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Test ID: BALMF B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies


Ordering Guidance


This test is intended for instances when targeted B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) fluorescence in situ hybridization (FISH) probes are needed based on specific abnormality or abnormalities identified in the diagnostic sample. The FISH probes must be specified on the request when ordering.

 

If targeted FISH probes are not included with this test order, test processing will be delayed, and the test may be canceled by the laboratory.

 

If targeted probes are not included with this test request, the test may be canceled and automatically reordered by the laboratory as BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies depending on the age of the patient.

 

For an adult patient, if the entire B-cell ALL FISH panel is preferred, order BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies.

 

For a pediatric patient, if the entire B-cell ALL FISH panel is preferred, order BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies.

 

At diagnosis, both conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies should be performed.

 

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 therapy-related myeloid clone.

 

 

If this test is ordered and the laboratory is informed that the patient is 30 years of age and under AND is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies.

   

For patients with B-cell lymphoma, order BLPMF / B-Cell Lymphoma, Specified FISH, Varies.

 

For testing paraffin-embedded tissue samples from patients with B-ALL/LBL, order BLBLF / B-Cell Acute 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.



Shipping Instructions


Advise Express Mail or equivalent if not on courier service.



Necessary Information


1. A list of probes requested for analysis is required. Probes available for this test are listed in the Testing Algorithm section.

2. 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.



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 a neoplastic clone associated with 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) using client specified probes

 

As an adjunct to conventional chromosome studies in 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 one probe set (2 individual fluorescence in situ hybridization (FISH) probes or 3 individual FISH probes). Additional charges will be incurred for all reflex or additional probe sets performed.

 

If the patient is being treated for known abnormalities, indicate the abnormality and which probes should be used.

 

Testing will be performed using the probes specified by the client:

t(1q25;var) or ABL2 rearrangement, request probe ABL2 break-apart

t(5q32;var) or PDGFRB rearrangement, request probe PDGFRB break-apart

7p- or IKZF1 deletion, request probe: IKZF1/CEP7

t(9p24.1;var) or JAK2 rearrangement, request probe JAK2 break-apart

+9/9p- or trisomy 9, CDKN2A deletion, request probe CDKN2A/D9Z1

t(9;22)(q34;q11.2) or BCR::ABL1 fusion, request probe BCR/ABL1

t(9q34;var) or ABL1 rearrangement, request probe: ABL1 break-apart

t(11q23;var) or MLL(KMT2A) rearrangement, request probe MLL break-apart

t(4;11)(q21;q23) or AFF1::MLL(KMT2A) fusion, request probe AFF1/MLL

t(6;11)(q27;q23) or MLLT4(AFDN)::MLL(KMT2A) fusion, request probe MLLT4/MLL

t(9;11)(p21;q23) or MLLT3::MLL(KMT2A) fusion, request probe MLLT3/MLL

t(10;11)(p13;q23) or MLLT10::MLL(KMT2A) fusion, request probe MLLT10/MLL

t(11;19)(q23;p13.3) or MLL::MLLT1(KMT2A) fusion, request probe MLL/MLLT1

t(11;19)(q23;p13.1) or MLL(KMT2A)::ELL fusion, request probe MLL/ELL

-17/17p- or TP53 deletion, request probe TP53/D17Z1

t(1;19)(q23;p13) or PBX1::TCF3 fusion, request probe PBX1/TCF3

Hyperdiploidy or +4,+10,+17, request probe D4Z1/D10Z1/D17Z1

t(12;21)(p13;q22), ETV6::RUNX1 fusion and iAMP21, request probe ETV6/RUNX1

t(12p13;var) or ETV6 rearrangement, request probe ETV6 break-apart

t(14q32;var) or IGH rearrangement, request probe IGH break-apart

t(Xp22.33;var) or t(Yp11.32;var) or P2RY8 rearrangement, request probe P2RY8 break-apart

t(Xp22.33;var) or t(Yp11.32;var) or CRLF2 rearrangement, request probe CRLF2 break-apart

t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) or CRLF2::IGH fusion, request probe CRLF2/IGH

t(8q24.2;var) or MYC rearrangement, request probe MYC break-apart

 

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 Algorithm

-Acute Leukemias of Ambiguous Lineage Testing Algorithm

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

ALL (B-cell), Specified FISH

Specimen Type

Varies

Specimen 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 pediatric 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
*representing Burkitt or other mature B-cell lymphoma

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 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 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. 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(3):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. Arber DA, Orazi A, Hasserjian R, et al: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. doi:10.1182/blood-2016-03-643544

Day(s) Performed

Monday through Friday

Report Available

7 to 10 days

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 x2, 88275 x1, 88291 x1- FISH Probe, Analysis, Interpretation; 1 probe sets

88271 x2, 88275 x1 - FISH Probe, Analysis; each additional probe set (if appropriate)

88271 x1 -FISH Probe; coverage for sets containing 3 probes (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
BALMF ALL (B-cell), Specified FISH 102099-9

 

Result ID Test Result Name Result LOINC Value
614217 Result Summary 50397-9
614218 Interpretation 69965-2
614219 Result Table 93356-4
614220 Result 62356-1
GC101 Reason for Referral 42349-1
GC102 Probes Requested 78040-3
GC103 Specimen 31208-2
614221 Source 31208-2
614222 Method 85069-3
614223 Additional Information 48767-8
614224 Disclaimer 62364-5
614225 Released By 18771-6

Forms

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Mayo Clinic Laboratories | Genetics and Genomics Additional Information:

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