98: Radio-Immunotherapy for Low Grade Non-Hodgkin's Lymphoma May Impair the Ability to Mobilize Autologous Peripheral Blood Stem Cells

Abstract Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements, using Southern blot hybridization, has been applied to peripheral blood lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma. The incidence of circulating lymphoma cells detected by gene rearrangement analyses is related to the histologic subtype, clinical stage of disease, and clinical status. Among 104 patients studied at diagnosis, the incidence of positive analyses was 34% in low-grade lymphoma and only 8% in intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected nearly universally in the small lymphocytic histologic subtype. PBL studies were related to the initial stage of disease: positive studies were seen in 35% of patients with stage IV disease, 29% of patients with stage III disease, and 12% of patients with stages I-II disease. The incidence of PBL rearrangements at the time of disease recurrence in 32 patients requiring cytoreductive therapy was 48%, somewhat greater than at initial diagnosis. A group of patients with low-grade lymphoma, who had treatment deferred after diagnosis or recurrence, was also studied; the incidence of PBL rearrangements was 38% in this population. Among 157 patients clinically free of disease, DNA analyses of the PBL were positive in only 10%. Subsequent relapse of disease in 26 patients was antedated by PBL rearrangement in only one patient. Clonal rearrangements detected in 15 patients have been followed by recurrence of clinical disease in only one patient over a median of 24 months from the time of analysis. The lack of detectable rearrangements in the peripheral blood in the majority of patients may be due to methodology or the biology of the disease. These issues may be further addressed with alternative methods for assessment of minimal disease. However, rigorous testing of any new molecular tool requires an adequate patient population in which disease status is closely monitored over a sufficient period of time.

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Long-Term Results of a Phase-I/II Study of Sequential High-Dose Chemotherapy with Autologous Stem Cell Transplantation in the Initial Treatment of Aggressive Non-Hodgkin's Lymphoma

Tumori Journal ◽

10.1177/030089160709300501 ◽

2007 ◽

Vol 93 (5) ◽

pp. 409-416 ◽

Cited By ~ 1

Author(s):

Anja Welt ◽

Philipp Schütt ◽

Cordula Derks ◽

Peter Ebeling ◽

Siemke Müller ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

High Dose Chemotherapy ◽

Hodgkin's Lymphoma ◽

Long Term Results ◽

High Dose ◽

Peripheral Blood Stem Cells ◽

Conventional Dose ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Blood Stem Cells

Aims and Background To improve the survival of patients with aggressive non-Hodgkin's lymphoma, we evaluated a risk-adapted therapeutic approach using high-dose (HD) or conventional-dose (CD) chemotherapy (CT) for poor-risk and good-risk patients, respectively. Methods Twenty patients were treated in each group. In both groups, the first chemotherapy cycle consisted of dexamethasone, vincristine, ifosfamide, and etoposide. Thereafter, the CD or HD patients received 3 or 2 cycles of dexamethasone, vincristine, epirubicin, and cyclophosphamide, respectively, followed by 1 cycle of dexamethasone, carboplatin, and etoposide. In the HD group cyclophosphamide, epirubicin, carboplatin, and etoposide were dose-escalated by a factor of 6, 3, 3, and 3, respectively, as compared to the CD group, and autologous peripheral blood stem cells were administered after each HD-CT cycle. Results Grade III-IV toxicities were neutropenia and thrombocytopenia (100%), anemia (55%), and stomatitis (30%) in patients with HD-CT, and neutropenia (90%) in patients with CD-CT. One toxic death occurred in a patient with HD-CT. The overall response rate was 100% in HD-CT patients, including 70% complete remissions, and 80% in CD-CT patients, including 60% complete remissions. The 10-year overall survival was 55% for patients with HD-CT and 80% for patients with CD-CT. Conclusions The risk-adapted treatment approach showed tolerable toxicities and was associated with encouraging results.

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Detection of non-Hodgkin's lymphoma in the peripheral blood by analysis of antigen receptor gene rearrangements: results of a prospective study

Blood ◽

10.1182/blood.v75.5.1139.bloodjournal7551139 ◽

1990 ◽

Vol 75 (5) ◽

pp. 1139-1145

Author(s):

SJ Horning ◽

N Galili ◽

M Cleary ◽

J Sklar

Keyword(s):

Peripheral Blood ◽

Hodgkin’S Lymphoma ◽

Receptor Gene ◽

Hodgkin's Lymphoma ◽

Low Grade ◽

Gene Rearrangements ◽

Histologic Subtype ◽

Stage Of Disease ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements, using Southern blot hybridization, has been applied to peripheral blood lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma. The incidence of circulating lymphoma cells detected by gene rearrangement analyses is related to the histologic subtype, clinical stage of disease, and clinical status. Among 104 patients studied at diagnosis, the incidence of positive analyses was 34% in low-grade lymphoma and only 8% in intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected nearly universally in the small lymphocytic histologic subtype. PBL studies were related to the initial stage of disease: positive studies were seen in 35% of patients with stage IV disease, 29% of patients with stage III disease, and 12% of patients with stages I-II disease. The incidence of PBL rearrangements at the time of disease recurrence in 32 patients requiring cytoreductive therapy was 48%, somewhat greater than at initial diagnosis. A group of patients with low-grade lymphoma, who had treatment deferred after diagnosis or recurrence, was also studied; the incidence of PBL rearrangements was 38% in this population. Among 157 patients clinically free of disease, DNA analyses of the PBL were positive in only 10%. Subsequent relapse of disease in 26 patients was antedated by PBL rearrangement in only one patient. Clonal rearrangements detected in 15 patients have been followed by recurrence of clinical disease in only one patient over a median of 24 months from the time of analysis. The lack of detectable rearrangements in the peripheral blood in the majority of patients may be due to methodology or the biology of the disease. These issues may be further addressed with alternative methods for assessment of minimal disease. However, rigorous testing of any new molecular tool requires an adequate patient population in which disease status is closely monitored over a sufficient period of time.

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