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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Non-Hodgkin's Lymphoma - February 2002
National Cancer Institute®
Last Modified: February 1, 2002
Table of Contents
1
UI - 11807147
AU - Coiffier B; Lepage E; Briere J; Herbrecht R; Tilly H; Bouabdallah R;
TI -
Morel P; Van Den Neste E; Salles G; Gaulard P; Reyes F; Lederlin P;
Gisselbrecht C
CHOP chemotherapy plus rituximab compared with CHOP alone in elderly
patients with diffuse large-B-cell lymphoma.
SO - N Engl J Med 2002 Jan 24;346(4):235-42
AD - Hospices Civils de Lyon and the Universite Claude Bernard, Lyons,
France. bertrand.coiffier@chu-lyon.fr
BACKGROUND: The standard treatment for patients with diffuse
large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and
prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the
CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell
lymphoma. We conducted a randomized trial to compare CHOP chemotherapy
plus rituximab with CHOP alone in elderly patients with diffuse
large-B-cell lymphoma. METHODS: Previously untreated patients with
diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly
assigned to receive either eight cycles of CHOP every three weeks (197
patients) or eight cycles of CHOP plus rituximab given on day 1 of each
cycle (202 patients). RESULTS: The rate of complete response was
significantly higher in the group that received CHOP plus rituximab than
in the group that received CHOP alone (76 percent vs. 63 percent,
P=0.005). With a median follow-up of two years, event-free and overall
survival times were significantly higher in the CHOP-plus-rituximab
group (P<0.001 and P=0.007, respectively). The addition of rituximab to
standard CHOP chemotherapy significantly reduced the risk of treatment
failure and death (risk ratios, 0.58 [95 percent confidence interval,
0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically
relevant toxicity was not significantly greater with CHOP plus
rituximab. CONCLUSIONS: The addition of rituximab to the CHOP regimen
increases the complete-response rate and prolongs event-free and overall
survival in elderly patients with diffuse large-B-cell lymphoma, without
a clinically significant increase in toxicity.
2
UI - 11807154
AU - Cheson BD
TI -
CHOP plus rituximab--balancing facts and opinion.
SO - N Engl J Med 2002 Jan 24;346(4):280-2
3
UI - 11521796
AU - Younes A; Preti HA; Hagemeister FB; McLaughlin P; Romaguera JE;
TI -
Rodriguez MA; Samuels BI; Palmer JL; Cabanillas F
Paclitaxel plus topotecan treatment for patients with relapsed or
refractory aggressive non-Hodgkin's lymphoma.
SO - Ann Oncol 2001 Jul;12(7):923-7
AD - Department of Lymphoma and Myeloma, The University of Texas M. D.
Anderson Cancer Center, Houston 77030, USA. ayounes@mail.mdanderson.org
BACKGROUND: Used as single agents, paclitaxel and topotecan have
demonstrated promising activity in treating patients with relapsed
aggressive non-Hodgkin's lymphoma (NHL). We conducted a phase II
clinical trial to investigate the activity and tolerability of the
combination of both drugs. PATIENTS AND METHODS: Patients with
refractory or relapsed aggressive NHL who had previously been treated
with a maximum of two prior chemotherapeutic regimens were given
intravenous infusions of paclitaxel 200 mg/m2 over three hours on day
one and topotecan 1 mg/m2 over 30 minutes daily from days one to five.
All patients received daily subcutaneous injections of filgrastim
(granulocyte colony-stimulating factor) 5 microg/kg starting 24 hours
after the last dose of chemotherapy until neutrophil recovery.
Treatments were repeated every three weeks for a maximum of six courses.
Patients who achieved partial remission or complete remission (CR) after
at least two courses were offered stem cell transplantation, if
eligible. RESULTS: Of the 71 patients eligible for this trial, 66 (93%)
were evaluable for treatment response. The median age was 53 years
(range 23 to 74 years). Thirty-six percent of the patients had
previously been treated with ara-C/platinum-based regimens, and 48%
failed to achieve CR after primary induction therapy. Sixty-seven
percent of the patients had elevated lactate dehydrogenase levels at the
time of treatment initiation. The overall response rate was 48% (95%
confidence interval (95% CI): 36%-61%). Patients who had primary
refractory disease had a response rate of 31%, compared with 65% for
patients who did not. Similarly, the response rate of patients who
failed to achieve CR after their most recent previous therapy was 37%,
compared with a 65% response rate in patients who relapsed from a first
or second CR. The median duration of response was six months. A total of
199 courses were given, with a median of three courses per patient.
Neutropenia at levels < or = 500 leukocytes per microliter was observed
after 32% of the courses, and thrombocytopenia at levels < or = 20,000
platelets per microliter was observed after 17% of the courses. Grade
3-4 neutropenic fever occurred after 6% of the courses. Non-hematologic
toxic effects were predominantly grade 1-2. CONCLUSION: The combination
of paclitaxel and topotecan is an effective first or second line salvage
therapy for patients with relapsed or refractory aggressive NHL who had
prior anthracycline- or platinum-based chemotherapy.
4
UI - 11573857
AU - Wong SF
TI -
Oral bexarotene in the treatment of cutaneous T-cell lymphoma.
SO - Ann Pharmacother 2001 Sep;35(9):1056-65
AD - College of Pharmacy, Western University of Health Sciences, Irvine, CA,
USA. siuwong@westernu.edu
OBJECTIVE: To review the preclinical and clinical information related to
oral bexarotene approved by the Food and Drug Administration for the
treatment of cutaneous manifestations of cutaneous T-cell lymphoma
(CTCL) in patients who are refractory to at least one prior systemic
therapy. DATA SOURCES: Literature accessed through MEDLINE (from 1990 to
bexarotene, Targretin, LGD1069, and cutaneous T-cell lymphoma. DATA
SYNTHESIS: The management of CTCL remains controversial due to its
rarity in the US and its heterogeneity. An evaluation focusing on the
pharmacology of bexarotene and its role in the management of the
different stages of CTCL was conducted. CONCLUSIONS: Bexarotene has
demonstrated activity in the treatment of CTCL. The oral route of
administration and the adverse effect profile of bexarotene appear to
make this drug a favorable option for the treatment of CTCL. Compared
with other systemic therapies. Phase III randomized studies are needed
to determine the clinical benefits of bexarotene as monotherapy or
combination therapy in the treatment of CTCL.
5
UI - 11808104
AU - Hisada S; Shiratori K; Shimizu K; Hoshino Y; Tsuchiya N; Hayashi N;
TI -
Mizoguchi H
[A case of L-asparaginase-induced severe acute pancreatitis]
SO - Nippon Shokakibyo Gakkai Zasshi 2001 Dec;98(12):1374-8
AD - Department of Gastroenterology, Tokyo Women's Medical University, School
of Medicine.
6
UI - 11753078
AU - Wotherspoon AC; Dogan A; Du MQ
TI -
Mucosa-associated lymphoid tissue lymphoma.
SO - Curr Opin Hematol 2002 Jan;9(1):50-5
AD - Department of Histopathology, Royal Marsden Hospital, London, UK.
Andrew.Wotherspoon@rmh.nthames.nhs.uk
Since the first description of mucosa-associated lymphoid tissue (MALT)
lymphoma in 1983 rapid advances have been made in the understanding of
the pathogenesis and underlying molecular events associated with the
development of this tumor. Lymphoma arises at extranodal sites in which
a pre-existing inflammatory response has provoked the acquisition of
organized lymphoid tissue. Specific molecular events have been
associated with the development of MALT lymphoma including t(11;18) and
alterations in Bcl-10 protein expression, and these appear to be
interlinked. In gastric MALT lymphoma Helicobacter pylori is the most
common stimulus for the acquisition of lymphoid tissue. Eradication of
this organism has been shown to result in regression of the tumor in
many cases, but there are a few that will not respond to this approach.
Predicting those cases unlikely to respond to H pylori eradication alone
has been investigated in a number of ways. An underlying t(11;18) within
the tumor cells appears to predict for a lack of response. Clinical
measurement of the depth of infiltration of the wall by gastric MALT
lymphoma as measured by endoscopic ultrasound has been less clear. More
superficial tumors are more likely to respond, but regression has been
reported even in cases with local lymph node involvement. For
superficial lymphomas at other sites alternatives to radiotherapy,
chemotherapy, or surgery have been sought. Local injections of
interferon (IF) alpha have been successful in treating conjunctival
lymphoma, and this approach may be of use for other superficial lesions.
7
UI - 11400952
AU - Cao TM; Horning S; Negrin RS; Hu WW; Johnston LJ; Taylor TL; Shizuru JA;
TI -
Hoppe RT; Brown BW; Blume KG; Stockerl-Goldstein KE
High-dose therapy and autologous hematopoietic-cell transplantation for
follicular lymphoma beyond first remission: the Stanford University
experience.
SO - Biol Blood Marrow Transplant 2001;7(5):294-301
AD - Department of Medicine, Division of Bone Marrow Transplantation,
Stanford University Medical Center, California 94305-5623, USA.
A retrospective analysis was performed to investigate the outcome of
high-dose therapy (HDT) and autologous hematopoietic cell
transplantation in patients with follicular lymphomas beyond first
remission. Ninety-two patients with primary induction failure or
relapsed follicular low-grade lymphoma (FLGL), follicular large cell
lymphoma (FLCL), and transformed follicular lymphoma (TFL) were treated
with myeloablative therapy consisting of etoposide (60 mg/kg),
cyclophosphamide (100 mg/kg), and either carmustine (BCNU;15 mg/kg) or
fractionated total body irradiation (FTBI; 1200 cGy) followed by
transplantation of purged autologous bone marrow or peripheral blood
hematopoietic cells. For the 49 patients with relapsed FLGL, the median
age was 49 years and the median interval from diagnosis to HDT was 30
months. The 4-year estimate of overall survival (OS) was 60% (95%
confidence interval [CI], 45%-75%) and of disease-free survival (DFS)
was 44% (95% CI, 29%-59%). Treatment with the FTBI-containing HDT
regimen was associated with significantly longer DFS (P = .04) and OS (P
= .04) in our multivariate analysis. OS was also significantly longer
among those treated with 3 or fewer chemotherapy regimens. For the 26
FLCL patients, the median age was 51 years and in 31% the indication for
HDT was primary induction failure. For FLCL patients, the 4-year
estimate of OS was 58% (95% CI, 37%-79%) and of DFS was 51% (95% CI,
30%-72%). Among the 17 patients with TFL, 13 (76%) transformed at first
relapse, and only 6 patients (35%) achieved complete remission with
salvage therapy prior to HDT. For TFL patients, the 4-year estimate of
OS was 50% (95% CI, 24%-76%) and of DFS 49% (95% CI, 20%-78%). There
were 3 occurrences of myelodysplasia (1 after treatment with TBI, 2
after BCNU treatment), yielding an estimated incidence of 7% (95% CI,
0%-16%) at 56 months. This analysis shows that relapsed FLGL patients
treated with 3 or fewer different chemotherapy regimens show inferior
survival. The HDT regimen containing FTBI appears to be superior to the
BCNU-based regimen for relapsed FLGL, although longer follow-up is
needed to evaluate late effects. Lastly, patients with TFL or induction
failure and relapsed FLCL can achieve survival outcome comparable to
those observed with the indolent follicular lymphomas.
8
UI - 11464975
AU - Habn T; Wolff SN; Czuczman M; Fisher RI; Lazarus HM; Vose J; Warren L;
TI -
Watt R; McCarthy PL Jr; ASBMT Expert Panel
The role of cytotoxic therapy with hematopoietic stem cell
transplantation in the therapy of diffuse large cell B-cell
non-Hodgkin's lymphoma: an evidence-based review.
SO - Biol Blood Marrow Transplant 2001;7(6):308-31
AD - Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
theresa.hahn@roswellpark.org
9
UI - 11554623
AU - Quraishi MS; Bessell EM; Clark DM; Jones NS; Bradley PJ
TI -
Aggressive sino-nasal non-Hodgkin's lymphoma diagnosed in
Nottinghamshire, UK, between 1987 and 1996.
SO - Clin Oncol (R Coll Radiol) 2001;13(4):269-72
AD - University Hospital, Nottingham, UK.
In the 10-year period 1987 to 1996, 24 patients were diagnosed with
aggressive non-Hodgkin's lymphoma of the nasal cavities or paranasal
sinuses. The disease occurred in a relatively elderly population of
median age 72 years (range 42 to 96) with a male predominance (male 15;
female nine). The histology on review was mostly of the large B-cell
subtype (21 patients); peripheral T-cell subtype (one), anaplastic large
cell of T-cell type (one) and T/natural killer cell nasal lymphoma
(one). The disease was localized in 20 patients (Stage IEA). The overall
survival at 5 years was 40% (95% confidence interval (CI) 19-61); at 10
years it was 33% (95% CI 12-54). The cause-specific survival (excluding
deaths from causes other than lymphoma) at 5 years and 10 years was 62%
(95% CI 39-86).
10
UI - 11554624
AU - Churn M; Clough V
TI -
Autoimmune thrombocytopenia associated with the first cycle of
fludarabine therapy in the treatment of relapsed non-Hodgkin's lymphoma.
SO - Clin Oncol (R Coll Radiol) 2001;13(4):273-5
AD - Clatterbridge Centre for Oncology, Bebington, UK. mchurn@hotmail.com
Fludarabine phosphate is a purine analogue now commonly used in the
treatment of low-grade lymphoid malignancies. An increased incidence of
autoimmune haemolytic anaemia is reported with the use of fludarabine
for the treatment of chronic lymphocytic leukaemia (CLL). CLL already
confers a high risk of autoimmune disorders and, although these are
recognized in non-Hodgkiin's lymphoma (NHL), they are less common.
Immune thrombocytopenia occurring in patients with CLL treated with
fludarabine has been reported and we describe a further case in a
patient with relapsed NHL. Possible mechanisms of the effect of
fludarabine on autoimmune disorders are discussed.
11
UI - 11554636
AU - Wilkins M; Moe MM
TI -
Acute painless thyroiditis with transient thyrotoxicosis during external
beam irradiation to non-Hodgkin's lymphoma of the thyroid gland.
SO - Clin Oncol (R Coll Radiol) 2001;13(4):311
12
UI - 11705358
AU - Apisarnthanarax N; Duvic M
TI -
Cutaneous T-cell lymphoma. New immunomodulators.
SO - Dermatol Clin 2001 Oct;19(4):737-48
AD - Division of Internal Medicine, Department of Dermatology, University of
Texas, MD Anderson Cancer Center, Houston, Texas, USA.
During the most recent decades, much knowledge has been gained
concerning the immunologic and pathologic mechanisms of CTCL. The
development of immunomodulators aimed at correcting aberrations in
immunology and cellular growth and differentiation reflects this
increased understanding. This review of the currently available
immune-response modifying drugs shows that recombinant forms of natural
cytokines and retinoids can be developed with tolerable toxicity
profiles and substantial efficacy. Although milestone drugs such as
bexarotene have been approved by the FDA- for treatment of CTCL, other
agents such as IL-12 may also have a place in treatment of the disease.
Even though unapproved, IFN-alpha may be the most active single
immunomodulating agent against CTCL. It seems that further delineation
of CTCL cytokine profile changes and immunologic aberrations are key in
developing effective immunomodulators that are able to reverse these
alterations.
13
UI - 11776629
AU - Li Z; Tang P; Huang Y
TI -
[The role of surgery in the management of thyroid lymphoma]
SO - Zhonghua Zhong Liu Za Zhi 1999 Nov;21(6):464-6
AD - Department of Head and Neck Surgery, Cancer Hospital, Peking Union
Medical College, Chinese Academy of Medical Science, Beijing 100021.
OBJECTIVE: To evaluate the role of surgery in the management of thyroid
lymphoma. METHODS: A retrospective analysis was performed of 14 patients
with thyroid lymphoma treated at the Cancer Hospital, Peking Union
Medical College, Chinese Academy Medical Science from 1964 to March
1998. There were 5 males and 9 females, with a median age of 54 years
(range 15-75). There were 4 cases in stage IEA, 9 in stage IIEA, 1 in
stage II EB. Fine needle aspiration biopsy was performed in 1 case,
excision biopsy in 4, thyroid lobectomy in 8, and total thyroidectomy in
1. Radiotherapy was used alone in 4 patients, chemotherapy alone in 2,
radiotherapy combined with chemotherapy in 7, no postoperative treatment
in 1. RESULTS: All but 1 patients were histopathologically diagnosed as
non-Hodgkin's lymphoma. It was of B cell origin in 11 cases, T cell
origin in 2. Seven patients were alive without evidence of recurrent
disease at follow-up, ranging from 5 to 112 months. Three patients died
of lymphoma, 1 died of treatment complication, 2 died of other diseases,
and 1 lost from follow-up. The major surgical resection did not
appreciably affect survival. CONCLUSION: Radiotherapy or chemotherapy,
alone or in combination, is the treatment of choice for thyroid
lymphoma. Surgical resection combined with radiotherapy or chemotherapy
may be beneficial to survival in patients with intrathyroid lymphoma. It
is otherwise limited to make a tissue diagnosis.
14
UI - 11418723
AU - Vats TS
TI -
Pediatric non-Hodgkin lymphomas in children: diagnosis and current
management.
SO - Indian Pediatr 2001 Jun;38(6):583-8
15
UI - 11578915
AU - Weiden PL; Breitz HB
TI -
Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's
lymphoma (NHL).
SO - Crit Rev Oncol Hematol 2001 Oct;40(1):37-51
AD - Virginia Mason Medical Center, 1100 Ninth Avenue, Seattle, WA 98101,
USA. plweiden@aol.com
Pretargeted radioimmunotherapy (PRIT) was first investigated in a series
of phase I and phase II studies in patients with adenocarcinoma using a
pancarcinoma antibody, NR-LU-10. The principles and schema developed
were then applied to an initial study in patients with non-Hodgkin's
lymphoma (NHL). The PRIT approach used is a multi-step delivery system
in which an antibody is used to target streptavidin to a
tumor-associated antigen receptor, and subsequently, biotin is used to
target the 90Y radioisotope to the tumor localized streptavidin. In the
NHL study, a chimeric, IgG1, anti-CD20 antibody (Rituximab) was
conjugated to streptavidin (SA) and administered to patients.
Thirty-four hours later, a clearing agent, synthetic
biotin-N-acetyl-galactosamine, was administered to remove non-localized
conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled
with 111In for imaging and/or 90Y for therapy was administered. Ten
patients with relapsed or refractory NHL were studied, and seven
received 30 or 50 mCi/m(2) 90Y DOTA-biotin. Preliminary studies using
186Re labeled conjugate confirmed that it localized to tumor and that
the clearing agent removed >95% of the conjugate from the circulation.
Radiolabeled biotin localized well to tumor. Unbound radiobiotin was
rapidly excreted from the whole body and normal organs. The mean tumor
dose calculated was 29+/-23 cGy/mCi 90Y, and the mean tumor to whole
body dose ratio was 38:1. Only grade I/II non-hematologic toxicity was
observed. Hematologic toxicity was also not severe; i.e. five of the
seven patients who received 30 or 50 mCi/m(2) of 90Y-DOTA-biotin
experienced only transient grade III (but no grade IV) hematologic
toxicity. Although six of 10 patients developed humoral immune responses
to the streptavidin, these were delayed and transient and hence may not
preclude retreatment. Six of seven patients who received 30 or
50mCi/m(2) 90Y achieved objective tumor regression, including three
complete and one partial response. The estimate of tumor to whole body
dose ratio (38:1) achieved with PRIT in these NHL patients is higher
than that achieved in other studies using conventional RIT. Toxicity was
mild and tumor response encouraging. PRIT clearly deserves additional
study in patients with NHL.
16
UI - 11797111
AU - Mukai M; Bohgaki T; Kondo M; Notoya A; Kohno M
TI -
Changes in the T-helper cell 1/T-helper cell 2 balance of peripheral
T-helper cells after autologous peripheral blood stem cell
transplantation for non-Hodgkin's lymphoma.
SO - Ann Hematol 2001 Dec;80(12):715-21
AD - Division of Clinical Immunology and Hematology, Department of Medicine,
Sapporo City General Hospital, Kita 11-jo, Nishi 13-chome, Chuo-ku,
Sapporo 060-8604, Japan. masaya-mukai@hokkaido.med.or.jp
The purpose of this study was to analyze changes in the T-helper cell
1/T-helper cell 2 (Th1/Th2) balance of peripheral T-helper cells after
autologous peripheral blood stem cell transplantation (auto-PBSCT) for
non-Hodgkin's lymphoma (NHL) and to evaluate the effects of chemotherapy
and granulocyte colony-stimulating factor (G-CSF) on the Th1/Th2
balance. A series of peripheral blood samples from four patients with
NHL were collected before peripheral blood stem cell harvest and after
auto-PBSCT. Using flow cytometry, Th1 and Th2 cells were identified by
their intracellular cytokines: interleukin (IL)-4-/interferon
(IFN)-gamma+ and IL-4+/IFN-gamma-, respectively. The Th1/Th2 balance was
estimated as the ratio of IL4-/IFN-gamma+ cells to IL-4+/IFN-gamma-
cells. Although the Th1/Th2 balance decreased initially, it increased
markedly 28 days after the cessation of G-CSF, following auto-PBSCT, in
parallel with an increase in lymphocytes. This increase was mainly due
to an increase in the proportion of Th1 cells. The Th1/Th2 balance did
not change appreciably before PBSC harvest. Serum IFN-gamma increased
after auto-PBSCT in three patients. These preliminary data demonstrate
that, after auto-PBSCT for NHL, the Th1/Th2 balance decreases initially
and then increases after 1 month to levels above pretreatment levels and
that the effects of chemotherapy and G-CSF on the Th1/Th2 balance are
negligible before PBSC harvest. Further evaluation of the Th1/Th2
balance after allogeneic PBSCT at the single-cell level should be
undertaken using this method.
17
UI - 11778760
AU - Walewski J; Kraszewska E; Mioduszewska O; Romejko-Jarosinska J; Hellmann
TI -
A; Czyz J; Holowiecki J; Kopera M; Grosicki S; Komarnicki M; Rumianowski
L; Kuliczkowski K; Wrobel T; Dwilewicz-Trojaczek J; Robak T; Warzocha K;
Zaluski J; Wojcik E; Dmoszynska A; Walter-Croneck A; Polish Lymphoma
Research Group
Rituximab (Mabthera, Rituxan) in patients with recurrent indolent
lymphoma: evaluation of safety and efficacy in a multicenter study.
SO - Med Oncol 2001;18(2):141-8
AD - The Maria Sklodowska-Curie Memorial Cancer Center and Institute of
Oncology, Warszawa, Poland. walewski@coi.waw.pl
The objective of this multiinstitutional study was to evaluate the
safety and efficacy of rituximab at standard four weekly doses in
patients with recurrent indolent lymphoma. Thirty-eight patients entered
into this study, 63% had follicular lymphoma and 61% had an IPI score of
2 or more. Median disease duration was 3 yr, median number of prior
treatments was three, and 66% of patients responded to the immediate
past treatment with a median remission duration of 3 mo. A total of 158
antibody doses were given, including two patients who received two
courses of four infusions each. One patient developed acute respiratory
failure after the second dose and required assisted ventilation. There
was no immediate relationship to the antibody infusion and no evidence
of infection. This complication resolved and the patient successfully
completed the full course of the antibody treatment. Another patient
discontinued therapy after the second dose owing to intolerable fever
and painful erythema. Sixty percent of the first, and 20% of subsequent
rituximab infusions were associated with infusion-related reactions
including mild fever, chills, and occasional skin eruptions. Complete
and partial responses were achieved in 24% and 35% of 34 evaluable
patients, respectively, for an overall response rate of 59%. The median
time to progression/relapse in responding patients was 16 mo (95% CI,
6.4, 25.6) compared with a median of 3 mo duration of response to the
immediate previous therapy in these patients. Longer response duration
post rituximab monotherapy than with previous treatment in this series
of heavily pretreated patients suggests a major role for the antibody in
the therapy of patients with indolent lymphoma.
18
UI - 11778765
AU - Pangalis GA; Dimopoulou MN; Angelopoulou MK; Tsekouras C;
TI -
Vassilakopoulos TP; Vaiopoulos G; Siakantaris MP
Campath-1H (anti-CD52) monoclonal antibody therapy in
lymphoproliferative disorders.
SO - Med Oncol 2001;18(2):99-107
AD - 1st Department of Internal Medicine, National and Kapodistrian
University of Athens, Laikon General Hospital, Greece.
pangalis@otenet.gr
Campath-1H is a humanized monoclonal antibody targeted against the CDw52
membrane antigen of lymphocytes, which causes complement and
antibody-dependent cell-mediated cytotoxicity. Campath-1H has been used
in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia
(T-PLL), and low-grade non-Hodgkin's lymphoma (LGNHL). Campath-1H is
administered intravenously thrice weekly for up to 12 wk, at an initial
dose of 3 mg, escalated to 10 and 30 mg. The responses (complete [CR]
and partial [PR]) obtained in untreated B-CLL patients are of the order
of 90%. In previously treated B-CLL patients, responses are of the order
of approximately 40%, with 2-4% CRs. Responses are more prominent in the
blood and bone marrow compared to the lymph nodes. The median duration
of response is 9-12 mo. Because of the antibody's higher activity on
circulating lymphocytes, it has been used for in vivo purging of
residual disease in B-CLL, followed by autologous stem-cell
transplantation. In heavily pretreated advanced stage LGNHL, response is
achieved only in 14% of cases with B-phenotype; a 50% response rate is
noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%.
Promising results have been reported in a small number of patients with
refractory autoimmune thrombocytopenia of lymphoproliferative disorders.
The main complications of Campath-1H treatment are caused by tumor
necrosis factor (TNF)-alpha and interleukin (IL)-6 release, usually
during the first intravenous infusion, and include fever, rigor, nausea,
vomiting, and hypotension responsive to steroids. These side effects are
usually less severe with subsequent infusions and can be prevented by
paracetamol and antihistamines. Immunosupression resulting from normal
B- and T-lymphocyte depletion is frequent, resulting in an increased
risk for opportunistic infections. More clinical trials in a larger
number of patients are necessary to determine the exact role and
indications of Campath-1H in lymphoproliferative disorders.
19
UI - 11778974
AU - Jerkeman M; Kaasa S; Hjermstad M; Kvaloy S; Cavallin-Stahl E
TI -
Health-related quality of life and its potential prognostic implications
in patients with aggressive lymphoma: a Nordic Lymphoma Group Trial.
SO - Med Oncol 2001;18(1):85-94
AD - Department of Oncology, Lund University Hospital, Lund, Sweden.
mats.jerkeman@onk.lu.se
This study was conducted to explore treatment and disease-related
effects on health-related quality of life (HRQoL) in patients with
aggressive lymphoma, to identify predictors for impaired long-term
HRQoL, and to analyze the prognostic value of pretreatment HRQoL.
Ninety-five patients with aggressive lymphoma, constituting a subset of
a randomized multicenter trial comparing CHOP and MACOP-B, entered a
HRQoL study, using the EORTC QLQ-C30 questionnaire. Patient scores were
compared to scores from an age- and gender-adjusted reference population
sample, and evaluation of the prognostic value of pretreatment QoL
scores in relation to clinical prognostic factors was performed. Before
treatment, patients exhibited lower scores of global QoL, physical,
role, and social functions, and more appetite loss, compared to the
reference population. Role functioning improved compared to baseline,
but remained depressed compared to the reference group more than 8 mo
after end of treatment. By then, the patient group displayed no
difference in other HRQoL variables compared to that of the reference
population. No reliable predictor for impaired long-term HRQoL could be
identified. In multivariate analysis, including the factors of the
International Prognostic Index, pretreatment global QoL was an
independent prognostic marker for overall survival. In conclusion, in
this population with aggressive lymphoma and favorable prognostic
features, HRQoL was not substantially affected during the first year
after diagnosis. Pretreatment global QoL may constitute a significant
prognostic factor, meriting further investigation in prospective
studies.
20
UI - 11707828
AU - Petryk M; Grossbard ML
TI -
Rituximab therapy of B-cell neoplasms.
SO - Clin Lymphoma 2000 Dec;1(3):186-94; discussion 195-6
AD - St. Luke's-Roosevelt Hospital Center, New York, NY 10019, USA.
The development of rituximab, an anti-CD20 monoclonal antibody,
represents a revolutionary advance in the therapy of hematological
malignancies. Rituximab was approved in 1997 by the Food and Drug
Administration for the treatment of relapsed or refractory, CD20(+),
B-cell, low-grade or follicular non-Hodgkin's lymphoma (NHL). Recent
studies have documented activity of rituximab in other CD20-expressing
hematological malignancies including mantle cell lymphoma, small
lymphocytic lymphoma, aggressive NHL, chronic lymphocytic leukemia, and
Waldenstrom's macroglobulinemia. When used in combination with cytotoxic
chemotherapy, rituximab achieves response rates of 90%-95% in low-grade
follicular and aggressive NHL patients. Currently, rituximab is
undergoing intensive investigation in several large phase II and III
trials, both as a single agent and in combination with chemotherapy.
Clinical research will help define the ultimate role of this agent and
its potential impact on survival of patients with B-cell neoplasms. This
article describes current clinical trials with rituximab and discusses
their significance.
21
UI - 11707832
AU - Jacobson JO; Grossbard M; Shulman LN; Neuberg D
TI -
CHOP chemotherapy with preemptive granulocyte colony-stimulating factor
in elderly patients with aggressive non-Hodgkin's lymphoma: a
dose-intensity analysis.
SO - Clin Lymphoma 2000 Dec;1(3):211-7; discussion 218
AD - North Shore Cancer Center, Peabody, MA 01960, USA.
jacobson@nsmc.partners.org
This prospective trial was designed to determine the safety and efficacy
of full-dose, on-time chemotherapy in elderly patients with aggressive
non-Hodgkin's lymphoma. Twenty patients (median age, 71 years; range, 66
to 80 years) were enrolled in a phase II, multicenter trial to receive
cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) supported by
granulocyte colony-stimulating factor (G-CSF). CHOP was given in
standard doses. Six cycles were planned every 21 days, with G-CSF
starting on day 3 and continuing until the absolute neutrophil count was
greater than 10,000/microL. Consolidation radiation therapy was
permitted. Restaging was performed following cycles 4 and 6. By the
age-adjusted International Prognostic Index, four patients were low, 10
were low-intermediate, four were high-intermediate, and two were high
risk. Eighteen cases completed all 6 cycles. The average cycle length
for all 112 cycles was 21.7 days. The dose intensities (corrected for
delay) for each agent were cyclophosphamide 97.3%, doxorubicin 97.3%,
vincristine 91.5%, and prednisone 97.3%. Treatment-related complications
included grade 4 leukopenia and grade 4 thrombocytopenia in 11.6% and
3.6% of cycles, respectively. Hospitalization for neutropenia and fever
was needed for 7.1% of cycles. There was no grade 3/4 cardiac toxicity.
No treatment-related mortality occurred. All toxicities were reversible.
There were 12 (60%) complete responses, four (20%) gallium-negative
partial responses, and four patients (20%) with progressive disease.
With a median follow-up of 2.29 years, progression-free and overall
survival rates at 2 years are 42% (90% confidence interval: 23%-61%) and
66% (90% confidence interval: 47%-85%), respectively. Using preemptive
G-CSF, full-dose CHOP can be administered safely to elderly patients.
22
UI - 11707834
AU - Intragumtornchai T; Prayoonwiwat W; Numbenjapon T; Assawametha N;
TI -
O'Charoen R; Swasdikul D
CHOP versus CHOP plus ESHAP and high-dose therapy with autologous
peripheral blood progenitor cell transplantation for
high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.
SO - Clin Lymphoma 2000 Dec;1(3):219-25
AD - Division of Hematology, Department of Medicine, Chulalongkorn
University, Bangkok, Thailand. itanin@netserv.chula.ac.th
The purpose of the study was to compare conventional
cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP)
chemotherapy with CHOP (3 courses) plus
etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP),
high-dose therapy (HDT), and autologous peripheral blood progenitor cell
transplantation (PBPCT) as front-line treatment for poor-prognosis
aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April
30, 1998, 58 patients, aged 15-55 years, newly diagnosed with
poor-prognosis aggressive NHL (category F-H by the Working Formulation)
were enrolled. According to the age-adjusted international prognostic
index, 65% of the patients were high-risk cases and 35% made up the
high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were
randomized to continue with CHOP, and 23 were randomized to receive 2-4
cycles of ESHAP followed by HDT and PBPCT. There was no significant
difference in the rate of complete remission between the two groups
(36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI:
23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39
months, the 4-year failure-free survival (FFS) was superior in the
ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P =
0.04). The disease-free survival was marginally different in favor of
the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P =
0.06). The 4-year overall survival between the two treatment arms was
comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48%
for CHOP) (P = 0.25). Treatment-related mortalities were not
significantly different between both groups (17%, 95% CI: 5%-39% for
ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61%
of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT.
As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to
improve the FFS in patients with newly diagnosed, poor-prognosis
aggressive NHL.
23
UI - 11707835
AU - Bolwell B; Kalaycio M; Andresen S; Goormastic M; McBee M; Kuczkowski E;
TI -
Wise K; Sobecks R; Pohlman B
Autologous peripheral blood progenitor cell transplantation for
transformed diffuse large-cell lymphoma.
SO - Clin Lymphoma 2000 Dec;1(3):226-31; discussion 232-3
AD - Department of Hematology and Medical Oncology and Transplant Center, The
Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. bolwelb@ccf.org
The outcome of patients with transformed diffuse large-cell lymphoma is
poor. High-dose chemotherapy and autologous peripheral blood progenitor
cell (PBPC) transplantation is the treatment of choice for patients with
relapsed nontransformed diffuse large-cell lymphoma. The role of
transplantation for transformed lymphoma is poorly studied. We
retrospectively reviewed 118 consecutive diffuse large-cell lymphoma
patients undergoing autologous PBPC transplantation from 1994 through
1999 and compared 18 transformed diffuse large-cell lymphoma patients
with 100 nontransformed patients. The transformed patients were more
likely to be older (median age, 52 years vs. 45 years, P = 0.03), had a
longer time from diagnosis to transplant (median, 35 months vs. 10
months; P < 0.0001), were more likely to have bone marrow involvement at
diagnosis (61% vs. 15%, P = 0.0001), and were more likely to have had 2
or more courses of prior chemotherapy (94% vs. 71%, P = 0.04) than were
nontransformed patients. Ninety-nine percent of patients received
high-dose busulfan/cyclophosphamide/etoposide as the transplant
preparative regimen. Event-free survival and overall survival were
similar in the two treatment groups. Four-year overall survival was 53%
in the nontransformed group versus 61% in the transformed group; 4-year
event-free survival was 37% in the nontransformed group versus 38% in
the transformed group. We concluded that autologous PBPC transplantation
is a viable and potentially effective treatment option for patients who
have transformed diffuse large-cell lymphoma.
24
UI - 11707827
AU - Emmanouilides C; Rosen P; Telatar M; Malone R; Bosserman L; Menco H;
TI -
Patel R; Barstis J; Grody WW
Excellent tolerance of rituximab when given after
mitoxantrone/cyclophosphamide: an effective and safe combination for
indolent non-Hodgkin's lymphoma.
SO - Clin Lymphoma 2000 Sep;1(2):146-51; discussion 152-3
AD - UCLA, Division of Oncology and Network and Division of Molecular
Pathology, Los Angeles, CA 90095, USA. cemmanou@mednet.ucla.edu
Treatment for extensive indolent lymphoma should provide optimization of
efficacy while avoiding excessive toxicity. Rituximab may be an ideal
agent to combine with chemotherapy because of its lack of classical
myelotoxicity. In this study, 27 patients with a variety of histologies
of indolent B-cell non-Hodgkin's lymphoma have been treated utilizing a
novel three-drug combination. Nine patients had relapsed disease and 18
were previously untreated. Patients first received cyclophosphamide 800
mg/m(2) and mitoxantrone 8 mg/m(2) i.v. on day 1, every 3 weeks for 2
cycles. Subsequently, patients received rituximab 375 mg/m(2) followed
by mitoxantrone 8 mg/m2 every 2 weeks for 4 cycles. This regimen and, in
particular, the rituximab infusion were extremely well tolerated. Only
two of 27 patients experienced a grade 1/2, infusion-related reaction
during the first rituximab infusion. Grade 4 neutropenia was noted at
some point in 16 patients who were then offered granulocyte-macrophage
colony-stimulating factor support for improvement of neutropenia. No
infections were noted. Alopecia was minimal. Of 27 patients, 19 achieved
a complete response (CR), one achieved an unconfirmed CR (CRu), and five
patients achieved a partial response, for an overall response rate of
92.5%. Molecular remissions were noted in seven of 12 tested patients in
CR. We concluded that the cyclophosphamide/mitoxantrone/rituximab
(CyMiR) regimen is effective and extremely well tolerated. Furthermore,
rituximab infusion-associated morbidity is markedly reduced.
25
UI - 11707826
AU - Kozuch P; Grossbard ML
TI -
The expanding frontier of radioimmunotherapy of relapsed Non-hodgkin's
lymphoma.
SO - Clin Lymphoma 2000 Sep;1(2):158-9
AD - Division of Hematology/Oncology, Department of Medicine, St.
Luke's-Roosevelt Hospital Center, New York, NY, USA.
26
UI - 11799856
AU - Kpemissi E; Tatagan A; Akakpo O; Napo-Koura G
TI -
[Malignant non-Hodgkin's lymphoma of the lip: a case report]
SO - Rev Laryngol Otol Rhinol (Bord) 2001;122(3):167-9
AD - CHU Tokoin, Service d'ORL, BP 8745, Lome, Togo.
The non Hodgkin's lymphoma of the lip is rare. A 3-year-old child with
non-Hodgkin's lymphoma of the upper lip (stage I in the Ann Harbor
system) was reported. An immunodeficiency, been in correspondence with a
food deficiency, was probably a causal factor. A post-chemotherapy
residual lesion justified a surgery.
27
UI - 11799423
AU - Jain S; Moger V; Kumari S; Varma S
TI -
Ifosfamide induced encephalopathy following chemotherapy of
Non-Hodgkin's Lymphoma.
SO - Neurol India 2001 Dec;49(4):416
28
UI - 11372619
AU - Davies AM; Cooper SA; Mangham DC; Grimer RJ
TI -
Metal-containing lymph nodes following prosthetic replacement of osseous
malignancy: potential role of MR imaging in characterisation.
SO - Eur Radiol 2001;11(5):841-4
AD - Department of Radiology, Royal Orthopaedic Hospital, Birmingham B31 2AP,
UK.
The identification of regional lymphadenopathy in patients with bone
malignancy treated by excision and insertion of a prosthesis usually
indicates metastatic disease. We present two cases in which the
lymphadenopathy was due to an uncommon but well-recognized foreign body
reaction. This is secondary to the lymphatic uptake of metal debris shed
by the prosthesis. In one case the metal within the excised lymph node
could be demonstrated on in vitro MR imaging and in retrospect on the
original in vivo scans. This condition should be considered when
undertaking an MR examination in patients with bone malignancy treated
by prosthetic replacement in whom there is a clinical suspicion of
metastatic spread to the regional lymph nodes.
29
UI - 11828719
AU - Tanaka K; Migitani A; Teshima H; Tatsumi Y; Inoue T; Ohta K; Yamane T;
TI -
Hino M; Takubo T; Tatsumi N
[Two cases of bronchus-associated lymphoid tissue lymphoma]
SO - Rinsho Ketsueki 2001 Dec;42(12):1170-5
AD - Department of Clinical Hematology and Clinical Diagnostics, Graduate
School of Medicine, Osaka City University.
We report 2 cases of bronchus-associated lymphoid tissue lymphoma (BALT
lymphoma), which is a rare disease. Patient 1 was a 76-year-old woman
with a chief complaint of cough. Since plain chest radiography revealed
an abnormal shadow in the hilum of the lung, she visited our hospital.
Patient 2 was a 56-year-old man, who had been diagnosed as having
pseudolymphoma at a medical check-up in a local hospital. During
follow-up, however, he was referred to our hospital because of enlarged
tumors and chest pain. In both patients, bronchofiberscopy demonstrated
submucosal tumors and biopsy samples showed formation of
lymphoepithelial lesions by centrocyte-like cells with a B-cell staining
pattern. The patients were therefore diagnosed as having BALT lymphoma.
Both received CEOP-E treatment, which improved the clinical symptoms but
did not result in complete remission. The patients have been followed up
after discontinuation of the medication. The progress of the disease has
30
UI - 11720423
AU - Loni L; Del Tacca M; Danesi R
TI -
Pharmacogenetics of anticancer drugs in non-Hodgkin lymphomas.
SO - Br J Cancer 2001 Nov 16;85(10):1425-31
AD - Interdepartmental Centre of Clinical Pharmacology and Experimental
Therapeutics, University of Pisa, Italy.
The variability of tumour responses to chemotherapeutic agents is a
topic of major interest in current oncology research. Advances in the
knowledge of molecular pathology of cancer make available strategies by
which tumour cells can be profiled for their genetic background in order
to select anticancer agents that might selectively kill cells in a
molecular context that matches the mechanism of action of drugs. The
next generation of anticancer treatments might thus be tailored on the
basis of the numerous molecular alterations identified in tumour cells
of a particular patient. However, to exploit these alterations, it is
necessary to understand how they influence the cellular pathways that
control the sensitivity or, conversely, resistance to chemotherapeutic
agents. The aim of this article is to outline major genetic
abnormalities in non-Hodgkin lymphomas that can be used to streamline
anticancer drug selection and to underscore the major role of
pharmacogenetics, which studies the interactions between genetic
background and drug activity, to the prediction of likelihood of
response and identification of potential new targets for pharmacological
intervention.
31
UI - 11697632
AU - Sarkodee-Adoo C; Pittarelli L; Jaffe E; Sorbara L; Raffeld M; Yao X;
TI -
Haddad R; Heller T
Regression and clonally distinct recurrence of human immunodeficiency
virus related Burkitt-like lymphoma during antiretroviral therapy.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):1125-31
AD - Department of Medicine, University of Maryland School of Medicine,
Marlene and Stewart Greenebaum Cancer Center, Baltimore 21201, USA.
csarkodee@umm.edu
An increased incidence of intermediate to high-grade Non Hodgkin's
Lymphoma i
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