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 HCT / cellular therapy
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 104: 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.
If the cytogenetic or molecular abnormalities present are listed on the Pre-TED form, check the sub-type rather than B-cell ALL, NOS option.
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*.
Question 105: 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. If the recipient has a documented history of a predisposing condition, select Yes. If there is no history of a predisposing condition or if predisposition is unknown, indicate No or Unknown.
Question 106 – 107: 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.
- Aplastic anemia is an acquired or inherited disorder of the bone marrow characterized by pancytopenia, where the body does not produce a sufficient number of new blood cells. Inherited aplastic anemias include Fanconi anemia (specified separately on this form), Shwachman-Diamond anemia, Diamond-Blackfan anemia, and dyskeratosis congenita. Acquired aplastic anemia may develop after exposures to toxins, radiation, and/or chemotherapy, or may result from an autoimmune condition such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). The majority of presenting signs and symptoms in aplastic anemia patients are directly related to their low blood counts and include fatigue, dizziness, shortness of breath, abnormal bleeding or bruising, and frequent infections.
- Bloom syndrome is an autosomal recessive genetic disorder characterized by excessive chromosome breakage and corresponding rearrangements, proportional dwarfism, and sun sensitivity. The chromosomal instability seen in Bloom syndrome is generally assumed to be responsible for these individuals’ predisposition to malignancy.
- Down syndrome is also a chromosomal disorder (trisomy 21). It is characterized by an additional chromosome 21. Down syndrome patients exhibit a particular set of facial characteristics, growth deficiency, and cognitive impairment. Although Down syndrome patients have a reduced risk of developing many common malignancies, they have an increased risk of developing leukemia.
- Fanconi anemia is a rare genetic blood disorder that prevents the body from producing a sufficient number of new blood cells to function properly. Abnormal blood cells may also be produced. These patients are short in stature, exhibit skeletal anomalies, and have an increased risk of developing solid tumors and leukemias.
Question 108: Were tyrosine kinase inhibitors (i.e., imatinib mestylate) given for pre-HCT therapy at any time prior to the start of the preparative regimen?
Report whether the recipient received any tyrosine kinase inhibitor from the diagnosis of ALL to the start of the preparative regimen / infusion. Examples include: Imatinib mesylate is also known as Gleevec, Glivec, STI-571, or CGP57148B.
This question is optional for international centers.
Question 109: Were cytogenetics tested (conventional or FISH)? (at diagnosis)
Cytogenetic analysis is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of a known chromosomal abnormality which reflects the recipient’s disease. Testing methods you may see include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C, Cytogenetic Assessments.
Karyotyping is 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.
FISH is 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.
Table 5. 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) |
2 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.
Indicate whether cytogenetic studies were performed at diagnosis (see At Diagnosis, In between, and Last Evaluation note box above). Do not report any testing performed after treatment for ALL has started. If cytogenetic studies were obtained at diagnosis, check Yes. If cytogenetic studies were not obtained at this time point or it is not known whether chromosome studies were performed, indicate No or Unknown, respectively.
Question 110 – 111: Were cytogenetics tested via FISH? (at diagnosis)
If FISH studies were performed at diagnosis (see At Diagnosis, In between, and Last Evaluation note box above), report Yes and indicate whether clonal abnormalities were detected. Do not report any testing performed after treatment for ALL has started. If FISH studies were not performed at this time point, FISH samples were inadequate, or it is unknown if performed, report No.
Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.
Question 112 – 115: Specify cytogenetic abnormalities (FISH) identified at diagnosis
Report the International System for Human Cytogenetic Nomenclature (ISCN) compatible string if applicable.
Report the number of abnormalities detected by FISH at diagnosis (see At Diagnosis, In between, and Last Evaluation note box above). After indicating the number of abnormalities, 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” in and attach the final report(s) for any other abnormalities detected. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 116 – 117: Were cytogenetics tested via karyotyping? (at diagnosis)
If karyotyping was performed at diagnosis (see At Diagnosis, In between, and Last Evaluation note box above), report Yes and indicate whether clonal abnormalities were detected. Do not report any testing performed after treatment for ALL has started. If karyotyping performed, but there wasn’t any evaluable metaphase, report, No evaluable metaphases. If karyotyping was not performed at this time point or it is unknown, indicate No.
Question 118 – 121: Specify cytogenetic abnormalities (karyotyping) at diagnosis
Report the International System for Human Cytogenetic Nomenclature (ISCN) compatible string if applicable. Refer to Appendix C for more information on how to report using the ISCN functionality.
Report the number of abnormalities detected by karyotyping at diagnosis (see At Diagnosis, In between, and Last Evaluation note box above). After indicating the number of abnormalities, 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. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 122: Was documentation submitted to the CIBMTR?
Indicate if a karyotyping or FISH testing report is attached to support the cytogenetic findings reported. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 123: Were tests for molecular markers performed (e.g., PCR)? (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; however, lower sensitivity testing, including FISH, may also be used to detect molecular markers. 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).
If testing for molecular markers was performed at diagnosis (see At Diagnosis, In between, and Last Evaluation note box above), report Yes.
If molecular marker testing was not performed at diagnosis or it is not known if testing was done, report No or Unknown, respectively.
Table 6. Common Molecular Markers Associated with ALL
| Molecular Abnormality | Characteristics |
|---|---|
| BCR-ABL | BCR-ABL, aka Philadelphia chromosome, refers to the tyrosine kinase gene fusion resulting from the translocation of material from chromosome 9 (ABL) onto chromosome 22 (BCR). Molecular weight varies depending on exact location of the translocation; isoform p190 is typically seen in ALL. Tyrosine kinase inhibitor therapies such as imatinib mesylate (Gleevec) target and block ABL from fusing with BCR. Presence of BCR-ABL gene fusion is associated with poorer outcomes.3 |
| TEL-AML/AML1 | TEL-AML1, aka ETV6-RUNX1, is a fusion gene resulting from the translocation of chromosomes 12 and 21. It is the most common fusion gene seen in childhood precursor B-cell ALL. Research in murine models shows that cell lines expressing TEL-AML1 proliferate more slowly than the non-expressing cell lines, but evade inhibition of proliferation typically regulated by tissue growth factor ß (TGF-ß), ultimately leading to the growth of the leukemic cell population. TEL-AML1 is considered a favorable prognostic indicator.45 |
| Other molecular marker | Assessments for other molecular markers known or believed to be associated with ALL may be performed. If these studies were performed, indicate Positive or Negative and specify the marker. |
3 Wassmann B, Pfeifer H, Scheuring UJ, et al. (2004). Early prediction of response in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib. Blood, 103(4):1495-8.
4 Ford AM, Palmi C, Bueno C, et al. (2009). The TEL-AML1 leukemia fusion gene dysregulates the TGF-ß pathway in early B lineage progenitor cells. J Clin Invest, 119(4):826-36.
5 Jamil A, Kahwash S, Ruymann FB, Klopfenstein KJ. (2000). TEL/AML-1 fusion gene: its frequency and prognostic significance in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet, 122(2):73-8.
Questions 124 – 127: Specify molecular markers identified at diagnosis
For each molecular marker, report whether testing was Positive, Negative, or Not done at diagnosis or at time of relapse (see At Diagnosis or at relapse, In between, and Last Evaluation note box above). If tests identified a molecular marker other than those listed, report the result, and specify the marker in the allocated spaces.
If testing for other molecular markers were performed, specify the results in the Other molecular marker data field, using the following guidelines:
- Report one instance for all Positive other molecular markers and specify the markers (or report ‘see attachment’ and upload the report(s) using the attachment feature in FormsNet3SM)
- Report one instance for any Negative other molecular markers and specify the markers (or report ‘see attachment’ and upload the report(s) using the attachment feature in FormsNet3SM)
Question 128: Were cytogenetics tested (karyotyping or FISH)? (between diagnosis, and last evaluation)
Indicate whether cytogenetic studies were performed between diagnosis and the last evaluation prior to HCT / cellular therapy (see At Diagnosis, In between, and Last Evaluation note box above). If cytogenetic studies were obtained during this time, check Yes. If cytogenetic studies were not obtained at this time point or it is not known whether chromosome studies were performed, indicate No or Unknown, respectively.
Question 129 – 130: Were cytogenetics tested via FISH?
If FISH studies were performed between diagnosis and the last evaluation prior to Infusion (see At Diagnosis, In between, and Last Evaluation note box above), report Yes and indicate whether clonal abnormalities were detected. If multiple FISH assessments were performed, report Abnormalities Identified if any testing showed clonal abnormalities during this period. If FISH studies were not performed during this period, FISH samples were inadequate, or if unknown if performed, report No.
Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.
Question 131 – 134: Specify cytogenetic abnormalities (FISH) identified between diagnosis and last evaluation
Report the International System for Human Cytogenetic Nomenclature (ISCN) compatible string if applicable.
Report the number of abnormalities detected by FISH between diagnosis and the last evaluation prior to Infusion (see At Diagnosis, In between, and Last Evaluation note box above). If FISH studies showed different clonal abnormalities during this time, report the total number of clonal abnormalities detected. After indicating the number of clonal abnormalities, select all clonal abnormalities detected during this period. This includes all clonal abnormalities detected any FISH assessment performed during this period.
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. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 135 – 136: Were cytogenetics tested via karyotyping?
If karyotyping was performed between diagnosis and the last evaluation prior to Infusion (see Reporting Disease Assessments at Different Timepoints note box above), report Yes and indicate whether clonal abnormalities were detected. If multiple karyotypes were performed, report Abnormalities Identified if any testing showed clonal abnormalities during this period. If karyotyping performed, but there wasn’t any evaluable metaphase, report, No evaluable metaphases. If karyotyping was not performed during this period, report No.
Question 137 – 140: Specify cytogenetic abnormalities (karyotyping)
Report the International System for Human Cytogenetic Nomenclature (ISCN) compatible string if applicable. Refer to Appendix C for more information on how to report using the ISCN functionality.
Report the number of abnormalities detected by karyotyping between diagnosis or relapse and the last evaluation prior to Infusion (see At Diagnosis, In between, and Last Evaluation note box above). If karyotype studies showed different clonal abnormalities during this time, report the total number of clonal abnormalities detected. After indicating the number of clonal abnormalities, select all clonal abnormalities detected during this period. This includes all clonal abnormalities detected any karyotype performed during this period.
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. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 141: Was documentation submitted to the CIBMTR?
Indicate if a karyotyping or FISH testing report is attached to support the cytogenetic findings reported. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 142: Were tests for molecular markers performed (e.g., PCR)? (between diagnosis and last evaluation)
Indicate whether testing for molecular markers was performed between diagnosis and the last evaluation prior to Infusion (see At Diagnosis or at relapse, In between, and Last Evaluation note box above). If testing for molecular markers was performed during this time, check Yes. If molecular markers were not obtained during this period or it is not known whether testing for molecular markers was performed, indicate No or Unknown, respectively.
Question 143 – 146: Specify molecular markers identified between diagnosis and last evaluation
For each molecular marker, report whether testing was Positive, Negative or Not done between diagnosis and the last evaluation prior to Infusion (see At Diagnosis, In between, and Last Evaluation note box above). If tests identified a molecular marker other than those listed, report the result in Other molecular marker, and specify the marker.
If testing for other molecular markers were performed, specify the results in the Other molecular marker data field, using the following guidelines:
- Report one instance for all Positive other molecular markers and specify the markers (or report ‘see attachment’ and upload the report(s) using the attachment feature in FormsNet3SM)
- Report one instance for any Negative other molecular markers and specify the markers (or report ‘see attachment’ and upload the report(s) using the attachment feature in FormsNet3SM)
Question 147: Were cytogenetics tested (karyotyping or FISH)? (at last evaluation)
Indicate whether cytogenetic studies were performed at the last evaluation prior to infusion (see At Diagnosis, In between, and Last Evaluation note box above). Do not report any testing performed after the start of the preparative regimen for ALL. If cytogenetic studies were obtained at this time point, check Yes. If cytogenetic studies were not obtained at this time point or it is not known whether chromosome studies were performed, indicate No or Unknown, respectively.
Question 148 – 149: Were cytogenetics tested via FISH?
If FISH studies were performed at the last evaluation prior to HCT / cellular (see At Diagnosis, In between, and Last Evaluation note box above), report Yes and indicate whether clonal abnormalities were detected. If FISH studies were not performed or FISH sample was inadequate at this time point or is unknown if performed, report No.
Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.
Question 150 – 153: Specify cytogenetic abnormalities (FISH) identified at last evaluation
Report the International System for Human Cytogenetic Nomenclature (ISCN) compatible string if applicable.
Report the number of abnormalities detected by FISH at the last evaluation prior to infusion (see At Diagnosis, In between, and Last Evaluation note box above). After indicating the number of abnormalities 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” in and attach the final report(s) for any other abnormalities detected. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 154 – 155: Were cytogenetics tested via karyotyping?
If karyotyping was performed at the last evaluation prior to infusion (see At Diagnosis, In between, and Last Evaluation note box above), report Yes and indicate whether clonal abnormalities were detected. If karyotyping was performed, but there weren’t any evaluable metaphase cells, report No evaluable metaphases. If karyotyping was not performed at this time point, indicate No.
Question 156 – 159: Specify cytogenetic abnormalities (karyotyping) identified at last evaluation
Report the International System for Human Cytogenetic Nomenclature (ISCN) compatible string if applicable. Refer to Appendix C for more information on how to report using the ISCN functionality.
Report the number of abnormalities detected by karyotyping at the last evaluation prior to infusion (see At Diagnosis, In between, and Last Evaluation note box above). Only consider clonal abnormalities associated with the recipient’s ALL when completing this section. After indicating the number of abnormalities, 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” in and attach the final report(s) for any other abnormalities detected. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 160: Was documentation submitted to the CIBMTR?
Indicate if a karyotyping or FISH testing report is attached to support the cytogenetic findings reported. For further instructions on how to attach documents in FormsNet3SM, refer to the Training Guide.
Question 161: Were tests for molecular markers performed (e.g., PCR)? (at last evaluation)
If testing for molecular markers was performed at the last evaluation prior to infusion (see At Diagnosis, In between, and Last Evaluation note box above), report Yes. If molecular marker testing was not performed at this time point or it is not known if testing was done, report No or Unknown, respectively.
Questions 162 – 165: Specify molecular markers identified at last
For each molecular marker listed, report whether testing was Positive, Negative, or Not done at the last evaluation prior to infusion (see At Diagnosis, In between, and Last Evaluation note box above). If tests identified a molecular marker other than those listed, report the result in Other molecular marker, and specify the marker.
If testing for other molecular markers were performed, specify the results in the Other molecular marker data field, using the following guidelines:
- Report one instance for all Positive other molecular markers and specify the markers (or report ‘see attachment’ and upload the report(s) using the attachment feature in FormsNet3SM)
- Report one instance for any Negative other molecular markers and specify the markers (or report ‘see attachment’ and upload the report(s) using the attachment feature in FormsNet3SM)
Question 166: 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.). If the recipient had documented involvement of ALL in the CNS, report Yes. 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 HCT / cellular therapy, report Unknown.
Question 167: What was the disease status (based on hematological test results)?
Indicate the disease status of ALL at the last evaluation prior to the start of the preparative regimen. Refer to the ALL Response Criteria section of the Forms Instructions Manual 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 / infusion, report No treatment and continue with Date assessed.
If the recipient’s disease status is Primary induction failure at the time of HCT / cellular therapy, continue with Date assessed.
If the recipient’s disease status is CR / CRi at the time of HCT / cellular therapy, continue with Date assessed.
If the recipient’s disease status is Relapse at the time of HCT / cellular therapy, continue with Date assessed.
Question 168: How many cycles of induction therapy were required to achieve CR?
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.
Indicate the number of cycles of induction therapy that were required to achieve the first CR. If this is a subsequent infusion and a CR was achieved prior to the previous infusion, the same value will be re-reported.
Example: A recipient diagnosed with ALL, received two cycles of induction, achieved a CR and then received one cycle of maintenance before going on to transplant. Post-transplant, the recipient relapsed, received two additional cycles of re-induction before achieving a second CR, followed by a cycle of consolidation and second transplant. The number of cycles of induction therapy to achieve the first CR should be reported as ‘two.’
Question 169: Specify method(s) that was used to assess measurable residual disease status (check all that apply)
Specify the method(s) how the minimal residual status was assessed at the last evaluation, approximately 30 days prior to the start of the preparative regimen / infusion. 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.
If the measurable residual disease status was assessed by FISH at the last evaluation, continue with question 170.
- 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.
If the measurable residual disease status was assessed by Karyotype at the last evaluation, continue with question 171.
- 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.
If the measurable residual disease status was assessed by Flow cytometry at the last evaluation, continue with question 172.
- 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.
If the measurable residual disease status was assessed by PCR at the last evaluation, continue with question 176.
- 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.
If the measurable residual disease status was assessed by NGS at the last evaluation, continue with question 177.
If the minimal residual status was Not assessed at the last evaluation, continue with question 179.
Question 170: Was measurable residual disease detected by FISH?
Indicate if measurable residual disease was detected by FISH at the last evaluation prior to the start of the preparative regimen / infusion.
If the results are not clear, seek physician clarification to determine if measurable residual disease was detected by FISH at the last evaluation.
Question 171: Was measurable residual disease detected by karyotyping assay?
Indicate if measurable residual disease was detected by karyotype at the last evaluation prior to the start of the preparative regimen / infusion.
If the results are not clear, seek physician clarification to determine if measurable residual disease was detected by karyotype at the last evaluation.
Questions 172 – 174: Which leukemia phenotype was used for detection? (check all that apply)
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 in question 173, and then indicate if minimal residual disease was detected by flow cytometry at the last evaluation prior to the start of the preparative regimen / infusion.
If an Aberrant phenotype was used, specify the lower limit of detection in question 174, and then indicate if minimal residual disease was detected by flow cytometry at the last evaluation prior to the start of the preparative regimen / infusion.
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 175: Was measurable residual disease detected by flow cytometry?
Indicate if measurable residual disease was detected by flow cytometry at the last evaluation prior to the start of the preparative regimen / infusion.
If the results are not clear, seek physician clarification to determine if measurable residual disease was detected by flow cytometry at the last evaluation assay at the last evaluation prior to the start of the preparative regimen / infusion.
Question 176: Was measurable residual disease detected by PCR?
Indicate if measurable residual disease was detected by PCR at the last evaluation prior to the start of the preparative regimen / infusion.
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 / infusion.
Question 177: Was minimal residual disease detected by NGS?
Indicate if minimal residual disease was detected by NGS at the last evaluation prior to the start of the preparative regimen / infusion.
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 / infusion.
Question 178: Date of most recent relapse
Enter the date of the most recent relapse prior to the start of the preparative regimen. If reporting a pathological evaluation (e.g., bone marrow) or blood/serum assessment (e.g., CBC, peripheral blood smear), enter the date the sample was collected. If extramedullary disease was detected by radiographic examination (e.g., X-ray, CT scan, MRI scan, PET scan), enter the date the imaging took place. If the physician determines cytogenetic or molecular relapse, enter the date the sample was collected for cytogenetic or molecular evaluation. 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, Guidelines for Completing Forms.
Question 179: Date assessed
Enter the date of the most recent assessment of disease status prior to the start of the preparative regimen. The date reported should be that of the most disease-specific assessment within the pre-transplant work-up period (approximately 30 days). Clinical and hematologic assessments include pathological evaluation (e.g., bone marrow biopsy), radiographic examination (e.g., X-ray, CT scan, MRI scan, PET scan), and laboratory assessment (e.g., CBC, peripheral blood smear), in addition to clinician evaluation and physical examination. Enter the date the sample was collected for pathological and laboratory evaluations; enter the date the imaging took place for radiographic assessments.
If the exact date is not known, use the process for reporting partial or unknown dates as described in General Instructions, Guidelines for Completing Forms.
Section Updates:
| Question Number | Date of Change | Add/Remove/Modify | Description | Reasoning (If applicable) |
|---|---|---|---|---|
| . | . | . | . | . |
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