Improving the Treatment Outcome of Patients with Chronic Lymphocytic Leukemia Through Targeted Antibody Therapy

2013 ◽  
Vol 27 (2) ◽  
pp. 303-327 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C. Byrd
Keyword(s):  
Treatment Outcome ◽  
Chronic Lymphocytic Leukemia ◽  
Antibody Therapy ◽  
Lymphocytic Leukemia

Select High-Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy With Fludarabine and Rituximab in Chronic Lymphocytic Leukemia: Justification for Risk-Adapted Therapy

2006 ◽  
Vol 24 (3) ◽  
pp. 437-443 ◽  
Author(s):  
John C. Byrd ◽  
John G. Gribben ◽  
Bercedis L. Peterson ◽  
Michael R. Grever ◽  
Gerard Lozanski ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Prognostic Factors ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Interphase Cytogenetics ◽  
Mutational Status ◽  
The Impact

Purpose Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutated Ig VH mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy. Methods We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase II study, Cancer and Leukemia Group B (CALGB) 9712. Results Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig VH mutational status to classify risk, there was no association between complete response rate with either unmutated Ig VH mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig VH unmutated patients as compared with the Ig VH mutated patients. Using the hierarchical classification of Döhner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk. Conclusion These data demonstrate that high-risk CLL patients characterized by Ig VH unmutated (≥ 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig VH mutational status and interphase cytogenetics on treatment outcome.

The Impact of Selected Apoptotic Markers and Adhesion Molecules on the Treatment Outcome of Chronic Lymphocytic Leukemia

2009 ◽  
Vol 9 (6) ◽  
pp. E35
Author(s):  
Thoraya Abdelhamid ◽  
Amira Khorshed ◽  
Nahed Abdelwahab ◽  
Hesham Shahin ◽  
Dhalia Khadry ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Chronic Lymphocytic Leukemia ◽  
Adhesion Molecules ◽  
Lymphocytic Leukemia ◽  
Apoptotic Markers ◽  
The Impact

scholarly journals Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 1036-1045 ◽  
Author(s):  
RO Dillman ◽  
DL Shawler ◽  
RE Sobol ◽  
HA Collins ◽  
JC Beauregard ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Injury ◽  
Antibody Therapy ◽  
Lymphocytic Leukemia ◽  
Murine Monoclonal Antibody ◽  
Rapid Infusion ◽  
Experimental Trials ◽  
Free Serum

We infused the murine monoclonal antibody T101 into two patients with advanced refractory chronic lymphocytic leukemia (CLL) after confirming its reactivity with their CLL cells. One patient received doses of 1, 3, and 12 mg; the second patient received 10 mg. Antibody was delivered over 10--15 min. The major observations were: (1) T101 murine monoclonal antibody did bind to cells with T65 surface antigen and saturated these cells in vivo; (2) cells that bound T101 disappeared from the circulation by 2 hr after treatment, as evidenced by a marked drop in lymphocyte counts; (3) T101 serotherapy resulted in some intravascular cell injury associated with sequestration and probably destruction in the liver and lung; (4) free serum T101 was demonstrable, but disappeared by 2--4 hr after infusion; (5) rapid infusion of T101 did not induce significant modulation of T65; (6) rapid infusion of greater than 10 mg of T101 was associated with significant systemic reactions. Monoclonal antibodies may someday have an application in leukemia therapy, but additional experimental trials are clearly indicated.

scholarly journals Expression of shared idiotypes in chronic lymphocytic leukemia and small lymphocytic lymphoma

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1977-1982
Author(s):  
EM Swisher ◽  
DL Shawler ◽  
HA Collins ◽  
A Bustria ◽  
S Hart ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Tumor Cells ◽  
Antibody Therapy ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma ◽  
B Cell Lymphomas ◽  
Murine Monoclonal Antibodies

The expression of shared idiotypes (Slds) has been studied on malignant CD5+B cells from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) using a panel of 37 murine monoclonal antibodies previously demonstrated to be reactive with Slds derived from follicular B-cell lymphomas. Thirteen anti-Slds identified tumor cells from 31 of 105 (30%) CLL patients and 4 of 6 SLL patients. In comparison, the same panel of anti-Slds is reactive with 33% of follicular and diffuse B-cell lymphomas. Ten of these anti-Slds reacted with CLL cases at similar frequencies to that of the B-cell lymphomas. Two anti-Slds, which are known to react with autoantibodies, were significantly more prevalent in CLL than in B-cell lymphomas. These data confirm the presence of Slds in CLL and provide further evidence of an association between CLL and autoimmunity. The identification of a panel of antibodies reactive with a significant number of CLL and SLL patients will facilitate the application of anti-idiotype antibody therapy in these diseases.

scholarly journals The clinical application of monoclonal antibodies in chronic lymphocytic leukemia

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3705-3714 ◽  
Author(s):  
Samantha M. Jaglowski ◽  
Lapo Alinari ◽  
Rosa Lapalombella ◽  
Natarajan Muthusamy ◽  
John C. Byrd
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Treatment Options ◽  
Antibody Therapy ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Therapeutic Antibodies ◽  
Leukemia Treatment ◽  
Relapsed Disease ◽  
Adult Leukemia ◽  
Number Of Treatment

Abstract Chronic lymphocytic leukemia (CLL) represents the most prevalent adult leukemia. Treatment with chemotherapy over the past 3 decades has been palliative. The introduction of therapeutic antibodies has increased the number of treatment options for this disease. Despite this increase, our true understanding of the mechanism of action of antibody therapy in CLL remains limited. Rituximab, a CD20 antibody, is currently widely used in combination-based strategies for both previously untreated symptomatic CLL and as salvage therapy. Recent data suggest that the addition of rituximab to fludarabine with or without cyclophosphamide prolongs survival in younger patients with CLL. Other improved CD20 antibodies with promising clinical activity, including ofatumumab and GA-101, are coming forward. Alemtuzumab, a CD52 antibody, likewise has demonstrated benefit in both symptomatic, previously untreated CLL and in patients with relapsed disease but has less selectivity. Development of other therapeutic antibodies targeting alternative B-cell–specific antigens in CLL has been less successful, although many promising candidate antibodies and/or small modular immune pharmaceuticals (SMIPs) are coming forward. In addition, recent efforts to combine currently applied therapeutic antibodies with other biologic and targeted therapies with efficacy in CLL offers the potential to move toward alternative non–chemotherapy-based treatment approaches.

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