Contributions
Abstract: PB1628
Type: Publication Only
Background
“Ph-like” acute lymphoblastic leukemia (ALL) is a subtype of B-cell precursor ALL characterized by a poor outcome and various kinase-activating alterations. These include rearrangements of CRLF2, JAK2 or EPOR, fusions involving ABL-class genes, mutations activating JAK-STAT or Ras signaling pathways, and other less common fusions. There are reports that suggest that the poor outcome of these patients (pts) may be improved with Tirosine Kinase (TK) inhibitors.
Aims
In this study we aimed to identify genomic rearrangements of some of the most frequent key tyrosine kinase genes in Philadelphia chromosome-negative (Ph-) and BCR-ABL1–negative (-) ALL adult patients.
Methods
We selected 39 consecutive B-ALL adult patients out of 93 diagnosed in our centre from 2009 to 2017, all of which were Ph(-) and BCR-ABL1(-), without translocations involving 11q23 (MLL gene) detectable by conventional cytogenetics. Fluorescent in situ hybridization (FISH) analysis was performed using break apart probes for CRLF2, ABL1, ABL2, JAK2 and CSF1R genes on the diagnostic samples. Retrospective analysis of patients’ records was performed.
Results
Twenty-two (56.4%) pts were female, with median age at diagnosis of 41 years old [17; 71]; 19 (48.7%) were young adults (<40 years old). Ten (25.6%) pts had hyperleukocytosis (>30x109/L) and three (7.7%) had central nervous system involvement. Conventional cytogenetic analysis was successful in 31 patients: 22 (56%) had normal karyotype, 3 (9.7%) complex karyotype, 2 (6.5%) hyperdiploidy and 2 (6.5%) hypodiploidy. TK rearrangements were observed in 7 (18%) pts: 4 (10%) CRLF2, 2 (5.1%) ABL1 and 1 (2.6%) CSF1R. No patient had ABL2 or JAK2 rearrangements. Of the 39 cases, 10 (27%) had copy number gains of one or more genes, including ABL2 and JAK2. None of the patients with TK rearrangements had complex or hypo/hyperdiploid karyotype. All patients were eligible for intensive chemotherapy protocols (31 HOVON100; 4 HyperCVAD; 4 CLGC). Thirty-three (84.6%) obtained complete remission (CR) after induction, 4 (10.3%) were refractory, and 1 patient died during induction. Sixteen (41%) pts proceeded to allogeneic stem cell transplantation, 14 in first CR. Ten (25.6%) pts relapsed and 15 (38.5%) died (5 in CR). Those patients with TK rearrangements (7) showed inferior median time-to-relapse (9 vs. 34 months; p=0.003), 5-year disease-free survival (0% vs. 65.1%; p=0.016) and 5-year overall survival (0% vs. 66.5%; p=0.012).
Conclusion
Our study demonstrated that, among the Ph(-) ALL patients, those with TK rearrangements had inferior outcome. In a real life perspective, and in the absence of gene-expression profiling or next-generation sequencing, FISH analysis seems like a reliable and cost-effective screening method to identify known rearrangements probably responsible for unfavorable “Ph-like” behavior and potentially targetable with TK inhibitors.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia
Abstract: PB1628
Type: Publication Only
Background
“Ph-like” acute lymphoblastic leukemia (ALL) is a subtype of B-cell precursor ALL characterized by a poor outcome and various kinase-activating alterations. These include rearrangements of CRLF2, JAK2 or EPOR, fusions involving ABL-class genes, mutations activating JAK-STAT or Ras signaling pathways, and other less common fusions. There are reports that suggest that the poor outcome of these patients (pts) may be improved with Tirosine Kinase (TK) inhibitors.
Aims
In this study we aimed to identify genomic rearrangements of some of the most frequent key tyrosine kinase genes in Philadelphia chromosome-negative (Ph-) and BCR-ABL1–negative (-) ALL adult patients.
Methods
We selected 39 consecutive B-ALL adult patients out of 93 diagnosed in our centre from 2009 to 2017, all of which were Ph(-) and BCR-ABL1(-), without translocations involving 11q23 (MLL gene) detectable by conventional cytogenetics. Fluorescent in situ hybridization (FISH) analysis was performed using break apart probes for CRLF2, ABL1, ABL2, JAK2 and CSF1R genes on the diagnostic samples. Retrospective analysis of patients’ records was performed.
Results
Twenty-two (56.4%) pts were female, with median age at diagnosis of 41 years old [17; 71]; 19 (48.7%) were young adults (<40 years old). Ten (25.6%) pts had hyperleukocytosis (>30x109/L) and three (7.7%) had central nervous system involvement. Conventional cytogenetic analysis was successful in 31 patients: 22 (56%) had normal karyotype, 3 (9.7%) complex karyotype, 2 (6.5%) hyperdiploidy and 2 (6.5%) hypodiploidy. TK rearrangements were observed in 7 (18%) pts: 4 (10%) CRLF2, 2 (5.1%) ABL1 and 1 (2.6%) CSF1R. No patient had ABL2 or JAK2 rearrangements. Of the 39 cases, 10 (27%) had copy number gains of one or more genes, including ABL2 and JAK2. None of the patients with TK rearrangements had complex or hypo/hyperdiploid karyotype. All patients were eligible for intensive chemotherapy protocols (31 HOVON100; 4 HyperCVAD; 4 CLGC). Thirty-three (84.6%) obtained complete remission (CR) after induction, 4 (10.3%) were refractory, and 1 patient died during induction. Sixteen (41%) pts proceeded to allogeneic stem cell transplantation, 14 in first CR. Ten (25.6%) pts relapsed and 15 (38.5%) died (5 in CR). Those patients with TK rearrangements (7) showed inferior median time-to-relapse (9 vs. 34 months; p=0.003), 5-year disease-free survival (0% vs. 65.1%; p=0.016) and 5-year overall survival (0% vs. 66.5%; p=0.012).
Conclusion
Our study demonstrated that, among the Ph(-) ALL patients, those with TK rearrangements had inferior outcome. In a real life perspective, and in the absence of gene-expression profiling or next-generation sequencing, FISH analysis seems like a reliable and cost-effective screening method to identify known rearrangements probably responsible for unfavorable “Ph-like” behavior and potentially targetable with TK inhibitors.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia