scholarly journals Accelerated Telomere Shortening Precedes Development of Therapy-Related Myelodysplasia or Acute Myelogenous Leukemia After Autologous Transplantation for Lymphoma

2009 ◽  
Vol 27 (5) ◽  
pp. 791-798 ◽  
Author(s):  
Sujata Chakraborty ◽  
Can-Lan Sun ◽  
Liton Francisco ◽  
Melanie Sabado ◽  
Liang Li ◽  
...  
Keyword(s):  
Telomere Length ◽  
Acute Myelogenous Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Myelogenous Leukemia ◽  
Hodgkin's Lymphoma ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Molecular Abnormalities ◽  
Acute Myelogenous ◽  
Prospective Longitudinal

Purpose Therapy-related myelodysplasia or acute myelogenous leukemia (t-MDS/AML) is a lethal complication of autologous hematopoietic stem-cell transplantation (aHCT) for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). Here, we investigated the hypothesis that accelerated telomere shortening after aHCT could contribute to the development of t-MDS/AML. Patients and Methods A prospective longitudinal cohort was constructed to investigate the sequence of cellular and molecular abnormalities leading to development of t-MDS/AML after aHCT for HL/NHL. This cohort formed the sampling frame for a nested case-control study to compare changes in telomere length in serial blood samples from patients who developed t-MDS/AML with matched controls who did not develop t-MDS/AML. Results An initial increase in telomere length at day 100 after aHCT was followed by an accelerated telomere shortening in t-MDS/AML patients when compared with controls. These telomere alterations preceded the onset of t-MDS and were independent of other known risk factors associated with development of t-MDS/AML on multivariate analysis. Additionally, we observed reduced generation of committed progenitors in patients who developed t-MDS/AML, indicating that these telomere alterations were associated with reduced regenerative capacity of hematopoietic stem cells. Conclusion The development of t-MDS/AML after aHCT is associated with and preceded by markedly altered telomere dynamics in hematopoietic cells. Accelerated telomere loss in patients developing t-MDS/AML may reflect increased clonal proliferation and/or altered telomere regulation in premalignant cells. Genetic instability associated with shortened telomeres may contribute to leukemic transformation in t-MDS/AML.

Detection of Chromosome Abnormalities Pre–High-Dose Treatment in Patients Developing Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After Treatment for Non-Hodgkin’s Lymphoma

2001 ◽  
Vol 19 (9) ◽  
pp. 2472-2481 ◽  
Author(s):  
Debra M. Lillington ◽  
Ivana N.M. Micallef ◽  
Emily Carpenter ◽  
Michael J. Neat ◽  
John A.L. Amess ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Myelogenous Leukemia ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Non Hodgkin’S Lymphoma ◽  
Increased Risk ◽  
Non Hodgkin's Lymphoma ◽  
Acute Myelogenous ◽  
Abnormal Cells

PURPOSE: To assess whether pre–high-dose therapy (HDT)–related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). PATIENTS AND METHODS: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin’s lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. RESULTS: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus–specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. CONCLUSION: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

Non-Hodgkin’s Lymphoma Terminating in Acute Myelogenous Leukemia

1978 ◽  
Vol 60 (4) ◽  
pp. 250-256 ◽  
Author(s):  
Franco Cavalli ◽  
Roland W. Sonntag ◽  
Andreas Zimmermann ◽  
Kurt Deubelbeiss ◽  
Hans-Jörg Ryssel
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Myelogenous Leukemia ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Acute Myelogenous

Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and hematopoietic stem cell infusion for acute myelogenous leukemia

2006 ◽  
Vol 47 (8) ◽  
pp. 1583-1592 ◽  
Author(s):  
Vilmarie Rodriguez ◽  
Peter M. Anderson ◽  
Mark R. Litzow ◽  
Linda Erlandson ◽  
Barbara A. Trotz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Acute Myelogenous

Longitudinal Assessment of Hematopoietic Abnormalities After Autologous Hematopoietic Cell Transplantation for Lymphoma

2005 ◽  
Vol 23 (27) ◽  
pp. 6699-6711 ◽  
Author(s):  
Ravi Bhatia ◽  
Khristine Van Heijzen ◽  
Ann Palmer ◽  
Asako Komiya ◽  
Marilyn L. Slovak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Hodgkin's Lymphoma ◽  
Autologous Hct ◽  
Prospective Longitudinal ◽  
Autologous Hematopoietic Cell Transplantation

Purpose Autologous hematopoietic cell transplantation (HCT) is being increasingly used as an effective treatment strategy for patients with relapsed or refractory Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL) but is associated with therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) as a major cause of nonrelapse mortality. The phenomenon of hematopoietic reconstitution after autologous HCT and the role of proliferative stress in the pathogenesis of t-MDS/AML are poorly understood. Patients and Methods Using a prospective longitudinal study design, we evaluated the nature and timing of alterations in hematopoietic progenitors and telomere length after HCT in patients undergoing autologous HCT at City of Hope Cancer Center (Duarte, CA). Results A significant reduction in primitive and committed progenitors was observed before HCT compared with healthy controls. Further profound and persistent reduction in primitive progenitors but only transient reduction in committed progenitors were seen after HCT. Primitive progenitor frequency in pre-HCT marrow and peripheral-blood stem cells predicted for primitive progenitor recovery after HCT. Shortening of telomere length was observed in marrow cells early after HCT, with subsequent restoration to pre-HCT levels. Patients within this cohort who developed t-MDS/AML had reduced recovery of committed progenitors and poorer telomere recovery, possibly indicating a functional defect in primitive hematopoietic cells. Conclusion Our studies suggest that hematopoietic regeneration after HCT is associated with increased proliferation and differentiation of primitive progenitors. Increased proliferative stress on stem cells bearing genotoxic damage could contribute to the pathogenesis of t-MDS/AML. Extended follow-up of a larger number of patients is required to confirm whether alterations in progenitor and telomere recovery predict for increased risk of t-MDS/AML.

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