Complete resolution of chylopericardium after chemotherapy for chronic lymphocytic leukemia

Nontraumatic chylous pleural effusions (chylothorax) and pericardial effusions (chylopericardium) are rare. They can, however, accompany intrathoracic malignancies and, most commonly, lymphomas. An association of chronic lymphocytic leukemia (cll) with chylopericardium has rarely been reported. A 68-year-old woman with cll, previously treated with single-agent fludarabine in the community, developed pleuritic chest pain and a new pericardial effusion. Computed tomography (ct) imaging of her chest revealed a large pericardial effusion with progressive lymphadenopathy. Pericardiocentesis identified a chylous effusion, and complete evacuation was achieved by catheter drainage. The cll was not treated. An asymptomatic pericardial effusion subsequently recurred. Pericardiocentesis was not repeated. Lymph node biopsy and flow cytometry revealed no evidence of large-cell lymphoma transformation. The patient was treated with 6 cycles of chlorambucil and obinutuzumab. Imaging of her chest by ct between cycles 2 and 3 revealed a marked resolution of the intrathoracic lymphadenopathy, with complete disappearance of the pericardial effusion. Repeat imaging at 5 months and again at 3 years after completion of chemotherapy demonstrated no recurrence of either the lymphadenopathy or the pericardial effusion. The mechanism of production and the treatment of chylous effusions are poorly defined. In this case, resolution of the pericardial effusion with effective chemotherapy is postulated to have alleviated obstruction of anterograde lymphatic flow facilitating drainage into the systemic venous system and allowing for spontaneous complete resolution of the pericardial effusion without surgical intervention.

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Phase I to II Multicenter Study of Oblimersen Sodium, a Bcl-2 Antisense Oligonucleotide, in Patients With Advanced Chronic Lymphocytic Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.4364 ◽

2005 ◽

Vol 23 (30) ◽

pp. 7697-7702 ◽

Cited By ~ 142

Author(s):

Susan M. O'Brien ◽

Charles C. Cunningham ◽

Anatoliy K. Golenkov ◽

Anna G. Turkina ◽

Steven C. Novick ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Phase I ◽

Phase Ii ◽

Intravenous Infusion ◽

Single Agent ◽

Plasma Concentrations ◽

Parent Drug ◽

Lymphocytic Leukemia ◽

Complete Disappearance ◽

Continuous Intravenous Infusion

Purpose To determine the maximum-tolerated dose (MTD), efficacy, safety, and pharmacokinetics of oblimersen sodium in patients with advanced chronic lymphocytic leukemia (CLL). Patients and Methods Eligible patients had relapsed or refractory CLL after treatment with fludarabine. Oblimersen was administered at doses ranging from 3 to 7 mg/kg/d as a 5-day continuous intravenous infusion in cycle 1 and as a 7-day continuous intravenous infusion in subsequent cycles every 3 weeks in stable or responding patients. Results Forty patients were enrolled and treated (14 patients in phase I and 26 patients in phase II). Dose-limiting reactions in phase I included hypotension and fever, and the MTD for phase II dosing was established at 3 mg/kg/d. Two (8%) of 26 assessable patients achieved a partial response. Other evidence of antitumor activity included ≥ 50% reduction in splenomegaly (seven of 17 patients; 41%), complete disappearance of hepatomegaly (two of seven patients; 29%), ≥ 50% reduction of lymphadenopathy (seven of 22 patients; 32%), and ≥ 50% reduction in circulating lymphocyte counts (11 of 22 patients; 50%). Adverse events included transient hypotension, fever, fatigue, night sweats, diarrhea, nausea, vomiting, hypokalemia, and cough. Plasma concentrations of oblimersen (parent drug) and its major metabolites were variable. Renal clearance represented only a small portion of total parent drug clearance. Conclusion Dosing with oblimersen sodium in patients with CLL is limited by development of a cytokine release syndrome that is characterized by fever, hypotension, and back pain. Oblimersen sodium has modest single-agent activity in heavily pretreated patients with advanced CLL, and further evaluation of its activity in combination with cytotoxic drugs is warranted.

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Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent

Blood ◽

10.1182/blood.v81.11.2878.2878 ◽

1993 ◽

Vol 81 (11) ◽

pp. 2878-2884 ◽

Cited By ~ 178

Author(s):

MJ Keating ◽

S O'Brien ◽

H Kantarjian ◽

W Plunkett ◽

E Estey ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Clinical Response ◽

Alkylating Agents ◽

Single Agent ◽

Response To Therapy ◽

Lymphocytic Leukemia ◽

Strongly Correlated ◽

Prior Therapy ◽

Previously Treated

Abstract The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown.

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Impact of novel chronic lymphocytic leukemia drugs on public spending.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.30_suppl.103 ◽

2018 ◽

Vol 36 (30_suppl) ◽

pp. 103-103

Author(s):

Elena Mow ◽

James Keech ◽

Rohini Naipaul ◽

Jaclyn Marie Beca ◽

Scott Gavura ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Single Agent ◽

Public Spending ◽

Lymphocytic Leukemia ◽

Cost Driver ◽

Drug Benefit ◽

Novel Agents ◽

The Past ◽

Funding Program ◽

Previously Treated

103 Title: Impact Of Novel Chronic Lymphocytic Leukemia Drugs On Public Spending Background: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy that mainly affects the elderly. Over the past five years, the treatment pathway for CLL has dramatically changed with the emergence of multiple novel agents. In Ontario, Canada, the Ontario Drug Benefit (ODB) program and the New Drug Funding Program (NDFP) primarily provide public coverage for CLL drugs. Given advances in treatment, we evaluated utilization trends for publicly-funded CLL drugs over a five year period (fiscal years 2012/13 to 2016/17). Methods: Drugs with primary CLL indications funded under the two public funding programs (i.e., ODB and NDFP) by 16/17 were included (n = 6). Claims and costs data were obtained from the Institute for Clinical Evaluative Sciences and Cancer Care Ontario‘s datasets. Results: Over five years, expenditures on CLL drugs have increased approximately ten-fold (1000 percent), reaching nearly CAD 43 million (i.e., USD 32.8 million) in 16/17. In the front-line setting, spending on rituximab remained consistent over the five years. Spending on single agent bendamustine decreased with the introduction of obinutuzumab which became the main cost driver by 16/17. In the previously-treated CLL population, ibrutinib has dominated expenditures since it was funded in July 2015. By 16/17, ibrutinib accounted for approximately ninety eight percent of spending in the previously-treated population. Conclusions: In the past five years, public spending on CLL drugs increased rapidly and substantially with the introduction of four novel agents, and may continue to evolve as Canadian provinces consider funding additional indications or newer agents. These findings warrant exploring whether the incremental spending is providing survival benefit or improvement in patients’ quality of life in a real-world setting. Declaration of funding: None

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Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent

Blood ◽

10.1182/blood.v81.11.2878.bloodjournal81112878 ◽

1993 ◽

Vol 81 (11) ◽

pp. 2878-2884 ◽

Cited By ~ 2

Author(s):

MJ Keating ◽

S O'Brien ◽

H Kantarjian ◽

W Plunkett ◽

E Estey ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Clinical Response ◽

Alkylating Agents ◽

Single Agent ◽

Response To Therapy ◽

Lymphocytic Leukemia ◽

Strongly Correlated ◽

Prior Therapy ◽

Previously Treated

The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown.

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FIRST RESULTS OF A HEAD‐TO‐HEAD TRIAL OF ACALABRUTINIB VERSUS IBRUTINIB IN PREVIOUSLY TREATED CHRONIC LYMPHOCYTIC LEUKEMIA

Hematological Oncology ◽

10.1002/hon.33_2879 ◽

2021 ◽

Vol 39 (S2) ◽

Author(s):

P. Hillmen ◽

J. C. Byrd ◽

P. Ghia ◽

A. P. Kater ◽

A. Chanan‐Khan ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

First Results ◽

Previously Treated

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Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome)

Blood ◽

10.1182/blood.v70.1.45.45 ◽

1987 ◽

Vol 70 (1) ◽

pp. 45-50 ◽

Cited By ~ 30

Author(s):

LF Bertoli ◽

H Kubagawa ◽

GV Borzillo ◽

M Mayumi ◽

JT Prchal ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

Plasma Cells ◽

Cell Lymphoma ◽

Large Cell ◽

Lymphocytic Leukemia ◽

Immunoglobulin Gene ◽

Anaplastic Lymphoma ◽

Large Cell Lymphoma ◽

Richter’S Syndrome

Abstract A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly “frozen” in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.

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