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HelpTest Code BALAF B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies
Ordering Guidance
This test is only performed on specimens from patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) who are aged 31 years or older.
This test is intended for instances when the entire B-ALL/LBL fluorescence in situ hybridization (FISH) panel is needed for an adult patient.
This test should NOT be used to screen for residual B-ALL/LBL. At follow-up, or if the patient clinically relapses, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) are useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone. Additionally, targeted B-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study.
If targeted B-cell ALL FISH probes are preferred, order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies, and request specific probes for targeted abnormalities.
If this test is ordered on a patient aged 30 years or younger, this test will be canceled and automatically reordered by the laboratory as BALFP / Pediatric B-Lymphoblastic Leukemia/Lymphoma panel, FISH, Varies.
If this test is ordered and the laboratory is informed that the patient is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory as COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies.
If either AMLFA / Adult Acute Myeloid Leukemia Panel, FISH, Varies?or TALAF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies, are ordered concurrently with this test, the laboratory may cancel this test and automatically reorder as BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies with the following FISH probes: ETV6/RUNX1, PBX1/TCF3, 4/10/17, break-apart IGH, break-apart CRLF2, break-apart ABL2, and IKZF1/cep7. If an abnormality is identified that would result in reflex testing in BALAF, the same reflex testing will be performed in the BALMF. This cancellation is necessary to avoid duplicate testing. Probes for break-apart PDGFRB, break-apart JAK2, ABL1/BCR, break-apart ABL1, break-apart KMT2A will still be performed as part of the adult T-ALL FISH panel.
If PHLDF / Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (Ph-like ALL), Diagnostic FISH, Varies, is ordered concurrently with this test, PHLDF testing will be canceled. This cancellation is necessary to avoid duplicate testing as PHLDF probes are included within this test when appropriate.
For patients with B-cell lymphoma, order BLPMF / B-Cell Lymphoma, Specified FISH, Varies.
For testing paraffin-embedded tissue samples from patients with B-LBL, order BLBLF / B-Cell Lymphoblastic Leukemia/Lymphoma, FISH, Tissue. If a paraffin-embedded tissue sample is submitted for this test, it will be canceled and BLBLF will be added and performed as the appropriate test.
Additional Testing Requirements
At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and this fluorescence in situ hybridization panel should be performed. If there is limited specimen available, only this test will be performed.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
1. A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
2. A flow cytometry and/or a bone marrow pathology report should be submitted with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
3. If the patient has received an opposite sex bone marrow transplant, note this information on the request.
4. If the patient has Down syndrome, note this information on the request.
Specimen Required
Submit only 1 of the following specimens:
Preferred
Specimen Type: Bone marrow
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (sodium heparin) or lavender top (EDTA)
Specimen Volume: 2 to 3 mL
Collection Instructions:
1. It is preferable to send the first aspirate from the bone marrow collection.
2. Invert several times to mix bone marrow.
3. Send bone marrow specimen in original tube. Do not aliquot.
Acceptable
Specimen Type: Whole blood
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (sodium heparin) or lavender top (EDTA)
Specimen Volume: 6 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Useful For
Detecting, at diagnosis, recurrent common chromosome abnormalities associated with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) and BCR::ABL1-like B-ALL in adult patients using a laboratory-designated probe set algorithm
As an adjunct to conventional chromosome studies in adult patients with B-ALL/LBL
Evaluating specimens in which chromosome studies are unsuccessful
This test should not be used to screen for residual B-ALL/LBL
Testing Algorithm
This test includes a charge for the probe application, analysis, and professional interpretation of results for 2 probe sets (4 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.
This test is performed as panel testing only using the following analysis algorithm.
The diagnostic adult B-lymphoblastic leukemia (B-ALL) FISH panel includes testing for the following abnormalities using the FISH probes listed:
t(9;22)(q34;q11.2) or BCR::ABL1 fusion, ABL1/BCR probe set
CRLF2 (Xp22.33) or (Yp11.32) rearrangement, CRLF2 break-apart probe set
If results for the initial panel are negative or demonstrate nonclassical abnormalities, the following Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel will be performed as a secondary panel. The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below, as well as IKZF1 deletion, which often accompanies Ph-like ALL.
t(1q25;var) or ABL2 rearrangement, ABL2 break-apart probe set
t(5q32;var) or PDGFRB rearrangement, PDGFRB break-apart probe set
t(9p24.1;var) or JAK2 rearrangement, JAK2 break-apart probe set
t(9q34;var) or ABL1 rearrangement, ABL1 break-apart probe set
Finally, if results for the initial and secondary panels are negative or demonstrate nonclassical abnormalities, the following probe sets will be performed as a tertiary panel:
t(1;19)(q23;p13) or TCF3::PBX1 fusion, PBX1/TCF3 probe set
Hyperdiploidy or +4,+10,+17, D4Z1/D10Z1/D17Z1 probe set
7p- or IKZF1 deletion, IKZF1/CEP7 probe set
t(11q23;var) or KMT2A rearrangement, KMT2A break-apart probe set
t(12;21)(p13;q22) or ETV6::RUNX1 fusion or iAMP21, ETV6/RUNX1 probe set
t(14q32;var) or IGH rearrangement, IGH break-apart probe set
Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes used will have the results included within the final report and will be performed at an additional charge. In the following situations, additional (reflex) testing may be performed at the laboratory's discretion and may be influenced by available karyotype results or other FISH testing.
When a KMT2A rearrangement is identified, appropriate reflex testing with 1 or more dual-fusion FISH (D-FISH) probe sets may be performed in an attempt to identify the translocation partner for the following abnormalities:
t(4;11)(q21;q23) or KMT2A::AFF1 fusion, AFF1/KMT2A probe set
t(6;11)(q27;q23) or KMT2A::AFDN ;fusion, AFDN/KMT2A probe set
t(9;11)(p22;q23) or KMT2A::MLLT3 fusion, MLLT3/KMT2A probe set
t(10;11)(p12;q23) or KMT2A::MLLT10 fusion, MLLT10/KMT2A probe set
t(11;19)(q23;p13.1) or KMT2A::MLLT1 fusion, KMT2A/ELL probe set
t(11;19)(q23;p13.3) or KMT2A::ELL fusion, KMT2A/MLLT1 probe set
When an unbalanced CRLF2 rearrangement is identified concurrently with an IGH rearrangement, testing using the CRLF2/IGH probe set will be considered to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.
When a MYC rearrangement is identified, testing using both the BCL2 and BCL6 break-apart probe sets will be performed.
If an unbalanced rearrangement of the BCL2 is identified, testing using the IGH/BCL2 probe set will be performed to identify a potential t(14;18)(q32;q21) or IGH::BCL2 fusion.
Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.
For more information see B-Lymphoblastic Leukemia/Lymphoma Genetic Testing Guidelines.
Method Name
Fluorescence In Situ Hybridization (FISH)
Reporting Name
Adult ALL (B-cell), FISHSpecimen Type
VariesSpecimen Minimum Volume
Bone marrow: 1 mL; Whole blood: 2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Refrigerated | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
In the United States, the incidence of B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is roughly 6000 new cases per year or approximately 1 in 50,000. B-ALL/LBL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer. It has a peak incidence at 2 to 5 yearsof age. This incidence decreases with age before increasing again at around age 50. B-ALL/LBL is slightly more common in male patients than female patients. There is also an increased incidence of B-ALL/LBL in individuals with genetic conditions such as Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, Li-Fraumeni syndrome, X-linked agammaglobulinemia, and severe combined immunodeficiency. The overall cure rate for B-ALL/LBL in children is approximately 90%, and about 45% to 60% of adults have long-term disease-free survival. Of note the, IGH::CRLF2 fusion is more commonly observed in patients with Down syndrome or of Hispanic descent.
Specific cytogenetic abnormalities are identified in most of cases of B-ALL/LBL, by conventional chromosome studies or fluorescence in situ hybridization (FISH) studies. B-ALL genetic subgroups are important to detect and can be critical prognostic markers. For example, a decision for early transplantation may be made if BCR::ABL1 fusion, KMT2A rearrangement, iAMP21, or a hypodiploid clone is identified. In contrast, if the ETV6::RUNX1 fusion or hyperdiploidy is identified, the patient has a more favorable prognosis and transplantation is rarely initially considered.
A newly recognized World Health Organization entity called B-ALL with BCR::ABL1-like features is increasing in importance due to the poor prognosis seen in pediatric, adolescent, and young adult ALL. Common features of this entity involve rearrangements with tyrosine kinase genes involving the following genes: ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8, as well as deletions involving IKZF1. Patients who have failed conventional therapies have demonstrated favorable responses to targeted therapies when rearrangements involving these specific gene regions have been identified.
Evaluation of the MYC gene region is included in all diagnostic B-ALL panels to evaluate for Burkitt lymphoma. If a positive result is obtained, additional testing for the BCL2 and BCL6 gene regions will be performed.
Per National Comprehensive Cancer Network guidelines, a combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients with B-ALL/lymphoblastic lymphoma (LBL). Additional cytogenetic techniques such as chromosomal microarray (CMAH / Chromosomal Microarray, Hematologic Disorders, Varies) may be helpful to resolve questions related to ploidy (hyperdiploid clone vs doubled hypodiploid clone) or to resolve certain clonal structural rearrangements such as the presence or absence of intrachromosomal amplification of chromosome 21 (iAMP21). A summary of the characteristic chromosome abnormalities identified in B-ALL is listed in the following table.
Table. Common Chromosome Abnormalities in B-cell Acute Lymphoblastic Leukemia
|
Leukemia type |
Cytogenetic change |
Typical demographic |
Risk category |
|
B-acute lymphoblastic leukemia/lymphoma
|
t(12;21)(p13;q22), ETV6::RUNX1 |
Pediatric |
Favorable |
|
Hyperdiploidy |
Pediatric |
Favorable |
|
|
t(1;19)(q23;p13.3), TCF3::PBX1 |
Pediatric |
Intermediate to favorable |
|
|
t(9;22)(q34;q11.2), BCR::ABL1 |
All ages |
Unfavorable |
|
|
iAMP21, RUNX1 |
Pediatric |
Unfavorable |
|
|
t(11q23;var), KMT2A rearrangement |
All ages |
Unfavorable |
|
|
t(4;11)(q21;q23), KMT2A::AFF1 |
All ages |
Unfavorable |
|
|
t(6;11)(q27;q23), KMT2A::AFDN |
All ages |
Unfavorable |
|
|
t(9;11)(p21.3;q23), KMT2A::MLLT3 |
All ages |
Unfavorable |
|
|
t(10;11)(p12;q23), KMT2A::MLLT10 |
All ages |
Unfavorable |
|
|
t(11;19)(q23;p13.3), KMT2A::MLLT1 |
All ages |
Unfavorable |
|
|
t(11;19)(q23;p13.1), KMT2A::ELL |
All ages |
Unfavorable |
|
|
t(14q32;var), IGH rearrangement |
All ages |
Variable |
|
|
t(X;14)(p22;q32)/t(Y;14)(p11;q32), IGH::CRLF2 |
Adolescent/ young adult |
Unfavorable |
|
|
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement |
All ages |
Unfavorable |
|
|
t(8q24.21;var), MYC rearrangement |
Pediatric/ adolescent/ young adult |
||
|
Complex karyotype (≥4 abnormalities) |
Adult |
Unfavorable |
|
|
Low hypodiploidy/near-triploidy |
Adult |
Unfavorable |
|
|
Near-haploid/hypodiploid |
All ages |
Unfavorable |
|
|
del(7p) IKZF1 deletion |
All ages |
Unfavorable in absence of ERG deletion |
|
|
BCR::ABL1-like acute lymphoblastic leukemia/lymphoma |
t(1q25;var), ABL2 rearrangement |
Pediatric/ adolescent/ young adult |
Unfavorable |
|
t(5q32;var), PDGFRB rearrangement |
|||
|
t(9p24.1;var), JAK2 rearrangement |
|||
|
t(9q34;var), ABL1 rearrangement |
|||
|
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement |
|||
|
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement |
Reference Values
An interpretive report will be provided.
Interpretation
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe set.
The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.
Cautions
This test is not approved by the US Food and Drug Administration, and it is best used as an adjunct to clinical and pathologic information.
Fluorescence in situ hybridization (FISH) is not a substitute for conventional chromosome studies because the latter detects chromosome abnormalities associated with other hematological disorders that would be missed in a targeted B-cell acute lymphoblastic leukemia FISH panel test.
Bone marrow is the preferred specimen type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are circulating malignant cells in the blood specimen (as verified by a hematopathologist). If no FISH signals are observed post-hybridization, the case will be released indicating a lack of FISH results.
Clinical Reference
1. Moorman AV, Harrison CJ, Buck GA, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109(8):3189-3197. doi:10.1182/blood-2006-10-051912
2. Moorman AV. The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood Rev. 2012;26:123-135. doi:10.1016/j.blre.2012.01.001
3. Roberts KG, Li Y, Payne-Turner D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005-1015. doi:10.1056/NEJMoa1403088
4. Mullighan CG. The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014;2014(1):174-180. doi:10.1182/asheducation-2014.1.174
5. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press; 2017. WHO Classification of Tumours. Vol 2.
Day(s) Performed
Monday through Friday
Report Available
7 to 10 daysSpecimen Retention Time
4 weeksPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
88271 x4,88275 x2, 88291 - FISH Probe, Analysis, Interpretation; 2 probe sets
88271 x2, 88275 - FISH Probe, Analysis; each additional probe set (if appropriate)
88271 - FISH Probe (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| BALAF | Adult ALL (B-cell), FISH | 102099-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 609538 | Result Summary | 50397-9 |
| 609539 | Interpretation | 69965-2 |
| 609540 | Result Table | 93356-4 |
| 609541 | Result | 62356-1 |
| GC065 | Reason for Referral | 42349-1 |
| GC066 | Specimen | 31208-2 |
| 609542 | Source | 31208-2 |
| 609543 | Method | 85069-3 |
| 609544 | Additional Information | 48767-8 |
| 609545 | Disclaimer | 62364-5 |
| 609546 | Released By | 18771-6 |
Forms
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.