be selected if other molecular markers were tested and resulted as negative.

*Last Evaluation Assessments
Assessments performed at diagnosis, last evaluation and in between questions ask about testing performed at different time points prior to infusion. For reporting purposes, the last evaluation time point is defined as the most recent testing performed during the recipient’s work-up for infusion. Assessments performed during the last line of therapy or after the last line of therapy may be reported. If multiple assessments were performed, report the most recent. If additional therapy was given after the last assessment, do not report the test.

Question 266: Were cytogenetics tested (karyotyping or FISH)? (at last evaluation)

Cytogenetics is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of known chromosomal abnormalities that reflect the recipient’s disease.

Testing methods include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C: Cytogenetics.

Indicate if cytogenetic studies were at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). If cytogenetic studies were not obtained at this time point or it is not known whether chromosome studies were performed, indicate No.

Question 267: Were cytogenetics tested via FISH? (at last evaluation)

Specify if FISH studies were performed at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). If FISH studies were not performed at this time point, FISH sample was inadequate, the result ‘failed,’ or it is unknown if performed, report No.

Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.

Question 268: Results of tests

Specify if FISH abnormalities were identified at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

!International System for Human Cytogenetic Nomenclature (ISCN) for FISH
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled for FISH and cannot be answered at this time.

*Submitting FISH Documentation
CIBMTR strongly encourages attaching the FISH report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 269 – 272: Specify FISH abnormalities (at last evaluation)

Report the ISCN compatible string, if the data field is enabled. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select the number of abnormalities detected by FISH at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

Question 273: Were cytogenetics tested via karyotyping? (at last evaluation)

Specify if karyotyping studies were performed at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Report Yes even if there were no evaluable metaphase cells (these results will be specified below).

If karyotyping studies were not performed at this time point or it is unknown if performed, report No.

Question 274: Results of tests

Specify if abnormalities were detected by karyotype at the last evaluation prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If karyotyping failed or the sample was inadequate, select No evaluable metaphases.

*Submitting Karyotype Documentation
CIBMTR strongly encourages attaching the karyotype report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 275 – 278: Specify karyotype abnormalities (at last evaluation)

Report the ISCN compatible string, if applicable. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select the number of abnormalities detected by karyotype at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy) and select all abnormalities detected.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

*Molecular Marker Results
Questions capturing molecular marker results are intended to capture molecular abnormalities identified by molecular methods. Additional testing methods, such as FISH and chromosomal microarray, may identify molecular marker results but should not be reported in the molecular section(s) of the Disease Classification (2402) form. Abnormalities identified by karyotyping, FISH, or chromosomal microarray should only be reported in the cytogenetic section of the Disease Classification (2402) form.

*Submitting Molecular Marker Documentation
CIBMTR strongly encourages attaching the molecular report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 279 – 298: Specify molecular marker results_ (at last evaluation)_

Molecular markers for disease refer to specific genetic sequences which are believed to be associated with the recipient’s primary disease. Testing for these sequences is often performed using PCR based methods. Once a marker has been identified, these methods can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue. 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).

The molecular markers listed below are ELN AML markers and prognostic of leukemia. Due to the importance of these markers, it is necessary to know if the marker was positive, negative, or not assessed.

• ASXL1
• BCOR
• BCR::ABL1
• CEBPA
• DDX41
• EZH2
• FLT3-ITD
• GATA2
• NPM1
• RUNX1
• SF3B1
• SRSF2
• STAG2
• TP53
• U2AF1
• ZRSR2

For each molecular marker, specify if the marker was Positive or Negative at the last evaluation and answer additional questions. If the molecular marker was not assessed at the last evaluation, select Not done.

If CEBPA was Positive, specify the CEBPA variant mutation and allelic expression. If the variant mutation is not documented, report the mutation as Unknown. If the allelic expression is not documented, confirm with the lab if this information can be determined prior to reporting Unknown.

If FLT3-ITD was Positive, specify the allelic ratio at the last evaluation, if known. If the allelic ratio is not documented, confirm with the lab if this information can be determined prior to reporting Unknown.

The allelic ratio data field is intended to capture the ratio of the FLT3-ITD mutation. This data field does not collect the allelic frequency; the allelic frequency is used to calculate the allelic ratio. The FLT-3 ITD allelic ratio (or signal ratio) compares the number of ITD-mutated alleles to the number of wild-type (normal) alleles. If the allele frequency was assessed, the ITD-mutated allele frequency will be documented on the molecular report; however, the wild-type allele frequency will need to be calculated. To determine the wild-type allele frequency, subtract the ITD-mutated allele frequency from 1 (or 100.0%). After determining the wild-type allele frequency, the allelic ratio can be assessed. To calculate the allelic ratio, divide the mutant allele frequency by the wild-type (normal) allele frequency. Review example 4 below for more information:

• Example 4:

• ITD variant allele frequency: 1.14% (0.0114)
  • As documented in the molecular report
• Wild-type allele frequency: 98.86% (0.9886)
  • Determined by subtraction 1.14% from 100.0%
• FLT3-ITD allelic ratio: 0.0114 / 0.9886 = 0.0115

Report the FLT3-ITD allelic ratio as 0.01

*Submitting Molecular Marker Documentation
CIBMTR strongly encourages attaching the molecular report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 299 – 300: Specify any other positive molecular marker(s) identified (check all that apply)

Indicate if any other positive molecular markers (excluding the ELN AML molecular markers listed above), including variance of unknown significant markers, were detected at the last evaluation.

If a molecular marker was detected, but not listed as an option, select Other molecular marker and specify the abnormality.

If molecular markers were not detected at the last evaluation, the sample failed, testing was not completed or unknown if completed at diagnosis report None. This option should also be selected if other molecular markers were tested and resulted as negative.,

Question 301: What was the disease status? (based on hematological test results) (at infusion)

This data field is intended to capture the pre-infusion disease status, based on clinical / hematologic and / or radiologic (if applicable) assessments. Refer to table 1 below for definitions of each response.

Table 1. Disease Status of Acute Leukemia

Table 1. Disease Status of Acute Leukemia

Disease Status	Definition
Primary Induction Failure (PIF)	The patient received treatment for acute leukemia but never achieved complete remission at any time. PIF is not limited by the number of unsuccessful treatments; this disease status only applies to recipients who have never been in complete remission.
Complete Remission (CR)	Hematologic complete remission is defined as meeting all of the following response criteria for at least four weeks. < 5% blasts in the bone marrow Normal maturation of all cellular components in the bone marrow No extramedullary disease (e.g., CNS, soft tissue disease) Neutrophils ≥ 1,000/µL Platelets ≥ 100,000/µL Transfusion independent In some cases, there may not be a four-week interval between completion of therapy and the pre-transplant disease assessment; in this case, CR should still be reported as the status at transplant, since it represents the “best assessment” prior to HCT. This is an exception to the criteria that CR be durable beyond four weeks; the pre-transplant disease status should not be changed based on early relapse or disease assessment post-transplant. Include recipients with persistent cytogenetic or molecular abnormalities who meet the above CR criteria for hematologic CR. Include recipients meeting the above CR criteria regardless of how many courses of therapy were required to achieve CR. The number of this complete remission can be determined by using the following guidelines: 1st CR: no prior relapse 2nd CR: one prior relapse 3rd or higher: two or more prior relapses
Relapse (REL)	Relapse is defined as the recurrence of disease after CR, meeting the following criteria: ≥ 5% blasts in the marrow or peripheral blood Extramedullary disease Reappearance of cytogenetic and/or molecular abnormalities associated with diagnosis that, in the judgment of a physician, are at a level representing relapse Disease presence determined by a physician upon clinical assessment The number of this relapse can be determined by using the following guidelines: 1st relapse: one prior CR 2nd relapse: two prior CRs 3rd or higher: three or more CRs Do not include a partial response (PR) when determining number of relapse. Recipients who achieve a PR to treatment should be classified as either PIF or relapse; PR in acute leukemia is generally of short duration and is unlikely to predict clinical benefit.
No Treatment	The recipient was diagnosed with acute leukemia and never received therapeutic agents; include patients who have received only supportive therapy, including growth factors and/or blood transfusions.

Section Updates:

Question Number	Date of Change	Add/Remove/Modify	Description	Reasoning (If applicable)
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CIBMTR® (Center for International Blood and Marrow Transplant Research) is a research collaboration between the Medical College of Wisconsin and NMDP.