5′-ABL Gene Deletion on Derivative Chromosome 9 Detected by FISH: Prognostic Significance in CML Patients after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Abstract

BACKGROUND AND OBJECTIVELarge cryptic deletions of the 5′-ABL regions on derivative chromosome 9 can be identified by FISH in 10%–15% of Ph+ CML patients. This abnormality may be associated with unfavorable prognosis with conventional therapies. There is limited data regarding the prognosis of 5′-ABL gene deletion abnormality in recipients of allogeneic HSCT. We performed an analysis of our prospectively collected database to evaluate the prognostic importance of this karyotypic abnormality in HSCT patients.METHODS:Between1989–2004, 24 allogeneic HSCT patients with 5′-ABL gene deletion detected by FISH using ES-BCR/ABL probe were identified. The diagnosis was CML CP1, 16(66.6%), CML CP2, 5(20.8%), CML AP 2(8.3%), CML blastic phase 1(4.1%). Sex ratio: M/F 8/17; median age: 25.06 (14.7–51.9) years. All donors were HLA matched identical sibling. Stem cell source was BM in 15(62.5%), PB in 9(37.5%). Mean CD34 cells x106/kg dose was, BM 5.0 (2.05–7.67), PB 7.18 (1.64–10.71). Conditioning regimen was BU/CY2 in 19, CY/TBI in 4 and FLU/TBI in 1 patient.A second group of 206 Ph+ CML pts was evaluated for comparison. These were patients with CML without 5′-ABL gene deletions that underwent allogeneic SCT from 1989–2004. This group was matched for age, sex, conditioning regimen, type of SCT, stem cell source and HLA matched sibling donors. The diagnosis was CML CP 148(71.8%), CML CP2 37(18.0%) AP 21(10.2%).RESULTS:After a median follow up of 17.5 mths in group 1 (del 9) and 17.05 mths in group 2 (without del 9), relapse occurred in 11/24(45.8%) in group 1 and 48/206(23.3%) in group 2, indicating RFS of 54.2% vs 76.7% respectively (P= .03). A sub-group analysis was made between CML CP1 patients only, between both groups. With 16 patients in group 1 and 148 pts in group 2 with a median FU of 21.5 vs 26.5 mths, the RFS was 7/16(43.7%) vs 118/148 (79.7%) respectively (P=. 001).CONCLUSIONPatients with 5′-ABL gene deletions on derivative chromosome 9 have a significantly higher relapse rate even after high dose chemotherapy and allogeneic HSCT as compared to patients without this abnormality. We recommend close monitoring of these patients by RT-PCR to detect early molecular relapse and treatment with DLI and/or Imatinib Mesylate.