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Test Code BALLF B-Lymphoblastic Leukemia/Lymphoma, FISH

Useful For

Detecting a neoplastic clone associated with the common chromosome abnormalities seen in patients with B-cell acute lymphoblastic leukemia (B-ALL) and Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL)

 

Identifying and tracking known chromosome abnormalities in patients with B-ALL and Ph-like ALL and tracking response to therapy

 

As an adjunct to conventional chromosome studies in patients with B-ALL and Ph-like ALL

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
_PBCT Probe, +2 No, (Bill Only) No
_PADD Probe, +1 No, (Bill Only) No
_PB02 Probe, +2 No, (Bill Only) No
_PB03 Probe, +3 No, (Bill Only) No
_IL25 Interphases, <25 No, (Bill Only) No
_I099 Interphases, 25-99 No, (Bill Only) No
_I300 Interphases, >=100 No, (Bill Only) No

Testing Algorithm

This B-cell acute lymphoblastic leukemia (B-ALL) FISH test may be ordered in 4 distinct ways allowing different combinations of probes to be utilized based on the clinical question. The 4 ways this B-ALL FISH test can be ordered are as follows:

-Standard (diagnostic) B-ALL FISH panel

-Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel

-Combined-Standard (diagnostic) B-ALL FISH panel + Ph-like ALL panel

-Individual B-ALL FISH probes (per client request)

 

The specific B-ALL FISH panel or FISH probes requested must be noted on the request form or in the reason for referral. If no specific panel or FISH probe request is indicated, the "Standard (diagnostic) B-ALL FISH panel" will be performed.

 

The Standard (diagnostic) B-ALL FISH panel includes testing for the following abnormalities, using the FISH probes listed:

 

Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1

t(12;21)(p13;q22), ETV6/RUNX1 fusion, ETV6/RUNX1 D-FISH

iAMP21, RUNX1 amplification, ETV6/RUNX1 D-FISH

t(9;22)(q34;q11.2), BCR/ABL1 fusion, BCR/ABL1 D-FISH

t(1;19)(q23;p13), PBX1/TCF3 fusion, PBX1/TCF3 D-FISH

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

del(9p), CDKN2A deletions, CDKN2A/D9Z1

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

del(17p), TP53 deletions, TP53/D17Z1

8q24.1 rearrangement, MYC break-apart

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

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

 

-When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1/MLL, t(6;11)(q27;q23) MLLT4/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p13;q23) MLLT10/MLL, t(11;19)(q23;p13.1) MLL/ELL, or t(11;19)(q23;p13.3) MLL/MLLT1.

-When an IGH and/or CRLF rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14) (p11.32;q32) "cryptic translocation."

 

The Philadelphia Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed:

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

-t(5q33;var), PDGFRB rearrangement, PDGFRB break-apart

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

-t(9q34;var), ABL1 rearrangement, ABL1 break-apart

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

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

 

-When a PDGFRB rearrangement is identified, reflex testing will be performed using the PDGFRB/ETV6 fusion probe set to identify the potential t(5;12)(q33;p13) translocation.

-When a CRLF rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14) (p11.32;q32) "cryptic translocation."

 

 

This test includes a charge for application of the first probe set (2 FISH probes) and professional interpretation of results. Additional charges will be incurred for all reflex probes 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.

 

We recommend the following testing algorithm for patients with B-acute lymphoblastic leukemia (B-ALL):

-At diagnosis, standard (diagnostic) B-ALL FISH panel and/or conventional chromosome studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) should be performed. If there is limited specimen available, the BALLF test will be performed.

-If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.

 

See B-Lymphoblastic Leukemia/Lymphoma Algorithm in Special Instructions.

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

ALL (B-cell), FISH

Specimen Type

Varies


Shipping Instructions


Advise Express Mail or equivalent if not on courier service.



Necessary Information


Provide a reason for referral 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.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Blood
Container/Tube: Green top (sodium heparin)
Specimen Volume: 7-10 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Other anticoagulants are not recommended and are harmful to the viability of the cells.

 

Specimen Type: Bone marrow
Container/Tube: Green top (sodium heparin)
Specimen Volume: 1-2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Other anticoagulants are not recommended and are harmful to the viability of the cells.


Specimen Minimum Volume

Blood: 2 mL
Bone Marrow: 1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Refrigerated 

Clinical Information

In the United States the incidence of acute lymphoblastic leukemia (ALL) is roughly 6,000 new cases per year (as of 2009), or approximately 1 in 50,000. ALL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer. Approximately 85% of pediatric cases of ALL are B-cell lineage (B-ALL) and 15% are T-cell lineage (T-ALL). It has a peak incidence at 2 to 5 years of age. The incidence decreases with increasing age, before increasing again at around 50 years of age. ALL is slightly more common in males than females. There is an increased incidence of ALL in individuals with Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, X-linked agammaglobulinemia, and severe combined immunodeficiency. The overall cure rate for ALL in children is about 90% and about 45% to 60% of adults have long-term disease-free survival. CRLF2/IGH rearrangements are more commonly observed in patients with Down syndrome or of Hispanic descent.

 

Specific genetic abnormalities are identified in the majority of cases of B-ALL, either by conventional chromosome studies or FISH studies. Each of the genetic subgroups are important to detect and can be critical prognostic markers. The decision for early transplantation may be made if t(9;22)(q34;q11.2), MLL (KMT2A) translocations, RUNX1 duplication/amplification or a hypodiploid clone is identified. In contrast, if ETV6/RUNX1 fusion is detected by FISH or hyperdiploidy is identified by chromosome studies, the patient has a favorable prognosis and transplantation is rarely considered.

 

A newly recognized World Health Organization (WHO) entity BCR-ABL1-like ALL or also known as Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) 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. Patients that have failed on 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.

 

A combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients to characterize the B-ALL clone for the important prognostic genetic subgroups. A summary of the characteristic chromosome abnormalities identified in B-ALL is listed in the following table.

 

Common Chromosome Abnormalities in B-Acute Lymphoblastic Leukemia

Leukemia Type

Cytogenetic change

Typical demographic

Risk category

B-Acute Lymphoblastic Leukemia

t(12;21)(p13;q22), ETV6(TEL)/RUNX1(AML1)

Pediatric

Favorable

Hyperdiploidy

Pediatric

Favorable

t(1;19)(q23;p13.3), PBX1/TCF3

Pediatric

Intermediate

t(9;22)(q34;q11.2) BCR/ABL1

Pediatric/Adult

Unfavorable

iAMP21, RUNX1

Pediatric

Unfavorable

del(9p), CDKN2A(p16)

All ages

Variable

t(11q23;var), MLL

All ages

Unfavorable

t(4;11)(q21;q23), AFF1(AF4)/MLL

All ages

Unfavorable

t(6 ;11)(q27;q23), MLLT4/MLL

All ages

Unfavorable

t(9;11)(p22;q23), MLLT3(AF9)/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(ENL)

All ages

Unfavorable

t(14q32;var), IGH

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

All ages

Unfavorable

t(Xp22.3;var) or t(Yp11.32;var), P2RY8

All ages

Unfavorable

del(17p), TP53

All ages

Unfavorable

t(8q24.1;var), MYC

Pediatric/ Adolescent/

Young Adult

 

Complex karyotype (≥4 abnormalities)

Adult

Unfavorable

Low hypodiploidy/near triploidy

Adult

Unfavorable

Near-haploid/hypodiploid

All ages

Unfavorable

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL)

t(1q25;var), ABL2

Pediatric/ Adolescent/

Young Adult

High Risk

 

 

 

 

t(5q33;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.

Day(s) and Time(s) Performed

Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m.

Analytic Time

7 days

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

88271 x 2, 88291-DNA probe, each (first probe set), Interpretation and report

88271 x 2-DNA probe, each; each additional probe set (if appropriate)

88271-DNA probe, each; coverage for sets containing 3 probes (if appropriate)

88271 x 2-DNA probe, each; coverage for sets containing 4 probes (if appropriate)

88271 x 3-DNA probe, each; coverage for sets containing 5 probes (if appropriate)

88274 w/modifier 52-Interphase in situ hybridization, <25 cells, each probe set (if appropriate)

88274-Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)

88275-Interphase in situ hybridization, 100 to 300 cells, each probe set (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
BALLF ALL (B-cell), FISH In Process

 

Result ID Test Result Name Result LOINC Value
51786 Result Summary 50397-9
51788 Interpretation In Process
51787 Result Table No LOINC Needed
54528 Result 62356-1
CG651 Reason for Referral 42349-1
CG652 Specimen 31208-2
51789 Source 31208-2
51790 Method 49549-9
53426 Additional Information 48767-8
55272 Disclaimer 62364-5
51791 Released By No LOINC Needed

NY State Approved

Yes

Forms

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

(http://www.mayomedicallaboratories.com/it-mmfiles/hematopathology-request-form.pdf)