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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Non-Hodgkin's Lymphoma - September 2002
National Cancer Institute®
Last Modified: September 1, 2002
- High-dose chemotherapy and autologous bone marrow transplantation in diffuse intermediate- and high-grade non-Hodgkin lymphoma.
- High-dose therapy for indolent lymphoma.
- [Autologous stem cell transplantations in non-Hodgkin lymphomas]
- [MALT lymphoma of the bladder. Report of a case]
- [Reversible posterior leukoencephalopathy in a patient with non-Hodgkin's lymphoma after treatment with CHOP]
- Primary non-Hodgkin lymphoma of the right colon: a retrospective clinical-pathological study.
- Bendamustine in the treatment of non-Hodgkin's lymphoma: results and future perspectives.
- Radiolabeled anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoma.
- Anemia of cancer in intermediate-grade non-Hodgkin's lymphoma.
- New approaches to the management of Non-Hodgkin's lymphoma.
- Immunotherapy: a novel treatment for Non-Hodgkin's lymphoma.
- Monoclonal antibodies conjugated with radioisotopes for the treatment of Non-Hodgkin's lymphoma.
- Establishing a radioimmunotherapy outpatient care clinic for Non-Hodgkin's lymphoma.
- Current therapeutic approaches in the treatment of Non-Hodgkin's lymphoma.
- Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma.
- Current treatment of follicular non-Hodgkin's lymphoma.
- Is cutaneous T-cell lymphoma curable?
- Ennui or not ennui, that is the question...
- 2-chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients with follicular stage III-IV non-Hodgkin's lymphoma.
- Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow
- A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed
- Diagnostic advances and new trends for the treatment of primary central nervous system lymphoma.
- Extragastric MALT lymphoma.
- A case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus.
- Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on The United Kingdom Children's Cancer Study Group chemotherapy
- Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma.
- Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment with pentostatin.
- PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease.
- 131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas failing chemotherapy. Treatment outcome, haematological toxicity and
- Lymphoma in an ileostomy.
- Continuous complete clinical and molecular remission in two patients with refractory lymphoid malignancies after autografting followed by
- Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study.
- The modified International Prognostic Index can predict the outcome of localized primary intestinal lymphoma of both extranodal marginal zone
- Granulocyte colony-stimulating factor mobilized whole blood containing over 0.3 x 106/kg CD34+ cells is a sufficient graft in autologous
- Clinical characteristics and treatment results of LMB/LMT regimen in children with non-Hodgkin's lymphoma.
- Intensive therapies in follicular non-Hodgkin lymphomas.
- [Reye syndrome in a child having received chemotherapy]
- Successful treatment of progressive NK cell lymphoma with allogeneic peripheral stem cell transplantation followed by early cyclosporine
- Pegylated liposomal doxorubicin in the CHOP regimen for older patients with aggressive (stages III/IV) non-Hodgkin's lymphoma.
- High rate of clinical and molecular remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at
- Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin
- Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients.
- AIDS-related primary central nervous system lymphoma: prolonged remission associated with highly active antiretroviral therapy.
- Burkitt's lymphoma: single-centre experience with modified BFM protocol.
- Primary pancreatic lymphoma.
- Chemotherapy with irinotecan (CPT-11), a topoisomerase-I inhibitor, for refractory and relapsed non-Hodgkin's lymphoma.
- Complement activation in circulation and central nervous system after rituximab (anti-CD20) treatment of B-cell lymphoma.
- 2'-Deoxycoformycin for hepatosplenic gammadelta T-cell lymphoma.
- Primary malignant lymphoma of the prostate--a report of three cases.
- Stage IV CD30+ anaplastic large cell lymphoma: response to acitretin and interferon-alpha.
- Outcome of B-cell non-Hodgkin lymphoma protocol CCCG-B NHL97: a report from Chinese multi-center cooperative group.
- Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.
- [Non-Hodgkin lymphomas in Southern Karelia]
- L-asparaginase induced durable remission of relapsed nasal NK/T-cell lymphoma after autologous peripheral blood stem cell transplantation.
- Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement.
- Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of
- [Treatment of high-grade, disseminated non-Hodgkin's lymphoma in elderly patients]
- Designing clinical trials on gastric lymphomas and reporting outcomes.
- Childhood cutaneous natural killer/T lymphoma successfully treated with only one course of chemotherapy and incomplete tumor resection.
- Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin's
- First successful treatment of a primary high-grade gastric MALT lymphoma by eradication therapy for Helicobacter pylori.
- The impact of external beam radiation therapy prior to autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma.
- [Polyembrioma of the testis: case report following chemotherapy for non-Hodgkin's lymphoma]
- Non-Hodgkin's lymphoma. Treatments are advancing.
- Early stage nasal NK/T-cell lymphoma: clinical outcome, prognostic factors, and the effect of treatment modality.
- Immunotherapy for low-grade non-hodgkin secondary lymphoma of the orbit.
- Using unconjugated antibodies as an immunotherapeutic approach to treatment of B-cell neoplasms.
- GM-CSF: clinical trials in non-Hodgkin's lymphoma patients with chemotherapy induced leucopenia.
- Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin's lymphoma.
- [Lamivudine for the prevention of chronic hepatitis B exacerbations during chemotherapy for non-Hodgkin's lymphoma]
- [The efficacy of L-asparaginase in the treatment of refractory midline peripheral T-cell lymphoma]
- High dose of idarubicin-based regimen for diffuse large cell AIDS-related non-Hodgkin's lymphoma patients: a pilot study.
- Successful allogeneic bone marrow transplantation for hepatosplenic gammadelta T cell lymphoma.
Table of Contents
1
UI - 11856597
AU - Philip T; Biron P
TI -
High-dose chemotherapy and autologous bone marrow transplantation in
diffuse intermediate- and high-grade non-Hodgkin lymphoma.
SO - Crit Rev Oncol Hematol 2002 Feb;41(2):213-23
AD - Bone Marrow Transplant Department, Centre Leon Berard, 28 rue Laennec,
69008, Lyon, France. philip@lyon.fnclcc.fr
This is a review of data published in the literature on the role of
marrow ablative treatment and blood or marrow transplantation for
high-grade and intermediate-grade lymphoma. Timing and epidemiology are
reviewed before the various clinical situations (primary refractory
partial responses, complete responses and relapses). The Lyon consensus
conference held in 1998 has also extensively been used and quoted.
2
UI - 11856598
AU - Mounier N; Socie G; Gisselbrecht C
TI -
High-dose therapy for indolent lymphoma.
SO - Crit Rev Oncol Hematol 2002 Feb;41(2):225-39
AD - Institut d'Hematologie, Hopital Saint-Louis, 1, avenue Claude-Vellefaux,
75475 10, Paris Cedex, France.
Stem-cell transplantation (SCT) has become the treatment of choice for
patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). However,
the role of SCT in the management of patients with indolent NHL remains
controversial. Indolent follicular lymphomas are diseases which are
generally incurable with conventional therapy. Although patients can
survive for prolonged periods, the median duration of first remission is
approximately 3 years, and subsequent remissions are progressively
shorter with time. Emerging evidence suggests that high-dose
chemotherapy with SCT leads to prolonged disease-free and overall
survival in a subset of patients with indolent NHL. However, there is
increasing concern regarding the toxicity of SCT, especially the
long-term risk of developing myelodysplastic syndrome. It is still
unclear as to when this approach should be used. Poorer outcomes have
been obtained in heavily pretreated patients but encouraging results are
being reported for patients undergoing SCT early during the course of
their disease. Investigators are now focusing on how to improve SCT
efficacy in order to eradicate minimal residual disease. Many ongoing
studies are especially exploring the impact of stem-cell purging and
novel ablative regimens combined with allogeneic transplantation.
3
UI - 12116714
AU - Jantunen E; Kuittinen T; Mahlamaki E; Nousiainen T
TI -
[Autologous stem cell transplantations in non-Hodgkin lymphomas]
SO - Duodecim 2001;117(11):1151-7
AD - KYS:n sisatautien klinikka PL 1777, 70211 Kuopio. esa.jantunen@kuh.fi
4
UI - 11852527
AU - Painemal Duarte C; Gallardo J; Valdebenito JP; Gamargo C; Rubio B;
TI -
Harbst H
[MALT lymphoma of the bladder. Report of a case]
SO - Arch Esp Urol 2001 Dec;54(10):1138-40
AD - Seccion de Oncologia, Departamento de Medicina Interna Hospital Clinico
de la Universidad de Chile Santos Dumontt 999 Santiago, Chile.
claudiopainemal@enteldhile.net
OBJECTIVE: To describe and discuss primary malignant lymphoreticular
proliferative tumors of the bladder. METHODS: A case of a 70-year-old
woman with hematuria, dysuria, malaise and 5-kg weight loss is
presented. RESULTS: Pelvic ultrasound examination showed an 8 x 7 x 8 cm
solid and cystic mass adjacent to the bladder and uterus. Cystoscopic
biopsy disclosed a low grade B cell non-Hodgkin lymphoma. Disappearance
of the mass was achieved with 6 cycles of chemotherapy and radiotherapy.
Four years thereafter the patient remains free of disease. CONCLUSIONS:
Primary malignant lymphoma of the bladder is uncommon. The
anatomopathological study is essential to differential diagnosis from
other diseases. The response to chemotherapy and radiotherapy are
excellent and permits bladder preservation.
5
UI - 11862771
AU - Gimenez-Mesa E; Martinez-Salio A; Porta-Etessam J; Berbel Garcia A;
TI -
Cedena Romero T; Salama Bendoyan P
[Reversible posterior leukoencephalopathy in a patient with
non-Hodgkin's lymphoma after treatment with CHOP]
SO - An Med Interna 2001 Nov;18(11):591-3
AD - Servicio de Neurologia, Hospital Universitario Doce de Octubre, Ctra de
Andalucia km 5,400, 28041 Madrid.
Reversible posterior leukoencephalopathy syndrome is a newly
characterised and increasingly recognized clinico-radiologic syndrome.
Underlying conditions that reportedly trigger this syndrome include
hypertensive encephalopathy, eclampsia, renal failure, and
immunosuppressive drug therapy with cyclosporine, tacrolimus and
interferon alpha. We describe a 51-year-old woman with non-Hodgkin's
lymphoma treated with conventional CHOP chemotherapy. Eight days after
this treatment she developed severe headache, bilateral visual loss and
focal seizures with secondary generalization. Neurologic examination
showed confusion, cortical blindness, and left hemiparesis with
hyperreflexia and sensory loss. A cranial T2-weighted magnetic resonance
imaging revealed increased signal intensity in the occipital and frontal
lobes in both hemispheres and right parietal lobe. A diagnosis of
reversible posterior leukoencephalopathy was made. She presented a
favourable outcome with conservative treatment with mannitol and
phenytoin. A new cranial scanning showed nearly complete resolution of
the abnormalities. To the best of our knowledge, this is the first case
of reversible posterior leukoencephalopathy in a patient treated with
standard-dose CHOP. In this patient, we confirm the theoretical
pathophysiologic mechanisms suggested explaining how these drugs can
cause the syndrome.
6
UI - 11890335
AU - Waisberg J; Bromberg SH; Franco MI; Matheus CO; Zanotto A; Petrolino LF;
TI -
Beltrami AM; Godoy AC
Primary non-Hodgkin lymphoma of the right colon: a retrospective
clinical-pathological study.
SO - Int Surg 2001 Jan-Mar;86(1):20-5
AD - Department of Digestive Surgery, Hospital do Servidor Publico Estadual,
Sao Paulo, Brazil. jaqueswaisberguol.com.br
The objective of this study was to analyze the results of surgical
treatment of primary non-Hodgkin lymphomas of the right colon. Ten
patients were operated on with curative intention. Dawson's criteria
were used to characterize the colonic lymphoma as a primary lymphomas.
In the staging of the tumor, the Ann Arbor classification for
gastrointestinal lymphomas modified by Musshoff and Schmidt-Vollmer was
used. The histological classification was made by using the
International Working Formulation Group system. All patients were
submitted to radical right colectomy and 6 of them received
postoperative chemotherapy. The overall average survival was 39.2
months. Four of the patients are still alive, without active disease,
with an average survival of 85.2 months. Six patients died due to
relapse in the abdomen, with an average survival of 8.2 months. These
results suggest that it is advantageous to patient survival to have them
submitted for resection of their lesions at an initial stage of the
disease (IE and IIE1). Chemotherapy must be used as a complementary
treatment in locally advanced lesions, in an attempt to control the
residual microscopic disease.
7
UI - 12170430
AU - Rummel MJ; Mitrou PS; Hoelzer D
TI -
Bendamustine in the treatment of non-Hodgkin's lymphoma: results and
future perspectives.
SO - Semin Oncol 2002 Aug;29(4 Suppl 13):27-32
AD - Department of Hamatologie/Onkologie, Medizinische Universitatsklinik,
Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Bendamustine has clinical potential in the treatment of low-grade
non-Hodgkin's lymphoma (NHL). As a single agent, bendamustine has been
used in two studies in patients with relapsed or refractory low-grade
NHL. When bendamustine 120 mg/m(2) was given on days 1 and 2, the
overall response rate was 73% with complete responses in 11%. When
bendamustine 50 to 60 mg/m(2) was given on days 1 through 5, the overall
response rate was 82.5%, with 14.5% complete responses. Bendamustine
shows only partial cross-resistance with other agents used in the
treatment of NHL and combination regimens have been investigated. The
combination of bendamustine/vincristine/prednisolone (BOP) has been
compared with cyclophosphamide/vincristine/prednisolone (COP) in a phase
III study involving 162 patients with low-grade NHL. No differences were
seen between the treatment arms with regard to response rate or
survival, but the BOP regimen was significantly better tolerated than
the COP regimen. The combination of rituximab/bendamustine has shown
encouraging activity in patients with relapsed/refractory NHL and a
trial is ongoing in which this combination is used in patients with
advanced low-grade NHL or mantle cell lymphoma. Preliminary results from
this trial are presented. The 93% overall response rate attained in the
patients presently evaluable indicates that this combination is very
active in this poor-prognosis population. Optimal treatment regimens
with bendamustine in the treatment of low-grade NHL are yet to be
defined, but results obtained to date indicate that further studies are
warranted. Copyright 2002, Elsevier Science (USA). All rights reserved.
8
UI - 12177115
AU - Dillman RO
TI -
Radiolabeled anti-CD20 monoclonal antibodies for the treatment of B-cell
lymphoma.
SO - J Clin Oncol 2002 Aug 15;20(16):3545-57
AD - Clinical and Laboratory Cancer Research, Hoag Hospital, Hoag Cancer
Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
9
UI - 12190227
AU - Morrow TJ; Volpe S; Gupta S; Tannous RE; Fridman M
TI -
Anemia of cancer in intermediate-grade non-Hodgkin's lymphoma.
SO - South Med J 2002 Aug;95(8):889-96
AD - One Health Plan, Atlanta, GA, USA.
BACKGROUND: Current literature suggests that anemia at baseline is an
important adverse prognostic factor for lymphoma-related outcomes. We
evaluated the prevalence, risk factors, and prognostic value of anemia
in patients with intermediate-grade non-Hodgkin's lymphoma (IGNHL)
treated in a community-based practice. METHODS: The retrospective sample
included 591 patients who had IGNHL diagnosed between 1993 and 1999 and
who were subsequently treated with CHOP chemotherapy. Anemia was defined
as a hemoglobin (Hb) value < 12 g/dL. RESULTS: Anemia was present in 193
of 546 patients (35.3%). Baseline anemia was significantly associated
with age > 60, extranodal sites > or = 2, Ann Arbor stage III or IV,
elevated lactate dehydrogenase (LDH) level, B symptoms, and histology
type. Baseline Hb was also a significant predictor of nonresponse to
chemotherapy. CONCLUSIONS: Our study results support previous findings
of a high prevalence of anemia in cancer patients before cytotoxic
therapy and the adverse impact that baseline anemia has on response to
chemotherapy.
10
UI - 11878045
AU - Estes J
TI -
New approaches to the management of Non-Hodgkin's lymphoma.
SO - Semin Oncol Nurs 2002 Feb;18(1 Suppl 1):1-2
AD - Comprehensive Cancer Care Center, University of Michigan Hospital, Ann
Arbor, MI, USA.
11
UI - 11878046
AU - Hohenstein M
TI -
Immunotherapy: a novel treatment for Non-Hodgkin's lymphoma.
SO - Semin Oncol Nurs 2002 Feb;18(1 Suppl 1):10-5
AD - Department of Oncology/Hematology, University of Nebraska Medical
Center, Lied Transplant Center, 668 S 41st St, Omaha, NE 68198, USA.
OBJECTIVES: To provide an overview of the principles of immunology,
including immunotherapy, and information about monoclonal antibody
therapy in the treatment of non-Hodgkin's lymphoma. DATA SOURCES:
Published literature. CONCLUSIONS: Immunotherapy is a form of disease
treatment that enhances the immune system with the use of biologic
agents. One such agent is the monoclonal antibody, which can be combined
with a radioisotope (e.g., iodine-131 or yttrium-90) or chemotherapeutic
drug to deliver treatment directly to tumor cells with less toxicity to
normal cells. IMPLICATIONS FOR NURSING PRACTICE: As the field of
monoclonal antibody therapy continues to grow, nurses will play an
important role in treatment and patient education. Nurses need to become
knowledgeable in this area of cancer treatment and gain a better
understanding of basic principles involved in immunotherapy.
12
UI - 11878047
AU - Bush S
TI -
Monoclonal antibodies conjugated with radioisotopes for the treatment of
Non-Hodgkin's lymphoma.
SO - Semin Oncol Nurs 2002 Feb;18(1 Suppl 1):16-21
AD - Division of Medical Oncology, University of Washington Medical Center,
Seattle Cancer Care Alliance, 825 Eastlake Ave East, G6800, Seattle, WA
98109, USA.
OBJECTIVES: To describe the use of monoclonal antibodies labeled with
iodine-131 tositumomab and yttrium-90 ibritumomab-tiuxetan as treatment
for non-Hodgkin's lymphoma. DATA SOURCES: Literature review of trials of
radioimmunotherapy. CONCLUSIONS: Radiolabeled monoclonal antibodies
recognize and react with specific antigens to provide targeted therapy
to tumor cells, particularly hematopoietic tumor cells. This therapy
delivers greater amounts of radiation to malignant cells than normal
cells and spares critical organs that do not express the antigen. Strict
safety and patient precautions must be in place with the use of
radiotherapy. IMPLICATIONS FOR NURSING PRACTICE: As the use of
radiommunotherapy in the treatment of non-Hodgkin's lymphoma grows, the
role of nursing in the care of these patients will also grow. Nurses
will play an important part in patient and family education, as well as
staff preparation.
13
UI - 11878048
AU - Hendrix C; de Leon C
TI -
Establishing a radioimmunotherapy outpatient care clinic for
Non-Hodgkin's lymphoma.
SO - Semin Oncol Nurs 2002 Feb;18(1 Suppl 1):22-9
AD - Cancer Center Outpatient Treatment Clinic, Hoag Cancer Center, 4000 W.
Pacific Coast Hwy, Newport Beach, CA 92660, USA.
OBJECTIVES: To describe an outpatient treatment model for treating
non-Hodgkin's lymphoma with radioimmunotherapy. DATA SOURCES:
Experiences of The Hoag Cancer Canter (Newport Beach, CA) in developing
an outpatient treatment model. CONCLUSIONS: The Hoag Cancer Center has
put an outpatient radioimmunotherapy treatment model into place. Goals
include providing coordinated, collaborative care, safe delivery of
radioimmunotherapy in an outpatient setting, and establishing an
education program for the medical team, patient, and patient's family.
IMPLICATIONS FOR NURSING PRACTICE: In providing outpatient treatment for
non-Hodgkin's lymphoma, nurses will have many functions, including
educating patients and family, coordinating treatment schedules,
adhering to radiation safety guidelines, and reviewing post-therapy and
long-term side effects that might occur at home.
14
UI - 11878049
AU - O'Brien T
TI -
Current therapeutic approaches in the treatment of Non-Hodgkin's
lymphoma.
SO - Semin Oncol Nurs 2002 Feb;18(1 Suppl 1):3-9
AD - Section of Hematology, Rush, Presbyterian St. Luke's Medical Center,
1725 W Harrison, Suite 809, Chicago, IL 60612, USA.
OBJECTIVES: To review the causes, classification, treatment, and new
treatment modalities of non-Hodgkin's lymphoma. DATA SOURCES: Published
literature and experimental therapies. CONCLUSIONS: The increasing
incidence of non-Hodgkin's lymphoma can be attributed to a growth in the
number of immunodeficiency and autoimmune disorders, infectious agents,
and human T-cell leukemia-lymphoma virus. Treatment options include
watch-and-wait, radiation, chemotherapy, biologic therapy, and stem
cell/bone marrow transplant. New therapies include the use of monoclonal
antibodies and radioimmunotherapy. Experimental therapies include
high-dose radioimmunotherapy and stem cell transplantation, vaccines,
and antisense antiangiogensis agents. IMPLICATIONS FOR NURSING PRACTICE:
Nurses will need to become versed in this modality, and will play an
important part not only in therapy but also in patient education.
15
UI - 12149300
AU - Witzig TE; Flinn IW; Gordon LI; Emmanouilides C; Czuczman MS; Saleh MN;
TI -
Cripe L; Wiseman G; Olejnik T; Multani PS; White CA
Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with
rituximab-refractory follicular non-Hodgkin's lymphoma.
SO - J Clin Oncol 2002 Aug 1;20(15):3262-9
AD - Mayo Clinic, 620 Stabile Building, Rochester, MN 55905, USA.
witzig@mayo.edu
PURPOSE: Rituximab is commonly used as a single agent or in combination
therapy for non-Hodgkin's lymphoma (NHL). Ibritumomab tiuxetan
radioimmunotherapy targets the same antigen as rituximab and has
demonstrated efficacy in rituximab-naive NHL. This study evaluated
ibritumomab tiuxetan in the treatment of rituximab-refractory follicular
NHL. PATIENTS AND METHODS: Eligible patients were refractory to
rituximab; this was defined as no objective response to rituximab (375
mg/m(2) weekly for 4 weeks) or time to progression (TTP) of < or = 6
months. The ibritumomab tiuxetan treatment regimen consisted of
pretreatment with rituximab (250 mg/m(2) intravenously on days 1 and 8)
to deplete peripheral blood B cells, then yttrium-90 ibritumomab
tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8,
administered on an outpatient basis. An imaging/dosimetry dose of
indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab
(day 1) in 28 patients. RESULTS: Fifty-seven patients were treated. The
median age was 54 years, 74% had tumors > or = 5 cm, and all were
extensively pretreated (median, four prior therapies; range, one to
nine). The estimated radiation-absorbed doses to healthy organs were
below the study-defined limit in all patients studied with dosimetry.
The overall response rate for the 54 patients with follicular NHL was
74% (15% complete responses and 59% partial responses). The
Kaplan-Meier-estimated TTP was 6.8 months (range, 1.1 to > or = 25.9
months) for all patients and 8.7 months for responders. Adverse events
were primarily hematologic; the incidence of grade 4 neutropenia,
thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively.
CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in
rituximab-refractory patients. The only significant toxicity is
hematologic.
16
UI - 12044501
AU - Reiser M; Diehl V
TI -
Current treatment of follicular non-Hodgkin's lymphoma.
SO - Eur J Cancer 2002 Jun;38(9):1167-72
AD - Klinik I fur Innere Medizin, University Hospital Cologne,
Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.
marcel.reiser@uni-koeln.de
56200 new cases of NHL are expected to be diagnosed in the United States
(US) per year. For reasons that are not fully understood, the number of
new cases per year has nearly doubled in the past three decades. Most
patients with follicular lymphoma are over 50 years of age and present
with widespread disease at diagnosis. Nodal involvement is very common,
often accompanied by splenic and bone marrow disease. Despite the
advanced stage, the median survival ranges from 8 to 12 years. The vast
majority of patients with advanced stage follicular lymphoma are not
cured using the current therapeutic options. The rate of relapse is
fairly consistent over time, even in patients who have achieved complete
responses (CRs) to treatment. Therapeutic options in follicular NHL
include watchful waiting, oral alkylating agents, purine nucleoside
analogues, combination chemotherapy, interferon and monoclonal
antibodies. Radiolabelled monoclonal antibodies, autologous or
allogeneic bone marrow or peripheral stem cell transplantation are under
current clinical evaluation. The approval of rituximab, an unconjugated
chimeric antibody against the CD20 antigen for the treatment of relapsed
follicular B-cell NHL marked a milestone in the development of antibody
treatment. In addition, newer approaches like radioimmunoconjugates with
myeloablative activity induced response rates of 80-100% in heavily
pretreated patients. Various clinical trials combining monoclonal
antibodies with conventional therapies are currently ongoing to
determine whether these new biological agents will alter the natural
history of follicular lymphoma.
17
UI - 7661616
AU - Koh HK; Jacobson JO; Foss F; Lew RA
TI -
Is cutaneous T-cell lymphoma curable?
SO - Arch Dermatol 1995 Sep;131(9):1081-2
18
UI - 8922188
AU - Cheson BD
TI -
Ennui or not ennui, that is the question...
SO - Ann Oncol 1996 Oct;7(8):767-9
19
UI - 8922192
AU - Betticher DC; Zucca E; von Rohr A; Egger T; Radford JA; Ambrosetti A;
TI -
Burki K; Rufener B; Schmitz SF; Cerny T
2-chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients
with follicular stage III-IV non-Hodgkin's lymphoma.
SO - Ann Oncol 1996 Oct;7(8):793-9
AD - Institute of Medical Oncology, Inselspital, Berne, Switzerland.
PURPOSE: This phase II multi-institutional trial was designed to assess
response and toxicity of 2-chlorodeoxyadenosine (2-CDA) in patients with
previously untreated follicular lymphoma. The clinical significance of
detecting cells carrying the t(14;18) translocation (bcl-2/JH
rearrangement) in peripheral blood and bone marrow by polymerase chain
reaction (PCR) before, during and after treatment was also examined.
were accrued: male/female: 15/22, median age 51 years (range: 20-78),
stage III/IV: 9/28. Patients received a total 2-CDA dose of 0.7 mg/kg as
continuous s.c. or i.v. infusions over 7 days, every 28 days for a
maximum of 5 cycles. A total of 165 cycles were administered. In 25
patients, blood and bone marrow before, during and after treatment were
available for PCR analysis of the bcl-2/JH rearrangements. RESULTS: All
37 patients were evaluable for response and toxicity. The overall
response rate was 84% (95% confidence interval, 68%-94%) with 14% CR (n
= 5) and 70% PR (n = 26) and a median time to treatment failure of 15.7
months. bcl-2/JH rearrangement in peripheral blood and/or bone marrow
was found in 10/25 of patients (40%) before treatment and 5 of these
became repeatedly negative after 2-CDA therapy. There was no apparent
association between bcl-2/ JH result and response. In 11 patients, 2-CDA
was stopped because of progressive disease (n = 4), myelotoxicity (grade
2-3, n = 4), and other causes (n = 3, pulmonary embolism, metabolic
disorder, and patient's decision). Four patients (11%) suffered from
infections (grade 2-3). In 6 patients, persistent thrombocytopenia of
7.5 months (range: 3-21) occurred after completion of the 5 cycles.
CONCLUSION: 2-CDA is active in untreated follicular lymphomas, but time
to treatment failure suggests no advantage compared with standard
treatment and toxicity on haematopoietic stem cells appears to be more
pronounced. Molecular remission is induced in a considerable proportion
of patients with disappearance of the bcl-2/JH rearrangement, and its
possible significance as a predictive factor for quality of response and
relapse warrants further study.
20
UI - 10871932
AU - Zhou Y; Barnett MJ; Rivers JK
TI -
Clinical significance of skin biopsies in the diagnosis and management
of graft-vs-host disease in early postallogeneic bone marrow
transplantation.
SO - Arch Dermatol 2000 Jun;136(6):717-21
AD - Department of Medicine, Vancouver General Hospital and University of
British Columbia.
OBJECTIVE: To determine the value of skin biopsies in the management of
suspected graft-vs-host disease (GVHD) within 30 days of allogeneic bone
marrow transplantation (BMT). DESIGN: Retrospective study based on
review of a BMT database. SETTING: Leukemia/BMT ward of a tertiary care,
university teaching hospital. PATIENTS: One hundred and eighty-seven
consecutive patients who received allogeneic BMT between January 1,
1994, and June 30, 1997, at Vancouver General Hospital, Vancouver,
British Columbia. MAIN OUTCOME MEASURES: (1) Skin biopsy frequency for
patients with rashes suggestive of acute GVHD; (2) clinical significance
of skin biopsy in the management of patients with suspected acute GVHD
after BMT; (3) relationship between severity of clinical GVHD and the
likelihood to receive GVHD therapy; and (4) relationship between biopsy
status or biopsy result and outcome of BMT (acute and chronic GVHD,
transplant-related mortality, and overall and event-free survival).
RESULTS: During the early post-BMT period (<30 days after BMT), 88
patients had rashes suggestive of acute GVHD; of these, 51 (58%)
underwent skin biopsy to confirm the diagnosis. Skin biopsies were
performed more often for higher clinical stages of cutaneous GVHD. There
was no significant difference between the patients with positive biopsy
findings and those with negative findings, either in the clinical
severity of acute GVHD or in likelihood to receive treatment for GVHD.
Most (85%) of the patients who underwent biopsies and received GVHD
therapy had treatment initiated before skin biopsies were performed or
before the results were available. The higher the clinical grade of
overall acute GVHD, the more likely it was that the patients were
treated for GVHD (P<.001). The outcome of BMT was not influenced by the
skin biopsy status or biopsy result. CONCLUSIONS: The biopsy findings
correlated poorly with the clinical severity of skin rash suggestive of
acute GVHD soon after BMT. The decision to treat suspected acute GVHD
depended not on skin biopsy findings but rather on clinical severity of
acute GVHD. In this regard, skin biopsy has a limited role in the
management of patients early after allogeneic BMT.
21
UI - 11049969
AU - Press OW; Eary JF; Gooley T; Gopal AK; Liu S; Rajendran JG; Maloney DG;
TI -
Petersdorf S; Bush SA; Durack LD; Martin PJ; Fisher DR; Wood B; Borrow
JW; Porter B; Smith JP; Matthews DC; Appelbaum FR; Bernstein ID
A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide,
cyclophosphamide, and autologous stem cell transplantation for relapsed
B-cell lymphomas.
SO - Blood 2000 Nov 1;96(9):2934-42
AD - Departments of Medicine, Pathology, Pediatrics, Radiology, Biological
Structure, and Biostatistics, the University of Washington, Seattle, WA
98195, USA.
Relapsed B-cell lymphomas are incurable with conventional chemotherapy
and radiation therapy, although a fraction of patients can be cured with
high-dose chemoradiotherapy and autologous stem-cell transplantation
(ASCT). We conducted a phase I/II trial to estimate the maximum
tolerated dose (MTD) of iodine 131 ((131)I)-tositumomab (anti-CD20
antibody) that could be combined with etoposide and cyclophosphamide
followed by ASCT in patients with relapsed B-cell lymphomas. Fifty-two
patients received a trace-labeled infusion of 1.7 mg/kg
(131)I-tositumomab (185-370 MBq) followed by serial quantitative
gamma-camera imaging and estimation of absorbed doses of radiation to
tumor sites and normal organs. Ten days later, patients received a
therapeutic infusion of 1.7 mg/kg tositumomab labeled with an amount of
(131)I calculated to deliver the target dose of radiation (20-27 Gy) to
critical normal organs (liver, kidneys, and lungs). Patients were
maintained in radiation isolation until their total-body radioactivity
was less than 0.07 mSv/h at 1 m. They were then given etoposide and
cyclophosphamide followed by ASCT. The MTD of (131)I-tositumomab that
could be safely combined with 60 mg/kg etoposide and 100 mg/kg
cyclophosphamide delivered 25 Gy to critical normal organs. The
estimated overall survival (OS) and progression-free survival (PFS) of
all treated patients at 2 years was 83% and 68%, respectively. These
findings compare favorably with those in a nonrandomized control group
of patients who underwent transplantation, external-beam total-body
irradiation, and etoposide and cyclophosphamide therapy during the same
period (OS of 53% and PFS of 36% at 2 years), even after adjustment for
confounding variables in a multivariable analysis.
22
UI - 12091059
AU - Basso U; Brandes AA
TI -
Diagnostic advances and new trends for the treatment of primary central
nervous system lymphoma.
SO - Eur J Cancer 2002 Jul;38(10):1298-312
AD - Department of Medical Oncology, Azienda Ospedale-Universita, Via
Giustiniani 2, 35100 Padova, Italy.
Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin's
lymphoma arising in the brain. Recent increase in its incidence has been
noted both in immunocompetent individuals and patients with
immunodeficiency. This review will focus on the epidemiology,
pathogenesis, diagnosis and treatment of this aggressive extranodal
lymphoma in immunocompetent patients. Stereotactic biopsy is usually
required for diagnosis, while molecular biology and/or cytofluorimetric
analysis may confirm the presence of clonal proliferation in the
cerebrospinal fluid (CSF). Methotrexate-based chemotherapy plus
whole-brain radiotherapy are the standard treatment for PCNSL and
achieve a high rate of complete remissions (CR), but long-term
neurotoxicity may heavily compromise the patient's quality of life. The
metabolic rate of controversial gadolinium-enhancing lesions on magnetic
resonance (MR) scans may be assessed with positron emission tomography
(PET), which discriminates radiation necrosis from true recurrence.
Withholding radiotherapy in patients achieving CR after first-line
chemotherapy is a new and interesting treatment option, while the role
of high-dose chemotherapy with stem cell rescue is still uncertain.
23
UI - 12117868
AU - Wotherspoon AC
TI -
Extragastric MALT lymphoma.
SO - Gut 2002 Aug;51(2):148-9
AD - Department of Histopathology, Royal Marsden Hospital, Fulham Road,
London SW3 6JJ, UK. Andrew.Wotherspoon@rmh.nthames.nhs.uk
24
UI - 12117895
AU - Hosaka S; Nakamura N; Akamatsu T; Fujisawa T; Ogiwara Y; Kiyosawa K;
TI -
Hidaka E; Ota H; Katsuyama T; Inagaki H
A case of primary low grade mucosa associated lymphoid tissue (MALT)
lymphoma of the oesophagus.
SO - Gut 2002 Aug;51(2):281-4
AD - Second Department of Internal Medicine, Shinshu University School of
Medicine, Matsumoto, Nagano, Japan.
We report a very rare case of primary low grade mucosa associated
lymphoid tissue (MALT) lymphoma of the oesophagus. An 83 year old woman
treatment of oesophageal tumour. Although a physical examination and
laboratory data showed no significant abnormalities, endoscopic
observation revealed two slightly elevated submucosal tumour-like
lesions of the oesophagus. Tissue specimens were obtained by endoscopic
mucosal resection of the oesophagus using a cap fitted panendoscope. The
lesions were composed of diffuse small atypical lymphoid cells--that is,
centrocyte-like cells--which were stained with CD20, L26, BCL-2, and
kappa, but not with CD3, CD5, CD10, or cyclin D1. Monoclonality was
detected by polymerase chain reaction analysis using the primer for
CDR-3 of immunoglobulin H and diagnosed as low grade MALT lymphoma of
the oesophagus. The tumours were considered to be completely resected
and therefore additional treatment was not administered. The patient is
alive and well 22 months after treatment and diagnosis.
25
UI - 12060115
AU - Williams DM; Hobson R; Imeson J; Gerrard M; McCarthy K; Pinkerton CR;
TI -
The United Kingdom Children's Cancer Study Group
Anaplastic large cell lymphoma in childhood: analysis of 72 patients
treated on The United Kingdom Children's Cancer Study Group chemotherapy
regimens.
SO - Br J Haematol 2002 Jun;117(4):812-20
AD - Department of Paediatric Oncology, Addenbrookes NHS Trust, Hills Road,
Cambridge CB2 2QQ, UK. denise.williams@addenbrookes.nhs.uk
lymphoma (ALCL) were treated with short intensive multi-agent regimens
[non-Hodgkin's lymphoma (NHL) 9000 and 9602]. Diagnosis was based on
morphological and immunophenotypic criteria. Treatment for stage I
disease consisted of eight courses (2 x vincristine, doxorubicin,
prednisolone; 2 x methotrexate; 2 x cytarabine, thioguanine; and 2 x
methotrexate etoposide). For stage II, III and non-central nervous
system (CNS) stage IV, two COPADM (cyclophosphamide, doxorubicin,
prednisolone, methotrexate, vincristine), two CYM (cytarabine
methotrexate) and a COPADM was given. For CNS-positive disease,
treatment was intensified and contained methotrexate 8 g/m(2) and
cytarabine 3 g/m(2). Fifty-nine patients (82%) achieved a remission.
Thirteen of these relapsed, with a median time to relapse from the start
of treatment of 5 months (range 3-14). Relapse included a new site in
9/13 patients. The probabilities of overall and event free survival at 5
years were 65% (53-76%) and 59% (47-70%), respectively, with a median
follow up of 4.3 years. Mediastinal and visceral involvement at
presentation were found to be predictive of an increased risk of
failure.
26
UI - 12060117
AU - Friedberg JW; Neuberg D; Gribben JG; Fisher DC; Canning C; Koval M; Poor
TI -
CM; Green LM; Daley J; Soiffer R; Ritz J; Freedman AS
Combination immunotherapy with rituximab and interleukin 2 in patients
with relapsed or refractory follicular non-Hodgkin's lymphoma.
SO - Br J Haematol 2002 Jun;117(4):828-34
AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard
Medical School, Boston, MA, USA. jfriedberg@partners.org
Rituximab has significant activity as a single agent in the treatment of
follicular non-Hodgkin's lymphoma (NHL). Interleukin 2 (IL-2) is a
lymphokine that increases effector cell number. In an effort to augment
antibody-dependent cell-mediated cytotoxicity (ADCC) associated with
rituximab therapy, low-dose IL-2 was added to a standard rituximab
regimen and patients were evaluated for safety and efficacy. Twenty
patients with relapsed or refractory follicular NHL were treated with
IL-2 (1.2 MIU/m(2)/d for 56 d subcutaneously) as outpatients. Rituximab
(375 mg/m(2)) was given on d 15, 22, 29 and 36. The regimen was well
tolerated and only three patients required dose adjustments in IL-2.
Infusional toxicity associated with rituximab was not exacerbated by
IL-2. Peripheral blood immunophenotyping demonstrated significant
increases in circulating CD8+ and CD56+ lymphocytes in all evaluable
patients (P = 0.0002). Increases in total eosinophil number were
observed in all patients. Eleven patients responded to therapy, for an
overall response rate of 55%. Four additional patients had stable
disease. For these 15 patients, the median time to progression exceeded
13 months. We conclude concomitant cytokine therapy to enhance ADCC with
monoclonal antibody therapy was well tolerated and did not exacerbate
antibody-related infusional toxicity. Further studies of this rational
combination are warranted and ongoing.
27
UI - 12060145
AU - Iannitto E; Barbera V; Quintini G; Cirrincione S; Leone M
TI -
Hepatosplenic gammadelta T-cell lymphoma: complete response induced by
treatment with pentostatin.
SO - Br J Haematol 2002 Jun;117(4):995-6
28
UI - 12163626
AU - Kostakoglu L; Coleman M; Leonard JP; Kuji I; Zoe H; Goldsmith SJ
TI -
PET predicts prognosis after 1 cycle of chemotherapy in aggressive
lymphoma and Hodgkin's disease.
SO - J Nucl Med 2002 Aug;43(8):1018-27
AD - Division of Nuclear Medicine, Department of Radiology, Weill Medical
College of Cornell University and New York Presbyterian Hospital, New
York, New York 10021, USA. lak2005@mail.med.cornell.edu
Early identification of chemotherapy-refractory lymphoma patients
provides a basis for alternative treatment strategies. Metabolic imaging
with (18)F-FDG PET offers functional tissue characterization that is
useful for assessing response to therapy. Our objective was to determine
the predictive value of (18)F-FDG PET early during chemotherapy (after 1
cycle) and at the completion of chemotherapy for subsequent
progression-free survival (PFS) in patients with aggressive
non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). METHODS:
(18)F-FDG PET (dual-head coincidence camera with attenuation correction)
was performed before and after 1 cycle of chemotherapy on 30 patients
(17 NHL, 13 HD; mean age, 52.3 +/- 16.0 y). For 23 of the 30 patients,
(18)F-FDG PET data were also obtained after the completion of
chemotherapy. The patients had a median follow-up of 19 mo (range, 18-24
mo). Follow-up of PFS was compared between patients with positive and
negative (18)F-FDG PET results obtained after the first cycle of
chemotherapy and at the completion of chemotherapy. RESULTS: Positive
(18)F-FDG PET results obtained both after the first cycle and at the
completion of therapy were associated with a shorter PFS (median, 5 and
0 mo, respectively) than were negative (18)F-FDG PET results (PFS
medians not reached). A statistically significant difference in PFS
between positive and negative (18)F-FDG PET results was obtained both
after the first cycle and at the completion of chemotherapy (P < or =
0.001). The PFS and (18)F-FDG PET results obtained after the first cycle
correlated better than those obtained after the completion of
chemotherapy (r(2) = 0.45 vs. 0.17). (18)F-FDG PET had more
false-negative results after the last cycle (6/17 cases, or 35%) than
after the first cycle (2/13 cases, or 15%). Thus, (18)F-FDG PET had
greater sensitivity and positive predictive values after the first cycle
(82% vs. 45.5% and 90% vs. 83%, respectively) than after the last cycle.
CONCLUSION: (18)F-FDG PET after 1 cycle of chemotherapy is predictive of
18-mo outcome in patients with aggressive NHL and HD and may earlier
identify patients who would benefit from more intensive treatment
programs.
29
UI - 12195750
AU - Linden O; Tennvall J; Hindorf C; Cavallin-Stahl E; Lindner KJ; Ohlsson
TI -
T; Wingardh K; Strand SE
131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas
failing chemotherapy. Treatment outcome, haematological toxicity and
bone marrow absorbed dose estimates.
SO - Acta Oncol 2002;41(3):297-303
AD - Department of Oncology, Lund University Hospital, SE-221 85 Lund,
Sweden. ola.linden@onk.lu.se
The experience with radioimmunotherapy in B-cell lymphomas using the
rapidly internalizing antibody, anti-CD22 (LL2), is limited. In this
study we investigated the efficacy and toxicity of 131I-labelled-LL2 for
radioimmunotherapy in patients with B-cell lymphomas that failed one or
two cytostatic regimens. Eleven patients were treated with one or
repeated cycles of 131I-anti-CD22 antibody, 1330 MBq/m2 (36 mCi/m2). Six
of the 11 treated patients demonstrated an objective response, three of
them with complete remission. All follicular (3 patients) and
transformed lymphomas (2 patients) responded compared to one of four
diffuse large B-cell lymphomas. Two out of six responders exhibited
event-free survival (EFS), which was comparable with or longer than the
EFS following primary anthracycline-containing chemotherapy.
Non-haematological toxicity was mild. Haematological toxicity was
associated with pretreatment clinical characteristics but not with
estimated absorbed bone marrow doses. Objective remission following
treatment with 131I-anti-CD22 can be achieved in patients with various
subtypes of B-cell lymphomas, failing standard chemotherapy. Follicular
or transformed lymphomas seem particularly responsive. Haematological
toxicity seems to be dependent on the functional status of the bone
marrow before radioimmunotherapy.
30
UI - 12151696
AU - Pranesh N
TI -
Lymphoma in an ileostomy.
SO - Postgrad Med J 2002 Jun;78(920):368-9
AD - Department of Surgery, Milton Keynes General Hospital, Standing Way,
Eaglestone, Milton Keynes MK6 5LD, UK. npranesh@hotmail.com
Lymphoma developing in an ileostomy is an extremely rare complication.
The presentation is similar to the commoner, yet still rare,
adenocarcinoma but the staging and management of the condition differs.
31
UI - 12100137
AU - Mitterbauer M; Kalhs P; Keil F; Prinz E; Moser K; Mannhalter C;
TI -
Mitterbauer G; Brugger S; Gisslinger H; Lechner K; Greinix HT
Continuous complete clinical and molecular remission in two patients
with refractory lymphoid malignancies after autografting followed by
allogeneic stem cell transplantation with reduced intensity
conditioning.
SO - Br J Haematol 2002 Jul;118(1):132-5
AD - Department of Medicine I, Bone Marrow Transplantation, University
Hospital of Vienna, Vienna, Austria. Margit.Mitterbauer@akh-wien.ac.at
We present a 60-year-old patient with primary refractory non-Hodgkin's
lymphoma and a 58-year-old patient with multiple myeloma with relapse
after first autologous stem cell transplantation (ASCT), who underwent
ASCT followed by allogeneic stem cell transplantation (alloSCT) with
reduced intensity conditioning consisting of fludarabine and a single
dose of total body irradiation. For graft-versus-host disease
prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete
donor chimaerism was observed on d 28 after SCT. Both patients achieved
sustained complete haematological and molecular remission of the
immunoglobulin kappa light chain (Igkappa) rearrangement and are alive
and well 17 and 16 months after SCT respectively.
32
UI - 12100150
AU - Dumontet C; Mounier N; Munck JN; Bosly A; Morschauser F; Simon D; Marit
TI -
G; Casasnovas O; Reman O; Molina T; Reyes F; Coiffier B
Factors predictive of early death in patients receiving high-dose CHOP
(ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study.
SO - Br J Haematol 2002 Jul;118(1):210-7
AD - Hematology Department, Centre Hospitalier Lyon Sud, Pierre Benite,
France. charles.dumontet@chu-lyon.fr
Death during the induction phase of chemotherapy remains a common event
in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of
patients with aggressive NHL homogeneously treated with intensive
induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine,
bleomycin, prednisone) regimen], we determined the clinical and
biological parameters that were predictive of early death. Early death
was defined as death, for whatever reason, occurring within 100 d of
randomization. Predictive factors were identified by logistic regression
and an index predictive for individual risk of early death was designed.
Among the 2210 patients treated with ACVB, there were 162 (7.3%) early
deaths. There was no significant reduction in the
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