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.

Treatment-Related Myelodysplasia and Acute Leukemia in Non-Hodgkin’s Lymphoma Patients

2003 ◽  
Vol 21 (5) ◽  
pp. 897-906 ◽  
Author(s):  
James O. Armitage ◽  
Paul P. Carbone ◽  
Joseph M. Connors ◽  
Alexandra Levine ◽  
John M. Bennett ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Alkylating Agents ◽  
Myelogenous Leukemia ◽  
Hodgkin's Lymphoma ◽  
Careful Examination ◽  
High Dose ◽  
Primary Therapy ◽  
Non Hodgkin’S Lymphoma ◽  
Increased Risk ◽  
Non Hodgkin's Lymphoma

Purpose: Standard therapies for non-Hodgkin’s lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation. Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin’s disease patients. Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML. Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.

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

Comparison of treatment regimens for pediatric lymphoblastic non-Hodgkin's lymphoma: a Childrens Cancer Group study.

1995 ◽  
Vol 13 (6) ◽  
pp. 1368-1376 ◽  
Author(s):  
D G Tubergen ◽  
M D Krailo ◽  
A T Meadows ◽  
J Rosenstock ◽  
M Kadin ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Hodgkin’S Lymphoma ◽  
Myelogenous Leukemia ◽  
Hodgkin's Lymphoma ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Localized Disease ◽  
Extent Of Disease

PURPOSE Patients with lymphoblastic non-Hodgkin's lymphoma (LB NHL) were randomized to treatment with either modified LSA2L2 or ADCOMP, which added daunorubicin (DAUN) and asparaginase (L-ASP) to the methotrexate (MTX), cyclophosphamide (CYT), vincristine (VCR), and prednisone (PRED) (COMP) regimen, in a clinical trial to determine the relative effectiveness and toxicity of the two regimens. PATIENTS AND METHODS Patients with LB NHL were eligible for this randomized study if they were less than 22 years of age at diagnosis and had < or = 25% blasts in the bone marrow. Of 307 patients registered, 281 were fully eligible and assessable. Patients were stratified by extent of disease at diagnosis. RESULTS The 5-year event-free survival (EFS) rate for patients with localized disease was 84%, and for patients with disseminated disease, 67%. There were four relapses in 28 patients with localized disease. Two hundred six patients had mediastinal primary tumors and despite local radiation, 34 of 63 failures in these patients involved the primary tumor site with or without other involvement. After adjusting for extent of disease at diagnosis, the regimens did not differ significantly with respect to risk for adverse events. The acute toxicity was primarily neutropenia and thrombocytopenia, with greater initial toxicity in patients on the LSA2L2 regimen. Three patients developed acute myelogenous leukemia. CONCLUSION Long-term EFS in children with LB NHL can be achieved in the majority of patients. Disease progression, which includes recurrence at the primary tumor site, is a major cause of treatment failure in patients with mediastinal presentations. Addition of DAUN and L-ASP to the COMP regimen does not produce a more effective treatment than LSA2L2.

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