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

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

This test detects neoplastic clones associated with common chromosome abnormalities in patients with B-acute lymphoblastic leukemia (B-ALL).

This test identifies kinase-activating chromosome abnormalities. Patients with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) may benefit from combining kinase inhibitor with chemotherapy treatment.

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.

• B-Lymphoblastic Leukemia/Lymphoma Algorithm

Fluorescence In Situ Hybridization (FISH)