Q128 – 194: Acute Lymphoblastic Leukemia

!Acute Lymphoblastic Lymphoma
Due to the aggressive nature of precursor T- and precursor B-cell lymphoblastic lymphoma (or lymphoma / leukemia), the primary disease reported for recipients with these malignancies should be Acute lymphoblastic leukemia (T-cell lymphoblastic leukemia / lymphoma or B-lymphoblastic leukemia / lymphoma, NOS).

Acute Lymphoblastic Leukemia (ALL) is a cancer of the white blood cells. It is characterized by the rapid proliferation of abnormal, immature lymphocytes, known as lymphoblasts, in the bone marrow. This accumulation of blasts in the marrow prevents the formation of healthy red blood cells, white blood cells and/or platelets. Normal lymphoblasts develop into B and T lymphocytes that fight infection. In ALL, the leukemic lymphoblasts do not fully develop and therefore cannot fight infection. The symptoms of ALL are caused by the replacement of normal bone marrow with leukemic cells, resulting in a drop in red blood cells, platelets, and normal white blood cells. It is estimated that 80-85% of ALL cases occur in children, with peak incidence of pediatric ALL at age 5. Biologically, adult and pediatric ALL are very different. Pediatric cases are more often characterized by favorable prognostic indicators including a precursor B-cell population, TEL / AML1 fusion gene, and/or hyperdiploidy; adult cases are more often characterized by poor prognostic indicators including a precursor T-cell population and / or BCR / ABL fusion gene.¹

¹ Sallan S. Myths and Lessons from the Adult/Pediatric Interface in Acute Lymphoblastic Leukemia. ASH Education Book, 1st edition. 2006:128-32.

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

Question 128: Specify ALL classification

CIBMTR captures the classification of ALL based on the World Health Organization (WHO) 2022 but also recognizes International Consensus Classification (ICC) 2022 and those classifications are also included, when applicable. Indicate the disease classification at diagnosis.

Due to the aggressive nature of precursor T- and precursor B-cell lymphoblastic lymphoma (or lymphoma / leukemia), the primary disease reported for recipients with these malignancies should be acute lymphoblastic leukemia.

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 B-lymphoblastic leukemia / lymphoma, NOS.

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 ALL had only a bone marrow biopsy and FISH testing for BCR-ABL performed at diagnosis. The bone marrow identified B-lymphoblastic leukemia / lymphoma and FISH was negative for BCR-ABL. Induction began and additional molecular testing completed after starting treatment which identified ETV6-RUNX1 fusion. The disease classification should be reported as B-lymphoblastic leukemia / lymphoma with ETV6::RUNX1 fusion.

!Subsequent Infusion and Predisposing Conditions
If this is a subsequent infusion for the same disease, Did the recipient have a predisposing condition question is disabled.

Question 129: Did the recipient have a predisposing condition?

A predisposing condition is a condition that contributes to the susceptibility of developing leukemia. Therefore, diagnosis of the condition increases the likelihood that the recipient will develop leukemia.

Indicate if the recipient has a documented history of predisposing condition. If there is no history of a predisposing condition or it is not known, indicate No or Unknown, respectively.

Questions 130 – 131: Specify condition

Indicate the recipient’s predisposing condition prior to the diagnosis of leukemia. If the recipient has a documented history of a predisposing condition but it is not listed as an option, select Other condition and specify the condition.

Question 132: Were tyrosine kinase inhibitors given for therapy at any time prior to the start of the preparative regimen / infusion? (e.g., imatinib mesylate, dasatinib, etc.)

Report if the recipient received any tyrosine kinase inhibitor from the diagnosis of ALL to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Examples include, Imatinib mesylate which is also known as Gleevec, Glivec, STI-571, or CGP57148B.

If tyrosine kinase inhibitors were not given at any time prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy), or is unknown, report No.

Questions 133 – 134: Specify tyrosine kinase inhibitors (check all that apply)

Select all tyrosine kinase inhibitors given prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If a tyrosine kinase inhibitor was given but is not listed as an option on the form, select Other and specify the drug.

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

*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 ALL.

Question 109: 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 cytogenetic studies were obtained, select Yes. If no cytogenetic studies were obtained, or it is unknown if chromosome studies were performed, select No or Unknown, respectively.

Table 1. Examples of ALL Cytogenetic Findings Categorized by Prognosis (Adult Precursor B-cell ALL)

Favorable	Intermediate	Poor	Very Poor
High hyperdiploidy (51-65 chromosomes)	Normal 11q abnormalities del(6q) del(17p) del(9p) del(12p) -13/del(13q) t(14q32) t(10;14) Low hyperdiploidy (47-50 chromosomes) Tetraploidy (> 80 chromosomes)	-7/del(7p) +8 11q23 abnormalities/MLL t(1;19) t(17;19) t(5;14) t(9;22)	≥ 5 abnormalities t(4;11) t(8;14)

Pullarkat V, Slovak ML, Kopecky KJ, Forman SJ, Appelbaum FR. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008;111(5):2563-72.

Question 136: 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 137: Results of tests

Specify if FISH abnormalities were identified at diagnosis.

!International System for Human Cytogenetic Nomenclature (ISCN) Compatible String
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled 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 138 – 141: 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 142: 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 143: 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 144 – 147: 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 Markers Results
Questions capturing molecular marker results are intended to capture molecular abnormalities identified by molecular methods. Additional testing methods, such as FISH or chromosomal microarray, may identify molecular marker results but should not be reported in the molecular section(s) of the Pre-TED Disease Classification (2402) Form. Abnormalities identified by karyotyping, FISH, or chromosomal microarray should only be reported in the cytogenetic section of the Pre-TED 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 148 – 149: Specify any positive molecular marker(s) identified (check all that apply)

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).

Indicate if any other positive molecular markers, including variance of unknown significant markers, were detected at diagnosis.

If a molecular marker was positive, but not listed as an option, select Other 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 150: 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 151: 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 152: Results of tests

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

!International System for Human Cytogenetic Nomenclature (ISCN) Compatible String
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled 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 153 – 156: 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 157: 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 158: Results of tests

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

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 159 – 162: 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 Markers Results
Questions capturing molecular marker results are intended to capture molecular abnormalities identified by molecular methods. Additional testing methods, such as FISH or chromosomal microarray, may identify molecular marker results but should not be reported in the molecular section(s) of the Pre-TED Disease Classification (2402) Form. Abnormalities identified by karyotyping, FISH, or chromosomal microarray should only be reported in the cytogenetic section of the Pre-TED 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 163 – 164: 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).

Indicate if any positive molecular markers, 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 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 between diagnosis and the last evaluation 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 165: 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 166: 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 167: 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 168 – 171: Specify FISH 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 FISH 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.

Question 172: 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 173: Results of tests

Specify if abnormalities were 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).

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 174 – 177: 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 (or infusion if no preparative regimen) 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 Markers Results
Questions capturing molecular marker results are intended to capture molecular abnormalities identified by molecular methods. Additional testing methods, such as FISH or chromosomal microarray, may identify molecular marker results but should not be reported in the molecular section(s) of the Pre-TED Disease Classification (2402) Form. Abnormalities identified by karyotyping, FISH, or chromosomal microarray should only be reported in the cytogenetic section of the Pre-TED 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 178 – 179: Specify any positive molecular marker(s) identified (check all that apply)

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).

Indicate if any other positive molecular markers, 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 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 the last evaluation report None. This option should also be selected if other molecular markers were tested and resulted as negative.

Question 180: Did the recipient have central nervous system leukemia at any time prior to the start of the preparative regimen / infusion?

Central nervous system (CNS) involvement by leukemia may be detected via pathologic examination of cerebrospinal fluid or tumor tissue as well as by radiological examinations (e.g., MRI, PET/CT, MIBG, etc.).

Specify if the recipient had documented involvement of ALL in the CNS at any time prior to the start of the preparative regimen (or infusion if no preparative regimen).

If all CNS testing was negative since the time of diagnosis, report No.

If testing for CNS involvement was not performed from the time of diagnosis to the time of infusion, report Unknown.

Question 181: 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 the ALL Response Criteria section for definitions of each response. For reporting purposes, consider complete remission with incomplete hematologic recovery (CRi) a complete remission (CR1, CR2, or CR3+).

If the recipient did not receive any treatment for ALL from the time of diagnosis to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy report No treatment.

*Number of Induction Cycles
The intent of this question is to capture the number of induction cycles required to achieve the first CR (including CRi) the recipient’s disease history, regardless of if there have been prior relapses or infusions.

Question 182: How many cycles of induction therapy were required to achieve CR? (includes CRi)

Chemotherapy is initially given as induction therapy intended to bring the disease into remission. Recipients usually have one to two cycles of induction therapy. An example of a common induction therapy for precursor B-cell ALL in children with higher-risk prognostic indicators is a combination of vincristine, prednisone, an anthracycline, and L-asparaginase given over 4-6 weeks. Patients with a rapid response, defined as < 5% blasts within 7 to 14 days of starting induction, have improved outcomes.¹

¹ Gaynon PS, Desai AA, Bostrom BC, et al. Early response to therapy and outcome in childhood acute lymphoblastic leukemia: a review. Cancer. 1997;80(9):1717-26.

The second phase of chemotherapy is known as consolidation therapy. The goal of consolidation therapy is to destroy any remaining leukemia cells and sustain remission. An example of a consolidation therapy for precursor B-cell ALL in children is daunorubicin and cytarabine; several studies support the use of consolidation therapy in ALL.

Maintenance therapy typically involves daily doses of mercaptopurine and weekly doses of methotrexate. Treatment continues for 2-3 years for most children with ALL. Treatment may also be administered for relapsed disease. Much like induction therapy, treatment for relapse is intended to bring the disease back into remission. Systemic therapeutic agents used to induce remission following relapse often differ from those used during initial induction, since the disease is considered high-risk with a poor prognosis and is often resistant to many of the agents used earlier in the disease course. Allogeneic HCT is often considered the only potential “cure” for relapsed disease, if the patient has not already been transplanted.

If the pre-infusion disease status is CR1, report the number of cycles of induction therapy that were required to achieve the first CR.

Question 183: Date CR first achieved

This question is intended to capture the date when the first clinical / hematologic CR was achieved.

Report the date when the first CR was achieved. This should be the earliest date all international working group criteria for CR were met. Report the date the sample was collected for pathologic evaluation (i.e., bone marrow biopsy) or blood / serum assessments (i.e., CBC, peripheral blood smear).

If only CRi was achieved (which is reported as CR), report the first date when the CRi criteria was met.

If the exact date is not known, use the process for reporting partial or unknown dates as described in General Instructions, General Guidelines for Completing Forms.

Question 184: Date of most recent relapse

Enter the date of the most recent relapse prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). If reporting a pathological evaluation (i.e., bone marrow) or blood / serum assessment (i.e., CBC, peripheral blood smear), enter the date the sample was collected.

If extramedullary disease was detected by radiographic examination (i.e.., X-ray, CT scan, MRI scan, PET scan), enter the date the imaging took place.

If the physician determines evidence of relapse following a clinical assessment during an office visit, report the date of assessment.

If the exact date is not known, use the process for reporting partial or unknown dates as described in General Instructions, General Guidelines for Completing Forms.

Question 185: Specify method(s) that was used to assess measurable residual disease status (check all that apply) (at infusion)

Specify the method(s) how the minimal residual status was assessed at the last evaluation prior to the start the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Select all that apply.

• FISH: A sensitive technique that assesses a large number of cells. This technique uses special probes that recognize and bind to fragments of DNA. These probes are mixed with cells from the recipient’s blood or bone marrow. A fluorescent “tag” is then used to visualize the binding of the probe to the diseased cells.
• Karyotype: A technique performed by culturing cells (growing cells under controlled conditions) until they reach the dividing phase. Techniques are then performed to visualize the chromosomes during cell division so that various bands and reconfigurations can be seen. Banding pattern differentiation and chromosomal reconfiguration demonstrate evidence of disease.
• Flow cytometry: A method of analyzing peripheral blood, bone marrow, or tissue preparations for multiple unique cell characteristics. Its primary clinical purpose in the setting of leukemias is to quantify blasts in the peripheral blood or bone marrow, or to identify unique cell populations through immunophenotyping. Flow cytometry assessment may also be referred to as “MRD,” or minimal residual disease, testing.
• PCR: Polymerase chain reaction (PCR) amplification is a molecular assessment used to detect single specific disease markers. Testing for molecular markers is often performed using PCR based methods. Once a marker has been identified, this method can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue.
• NGS: Next-generation sequencing (NGS), also known as massive parallel sequencing is another molecular assessment which is used to determine the order of nucleotides in a genome.
• ClonoSEQ®: A type of measurable residual disease testing, which identifies and quantifies the number of cancer cells.²

If testing for measurable residual status was not completed at the last evaluation, select Not assessed.

² clonoSEQ® by Adaptive Biotechnologies. (n.d.). ClonoSEQ. https://www.clonoseq.com/hcp-home/?gad_source=1&gclid=CjwKCAjwuMC2BhA7EiwAmJKRrCLoK5aZwMM5jAHZu3o3GBCYmIAK4Z0-OSyM9up8GkCWAw7-J1O9BRoCShYQAvD_BwE&utm_source=google&utm_medium=cpc&utm_campaign=hcp_priority&utm_medium=cpc&utm_campaign=hcp_priority

Question 186: Was measurable residual disease detected by FISH? (at infusion)

Indicate if measurable residual disease was 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 the results are not clear, seek physician clarification to determine if measurable residual disease was detected by FISH at the last evaluation.

Question 187: Was measurable residual disease detected by karyotyping assay? (at infusion)

Indicate if measurable residual disease was 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).

If the results are not clear, seek physician clarification to determine if measurable residual disease was detected by karyotype at the last evaluation.

Question 188: Was measurable residual disease detected by flow cytometry? (at infusion)

Indicate if measurable residual disease was detected by flow cytometry at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the results are not clear, seek physician clarification to determine if minimal residual disease was detected by flow cytometry at the last evaluation.

!Original vs Aberrant Phenotype
The original vs aberrant phenotype questions are currently disabled.

Questions 189 – 191: Which leukemia phenotype was used for detection? (check all that apply) (at infusion)

Specify which leukemia phenotype was used for detection. Select all that apply.

If the Original leukemia immunophenotype was used, specify the lower limit of detection, and then indicate if minimal residual disease was detected by flow cytometry at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If an Aberrant phenotype was used, specify the lower limit of, and then indicate if minimal residual disease was detected by flow cytometry at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the results are not clear, seek physician clarification to determine if minimal residual disease was detected by flow cytometry at the last evaluation.

Question 192: Was measurable residual disease detected by PCR? (at infusion)

Indicate if measurable residual disease was detected by PCR at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the results are not clear, seek physician clarification to determine if measurable residual disease was detected by PCR at the last evaluation assay at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

Question 193: Was minimal residual disease detected by NGS? (at infusion)

Indicate if minimal residual disease was detected by NGS at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the results are not clear, seek physician clarification to determine if minimal residual disease was detected by NGS at the last evaluation assay at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

Question 194: Was minimal residual disease detected by ClonoSEQ? (at infusion)

Indicate if minimal residual disease was detected by ClonoSEQ® at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the results are not clear, seek physician clarification to determine if minimal residual disease was detected by ClonoSEQ® at the last evaluation assay at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

Section Updates:

Question Number	Date of Change	Add/Remove/Modify	Description	Reasoning (If applicable)
.	.	.	.	.

Copyright © 2004-2025 The Medical College of Wisconsin, Inc. and NMDP. All Rights Reserved.
CIBMTR® (Center for International Blood and Marrow Transplant Research) is a research collaboration between the Medical College of Wisconsin and NMDP.