Long-Term Follow-Up of Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine Regimens as Initial Therapy

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1165-1171 ◽  
Author(s):  
M.J. Keating ◽  
S. O’Brien ◽  
S. Lerner ◽  
C. Koller ◽  
M. Beran ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Poor Correlation ◽  
American Society ◽  
Febrile Episodes

One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia (CLL) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone. The overall response rate was 78% and the median survival was 63 months. No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition. The median time to progression of responders was 31 months and the overall median survival was 74 months. Patients over the age of 70 years had shorter survivals. Patients with advanced stage disease (Rai III and IV) had a somewhat shorter survival than earlier stage patients. More than half the patients who relapsed after fludarabine therapy responded to salvage treatment, usually with fludarabine-based regimens. Second remissions were more common in patients who had achieved a complete remission on their initial treatment. The CD4 and CD8 T-lymphocyte subpopulations decreased to levels in the range of 150 to 200/μL after the first 3 courses of treatment. Although recovery towards normal levels was slow, the incidence of infections was low in patients in remission (1 episode of infection for every 3.33 patient years at risk) and decreased with time off treatment. There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission. Infectious episodes were less common in patients who had a complete response compared with partial responders. Richter’s transformation occurred in 9 patients and Hodgkin’s disease occurred in 4 patients. Five other patients died from other second malignancies. Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL. © 1998 by The American Society of Hematology.

Long-Term Follow-Up of Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine Regimens as Initial Therapy

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1165-1171 ◽  
Author(s):  
M.J. Keating ◽  
S. O’Brien ◽  
S. Lerner ◽  
C. Koller ◽  
M. Beran ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Poor Correlation ◽  
American Society ◽  
Febrile Episodes

Abstract One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia (CLL) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone. The overall response rate was 78% and the median survival was 63 months. No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition. The median time to progression of responders was 31 months and the overall median survival was 74 months. Patients over the age of 70 years had shorter survivals. Patients with advanced stage disease (Rai III and IV) had a somewhat shorter survival than earlier stage patients. More than half the patients who relapsed after fludarabine therapy responded to salvage treatment, usually with fludarabine-based regimens. Second remissions were more common in patients who had achieved a complete remission on their initial treatment. The CD4 and CD8 T-lymphocyte subpopulations decreased to levels in the range of 150 to 200/μL after the first 3 courses of treatment. Although recovery towards normal levels was slow, the incidence of infections was low in patients in remission (1 episode of infection for every 3.33 patient years at risk) and decreased with time off treatment. There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission. Infectious episodes were less common in patients who had a complete response compared with partial responders. Richter’s transformation occurred in 9 patients and Hodgkin’s disease occurred in 4 patients. Five other patients died from other second malignancies. Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL. © 1998 by The American Society of Hematology.

Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study.

1986 ◽  
Vol 4 (2) ◽  
pp. 128-136 ◽  
Author(s):  
M J O'Connell ◽  
J P Colgan ◽  
M M Oken ◽  
R E Ritts ◽  
N E Kay ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Severe Toxicity ◽  
Favorable Histology ◽  
Initiation Of Therapy ◽  
Hodgkin's Lymphomas

Twenty patients with disseminated favorable histology non-Hodgkin's lymphomas (16 patients) or chronic lymphocytic leukemia (four patients) who had not received previous chemotherapy were treated with recombinant leukocyte A interferon (IFL-rA) (Hoffmann-La Roche, Nutley, NJ). Treatment was administered in a moderate dose (12 X 10(6) U/m2) by intramuscular (IM) injection three times weekly for 8 weeks, followed by weekly maintenance therapy for an additional 16 weeks in patients responding to therapy. Five patients with stable disease at 8 weeks received four additional weeks of three-times-weekly treatment at an escalated dose (25 X 10(6) U/m2). Interferon was tolerated without severe toxicity by most patients, although treatment was discontinued prematurely due to side effects in four patients. Objective tumor responses (one complete response [CR] and six partial responses [PRs]) were seen in seven of 16 patients with lymphoma (44%). One of four patients with chronic lymphocytic leukemia also experienced a PR. Median time-to-progression from initiation of therapy among responding patients was 26 + weeks (range, 7 + to 84 + weeks). This study has demonstrated single agent antitumor activity of IFL-rA given in a tolerable outpatient dosage regimen in patients with advanced favorable histology non-Hodgkin's lymphomas, and serves as a basis for further trials of IFL-rA combined with chemotherapy as initial therapy for such patients in the future.

Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia.

1991 ◽  
Vol 9 (1) ◽  
pp. 44-49 ◽  
Author(s):  
M J Keating ◽  
H Kantarjian ◽  
S O'Brien ◽  
C Koller ◽  
M Talpaz ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Response Rate ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Total Response ◽  
Major Morbidity ◽  
Total Response Rate ◽  
Febrile Episodes ◽  
Minor Infection

Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL.

Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report.

1997 ◽  
Vol 15 (2) ◽  
pp. 458-465 ◽  
Author(s):  
J M Sorensen ◽  
D A Vena ◽  
A Fallavollita ◽  
H G Chun ◽  
B D Cheson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
National Cancer Institute ◽  
Response Rate ◽  
Performance Status ◽  
Treatment Protocol ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Motor Dysfunction ◽  
Hematologic Toxicity ◽  
Contributing Factors

PURPOSE To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. PATIENTS AND METHODS This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. RESULTS Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. CONCLUSION This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.

scholarly journals A Phase II trial of Ofatumumab and Complement Replacement in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia

2019 ◽  
Author(s):  
Joseph M Tuscano ◽  
Christina Poh ◽  
Aaron S Rosenberg ◽  
Brian A. Jonas ◽  
Gustavo Barisone ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Fresh Frozen Plasma ◽  
Lymphocytic Leukemia ◽  
Complement Activity ◽  
Fresh Frozen ◽  
Low Levels

Abstract Background: While many humanized monoclonal antibodies utilize complement dependent cytotoxicity, the complement depleting effects of these antibodies and the effect of complement replacement are not well-described. This study sought to examine complement levels and the effect of complement repletion after treatment with ofatumumab in patients with chronic lymphocytic leukemia (CLL). Methods: Twelve patients with relapsed or refractory CLL were treated with ofatumumab in combination with fresh frozen plasma used as complement replacement. The primary endpoint was objective response rate. Correlative endpoints included complement levels C3 and C4 and complement activity. Results: Adverse events were minimal, and efficacy was encouraging with an overall response rate of 83% and 2 patients (17%) achieving a complete response. While only 2 (17%) of patients had low complement activity at baseline, 8 (67%) developed low levels of complement activity. At a median follow-up time of 37 months the median progression-free survival was 12.5 months. Conclusions: While a minority of patients had low complement activity at baseline, a majority developed low levels of complement with ofatumumab treatment. The magnitude of complement depletion did not correlate with response. Future trials are needed to further explore complement replacement as a less toxic strategy to improve efficacy of monoclonal antibody-based regimens in CLL.

scholarly journals Updates from the American Society of Hematology 2019 annual meeting: practice-changing studies in treatment-naïve chronic lymphocytic leukemia

2020 ◽  
Vol 27 (2) ◽  
Author(s):  
Versha Banerji ◽  
Peter Anglin ◽  
Anna Christofides ◽  
Sarah Doucette ◽  
Pierre Laneuville
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Annual Meeting ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Meeting Report ◽  
Efficacy And Safety ◽  
Treatment Naïve ◽  
American Society

The 2019 annual meeting of the American Society of Hematology took place 7–10 December in Orlando, Florida. At the meeting, results from key studies in treatment-naïve chronic lymphocytic leukemia were presented. Of those studies, phase III oral presentations focused on the efficacy and safety of therapy with Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) inhibitors. One presentation reported updated results of the ECOG 1912 trial comparing the efficacy and safety of ibrutinib plus rituximab to fludarabine, cyclophosphamide, rituximab in patients with CLL younger than 70 years of age. A second presentation reported interim results of the ELEVATE-TN trial, which is investigating the efficacy and safety of acalabrutinib plus obinutuzumab or acalabrutinib monotherapy versus chlorambucil plus obinutuzumab. A third presentation reported on the single-agent zanubrutinib arm of the SEQUOIA trial in patients with del(17p). The final presentation reported a data update from the CLL14 trial, which is evaluating fixed-duration venetoclax and obinutuzumab versus chlorambucil and obinutuzumab, including the association of minimal residual disease status on progression-free survival. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice.

Impact of Therapy With Chlorambucil, Fludarabine, or Fludarabine Plus Chlorambucil on Infections in Patients With Chronic Lymphocytic Leukemia: Intergroup Study Cancer and Leukemia Group B 9011

2001 ◽  
Vol 19 (16) ◽  
pp. 3611-3621 ◽  
Author(s):  
Vicki A. Morrison ◽  
Kanti R. Rai ◽  
Bercedis L. Peterson ◽  
Jonathan E. Kolitz ◽  
Laurence Elias ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Initial Therapy ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Best Response ◽  
Stage Disease ◽  
Group B ◽  
Leukemia Group

PURPOSE: We sought to determine whether therapy with single-agent fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol. Patients were randomized to therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment arms were tested with the Kruskal-Wallis, Wilcoxon, and χ2 tests. RESULTS: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry until either reinstitution of initial therapy, therapy with a second agent, or death). Patients treated with fludarabine plus chlorambucil had more infections than those receiving either single agent (P < .0001). Comparing the two single-agent arms, there were more infections on the fludarabine arm (P = .055) per month of follow-up. Fludarabine therapy was associated with more major infections and more herpesvirus infections compared with chlorambucil (P = .008 and P = .004, respectively). Rai stage and best response to therapy were not associated with infection. A low serum immunoglobulin G was associated with number of infections (P = .02). Age was associated with incidence of major infection in the combination arm (P = .004). CONCLUSION: Combination therapy with fludarabine plus chlorambucil resulted in significantly more infections than treatment with either single agent. Patients receiving single-agent fludarabine had more major infections and herpesvirus infections compared with chlorambucil-treated patients.

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