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HelpTest ID: BALPF B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Pediatric, FISH, Varies
Ordering Guidance
This test is only performed on specimens from patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) who are 30 years of age or younger.
This test is intended to be ordered when the entire B-ALL fluorescence in situ hybridization (FISH) panel is needed for a pediatric patient.
This test should NOT be used to screen for residual B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL).
If using FISH to monitor B-ALL patients, it is recommended to use individual (or limited) FISH probe sets.
If limited 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 the patient clinically relapses, a conventional chromosome study may be useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.
If this test is ordered on a patient 31 years of age or older, this test will be canceled and automatically reordered by the laboratory as BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Adult, FISH, Varies.
If this test is ordered and the laboratory is informed that the patient is 30 years of age or younger AND is on a Children's Oncology Group 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, Pediatric, Varies.
If either (or both) AMLPF / Acute Myeloid Leukemia (AML), Specified FISH, Varies; or TALPF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Pediatric, FISH, Varies, is (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 P2RY8, break-apart MYC, break-apart ABL2, break-apart PDGFRB, break-apart JAK2, break-apart ABL1, and IKZF1/cep7. If an abnormality is identified that would result in reflex testing in BALPF, the same reflex testing will be performed in the BALMF. This cancellation is necessary to avoid duplicate testing. Probes for CDKN2A/D9Z1, ABL1/BCR, break-apart MLL, TP53/D17Z1 will still be performed as part of the pediatric 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-cell acute lymphoblastic lymphoma, 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 test should both be performed. If there is limited specimen available, this test only will be performed.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
1. A reason for testing and 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; however, appropriate testing and/or interpretation may be compromised or delayed in some instances. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
2. If the patient has received an opposite sex bone marrow transplant, 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 (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 (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 Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) in pediatric patients
As an adjunct to conventional chromosome studies for pediatric 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 11 probe sets (23 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The initial (diagnostic) pediatric/young adult B-cell acute lymphoblastic leukemia (B-ALL) FISH panel includes testing for the following abnormalities using the FISH probes listed:
+9/9p-, CDKN2A/D9Z1
t(9;22)(q34;q11.2), BCR/ABL1
11q23 rearrangement, MLL(KMT2A) break-apart
-17/17p-, TP53/D17Z1
t(1;19)(q23;p13), PBX1/TCF3
Hyperdiploidy or +4,+10,+17, D4Z1/D10Z1/D17Z1
t(12;21)(p13;q22) or iAMP21, ETV6/RUNX1
14q32 rearrangement, IGH break-apart
t(Xp22.33;var) or t(Yp11.32;var),rearrangement, CRLF2 break-apart
t(Xp22.33;var) or t(Yp11.32;var) rearrangement, P2RY8 break-apart
8q24.2 rearrangement, MYC break-apart
If results for the initial panel are negative or demonstrate nonclassical abnormalities, the 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.
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
7p-, IKZF1/CEP7
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.
When an MLL(KMT2A) rearrangement is identified, appropriate reflex testing will be performed to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1::MLL(KMT2A), t(6;11)(q27;q23) MLLT4(AFDN)::MLL(KMT2A), t(9;11)(p22;q23) MLLT3::MLL(KM2TA), t(10;11)(p12;q23) MLLT10::MLL(KMT2A), t(11;19)(q23;p13.3) MLL(KMT2A)::MLLT1, or t(11;19)(q23;p13.1) MLL(KMT2A)::ELL. In the event an 11q23 translocation is (or has been) identified by chromosome analysis, only the targeted MLL(KMT2A) reflex probe will be performed if applicable.
When an IGH or CRLF2 rearrangement is identified, appropriate reflex testing will be performed using the CRLF2/IGH probe set will be considered at the laboratory's discretion to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation. Laboratory discretion may be influenced by available karyotype or other FISH results.
In the absence of BCR::ABL1 fusion, when an extra ABL1 signal is identified, reflex testing may be performed at the laboratory's discretion using the ABL1 break-apart probe set to evaluate for the presence or absence of a potential rearrangement involving ABL1, t(9;var)(q34;?). Laboratory discretion may be influenced by available karyotype or other FISH results.
In the absence of ETV6::RUNX1 fusion, when an extra ETV6 signal is identified, reflex testing may be performed at the laboratory's discretion using the ETV6 break-apart probe set to evaluate for the presence or absence of a potential rearrangement involving ETV6 t(12;var)(p13;?). Laboratory discretion may be influenced by available karyotype or other FISH results.
If a MYC rearrangement is identified, both the BCL2 and BCL6 break-apart probe sets will be performed.
For more information see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Method Name
Fluorescence In Situ Hybridization (FISH)
Reporting Name
Pediatric ALL (B-cell), FISHSpecimen Type
VariesSpecimen Minimum Volume
Whole blood: 2 mL; Bone marrow: 1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
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 years of age. This incidence decreases with age before increasing again at around 50 years of age. 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, CRLF2::IGH fusion is more commonly observed in patients with Down syndrome or of Hispanic descent.
Specific cytogenetic abnormalities are identified in the majority 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 BCR-ABL1-like ALL, also known as Philadelphia chromosome-like acute lymphoblastic leukemia, 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 may be considered.
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 intra-chromosomal 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
|
t(12;21)(p13;q22), ETV6::RUNX1 |
Pediatric |
Favorable |
||
|
Hyperdiploidy |
Pediatric |
Favorable |
|||
|
t(1;19)(q23;p13.3), PBX1::TCF3 |
Pediatric |
Intermediate to favorable |
|||
|
t(9;22)(q34;q11.2), BCR::ABL1 |
All ages |
Unfavorable |
|||
|
iAMP21, RUNX1 |
Pediatric |
Unfavorable |
|||
|
del(9p), CDKN2A |
All ages |
Unknown |
|||
|
t(11q23;var), MLL rearrangement |
All ages |
Unfavorable |
|||
|
t(4;11)(q21;q23), AFF1::MLL |
All ages |
Unfavorable |
|||
|
t(6;11)(q27;q23), MLLT4(AFDN)::MLL |
All ages |
Unfavorable |
|||
|
t(9;11)(p22;q23), MLLT3::MLL |
All ages |
Unfavorable |
|||
|
t(10;11)(p12;q23), MLLT10::MLL |
All ages |
Unfavorable |
|||
|
t(11;19)(q23;p13.1), MLL::ELL |
All ages |
Unfavorable |
|||
|
t(11;19)(q23;p13.3), MLL::MLLT1 |
All ages |
Unfavorable |
|||
|
t(14q32;var), IGH rearrangement |
All ages |
Variable |
|||
|
t(X;14)(p22;q32)/t(Y;14)(p11;q32), CRLF2::IGH |
Adolescent/ young adult |
Unfavorable |
|||
|
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement |
All ages |
Unfavorable |
|||
|
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement |
All ages |
Unfavorable |
|||
|
-17/17p-, TP53 |
All ages |
Unfavorable |
|||
|
t(8q24.2;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 |
All ages |
Unfavorable in absence of ERG deletion |
|||
|
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) |
t(1q25;var), ABL2 |
Pediatric/ adolescent/ young adult |
Unfavorable |
||
|
t(5q32;var), PDGFRB |
|||||
|
t(9p24.1;var), JAK2 |
|||||
|
t(9q34;var), ABL1 |
|||||
|
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 |
|||||
|
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 |
|||||
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 an acute B-cell lymphoblastic leukemia/lymphoma or another neoplastic disorder.
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
2. Moorman AV. The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood Rev. 2012;26:123-135
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
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
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 daysTest 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 x 23, 88275 x 11, 88291 x 1-FISH Probe, Analysis, Interpretation; 11 probe sets
88271 x 2, 88275 x 1-FISH Probe, Analysis; each additional probe set (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| BALPF | Pediatric ALL (B-cell), FISH | 102099-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 609548 | Result Summary | 50397-9 |
| 609549 | Interpretation | 69965-2 |
| 609550 | Result Table | 93356-4 |
| 609551 | Result | 62356-1 |
| GC068 | Reason for Referral | 42349-1 |
| GC069 | Specimen | 31208-2 |
| 609552 | Source | 31208-2 |
| 609553 | Method | 85069-3 |
| 609554 | Additional Information | 48767-8 |
| 609555 | Disclaimer | 62364-5 |
| 609556 | Released By | 18771-6 |
Forms
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
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