title: Impact of Additional Cytogenetic Abnormalities in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.
abstract: The occurrence of additional cytogenetic abnormalities (ACAs) is common in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) but is of unknown significance in the tyrosine kinase inhibitor (TKI) era. We retrospectively analyzed data from a consecutive case series of adults with Ph+ ALL who had undergone allogeneic hematopoietic cell transplantation (alloHCT) at City of Hope between 2003 and 2014. Among 130 adults with Ph+ ALL who had TKI therapy before alloHCT, 78 patients had available data on conventional cytogenetics at diagnosis and were eligible for outcomes analysis. ACAs were observed in 41 patients (53%). There were no statistically significant differences in median age, median initial WBC count, post-HCT TKI maintenance, or disease status at the time of transplant between the Ph-only and ACA cohorts; however, the Ph-only cohort had a higher rate of minimal residual disease positivity at the time of HCT. Three-year leukemia-free survival (79.8% versus 39.5%, P = .01) and 3-year overall survival (83% versus 45.6%, P = .02) were superior in the Ph-only cohort compared with the ACA cohort, respectively. Monosomy 7 was the most common additional aberration observed in our ACA cohort (n = 12). Thus, when TKI therapy and alloHCT are used as part of adult Ph+ ALL therapy, the presence of ACAs appears to have a significant deleterious effect on outcomes post-HCT.
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California. Electronic address: aldoss_ibr@yahoo.com.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Aldoss
authors.affiliation: Department of Information Science, City of Hope, Duarte, California.
authors.forename: Tracey
authors.initials: T
authors.lastname: Stiller
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
authors.forename: Thai M
authors.initials: TM
authors.lastname: Cao
authors.affiliation: Department of Information Science, City of Hope, Duarte, California.
authors.forename: Joycelynne M
authors.initials: JM
authors.lastname: Palmer
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Thomas
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D012306:Risk; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D047428:Protein Kinase Inhibitors
keywords: Additional cytogenetic abnormalities; Allogeneic; Monosomy 7; Ph+; Philadelphia chromosome positive; Stem cell transplant
references.citation: Blood. 2002 Oct 1;100(7):2357-66
references.pmid: 12239143
references.citation: Blood. 1999 Jun 1;93(11):3983-93
references.pmid: 10339508
references.citation: J Clin Oncol. 2006 Jan 20;24(3):460-6
references.pmid: 16344315
references.citation: Blood. 2007 Apr 15;109(8):3189-97
references.pmid: 17170120
references.citation: Am J Hematol. 2002 Dec;71(4):291-9
references.pmid: 12447959
references.citation: Br J Haematol. 1997 Mar;96(3):601-10
references.pmid: 9054669
references.citation: Leukemia. 2004 Apr;18(4):693-702
references.pmid: 15044926
references.citation: IARC Sci Publ. 1987;(82):1-406
references.pmid: 3329634
references.citation: Blood. 1996 Apr 15;87(8):3135-42
references.pmid: 8605327
references.citation: J Clin Oncol. 2010 Aug 1;28(22):3644-52
references.pmid: 20606084
references.citation: Blood. 2002 Mar 1;99(5):1536-43
references.pmid: 11861265
references.citation: Br J Haematol. 2004 Feb;124(3):275-88
references.pmid: 14717774