Cytogenetic studies in untreated Hodgkin's disease

Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11–13, 13p11– 13, 3q26–28, 6q15–16, and 7q31–35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11–13 (P less than .01), 13p11–13 (P less than .01), 14p11 (P less than .01), 15p11– 13 (P less than .02), and 20q12–13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12–13 (P less than .01) and 13p11–13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

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Cytogenetic studies in untreated Hodgkin's disease

Blood ◽

10.1182/blood.v77.6.1298.1298 ◽

1991 ◽

Vol 77 (6) ◽

pp. 1298-1304 ◽

Cited By ~ 72

Author(s):

H Tilly ◽

C Bastard ◽

T Delastre ◽

C Duval ◽

M Bizet ◽

...

Keyword(s):

Hodgkin's Disease ◽

Chromosomal Abnormalities ◽

Hodgkin’S Disease ◽

Stage Iv ◽

Poor Survival ◽

T Cell Lymphomas ◽

Number Of Patients ◽

Structural Abnormalities

Abstract Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11–13, 13p11– 13, 3q26–28, 6q15–16, and 7q31–35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11–13 (P less than .01), 13p11–13 (P less than .01), 14p11 (P less than .01), 15p11– 13 (P less than .02), and 20q12–13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12–13 (P less than .01) and 13p11–13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

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Chromosomal abnormalities in Hodgkin's disease

Blood ◽

10.1182/blood.v73.8.2149.2149 ◽

1989 ◽

Vol 73 (8) ◽

pp. 2149-2154 ◽

Cited By ~ 63

Author(s):

HC Schouten ◽

WG Sanger ◽

M Duggan ◽

DD Weisenburger ◽

KA MacLennan ◽

...

Keyword(s):

Hodgkin's Disease ◽

Cytogenetic Analysis ◽

Clinical Characteristics ◽

Chromosomal Abnormalities ◽

Hodgkin’S Disease ◽

Normal Cells ◽

Number Of Patients ◽

Structural Abnormalities ◽

Cytogenetic Studies ◽

Previously Treated

Abstract Numerous neoplastic states have associated or causal cytogenetic abnormalities. In some cancers, specific chromosomal abnormalities appear to correlate with the clinical characteristics and prognosis. Cytogenetic analysis of Hodgkin's disease is thought to be technically difficult and only a small number of cases with evaluable results have been reported. We have attempted cytogenetic studies of lymph nodes from 37 patients with Hodgkin's disease. In 29 of the 37 patients (78%), successful chromosomal analysis was accomplished. Chromosomal abnormalities were found in 13 patients (45%); five of these patients had been previously treated with chemotherapy. Numerical changes were found in all patients, most commonly involving chromosomes 5, 9, 15, 18, 22, X, and marker chromosomes. Seven patients also had structural abnormalities. The breakpoints 4q32–34, 6q24, 12q13, 12q23–24, and 13p11–13 were each seen in at least two patients. All but two patients had an admixture of normal cells. Three patients had two or more clones, and one had subclones. No statistically significant correlations between chromosomal abnormalities and clinical characteristics were demonstrated, although the number of patients in each subgroup was small. We conclude that chromosomal studies of Hodgkin's disease are likely to be successful. Additional studies are needed to correlate the karyotypical abnormalities in Hodgkin's disease with clinical and biological characteristics.

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Chromosomal abnormalities in Hodgkin's disease

Blood ◽

10.1182/blood.v73.8.2149.bloodjournal7382149 ◽

1989 ◽

Vol 73 (8) ◽

pp. 2149-2154 ◽

Cited By ~ 2

Author(s):

HC Schouten ◽

WG Sanger ◽

M Duggan ◽

DD Weisenburger ◽

KA MacLennan ◽

...

Keyword(s):

Hodgkin's Disease ◽

Cytogenetic Analysis ◽

Clinical Characteristics ◽

Chromosomal Abnormalities ◽

Hodgkin’S Disease ◽

Normal Cells ◽

Number Of Patients ◽

Structural Abnormalities ◽

Cytogenetic Studies ◽

Previously Treated

Numerous neoplastic states have associated or causal cytogenetic abnormalities. In some cancers, specific chromosomal abnormalities appear to correlate with the clinical characteristics and prognosis. Cytogenetic analysis of Hodgkin's disease is thought to be technically difficult and only a small number of cases with evaluable results have been reported. We have attempted cytogenetic studies of lymph nodes from 37 patients with Hodgkin's disease. In 29 of the 37 patients (78%), successful chromosomal analysis was accomplished. Chromosomal abnormalities were found in 13 patients (45%); five of these patients had been previously treated with chemotherapy. Numerical changes were found in all patients, most commonly involving chromosomes 5, 9, 15, 18, 22, X, and marker chromosomes. Seven patients also had structural abnormalities. The breakpoints 4q32–34, 6q24, 12q13, 12q23–24, and 13p11–13 were each seen in at least two patients. All but two patients had an admixture of normal cells. Three patients had two or more clones, and one had subclones. No statistically significant correlations between chromosomal abnormalities and clinical characteristics were demonstrated, although the number of patients in each subgroup was small. We conclude that chromosomal studies of Hodgkin's disease are likely to be successful. Additional studies are needed to correlate the karyotypical abnormalities in Hodgkin's disease with clinical and biological characteristics.

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Stanford-Kaiser Permanente G1 study for clinical stage I to IIA Hodgkin's disease: subtotal lymphoid irradiation versus vinblastine, methotrexate, and bleomycin chemotherapy and regional irradiation.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.5.1736 ◽

1997 ◽

Vol 15 (5) ◽

pp. 1736-1744 ◽

Cited By ~ 59

Author(s):

S J Horning ◽

R T Hoppe ◽

J Mason ◽

B W Brown ◽

S L Hancock ◽

...

Keyword(s):

Hodgkin's Disease ◽

Early Stage ◽

Hodgkin’S Disease ◽

Clinical Stage ◽

Kaiser Permanente ◽

Number Of Patients ◽

Ann Arbor ◽

Extended Field ◽

Involved Field

PURPOSE We have demonstrated that a relatively mild chemotherapy regimen, vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy (IFRT) could substitute for extended-field radiotherapy in patients with favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of this study is to determine if VBM and regional radiotherapy can substitute for extended-field radiotherapy in favorable clinical stage (CS) I and II HD. PATIENTS AND METHODS Seventy-eight patients with favorable CS I to II HD were randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and regional radiotherapy. Randomization was stratified on the basis of age, sex, number of Ann Arbor sites, histology, and institution. Patients were evaluated for freedom from progressive HD, survival, and toxicity. Results were compared with the predecessor trial in pathologically staged patients. RESULTS With a median follow-up period of 4 years, the rate of freedom from progressive HD was 92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and 87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy. Six of seven patients who relapsed are alive and in remission following successful second-line therapy. CONCLUSION Given the caveat of a small number of patients, the results of extended-field radiotherapy and VBM and regional radiotherapy are comparable with a median follow-up period of 4 years. VBM serves as a paradigm to reduce late effects in favorable early-stage HD. We do not advocate its routine use in clinical practice, but instead encourage participation in clinical trials with the objective of maintaining efficacy while reducing toxicity in CS I and II HD.

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Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.4.1297 ◽

1996 ◽

Vol 14 (4) ◽

pp. 1297-1305 ◽

Cited By ~ 91

Author(s):

A Hirsch ◽

N Vander Els ◽

D J Straus ◽

E G Gomez ◽

D Leung ◽

...

Keyword(s):

Pulmonary Function ◽

Hodgkin's Disease ◽

Early Stage ◽

Hodgkin’S Disease ◽

Pulmonary Function Tests ◽

Cancer Center ◽

Mediastinal Irradiation ◽

Number Of Patients ◽

Abvd Chemotherapy

PURPOSE To evaluate the effect of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy alone and of ABVD with mantle or mediastinal irradiation (RT) on the pulmonary function of patients with early-stage Hodgkin's disease. PATIENTS AND METHODS Between 1989 and 1993, 60 patients with clinical stage I to IIIA HD enrolled onto randomized trials at Memorial Sloan-Kettering Cancer Center (MSKCC) underwent prospective evaluation of pulmonary function. All patients received six cycles of ABVD, and 30 patients received mantle or mediastinal RT. Pulmonary function tests (PFTs) and symptom evaluation were conducted before, during, and after completion of chemotherapy and RT, and at various intervals thereafter. The median follow-up time was 30 months. RESULTS During chemotherapy, symptoms of cough and dyspnea on exertion developed in 32 of 60 patients (53%) and declines in pulmonary function occurred in 22 of 60 patients (37%). Discontinuation of bleomycin was necessary in 14 of 60 patients (23%). Following chemotherapy, there was a significant decline in median forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO). In patients who received mantle or mediastinal RT, there was a further decline in FVC following radiation therapy. At the most recent follow-up evaluation, five of 29 patients (18%) who received ABVD alone and nine of 30 (30%) who received ABVD and RT reported persistent mild pulmonary symptoms (P = .36), which did not significantly affect normal daily activity. CONCLUSION ABVD chemotherapy induced acute pulmonary toxicity that required bleomycin dose modification in a substantial number of patients. The addition of RT resulted in a further decrease in FVC; however, this did not significantly affect the functional status of patients.

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