- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer Center
NCI CANCERLIT® Search: Chronic Lymphocytic Leukemia - October 2002
National Cancer Institute®
Last Modified: October 1, 2002
- Lack of allelic exclusion and isotype switching in B cell chronic lymphocytic leukemia.
- Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia.
- Evaluation of tumor necrosis factor-alpha and erythropoietin serum levels in B-cell chronic lymphocytic leukemia patients with anemia.
- T-cell clonal expansion in patients with B-cell lymphoproliferative disorders.
- Detection of minimal residual disease in B chronic lymphocytic leukemia (CLL).
- Diagnosis of transfusion-associated graft-versus-host disease by polymerase chain reaction in fludarabine-treated B-chronic lymphocytic
- T-cell form of chronic lymphocytic leukaemia: a reaffirmation of its existence.
- Transfusion-associated graft-versus-host disease (TA-GVHD) in fludarabine-treated patients: is it time to irradiate blood component?
- Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil:
- Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.
- Phosphomonoester concentrations differ between chronic lymphocytic leukemia cells and normal human lymphocytes.
- Chronic lymphocytic leukemia B cells can undergo somatic hypermutation and intraclonal immunoglobulin V(H)DJ(H) gene diversification.
- Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia.
- B-chronic lymphocytic leukemia: practical aspects.
- Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX.
- Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia.
- Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic anemia of chronic lymphocytic leukemia.
- In vitro evaluation of bendamustine induced apoptosis in B-chronic lymphocytic leukemia.
- Chronic lymphocytic leukaemia: only treat when symptomatic.
- Chronic lymphocytic leukaemia--the haematologic basis for diagnosis and treatment.
- High-grade uveal B-cell lymphoma as the initial feature in Richter syndrome.
- Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of
Table of Contents
1
UI - 11754422
AU - Katayama Y; Sakai A; Katsutani S; Takimoto Y; Kimura A
TI -
Lack of allelic exclusion and isotype switching in B cell chronic
lymphocytic leukemia.
SO - Am J Hematol 2001 Dec;68(4):295-7
AD - Department of Hematology and Oncology, Division of Clinical Research,
Research Institute for Radiation Biology and Medicine, Hiroshima
University, 1-2-3 Kasumi, Minami-ku Hiroshima 734-8553 Japan.
Two rearranged bands of the IgH gene were detected in a case with B cell
chronic lymphocytic leukemia (B-CLL). The expressed VH gene was only VH1
with no somatic mutations in IgM and IgD. The expressions of C mu, C
delta, and C gamma were detected by reverse transcription of RNA
followed by the polymerase chain reaction (RT-PCR). Sequence analysis of
the CDR3 regions of each PCR reaction product showed that the sequence
of one rearranged allele was identical to those of the expressed VH1
gene, C mu and C delta, and the sequence of another rearranged allele
was identical to that of C gamma. However, none of the expressed VH
genes was detected in IgG. These findings suggest that this is a case of
B-CLL lacking allelic exclusion and undergoing a class switch of one
allele with the incomplete expression of the VH gene. Copyright 2001
Wiley-Liss, Inc.
2
UI - 11877310
AU - Tobin G; Thunberg U; Johnson A; Thorn I; Soderberg O; Hultdin M; Botling
TI -
J; Enblad G; Sallstrom J; Sundstrom C; Roos G; Rosenquist R
Somatically mutated Ig V(H)3-21 genes characterize a new subset of
chronic lymphocytic leukemia.
SO - Blood 2002 Mar 15;99(6):2262-4
AD - Department of Genetics and Pathology, Uppsala University, SE-751 85
Uppsala, Sweden.
Recent studies on the immunoglobulin variable heavy chain (IgV(H)) genes
have revealed that B-cell chronic lymphocytic leukemia (B-CLL) consists
of at least 2 clinical entities with either somatically mutated or
unmutated V(H) genes. We have analyzed the V(H) gene mutation status and
V(H) gene usage in 119 B-CLL cases and correlated them to overall
survival. A novel finding was the preferential use of the V(H)3-21 gene
in mutated cases, whereas biased V(H)1-69 gene usage was found in
unmutated cases as previously reported. Interestingly, the subset of
mutated cases using the V(H)3-21 gene displayed distinctive
genotypic/phenotypic characteristics with shorter average length of the
complementarity determining region 3 and clonal expression of lambda
light chains. In addition, this mutated subset showed significantly
shorter survival than other mutated cases and a similar clinical course
to unmutated cases. We therefore suggest that B-CLL cases with mutated
V(H)3-21 genes may constitute an additional entity of B-CLL.
3
UI - 12187026
AU - Capalbo S; Battista C; Delia M; Ciancio A; De Santis G; Dargenio M;
TI -
Diomede D; Liso V
Evaluation of tumor necrosis factor-alpha and erythropoietin serum
levels in B-cell chronic lymphocytic leukemia patients with anemia.
SO - Acta Haematol 2002;108(2):84-9
AD - Institute of Hematology, University of Bari, Italy.
ematba@cimedoc.uniba.it
Serum levels of tumor necrosis factor-alpha (TNF-alpha) and of
erythropoietin (Epo) have been evaluated in 100 patients with B-cell
chronic lymphocytic leukemia (CLL) in order to determine whether these
factors could be significant in the development of anemia, which was
observed in some cases with advanced disease. In our series of patients,
TNF-alpha serum levels had an inverse correlation with hemoglobin levels
(r = -0.813). In patients with anemia, the serum levels of TNF-alpha
were significantly higher (p = 0.022) than in those without anemia
(186.7 +/- 84.7 vs. 39.8 +/- 20.7 pg/ml). Serum Epo levels were also
significantly (p = 0.0003) increased in CLL patients with anemia
compared to those without (134.1 +/- 225.9 vs. 12.3 +/- 4.8 mU/ml). The
ratio of observed/predicted (O/P) serum Epo was adequate (>0.8) for the
degree of anemia in 70% of patients with anemia and inadequate in the
remaining 30%. In the latter, the mean serum TNF-alpha level was
significantly higher (p = 0.005) than the mean for the anemic cases with
an adequate O/P ratio of serum Epo (234.1 vs. 166.4 pg/ml). These data
suggest that although CLL anemia is not characterized by inadequate Epo
production, in some CLL patients this factor may be correlated. In these
cases, the levels of TNF-alpha were significantly higher than in other
anemic cases. Compared to other CLL patients with anemia, these CLL
patients might better respond to therapy with recombinant human Epo in
pharmacological doses. Copyright 2002 S. Karger AG, Basel
4
UI - 9789198
AU - Alatrakchi N; Farace F; Frau E; Carde P; Munck JN; Triebel F
TI -
T-cell clonal expansion in patients with B-cell lymphoproliferative
disorders.
SO - J Immunother 1998 Sep;21(5):363-70
AD - Laboratoire d'Immunologie Cellulaire, INSERM U3331, Villejuif, France.
We investigated whether T-cell clonal expansion could be found in the
blood of 14 untreated patients with B-cell lymphoproliferative disorders
[5 B-chronic lymphocytic leukemia (CLL), 4 myelomas, 5 non-Hodgkin
lymphoma (NHL)]. The putative presence of T-cell clonotypes was analyzed
with a polymerase chain reaction-based method determining V-D-J junction
size patterns in 24 T-cell receptor (TCR) V beta subfamilies. This
high-resolution method, analyzing CDR3 sizes of TCR transcripts, was
used in conjunction with cytometric analysis of the corresponding T-cell
subpopulations with 18 TCR V beta-specific monoclonal antibody. We found
multiple dominant T-cell clonotypes in the blood of most patients with
B-CLL or myeloma as well of a patient with stage IV NHL. In some cases,
T-cell clonal expansion was so dominant that the percentage of these
clonal T-cell subpopulations in blood represented more than the mean +2
SD value determined in a series of healthy controls. We conclude that a
systemic antigen-specific (i.e., leading to clonotypic expansion) immune
reaction involving few TCR clonotypes is a hallmark of disseminated
B-cell malignancies. The nature of the putative antigens recognized is
not known presently. Nonetheless, such insights into the T-cell
repertoire of these patients may help to reassess the potential of
immunotherapeutic strategies in B-cell malignancies.
5
UI - 10193641
AU - Magnac C; Sutton L; Cazin B; Laurent C; Binet JL; Merle-Beral H;
TI -
Dighiero G; Maloum K
Detection of minimal residual disease in B chronic lymphocytic leukemia
(CLL).
SO - Hematol Cell Ther 1999 Feb;41(1):13-8
AD - Unite d'Immuno-Hematologie et d'Immunopathologie, Institut Pasteur,
Paris, France.
In the absence of specific chromosomal translocations the best method
for detecting minimal residual disease (MRD) in B cell malignancies is
based on the uniqueness of immunoglobulin (Ig) genes rearrangement. We
here report a very sensitive method for assessing MRD in complete
hematological remission (CHR) chronic lymphocytic leukemia (CLL)
patients as defined by the international workshop on CLL (IWCLL).
PATIENTS: Twelve CLL patients in CHR and complete phenotypic remission
(CPR) were included in the study. Eight of them received Fludarabine
(FDR), one was treated by Chop regimen, and the remaining 3 were rescued
by polychemotherapy followed by autologous bone marrow transplantation
(ABMT). METHODS: DNA extracted from peripheral blood lymphocytes (PBL)
of each patient was amplified with VH family specific and framework 3
primers in 5' and a consensus JH primer in 3', before treatment and
sequentially after the CPR completion. When no clonal rearrangement
could be detected by this assay, the CDR3 sequence specific probe of the
clone was used as the 3' primer, associated to the VH family specific
primer in 5'. PCR products were analyzed by classical procedures in
agarose and/or acrylamide gels. RESULTS: Mixtures of leukemic cells and
normal PBL showed detection of a single leukemic cell among more than
10(5) normal cells. Four out of the 12 patients achieved molecular
remission (MR) when employing CDR3 amplification. All 3 autografted
patients were in MR, whereas only one out of the 9 patients treated by
chemotherapy alone achieved MR. When using a clone specific probe, a
clonal signal was observed in all cases but one (ABMT). Results
presented here confirm that MR may be achieved in a few cases of B-CLL.
Further studies are needed to determine the exact relationship between
MRD and clinical outcome.
6
UI - 8547083
AU - Briz M; Cabrera R; Sanjuan I; Fores R; Diez JL; Herrero M; Regidor C;
TI -
Algora M; Fernandez MN
Diagnosis of transfusion-associated graft-versus-host disease by
polymerase chain reaction in fludarabine-treated B-chronic lymphocytic
leukaemia.
SO - Br J Haematol 1995 Oct;91(2):409-11
AD - Department of Haematology, Hospital Puerta de Hierro, Universidad
Autonoma de Madrid, Spain.
Transfusion-associated graft-versus-host disease (TA-GVHD), has rarely
been reported associated with B-chronic lymphocytic leukaemia (B-CLL).
We report a patient diagnosed with B-CLL, previously treated with
fludarabine, who developed TA-GVHD after being transfused during surgery
for splenectomy. Diagnosis was confirmed by polymerase chain reaction
(PCR) detection of donor DNA in the patient, by amplification of
Y-chromosome sequence and analysis of minisatellite polymorphisms. B-CLL
patients treated with fludarabine appear to be at risk for TA-GVHD and
should be regarded as candidates for transfusions with irradiated blood
products. This case illustrates that PCR is a rapid technique for the
early diagnosis of TA-GVHD.
7
UI - 8611452
AU - Wong KF; Chan JK; Sin VC
TI -
T-cell form of chronic lymphocytic leukaemia: a reaffirmation of its
existence.
SO - Br J Haematol 1996 Apr;93(1):157-9
AD - Department of Pathology, Queen Elizabeth Hospital, Hong Kong.
Early in the 1980s three categories of T-cell chronic lymphocytic
leukaemia were recognized: CD4+ CD8- knobby type, CD4- CD8+ azurophilic
type and CD4+ CD8- adult T-cell leukaemia (ATL) type. Both azurophilic
and ATL types were later shown to be distinctive disorders, whereas the
knobby type has been largely neglected and even considered non-existent
by some authors. In this report we describe two patients with leukaemia
of CD3+ CD4+ CD8- post-thymic T lymphocytes presenting with marked
lymphocytosis, generalized lymphadenopathy and hepatosplenomegaly. We
believe that CLL of the post-thymic T-lymphocytes is a distinct entity,
and merits a separate designation from other T-cell leukaemias.
8
UI - 8652406
AU - Briones J; Pereira A; Alcorta I
TI -
Transfusion-associated graft-versus-host disease (TA-GVHD) in
fludarabine-treated patients: is it time to irradiate blood component?
SO - Br J Haematol 1996 Jun;93(3):739-41
9
UI - 12228208
AU - Morrison VA; Rai KR; Peterson BL; Kolitz JE; Elias L; Appelbaum FR;
TI -
Hines JD; Shepherd L; Larson RA; Schiffer CA
Therapy-related myeloid leukemias are observed in patients with chronic
lymphocytic leukemia after treatment with fludarabine and chlorambucil:
results of an intergroup study, cancer and leukemia group B 9011.
SO - J Clin Oncol 2002 Sep 15;20(18):3878-84
AD - Section of Hematology/Oncology, Veterans Affairs Medical Center,
Minneapolis, MN 55417, USA. morri002@tc.umn.edu
PURPOSE: Patients with chronic lymphocytic leukemia (CLL) may have
disease transformation to non-Hodgkin's lymphoma or prolymphocytic
leukemia; however, development of therapy-related acute myeloid leukemia
(t-AML) is unusual. A series of patients enrolled onto an intergroup CLL
trial were examined for this complication. PATIENTS AND METHODS: A total
of 544 previously untreated B-cell CLL patients were enrolled onto a
randomized intergroup study comparing treatment with chlorambucil,
fludarabine, or fludarabine plus chlorambucil. Case report forms from
521 patients were reviewed for t-AML. RESULTS: With a median follow-up
of 4.2 years, six patients (1.2%) to date have developed therapy-related
myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS
evolving to t-AML (n = 1), from 27 to 53 months (median, 34 months)
after study entry. This included five (3.5%) of 142 patients treated
with fludarabine plus chlorambucil and one (0.5%) of 188 receiving
fludarabine; no chlorambucil-treated patients developed t-MDS or t-AML
(P =.007). At study entry, the median age among these six patients was
56 years (range, 44 to 72 years); three were male; the CLL Rai stage was
I/II (n = 4) or III/IV (n = 2). Response to CLL therapy was complete (n
= 4) or partial remission (n = 1) and stable disease (n = 1). Marrow
cytogenetics, obtained in three of six cases at diagnosis of t-MDS or
t-AML, were complex, with abnormalities in either or both chromosomes 5
and 7. Other abnormalities involved chromosomes X, 1, 8, 12, 17, and 19.
Median survival after diagnosis of t-MDS/AML was 3.5 months (range, 0.5
to 10.1 months). CONCLUSION: Our findings raise the possibility that
alkylator-purine analog combination therapy may increase the risk of
therapy-related myeloid malignancies, which is of particular relevance
with regard to ongoing trials using these combination therapies.
10
UI - 12228210
AU - Rai KR; Freter CE; Mercier RJ; Cooper MR; Mitchell BS; Stadtmauer EA;
TI -
Santabarbara P; Wacker B; Brettman L
Alemtuzumab in previously treated chronic lymphocytic leukemia patients
who also had received fludarabine.
SO - J Clin Oncol 2002 Sep 15;20(18):3891-7
AD - Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
rai@lij.edu
PURPOSE: This phase II pilot study determined the efficacy and safety of
alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients
with chronic lymphocytic leukemia (CLL), all of whom had previously
received fludarabine and other chemotherapy regimens. PATIENTS AND
METHODS: Twenty-four patients were treated with intravenous alemtuzumab
at six centers in the United States. The target dose of 30 mg over 2
hours, three times weekly, was administered for up to 16 weeks.
Responses were evaluated by an independent panel of experts using 1996
National Cancer Institute-sponsored Working Group criteria. Safety
assessments included analysis of lymphocyte subpopulations.
Antimicrobial prophylaxis was not mandatory. RESULTS: Eight patients
(33%) achieved a major response (all partial remissions), with a median
time to response of 3.9 months (range, 1.6 to 5.3 months). The median
duration of response was 15.4 months (range, 4.6 to >or= 38.0 months),
the median time to disease progression was 19.6 months (range, 7.7 to
>or= 42.0 months), and the median survival time was 35.8 months (range,
8.8 to >or= 47.1 months). Acute infusion-related events, mainly grades 1
and 2, were most common and most severe in the first week. Ten patients
(eight nonresponders and two responders) experienced major infections
on-study. Pneumocystis carinii pneumonia was reported in two patients
on-study; neither had received prophylaxis. Median CD4+ and CD8+ counts
decreased and then began to increase by the end of the study, with
further recovery by 1-month follow-up. One of 53 samples obtained from
10 patients had a low titer of alemtuzumab antibodies. CONCLUSION:
Alemtuzumab has significant activity in poor-prognosis,
fludarabine-treated CLL patients. However, because of a relatively high
incidence of opportunistic infections accompanying profound lymphopenia,
future protocols should include mandatory prophylaxis.
11
13
14
15
16
17
18
19
20
21
22
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
UI - 12163053
AU - Franks SE; Smith MR; Arias-Mendoza F; Shaller C; Padavic-Shaller K;
TI -
Kappler F; Zhang Y; Negendank WG; Brown TR
Phosphomonoester concentrations differ between chronic lymphocytic
leukemia cells and normal human lymphocytes.
SO - Leuk Res 2002 Oct;26(10):919-26
AD - NMR and Medical Spectroscopy, Fox Chase Cancer Center, 7701 Burholme
Avenue, Philadelphia, PA 19111, USA.
Levels of phospholipid-related metabolites of chronic lymphocytic
leukemia lymphocytes (CLL) and normal human lymphocytes were quantified
using phosphorus magnetic resonance spectroscopy. The CLL cells versus
normal lymphocytes showed significant increases of
phosphoethanolamine(Etn-P) (8.11+/-2.10 mean+/-S.E., micromol/g wet
weight, n=12 versus 3.63+/-1.10, n=3, P
UI - 12208878
AU - Gurrieri C; McGuire P; Zan H; Yan XJ; Cerutti A; Albesiano E; Allen SL;
TI -
Vinciguerra V; Rai KR; Ferrarini M; Casali P; Chiorazzi N
Chronic lymphocytic leukemia B cells can undergo somatic hypermutation
and intraclonal immunoglobulin V(H)DJ(H) gene diversification.
SO - J Exp Med 2002 Sep 2;196(5):629-39
AD - Division of Molecular Immunology, Department of Pathology, Cornell
University Weill Medical College, New York, NY 10021, USA.
Chronic lymphocytic leukemia (CLL) arises from the clonal expansion of a
CD5(+) B lymphocyte that is thought not to undergo intraclonal
diversification. Using V(H)DJ(H) cDNA single strand conformation
polymorphism analyses, we detected intraclonal mobility variants in 11
of 18 CLL cases. cDNA sequence analyses indicated that these variants
represented unique point-mutations (1-35/patient). In nine cases, these
mutations were unique to individual submembers of the CLL clone,
although in two cases they occurred in a large percentage of the clonal
submembers and genealogical trees could be identified. The
diversification process responsible for these changes led to single
nucleotide changes that favored transitions over transversions, but did
not target A nucleotides and did not have the replacement/silent
nucleotide change characteristics of antigen-selected B cells.
Intraclonal diversification did not correlate with the original
mutational load of an individual CLL case in that diversification was as
frequent in CLL cells with little or no somatic mutations as in those
with considerable mutations. Finally, CLL B cells that did not exhibit
intraclonal diversification in vivo could be induced to mutate their
V(H)DJ(H) genes in vitro after stimulation. These data indicate that a
somatic mutation mechanism remains functional in CLL cells and could
play a role in the evolution of the clone.
UI - 12360407
AU - MacFarlane M; Harper N; Snowden RT; Dyer MJ; Barnett GA; Pringle JH;
TI -
Cohen GM
Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell
chronic lymphocytic leukaemia.
SO - Oncogene 2002 Oct 3;21(44):6809-18
AD - MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box
138, Lancaster Road, Leicester LE1 9HN, UK.
Primary B cells from B cell chronic lymphocytic leukaemia (B-CLL) were
resistant to the novel selective cytotoxic agent, TNF-related
apoptosis-inducing ligand (TRAIL). Low levels of the death-inducing
TRAIL receptors, TRAIL-R1 and TRAIL-R2 but not the putative 'decoy'
receptors, TRAIL-R3 and TRAIL-R4, were expressed on the surface of B-CLL
cells. Resistance to TRAIL was upstream of caspase-8 activation, as
little or no caspase-8 was processed in TRAIL-treated B-CLL cells. Low
levels of a TRAIL death-inducing signalling complex (DISC) were formed
in these cells, accompanied by the recruitment of endogenous FADD,
caspase-8 and c-FLIP(L) but not c-FLIP(S). Both caspase-8 and c-FLIP(L)
were cleaved to form two stable intermediates of approximately 43 kDa,
which remained associated with the DISC. Caspase-8 was not further
processed to its active heterotetramer. Thus the resistance of B-CLL
cells to TRAIL may be due partly to low surface expression of the death
receptors resulting in low levels of DISC formation and also to the high
ratio of c-FLIP(L) to caspase-8 within the DISC, which would prevent
further activation of caspase-8. Our results highlight the possibility
of sensitising B-CLL cells to TRAIL by modulation of c-FLIP levels or by
upregulation of surface expression of death receptors.
UI - 12203655
AU - Pangalis GA; Vassilakopoulos TP; Dimopoulou MN; Siakantaris MP;
TI -
Kontopidou FN; Angelopoulou MK
B-chronic lymphocytic leukemia: practical aspects.
SO - Hematol Oncol 2002 Sep;20(3):103-46
AD - Hematology Section, 1st Department of Internal Medicine, School of
Medicine, National and Kapodistrian University of Athens, Laikon General
Hospital, Athens, Greece. pangalis@otenet.gr
B-CLL is the most common adult leukemia in the Western world. It is a
neoplasia of mature looking B-monoclonal lymphocytes co-expressing the
CD5 antigen (involving the blood, the bone marrow, the lymph nodes and
related organs). Much new information about the nature of the neoplastic
cells, including chromosomal and molecular changes as well as mechanisms
participating in the survival of the leukemic clone have been published
recently, in an attempt to elucidate the biology of the disease and
identify prognostic subgroups. For the time being, clinical stage based
on Rai and Binet staging systems remains the strongest predictor of
prognosis and patients' survival, and therefore it affects treatment
decisions. In the early stages treatment may be delayed until
progression. When treatment is necessary according to well-established
criteria, there are nowadays many different options. Chlorambucil has
been the standard regimen for many years. During the last decade novel
modalities have been tried with the emphasis on fludarabine and
2-chlorodeoxyadenosine and their combinations with other drugs. Such an
approach offers greater probability of a durable complete remission but
no effect on overall survival has been clearly proven so far. Other
modalities, included in the therapeutic armamentarium, are monoclonal
antibodies, stem cell transplantation (autologous or allogeneic) and new
experimental drugs. Supportive care is an important part of patient
management and it involves restoring hypogammaglobulinemia and
disease-related anemia by polyvalent immunoglobulin administration and
erythropoietin respectively. Copyright 2002 John Wiley & Sons, Ltd.
UI - 12200376
AU - Krackhardt AM; Witzens M; Harig S; Hodi FS; Zauls AJ; Chessia M; Barrett
TI -
P; Gribben JG
Identification of tumor-associated antigens in chronic lymphocytic
leukemia by SEREX.
SO - Blood 2002 Sep 15;100(6):2123-31
AD - Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney
Street, Boston, MA 02115, USA.
Chronic lymphocytic leukemia (CLL) is associated with a variety of
immunologic disturbances. Hypogammaglobulinemia and autoimmune phenomena
are both often present in this disease. In contrast, humoral or cellular
antitumor responses are rarely observed. It has been previously shown
that antigens detected in patients with malignant diseases can provide
information regarding intracellular molecules engaged in the
transformation process and can identify tumor antigens that may be
useful for development of immunotherapeutic strategies. Serologic
identification by recombinant expression cloning (SEREX) has been
demonstrated to be a useful method to detect tumor and tumor-associated
antigens in a variety of malignancies. Although this approach is
complicated in CLL, we used a modified SEREX approach and identified 14
antigens (KW-1 to KW-14) using this methodology. Several clones showed a
restricted expression pattern in normal tissues. Moreover, distinctive
expression of splice variants and aberrant gene expression in malignant
tissue were detected. In this study, 6 antigens were detected
exclusively in patients with CLL. Eight antigens were detected also in
lymphoma patients. Healthy donors showed antibody responses against only
3 of the identified antigens. T cells with specific cytotoxicity against
peptides derived from the 2 antigens tested could be generated from
healthy donors. These findings demonstrate that humoral and cellular
immune responses against CLL-associated antigens can be detected.
Ongoing experiments investigate their potential for the development of
immunotherapeutic strategies.
UI - 12200396
AU - Hegde UP; Wilson WH; White T; Cheson BD
TI -
Rituximab treatment of refractory fludarabine-associated immune
thrombocytopenia in chronic lymphocytic leukemia.
SO - Blood 2002 Sep 15;100(6):2260-2
AD - Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD, USA.
Fludarabine can exacerbate idiopathic thrombocytopenia (ITP) in chronic
lymphocytic leukemia (CLL). We report 3 CLL patients with refractory
fludarabine-associated ITP who responded to rituximab. The patients had
Rai stages III, III, and IV disease. Before fludarabine treatment, the
platelet counts were 141 000/microL, 118 000/microL, and 70 000/microL.
ITP developed within week 1 of cycle 3 in 2 patients and within week 2
of cycle 1 in 1 patient. Platelet count nadirs were 4000/microL,
1000/microL, and 2000/microL, respectively, and did not respond to
treatment with steroids or intravenous immunoglobulin. Rituximab therapy
(375 mg/m(2) per week for 4 weeks) was begun on days 18, 23, and 20 of
ITP. Patient 1 achieved a platelet count of more than 50 000/microL at
day 21 and more than 133 000/microL at day 28, patient 2 achieved a
platelet count of more than 50 000/microL at day 4 and more than 150
000/microL at day 10, and patient 3 achieved a platelet count of more
than 50 000/microL at day 5 and 72 000/microL at day 28 of rituximab
therapy, with platelet response durations of 17+, 6+, and 6 months.
These results suggest rituximab can rapidly reverse refractory
fludarabine-associated ITP.
UI - 12357362
AU - Gupta N; Kavuru S; Patel D; Janson D; Driscoll N; Ahmed S; Rai KR
TI -
Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic
anemia of chronic lymphocytic leukemia.
SO - Leukemia 2002 Oct;16(10):2092-5
AD - Division of Hematology/Oncology, Department of Medicine, Long Island
Jewish Medical Center, New Hyde Park, New York 11040, USA.
Autoimmune hemolytic anemia (AIHA) is a well known complication of
chronic lymphocytic leukemia (CLL). Steroids are the first line of
treatment and there are limited effective treatment options for steroid
refractory AIHA of CLL. Rituximab, an active agent against B cell
malignancies, has also been noted to be active in certain autoimmune
hematologic disorders. We used a combination of rituximab,
cyclophosphamide and dexamethasone (RCD) in eight CLL patients with
steroid refractory AIHA. Rituximab was given at a dose of 375 mg/m(2)
i.v. on day 1 (D-1). Cyclophosphamide was given at a dose of 750 mg/m(2)
on D-2. Twelve mg of dexamethasone was given i.v. on D-1, D-2 and orally
from D-3 to D-7. Cycles were repeated every 4 weeks till the best
response. Response in AIHA was evaluated by frequent blood counts and
Coombs test. All eight patients achieved a remission of their AIHA.
Median pretreatment hemoglobin was 8.3 g/dl and post-treatment
hemoglobin was 14.3 g/dl. Five patients converted to Coombs negative
after RCD. Median duration of response was 13 months (7-23+).
Retreatment with RCD was also effective in achieving a response on
relapse of AIHA. Our results indicate that a rituximab-based combination
regimen (RCD) is highly effective in treating steroid refractory AIHA of
CLL.
UI - 12357363
AU - Schwanen C; Hecker T; Hubinger G; Wolfle M; Rittgen W; Bergmann L;
TI -
Karakas T
In vitro evaluation of bendamustine induced apoptosis in B-chronic
lymphocytic leukemia.
SO - Leukemia 2002 Oct;16(10):2096-105
AD - Department of Internal Medicine III, University of Ulm, Germany.
Bendamustine is a novel cytostatic agent, with activity in non-Hodgkin's
lymphomas including B-chronic lymphocytic leukemia (B-CLL). The
knowledge about its mode of action, however, is still limited. Here, we
investigated the in vitro ability of bendamustine to induce apoptosis on
freshly isolated peripheral lymphocytes in B-CLL and analyze the
potential underlying mechanisms of action for inducing apoptosis. In CLL
cells taken from 37 previously treated and untreated CLL patients, we
investigated the influence of bendamustine alone, and in combination
with fludarabine, on the induction of apoptosis and changes of Bcl-2 and
Bax expression on mRNA and protein level using the RNase protection
assay or flow cytometry, respectively. Apoptotic cells were determined
with flow cytometry using the fluorescent DNA-binding agent 7-ADD. Using
bendamustine alone in concentrations from 1 microg/ml to 50 microg/ml, a
dose- and time-dependent manner of cytotoxicity from 30.4% to 94.8%
after 48 h could be observed. The LD50 for untreated and pretreated CLL
cells was 7.3 or 4.4 microg/ml, respectively. The median apoptotic rate
was similar in both groups. The combination of bendamustine with
fludarabine led to a highly synergistic effect in inducing apoptosis,
which was 150% higher than expected for bendamustine plus fludarabine.
The level of the initial Bcl-2 and Bax protein and the m-RNA expression
remained unchanged during the incubation with bendamustine. In
conclusion, this study demonstrates for the first time the in vitro
efficacy of bendamustine in inducing apoptosis in B-CLL cells alone and
in combination with fludarabine.
UI - 12378749
AU - Anonymous
TI -
Chronic lymphocytic leukaemia: only treat when symptomatic.
SO - Prescrire Int 2002 Oct;11(61):156-7
(1) Chronic lymphocytic leukaemia usually occurs after the age of 60. It
is more common in men than in women. (2) Life expectancy of asymptomatic
patients differs little from that of the general population, and simple
monitoring is generally recommended. (3) Chlorambucil is the standard
drug used to slow progression of symptomatic disease. Fludarabine is
used if chlorambucil fails. (4) There is no evidence that combination
cytotoxic therapy is any better than chlorambucil or fludarabine alone.
(5) Alemtuzumab is not yet adequately evaluated. It may prolong survival
by a few months, but only at the cost of sometimes serious side effects.
UI - 12171775
AU - Jacobs P; Wood L
TI -
Chronic lymphocytic leukaemia--the haematologic basis for diagnosis and
treatment.
SO - Hematology 2002 Feb;7(1):33-41
AD - The Department of Haematology and Boone Marrow Transplant Unit
incorporating the Searll Research Laboratory for Cellular and Molecular
Biology, Constantiaberg Medi-Clinic, Cape Town, South Africa.
haematol@icon.co.za
Clinically diagnosis may be incidental when absolute lymphocytosis is
uncovered at routine medical examination. More usually there is a
recurrent sinopulmonary infection reflecting a varying degree of humoral
and cellular immune deficiency. Autoimmune phenomena may result in
haemolytic anaemia or thrombocytopenia. Expanding tumour bulk underlies
the lymphadenopathy which may be prominent. Diagnosis is confirmed on
morphology of the smear where atypical variants need to be distinguished
from other indolent lymphoproliferative disorders. Immunophenotyping is
indispensable in classification. Prognosis is predicated by cytogenetics
and markers of tumour biology that include beta-2 microglobulin and
peripheral blood lymphocyte doubling time. Management is dictated by
symptoms and signs of progression superimposed upon performance status
that includes age. Disease that is asymptomatic and truly indolent,
particularly in the elderly, qualifies for a careful watch-and-wait
policy. In other circumstances stratification to therapy requires entry
into peer-reviewed protocols if optimal outcome is to be achieved.
Established regimens, of demonstrably equal efficacy, are pulsed
single-agents exemplified by chlorambucil or combinations of
cyclophosphamide with vincristine and prednisone. The purine analogues,
particularly when administered with an alkylating agent and
mitoxantrone, are emerging as superior options. In selected patients any
properly accredited program will make provision for escalation in
chemotherapy requiring haematopoietic stem cell transplantation on the
one hand or use of serotherapy with CD52 antibodies on the other. Less
commonly, but in a defined subgroup, immunoglobulins directed against
membrane CD20 may be effective. Perspective for the generalist is
anchored in recognising that the previous cavalier approach to drug
medication, with or without radiotherapy, is unwise whereas integrated
management is now the international standard of practice. The previous
anachronism of dabbling by occasional therapists is to be deprecated
since this will generally deny patients access to proper diagnosis and
risk-adjusted multi-disciplinary treatment.
UI - 12365922
AU - Fernandez-Suntay JP; Gragoudas ES; Ferry JA; Anderson ME; Dacey MP;
TI -
Dryja TP
High-grade uveal B-cell lymphoma as the initial feature in Richter
syndrome.
SO - Arch Ophthalmol 2002 Oct;120(10):1383-5
AD - Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114,
USA.
UI - 12036888
AU - Korz C; Pscherer A; Benner A; Mertens D; Schaffner C; Leupolt E; Dohner
TI -
H; Stilgenbauer S; Lichter P
Evidence for distinct pathomechanisms in B-cell chronic lymphocytic
leukemia and mantle cell lymphoma by quantitative expression analysis of
cell cycle and apoptosis-associated genes.
SO - Blood 2002 Jun 15;99(12):4554-61
AD - Abteilung Molekulare Genetik and Zentrale Einheit Biostatistik,
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
The B-cell lymphoproliferative malignancies B-cell chronic lymphocytic
leukemia (B-CLL) and mantle cell lymphoma (MCL) share characteristics,
including overlapping chromosomal aberrations with deletions on
chromosome bands 13q14, 11q23, 17p13, and 6q21 and gains on chromosome
bands 3q26, 12q13, and 8q24. To elucidate the biochemical processes
involved in the pathogenesis of B-CLL and MCL, we analyzed the
expression level of a set of genes that play central roles in apoptotic
or cell proliferation pathways and of candidate genes from frequently
altered genomic regions, namely ATM, BAX, BCL2, CCND1, CCND3, CDK2,
CDK4, CDKN1A, CDKN1B, E2F1, ETV5, MYC, RB1, SELL, TFDP2, TNFSF10, and
TP53. Performing real-time quantitative reverse transcription polymerase
chain reaction in a panel of patients with MCL and B-CLL and control
samples, significant overexpression and underexpression was observed for
most of these genes. Statistical analysis of the expression data
revealed the combination of CCND1 and CDK4 as the best classifier
concerning separation of both lymphoma types. Overexpression in these
malignancies suggests ETV5 as a new candidate for a pathogenic factor in
B-cell lymphomas. Characteristic deregulation of multiple genes analyzed
in this study could be combined in a comprehensive picture of 2
distinctive pathomechanisms in B-CLL and MCL. In B-CLL, the expression
parameters are in strong favor of protection of the malignant cells from
apoptosis but did not provide evidence for promoting cell cycle. In
contrast, in MCL the impairment of apoptosis induction seems to play a
minor role, whereas most expression data indicate an enhancement of cell
proliferation.
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
