TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: BALLF    
B-Lymphoblastic Leukemia/Lymphoma, FISH, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

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

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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

-7 or del(7p), IKZF1 deletions, IKZF1/CEN7

 

-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 CRLF2 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."

-When an extra signal of ABL1 is identified in BCR/ABL1 testing, reflex testing will be performed using the ABL1 break-apart probe set to identify the presence or absence of an ABL1 rearrangement.

-If a MYC rearrangement is identified, break-apart probe sets for BCL2 and BCL6 will be performed.

*The "Standard (diagnostic) B-ALL FISH panel" will be automatically reflexed to the Philadelphia Ph-like ALL panel on pediatric and young adult patients (age <30) who demonstrate normal or nonclassical abnormalities on the Standard (diagnostic) panel. In other circumstances, the Ph-like ALL panel may be recommended and the client notified before performing this testing.

 

The 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

-monosomy 7 or del(7p), IKZF1 deletions, IKZF1/CEN7 enumeration

 

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

-When a CRLF2 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."

-If an ABL1 rearrangement is identified, reflex testing will be performed using the BCR/ABL1 dual-color, double fusion FISH probe set to evaluate for the presence or absence of BCR/ABL1 fusion.

 

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.

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.

 

If this test is ordered and the laboratory is informed that the patient is on a COG protocol, this test will be canceled and automatically reordered by the laboratory as COGBF / B-Lymphoblastic Leukemia/Lymphoma, Children's Oncology Group Enrollment Testing, FISH, Varies.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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, P2RY8, and 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.

 

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

All ages

Intermediate

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

All ages

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

 Diagnosis of Burkitt lymphoma

Complex karyotype (> or =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

-7 or del(7p), IKZF1

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.

 

The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the US Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.

 

FISH is not a substitute for conventional chromosome studies because the latter detects many chromosome abnormalities associated with other hematological disorders that would be missed by this panel FISH 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 malignant cells in the blood specimen (as verified by hematopathology).

Supportive Data

Each probe was independently tested and verified on unstimulated peripheral blood and bone marrow specimens. Normal cutoffs were calculated based on the results of 25 normal specimens. For each probe set a series of chromosomally abnormal specimens was evaluated to confirm each probe set detected the abnormality it was designed to detect.

Clinical Reference Recommendations for in-depth reading of a clinical nature

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 Apr 15;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 Sept;371(11):1005-1015

4. Mullighan CG: The Genomic Landscape of Acute Lymphoblastic Leukemia in Children and Young Adult. Hematology Am Soc Hematol Educ Program 2014 Dec 5;2014(1):174-180

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 May 19;127(20):2391-2405

Special Instructions Library of PDFs including pertinent information and forms related to the test