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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Non-Hodgkin's Lymphoma - June 2002
National Cancer Institute®
Last Modified: June 1, 2002
- Treatment of post-transplant lymphomas with anti-B-cell monoclonal antibodies.
- Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma.
- Infusional CDE with rituximab for the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: preliminary
- Therapeutic outcome of Epstein-Barr virus positive T/NK cell lymphoma in the upper aerodigestive tract.
- Intestinal tuberculosis after successful treatment of advanced high-grade non-Hodgkin's lymphoma and AIDS.
- Onset of non-AIDS Kaposi sarcoma during therapy with interferon alfa-2a in an 82-year-old man with concomitant cutaneous T-cell lymphoma.
- Primary malignant lymphoma of the cavernous sinus--case report.
- Outcome of relapsed non-Hodgkin's lymphoma patients after allogeneic and autologous transplantation.
- Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with
- Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin Beta, in hematologic malignancies.
- MALToma versus marginal zone lymphoma versus diffuse large B cell lymphoma.
- Neurotoxicity with leukoencephalopathy after a single intravenous high dose of methotrexate in a patient with lymphoma.
- Therapeutic challenges of AIDS-related non-Hodgkin's lymphoma in the United States and East Africa.
- Intravascular lymphomatosis.
- Brief report: chronic myelopathy after combined chemo-radiotherapy in a patient with relapsed mediastinal B-cell lymphoma.
- Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides.
- [Ocular involvement during primary central nervous system lymphoma]
- Gastric MALT-lymphoma, gastrin and cyclooxygenases.
- CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.
- [Etiology and structure of infectious complications of cytostatic therapy in children with acute lymphoblastic leukemia and non-B-cell
- Successful long-term control with lamivudine against reactivated hepatitis B infection following intensive chemotherapy and autologous
- Rituximab plus CHOP for diffuse large-B-cell lymphoma.
- Transformation in mycosis fungoides: the role of methotrexate.
- Localized stage I-IE aggressive non-Hodgkin's lymphoma (NHL): results of prospective study with multimodality therapeutic approach.
- Outcome is not improved by the use of alternating chemotherapy in elderly patients with aggressive lymphoma.
- Treatment of cutaneous T cell lymphoma: current status and future directions.
- Monoclonal antibody therapy with autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.
- Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy.
- Survival of AIDS patients with primary central nervous system lymphoma may be improved by the radiosensitizing effects of highly active
- Treatment of prognosis of primary breast lymphoma: a review of 13 cases.
- Interleukin-2, ganciclovir, and high-dose zidovudine for the treatment of AIDS-associated primary central nervous system lymphoma.
- Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy
- [Role of surgery in the treatment of primary gastric lymphoma and assessment of new therapeutic approaches]
- Rituximab as third-line treatment for refractory or recurrent Stage III or IV follicular non-Hodgkin's lymphoma: a systematic review and
- Phase I study of recombinant human CD40 ligand in cancer patients.
- CD40 ligand therapy of lymphoma patients.
- [Three cases of the primary splenic malignant lymphoma: associated with hepatitis C virus infection]
- Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma.
- Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma?
- Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP.
- Combined therapy in advanced stages (III and IV) of follicular lymphoma increases the possibility of cure: results of a large controlled
- Immunochemotherapy in indolent non-Hodgkin's lymphoma.
- Rituximab in combination with CHOP improves survival in elderly patients with aggressive non-Hodgkin's lymphoma.
- Increasing treatment options in indolent non-Hodgkin's lymphoma.
- Improving outcomes in transplantation.
- Beyond immunochemotherapy: combinations of rituximab with cytokines interferon-alpha2a and granulocyte-macrophage colony stimulating factor.
- First radiopharmaceutical for non-Hodgkin's lymphoma.
- Successful treatment of gastrointestinal follicular lymphoma with rituxan and combination chemotherapy.
- Response to low-dose oral methotrexate and prednisone in two patients with angio-immunoblastic lymphadenopathy-type T-cell lymphoma.
- Development and rapid dissemination of Merkel-cell carcinomatosis following therapy with fludarabine and rituximab for relapsing
- Large-cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with
- [Non-Hodgkin's lymphoma]
Table of Contents
1
UI - 11785835
AU - Garnier JL; Stevenson G; Blanc-Brunat N; Touraine JL; Milpied N; Leblond
TI -
V; Blay JY
Treatment of post-transplant lymphomas with anti-B-cell monoclonal
antibodies.
SO - Recent Results Cancer Res 2002;159():113-22
AD - Hjpital Edouard Herriot, Nephrology, Transplantation and Clinical
Immunology Department, Lyon, France.
The treatment of post-transplant lymphomas still needs major
improvements in order to put the patient in remission and to retain
graft function. Chemotherapy is far too toxic in these patients. A more
specific treatment such as anti-B-cell monoclonal antibody is very
promising. The cytotoxic effect of antibody relies mainly on
complement-induced and antibody-dependent cellular cytotoxicity;
apoptosis may also induce tumor cell death. B-cell antigens expressed on
the cell surface are the targets of antibody attack; some specificities
may be chosen because of their level of expression or because of
signaling induced within the cell. Anti-B-cell antibodies can be
produced by genetic engineering in order to be humanized or to carry
bispecific Fabs. The efficacy and safety of anti-B-cell monoclonal
antibodies (mAbs) in transplant patients have been proven with different
antibodies such as anti-CD21/CD24 mAb, anti-CD38 mAb and anti-CD20 mAb.
In a retrospective analysis of different centers in France, rituximab
(anti-CD20 mAb, Roche Products) achieved an overall 69% remission rate
in 34 organ and bone-marrow transplant patients. But the conditions of
use of antibody must be better defined, particularly with regard to the
immunosuppressive therapy, the type of tumor and the dose of antibody.
We must also improve our understanding of the in vivo mechanisms of
action of antibody to develop more efficient antibody constructs.
2
UI - 11785838
AU - Straus DJ
TI -
Prognostic factors in the treatment of human immunodeficiency
virus-associated non-Hodgkin's lymphoma.
SO - Recent Results Cancer Res 2002;159():143-8
AD - Memorial Sloan-Kettering Cancer Center, Cornell University, New York, NY
10021, USA.
Chemotherapy regimens similar to those used for non-Hodgkin's lymphoma
(NHL) not associated with human immunodeficiency virus (HIV) infection
have been used for patients with HIV-associated NHL with less success.
In a recent trial, patients with intermediate or high-grade NHL were
randomized to either low-dose chemotherapy with methotrexate, bleomycin,
doxorubicin, vincristine and dexamethasone (m-BACOD) or to standard-dose
m-BACOD with sargramostim (granulocyte-macrophage colony-stimulating
factor, GM-CSF). With low-dose m-BACOD 41% of patients achieved a
complete remission and the median survival was 35 weeks. With
standard-dose m-BACOD and sargramostim, the percentage of complete
remissions was 52% with a median survival of 31 weeks (P=n.s.).
Myelosuppression was greater with standard-dose chemotherapy. In
univariate and multivariate analyses of 21 pretreatment features of
patients in this trial, four factors emerged as adversely prognostic
with respect to survival: age >35 years, intravenous drug use, CD4
counts < 100/mm3 and stage III/IV disease. In an analysis using the
proportional hazards model, a "favorable" group was defined by patients
with 0 or 1 adverse factor (median survival 46 weeks, survival at 144
weeks 29.5%) as compared with an unfavorable group with 3 or 4 adverse
factors (median survival 18 weeks, survival at 144 weeks 0). The outcome
of these patients may be improving with the use of highly active
antiretroviral therapy (HAART), which seems to improve immune function
and tolerance of chemotherapy. A recent trial of the AIDS Malignancy
Consortium found that low-dose chemotherapy (cyclophosphamide,
doxorubicin, vincristine and prednisone: CHOP) and standard-dose
chemotherapy had similar response rates, acceptable toxicity and minimal
alterations in cyclophosphamide, doxorubicin and indinavir
pharmacokinetics in HIV-associated lymphoma patients also on HAART
(stavudine, lamivudine and indinavir). There is a suggestion that
Burkitt-type lymphomas may tend to occur in HIV-infected patients with
relatively well preserved immune function and CD4 cell counts. Recent
results from our institution suggest that similar outcomes are
achievable with intensive chemotherapy in patients with Burkitt's
lymphomas with or without HIV infection. With improved immune status and
improved bone marrow function with the use of HAART, it will probably
become more possible to treat many patients with aggressive
HIV-associated NHL with more intensive treatment regimens.
3
UI - 11785839
AU - Tirelli U; Spina M; Jaeger U; Nigra E; Blanc PL; Liberati AM; Benci A;
TI -
Sparano JA
Infusional CDE with rituximab for the treatment of human
immunodeficiency virus-associated non-Hodgkin's lymphoma: preliminary
results of a phase I/II study.
SO - Recent Results Cancer Res 2002;159():149-53
AD - National Cancer Institute, Aviano, Italy.
Infusional CDE (cyclophosphamide, doxorubicin, etoposide; iCDE) is one
of the most effective chemotherapeutic regimen for human
immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL),
with a complete remission rate of 46% and a median overall survival of
8.2 months (Sparano JA, Blood 1993; 81:2810). Since the majority of
HIV-associated NHL are CD20-positive we reasoned that the addition of
rituximab to iCDE (R-iCDE) could also improve the poor outcome of these
patients. As a first step we investigated the safety of R-iCDE in a
phase I/II study. Thirty patients with aggressive HIV-associated NHL
evaluable patients were: median age: 38 years (range 29-65 years); male
sex 24/29; histology: DLCL 16 (55%), Burkitt 10 (35%), ALCL 2 (7%),
unclassified 1 (3%); stage: I (35%), II (10%), III (10%), IV (45%);
International Prognostic Index: 0, 1 (59%), 2 (24%), 3 (17%), 4, 5 (0);
CD4 count: median 132/ mm3 (range 3-470/mm3). Patients received
rituximab (375 mg/m2) in conjunction with iCDE (five or six cycles). All
patients were treated with G-CSF and highly active antiretroviral
therapy (HAART). Twenty-six of 29 patients received treatment as
planned, while chemotherapy had to be discontinued in three patients (2
persistent thrombocytopenias, 1 cerebral hemorrhage). Grade 3 or 4
toxicity was observed as follows: neutropenia 79%, anemia 45%,
thrombocytopenia 34%, bacterial infection 34%, opportunistic infection
7%, mucositis 17%. A dose reduction was necessary in 22%. Complete
remission was achieved in 86% of the patients, partial remission in 4%.
Ten percent had progressive disease. After a median follow-up of 9
months the median overall survival is not reached. The actuarial
survival at 2 years is 80% and the actuarial progression-free survival
is 79%. Four of 29 patients (14%) have died, three from NHL and one from
cryptosporidiosis. These findings suggest that the combination of
rituximab with iCDE in patients with HIV-associated NHL is safe and
feasible and that the addition of the anti-CD20 antibody does not
increase the risk for infections. The high complete remission rate also
indicates a potential therapeutic benefit and warrants further
randomized trials.
4
UI - 11971211
AU - Hahn JS; Lee ST; Min YH; Ko YW; Yang WI; Kim GE
TI -
Therapeutic outcome of Epstein-Barr virus positive T/NK cell lymphoma in
the upper aerodigestive tract.
SO - Yonsei Med J 2002 Apr;43(2):175-82
AD - Department of Internal Medicine, Yonsei University College of Medicine,
C.P.O. Box 8044, Seoul 120-752, Korea. medi@yumc.yonsei.ac.kr
Expression of the natural killer (NK) cell antigen CD56 is uncommon in
malignant lymphoma, but when it is, it is almost exclusively of the
non-B cell lineage and show a preference for the nasal and
nasopharyngeal region. T/NK cell lymphoma is known to be aggressive and
refractory to treatment. It is highly associated with the Epstein-Barr
Virus (EBV), but clinical investigations are rarely reported, that is
until recently. We report here, on the clinical features and therapeutic
outcomes of patients with T/NK cell lymphomas and its association with
EBV. We reviewed fifty-four cases with peripheral T cell lymphomas in
the upper aerodigestive tract between Jan. 1987 and Aug. 1998 from the
Severance Hospital, Yonsei University College of Medicine. The diagnosis
of T/NK cell lymphoma was made according to the expression of the NK
cell markers, CD56 antigen and cytoplasmic CD3epsilon, in tumor
specimens, by immunohistochemistry. Epstein-Barr early region (EBER) RNA
was detected using in situ hybridization on paraffin-embedded sections.
Among the 54 cases with malignant lymphomas occurring in the upper
aerodigestive tract, 20 had T/NK cell lymphoma (37%). The primary sites
of T/NK cell lymphomas were the nasal cavity, 12 cases (60%), the
tonsils, 4 cases (20%), the nasopharynx, 2 cases (10%), and the
oropharynx, 2 case (10%). There were no differences between the
features, at diagnosis or therapeutic modalities for patients with T/NK
cell lymphoma and non-T/NK cell lymphoma. The complete remission rate of
T/NK cell lymphomas was lower than non-T/NK cell lymphomas (65% vs 85%,
p=0.02). The overall survival of T/NK cell lymphomas was 13 months (1-74
month), which was significantly lower than non-T/NK cell lymphomas
[60.6% with a median follow up of 22 months (1-101 month, p=0.02)].
Disease free survival of T/NK cell lymphomas was 22 months (4-66 month),
significantly lower than non-T/NK cell lymphomas [73.8% with a median
follow up of 22 months (2-95 month), p=0.04]. The overall survival rates
for T/NK cell lymphomas were significantly lower than for EBV positive
non-T/NK cell lymphomas (p=0.018). EBER RNA was detected in the
paraffin-embedded tissue sections of all T/NK cell lymphomas, compared
to only 17.6% (6 of 34 cases) for non- T/NK cell lymphomas. In
conclusion, as patients with T/NK cell lymphomas showed poor clinical
outcomes, and a high association with EBV positivity, clinical trials
with more investigational therapeutic strategies, and further research
into the relationship of EBV infection with pathogenesis of T/NK cell
lymphoma is warranted.
5
UI - 11437056
AU - Samuel J; Mullai N; Firfir B
TI -
Intestinal tuberculosis after successful treatment of advanced
high-grade non-Hodgkin's lymphoma and AIDS.
SO - Endoscopy 2001 Jun;33(6):557
AD - Division of Medical Oncology, Cook County Hosptial, Chicago, Illinois,
60612, USA. jsamuel@rush.edu
6
UI - 11939825
AU - Giuliani M; Mastroianni A; Di Carlo A; Donati P; Miceli M; Monini P;
TI -
Rezza G
Onset of non-AIDS Kaposi sarcoma during therapy with interferon alfa-2a
in an 82-year-old man with concomitant cutaneous T-cell lymphoma.
SO - Arch Dermatol 2002 Apr;138(4):535-7
7
UI - 11980095
AU - Arimoto H; Shirotani T; Nakau H; Hashizume K; Sakai Y; Matsukuma S
TI -
Primary malignant lymphoma of the cavernous sinus--case report.
SO - Neurol Med Chir (Tokyo) 2000 May;40(5):275-9
AD - Department of Neurosurgery, Japan Self Defense Forces Central Hospital,
Tokyo.
A 59-year-old female presented with a very rare case of primary
malignant lymphoma of the cavernous sinus manifesting as diplopia and
right facial hypesthesia. Magnetic resonance (MR) imaging showed the
tumor located in the right cavernous sinus as low intensity with marked
enhancement by gadolinium. The tumor was partially removed by the
transzygomatic extradural approach. The histological diagnosis was
malignant lymphoma. Chest and abdominal computed tomography and
gallium-67 scintigraphy revealed no other lesions in the body. The
patient received conventional radiotherapy and her diplopia and right
facial hypesthesia gradually improved. At 1 month after radiotherapy, MR
imaging showed no evidence of residual tumor. Primary cavernous sinus
malignant lymphoma is extremely rare, but should be considered in the
differential diagnosis of cavernous sinus lesions. Histological
confirmation of tumors in this region is essential for choosing the most
appropriate treatment to achieve a better outcome.
8
UI - 12025224
AU - Vaishampayan U; Karanes C; Du W; Varterasian M; al-Katib A
TI -
Outcome of relapsed non-Hodgkin's lymphoma patients after allogeneic and
autologous transplantation.
SO - Cancer Invest 2002;20(3):303-10
AD - Division of Hematology and Oncology, Department of Internal Medicine,
Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit,
Michigan, USA. vaishamu@karmanos.org
A retrospective review of 58 patients with non-Hodgkin's lymphoma (NHL)
relapse or progression after autologous bone marrow transplantation
(auto BMT), peripheral stem cell transplantation (PSCT), or allogeneic
transplant and 12 (21%) patients had allogeneic transplant. Median time
to relapse post-transplant was 4.8 months with 49 relapses within 12
months after transplant. Overall 5-year survival was 22% (auto BMT or
PSCT 25%, allo BMT 18%, p = 0.38) with a median survival of 10 months
(auto BMT or PSCT 10.2 months, allo BMT 7 months, p = 0.38). Thirty-five
patients received salvage therapy and, of these, 13 demonstrated
objective response. The 3-year survival of responders and non-responders
was 55 and 14% and median survivals were 27.8 and 8 months, respectively
(p = 0.02). Interval between BMT and relapse (p = 0.0001), and response
to salvage therapy (p = 0.02) were the only significant predictors of
survival.
9
UI - 12011122
AU - Witzig TE; Gordon LI; Cabanillas F; Czuczman MS; Emmanouilides C; Joyce
TI -
R; Pohlman BL; Bartlett NL; Wiseman GA; Padre N; Grillo-Lopez AJ;
Multani P; White CA
Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan
radioimmunotherapy versus rituximab immunotherapy for patients with
relapsed or refractory low-grade, follicular, or transformed B-cell
non-Hodgkin's lymphoma.
SO - J Clin Oncol 2002 May 15;20(10):2453-63
AD - Division of Internal Medicine and Hematology, Nuclear Medicine, Mayo
Clinic and Mayo Foundation, 60 Stabile Building, Rochester, MN 55905,
USA. witzig@mayo.edu
PURPOSE: Radioimmunotherapy combines biologic and radiolytic mechanisms
to target and destroy tumor cells, thus offering a needed therapeutic
alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This
phase III randomized study compares the novel radioimmunotherapy
yttrium-90 ((90)Y) ibritumomab tiuxetan with a control immunotherapy,
rituximab, in 143 patients with relapsed or refractory low-grade,
follicular, or transformed CD20(+) transformed NHL. PATIENTS AND
METHODS: Patients received either a single intravenous (IV) dose of
(90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2)
IV weekly for four doses (n = 70). The radioimmunotherapy group was
pretreated with two rituximab doses (250 mg/m(2)) to improve
biodistribution and one dose of indium-111 ibritumomab tiuxetan for
imaging and dosimetry. The primary end point, overall response rate
(ORR), was assessed by an independent, blinded, lymphoma expert panel.
RESULTS: ORR was 80% for the (90)Y ibritumomab tiuxetan group versus 56%
for the rituximab group (P =.002). Complete response (CR) rates were 30%
and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups,
respectively (P =.04). An additional 4% achieved an unconfirmed CR in
each group. Kaplan-Meier estimated median duration of response was 14.2
months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the
control group (P =.6), and time to progression was 11.2 versus 10.1
months (P =.173) in all patients. Durable responses of > or = 6 months
were 64% versus 47% (P =.030). Reversible myelosuppression was the
primary toxicity noted with (90)Y ibritumomab tiuxetan. CONCLUSION:
Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and
produces statistically and clinically significant higher ORR and CR
compared with rituximab alone.
10
UI - 12011126
AU - Osterborg A; Brandberg Y; Molostova V; Iosava G; Abdulkadyrov K; Hedenus
TI -
M; Messinger D; Epoetin Beta Hematology Study Group
Randomized, double-blind, placebo-controlled trial of recombinant human
erythropoietin, epoetin Beta, in hematologic malignancies.
SO - J Clin Oncol 2002 May 15;20(10):2486-94
AD - Department of Oncology (Radiumhemmet), Karolinska Hospital, S-17176
Stockholm, Sweden. anders.osterborg@ks.se
PURPOSE: To investigate the effect of recombinant human erythropoietin
(epoetin beta) on anemia, transfusion need, and quality of life (QOL) in
severely anemic patients with low-grade non-Hodgkin's lymphoma (NHL),
chronic lymphocytic leukemia (CLL), or multiple myeloma (MM). PATIENTS
AND METHODS: Transfusion-dependent patients with NHL (n = 106), CLL (n =
126), or MM (n = 117) and a low serum erythropoietin concentration were
randomized to receive epoetin beta 150 IU/kg or placebo subcutaneously
three times a week for 16 weeks. Primary efficacy criteria were
transfusion-free and transfusion- and severe anemia-free survival
(hemoglobin [Hb] > 8.5 g/dL) between weeks 5 to 16. Response was defined
as an increase in Hb > or = 2 g/dL with elimination of transfusion need.
QOL was assessed by the Functional Assessment of Cancer Therapy scale.
RESULTS: Transfusion-free (P =.0012) survival and transfusion- and
severe anemia-free survival (P =.0001) were significantly greater in the
epoetin beta group versus placebo (Wald chi(2) test), giving a relative
risk reduction of 43% and 51%, respectively. The response rate was 67%
and 27% in the epoetin beta versus the placebo group, respectively (P
<.0001). After 12 and 16 weeks of treatment, QOL significantly improved
in the epoetin beta group compared with placebo (P <.05); this
improvement correlated with an increase in Hb concentration (> or = 2
g/dL). A target Hb that could be generally recommended could not be
identified. CONCLUSION: Many severely anemic and transfusion-dependent
patients with advanced MM, NHL, and CLL and a low performance status
benefited from epoetin therapy, with elimination of severe anemia and
transfusion need, and improvement in QOL.
11
UI - 11966958
AU - Ely SA
TI -
MALToma versus marginal zone lymphoma versus diffuse large B cell
lymphoma.
SO - J Gastroenterol Hepatol 2002 Feb;17(2):226; discussion 226-7
12
UI - 11978942
AU - Cohen Y; Lossos A; Polliack A
TI -
Neurotoxicity with leukoencephalopathy after a single intravenous high
dose of methotrexate in a patient with lymphoma.
SO - Acta Haematol 2002;107(3):185-6
AD - Department of Hematology, Hadassah University Hospital, Jerusalem,
Israel.
13
UI - 12011222
AU - Otieno MW; Banura C; Katongole-Mbidde E; Johnson JL; Ghannoum M; Dowlati
TI -
A; Renne R; Arts E; Whalen C; Lederman MM; Remick SC
Therapeutic challenges of AIDS-related non-Hodgkin's lymphoma in the
United States and East Africa.
SO - J Natl Cancer Inst 2002 May 15;94(10):718-32
AD - Department of Haematology and Blood Transfusion, College of Health
Sciences, University of Nairobi and the Kenyatta National Hospital,
Nairobi, Kenya.
Non-Hodgkin's lymphoma (NHL) remains the second most common malignant
complication in patients with human immunodeficiency virus (HIV)
infection. As we enter the third decade of the acquired immunodeficiency
syndrome (AIDS) epidemic, it is apparent that the evolution of
antiretroviral therapy and the emergence of combination antiviral
strategies have greatly affected the natural history of HIV infection
and its neoplastic complications. For example, there may be a trend for
declining incidence of AIDS-related lymphoma in the United States for
the first time. However, in regions of the world where the burden of HIV
infection is greatest, such as in East Africa, AIDS-related lymphoma is
an increasing cause of morbidity and mortality. Treatment of lymphoma
has evolved coincident with improvements in antiretroviral therapy.
Infusional chemotherapy regimens may offer advantages over other
regimens and schedules, but comparative trials have not been done.
Clinical trial data are available on which to develop therapeutic
strategies to treat this disease in East Africa where pragmatic
approaches are needed. Both the differences in manifestations of HIV
infection and the inherent difficulties in administering cytotoxic
chemotherapy in this part of the world must be taken into consideration
in planning therapeutic strategies. Improved understanding of the
pathogenesis of HIV infection and lymphoma will likely yield improved
therapeutic interventions as well.
14
UI - 11994970
AU - Oei ME; Kraft GH; Sarnat HB
TI -
Intravascular lymphomatosis.
SO - Muscle Nerve 2002 May;25(5):742-6
AD - Department of Rehabilitation Medicine, University of Washington Medical
Center, Seattle, USA. moei@everettclinic.com
Intravascular lymphomatosis, also known as endovascular lymphoma or
angiotropic large cell lymphoma, is a rare malignancy typically
diagnosed at autopsy. We describe a case in which the diagnosis was made
at an early stage. Specific electrodiagnostic findings suggested
concomitant polyneuropathy and myopathy. Suspicion of a paraneoplastic
syndrome during electrodiagnostic testing prompted muscle biopsy, which
revealed myopathy due to the direct infiltration of neoplastic cells.
Resultant treatment with a standard chemotherapy regimen not only
increased the patient's survival, but also improved neurological
function. Copyright 2002 Wiley Periodicals, Inc. Muscle Nerve
25:000-000, 2002
15
UI - 11984808
AU - Dormann S; Duffner U; Martini C; Bohm N; Korinthenberg R; Niemeyer C
TI -
Brief report: chronic myelopathy after combined chemo-radiotherapy in a
patient with relapsed mediastinal B-cell lymphoma.
SO - Med Pediatr Oncol 2002 Jun;38(6):442-4
AD - Division of Pediatric Hematology and Oncology, University Children's
Hospital, Freiburg, Germany.
16
UI - 11899124
AU - Mimouni D; David M; Feinmesser M; Coire CI; Hodak E
TI -
Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides.
SO - Br J Dermatol 2001 Dec;145(6):1008-14
AD - Department of Dermatology, Rabin Medical Centre, Petah Tikva, Israel.
mimouni@post.tau.ac.il
We describe four patients with mycosis fungoides (MF) in whom
depigmentation, and also leucotrichia in one, occurred following the
resolution of the eruption during phototherapy (psoralen plus
ultraviolet A treatment in three patients, climatotherapy in one). In
all cases, the depigmentation was localized to the area of the
pre-existing MF lesions. There was no clinically obvious phototoxicity.
Biopsy study including S100 staining in all cases, and electron
microscopy in one case, demonstrated the total absence of melanocytes,
with no evidence of MF. It is suggested that the phototherapy may have
activated a cell-mediated immunity leading to destruction of the
melanocytes. We recommend that vitiligo-like leucoderma be added to the
list of untoward effects of phototherapy in MF.
17
UI - 11941235
AU - Angioi-Duprez K; Taillandier L; Gerin M; Berrod JP; George JL; Maalouf T
TI -
[Ocular involvement during primary central nervous system lymphoma]
SO - J Fr Ophtalmol 2002 Feb;25(2):147-53
AD - Service d'Ophtalmologie B, CHU de Nancy-Brabois, rue du Morvan, 54511
Vandoeuvre Cedex.
PURPOSE: The aim of our study was to assess and to characterize the
ocular involvement in patients with primary central nervous system
lymphoma. Population and methods: We conducted a prospective study
patients affected by primary central nervous system lymphoma and who
underwent a systematic ophthalmological examination before treatment.
RESULTS: The study population comprised 24 patients (mean age, 57 years;
16 women and 8 men). Among these patients, 6 had ocular involvement (2
patients with ocular signs revealing the cerebral process, 2 evidenced
at the time of the initial ocular examination, and 1 as the disease
evolved). Ocular involvement was vitritis in all cases, anterior uveitis
in 1 patient, obliterant vasculitis in 1 patient and yellowish
subretinal lesions in 1 patient. In 1 case, a vitrectomy led to adequate
diagnosis of the disease. CONCLUSION: Our study shows a 25% incidence of
ocular involvement in patients with primary central nervous system
lymphoma, with posterior uveitis as the most common manifestation.
Because of the relatively high incidence of ocular involvement, a
systematic ophthalmological examination of this subset of patients
should be mandatory.
18
UI - 12014312
AU - Konturek PC; Konturek SJ; Pierzchalski P; Starzynska T; Marlicz K;
TI -
Hartwich A; Zuchowicz M; Darasz Z; Papiez D; Hahn EG
Gastric MALT-lymphoma, gastrin and cyclooxygenases.
SO - Acta Gastroenterol Belg 2002 Jan-Mar;65(1):17-23
AD - Department of Physiology, University College of Medicine, 16
Grzegorzecka str, 31-531 Krakow, Poland.
Malt-lymphoma, gastrin and COX-2 interaction. Low grade, mucosal
associated lymphoid tissue (MALT)-lymphoma is an unique among gastric
malignancies where causal involvement of Helicobacter pylori (H. pylori)
infection has been proposed based on complete regression of the tumor
following the eradication therapy. In this report ten primary, low-grade
MALT-lymphomas have been examined before and 6 months after one week of
successful eradication therapy (clarithromycin + amoxicillin +
omeprazole). Gastric biopsy samples from tumor and intact antrum and
corpus mucosa were obtained during endoscopy before and after
eradication for assessment of expression of gastrin and gastrin receptor
(CCKB-R) as well as cyclooxygenase (COX)-1 and COX-2 using RT-PCR. The
gastric lumen and serum gastrin and mucosal and tumor tissue PGE2
biosynthesis were determined by RIA before and after H. pylori
eradication. Eradication of H. pylori resulted in complete endoscopic
and histological remission of MALT-lymphoma in 9 out of 10 patients as
assessed 6 months after this eradication. Before eradication, the mRNA
expression for gastrin and CCKB-R as well as mRNA expression for COX-1
and COX-2 were observed in tumor tissue and infected mucosa, while
corpus mucosa expressed only CCKB-R and antrum mucosa only gastrin. Six
months upon the eradication when MALT-lymphoma completely regressed both
endoscopically and histologically in 9 of 10 tested subjects, the
expression of gastrin and COX-2 disappeared from the former area of
MALT-lymphoma tumor. Gastrin mRNA remained detectable only in antrum
mucosa, CCKB-R mRNA in corpus mucosa and COX-1 mRNA both in antrum and
corpus mucosa. Gastric luminal and serum gastrin levels and gastric
mucosa and tumor PGE2, which were greatly elevated before eradication,
became normalized after this procedure. This study demonstrates that
low-grade MALT-lymphoma is linked to H. pylori infection which may
promote the expression and excessive release of gastrin and COX-2
expression that could be involved in the pathogenesis of MALT-lymphoma.
19
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.
20
UI - 11949261
AU - Peshikova MV; Dolgushin II; Rusanova NN
TI -
[Etiology and structure of infectious complications of cytostatic
therapy in children with acute lymphoblastic leukemia and non-B-cell
non-Hodgkin lymphomas]
SO - Zh Mikrobiol Epidemiol Immunobiol 2002 Jan-Feb;(1):70-1
AD - State Medical Academy, Chelyabinsk, Russia.
A retrospective analysis of medical histories with acute lymphoblast
leucosis and non-B-cell non-Hodgkin lymphomas made it possible to reveal
infectious complications of cytostatic therapy in 100% of children,
namely: sepsis (0.3%), unidentified infection (12%), local infection
(87.7%). Infectious complications of the cytopenic nature were localized
mainly in the upper sections of the gastrointestinal tract and in upper
respiratory tract. Bacterial infectious complications caused by
opportunistic microorganisms with the prevalence of Gram positive flora,
resistant to cephalosporins of generations I and II, occurred most
frequently.
21
UI - 11994984
AU - Nakagawa M; Simizu Y; Suemura M; Sato B
TI -
Successful long-term control with lamivudine against reactivated
hepatitis B infection following intensive chemotherapy and autologous
peripheral blood stem cell transplantation in non-Hodgkin's lymphoma:
experience of 2 cases.
SO - Am J Hematol 2002 May;70(1):60-3
AD - Department of Medicine, Nissay Hospital, Nishi-ku Itachibori 6-3-8,
Osaka, Japan. rw9m-nkgw@asahi-net.or.jp
It is well documented that cytotoxic treatment in patients carrying the
hepatitis B virus (HBV) enhances the risk of severe hepatic damage.
Recently lamivudine has been reported to be effective in suppressing the
replication of HBV under such conditions. Here we report two cases with
HBV carrier status and with non-Hodgkin's lymphoma who were successfully
treated with high-dose chemotherapy followed by autologous peripheral
blood stem cell transplantation with the administration of lamivudine to
prevent HBV flare-up. The antiviral effect of lamivudine was fair, and
no objective side effect was experienced during the transplant
procedure. Both patients were followed carefully for more than a year
without the appearance of the resistant virus. The rebound phenomenon in
which HBV proliferates abruptly has not been experienced after
withdrawal of lamivudine. We suggest that lamivudine is indicated both
in the treatment of HBV viremia and in the prevention of proliferation
of HBV in patients with HBV carrier status undergoing high-dose
myeloablative chemotherapy.
22
UI - 12050349
AU - Akhtar S; Maghfoor I
TI -
Rituximab plus CHOP for diffuse large-B-cell lymphoma.
SO - N Engl J Med 2002 Jun 6;346(23):1830-1; discussion 1830-1
23
UI - 11992182
AU - Abd-el-Baki J; Demierre MF; Li N; Foss FM
TI -
Transformation in mycosis fungoides: the role of methotrexate.
SO - J Cutan Med Surg 2002 Mar-Apr;6(2):109-16
AD - Department of Dermatology, Boston University School of Medicine, 720
Harrison Avenue, Boston, MA 02118, USA.
BACKGROUND: Large cell transformation in patients with mycosis fungoides
(MF) has been well reported in the literature. Although the risk factors
have not been clearly elucidated, advanced stage seems to be associated
with a higher incidence of transformation. Because MF is a rare
disorder, little is known about the influence of other factors such as
immunosuppressive therapy in the occurrence of transformation.
OBJECTIVE: We questioned the role of methotrexate (MTX) in the
transformation of MF to large cell lymphoma (LCL). METHODS: We
identified all patients with MF who were registered in our cutaneous
lymphoma database. Transformation was defined by the presence of large
cells exceeding 25% of the infiltrate in at least one skin biopsy. In
one patient, we followed the histologic, immunophenotypic, and genotypic
changes taking place as transformation occurred. Results: A total of 134
patients with MF were identified. Of 21 patients who received MTX, 3
transformed, and of the 113 patients in the non-MTX group, only 2
transformed. The incidence of transformation in the patients who
received MTX was significantly higher than in those who did not receive
the drug (14.3% vs. 1.8%; p = 0.03). This significance was maintained,
even after controlling for stage and sex. For one patient who
transformed, we demonstrated an identical dominant T-cell clone in all
skin specimens, including the large cell lymphoma. CONCLUSION: Our
results demonstrate a significant association between MTX exposure and
transformation to LCL in patients with MF. In light of the small sample
size, short followup of patients, and the inherent tendency of mycosis
fungoides to transform, the role for MTX in transformation is unproven
and needs to be confirmed in a multicenter study.
24
UI - 11911313
AU - De Sanctis V; Martelli M; Anticoli AP; Caronna R; Chirletti P;
TI -
Giovannini M; Santarelli M; Enrici RM; Mandelli F
Localized stage I-IE aggressive non-Hodgkin's lymphoma (NHL): results of
prospective study with multimodality therapeutic approach.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4169-72
AD - Istituto di Radiologia, Universita degli Studi di Roma La Sapienza,
Italy. vitads@katamail.com
BACKGROUND: A brief course of chemotherapy followed by radiation therapy
was considered the best treatment for localized high-grade Non-Hodgkin's
Lymphoma (NHL). The purpose of this study was to determine the efficacy
and feasibility of a brief-course of anthracycline-based chemotherapy
(CHOP) and consolidation radiation therapy (CRT) in a series of 57
consecutive patients with stage I-IE intermediate-high grade NHL.
consecutive patients, stage I=31 (55%) and stage IE=26 (45%), were
treated with 3 cycles of CHOP regimen. Forty-four (77%) received a CRT
and thirteen (23%) with primitive gastric and splenic NHL underwent
radical surgery. Multivariate analysis was performed to evaluate age,
lactate dehydrogenase (LDH), bulky, nodal versus extranodal
localization, as prognostic factors of locoregional control and
survival. RESULTS: After a median follow-up of 84 months (range 4-128
months) the 5-year overall survival (OS), disease-free survival (DFS)
and event-free survival (EFS) rates were 88%, 87.5% and 84%,
respectively. Risk factor analysis revealed that the LDH value was the
most important adverse prognostic factor for OS and EFS. No differences
were found regarding the age and or extranodal localization. The 5-year
OS, DFS and EFS was 100% in thirteen patients with primitive gastric or
splenic NHL treated with a radical surgical approach followed by
chemotherapy without CRT. CONCLUSION: We confirm the efficacy and
feasibility of a brief course of CHOP chemotherapy followed by CRT in
localized I-IE intermediate-high grade NHL without adverse prognostic
factors. Randomized studies are warranted in order to define the dose
and the target volume of CRT (involved field or extended field) in this
setting of patients.
25
UI - 11920261
AU - Bosly A; Lepage E; Coiffier B; Fillet G; Herbrecht R; Divine M; Dupriez
TI -
B; Nouvel C; Deconninck E; Tilly H; Bordessoule D; Gaulard P;
Gisselbrecht C; The GELA
Outcome is not improved by the use of alternating chemotherapy in
elderly patients with aggressive lymphoma.
SO - Hematol J 2001;2(4):279-85
AD - Cliniques Universitaires UCL de Mont-Godinne, Yvoir, Belgium.
andre.bosly@sang.ucl.ac.be
INTRODUCTION: A prospective randomised study involving 810 elderly
patients was conducted in an attempt to compare alternating chemotherapy
with conventional first-line chemotherapy in aggressive non-Hodgkin's
lymphoma in order to improve prognosis with an acceptable toxicity for
elderly patients. PATIENTS AND METHODS: Patients included were 55-69
years old and had at least one adverse prognostic factor. Patients were
treated either with ACVBP followed by consolidation (n = 396) or with an
alternating regimen (n = 414). This regimen was an association of active
drugs in NHL relapsing patients, alternating VIMMM with ACVBP for
induction and alternation of VIM and ACVM in consolidation. Eight
hundred and sixty-six patients were randomised. After histological
review, 810 patients met the inclusion criteria: 396 in arm A, 414 in
arm B. RESULTS: The complete response rate after induction was superior
for conventional first-line therapy (58.5% vs 48%, P = 0.003) but at the
end of treatment, the CR rate was not statistically different (52% vs
48%, P = 0.19). Conventional chemotherapy had a better five-year
event-free survival than alternating regimen (33% (95% CI: 30-36%) vs
28% (95% CI: 26-30%), P = 0.0289) but overall survival was not
statistically different (40% (CI 95% 38-42%) vs 36% (CI 95% 34-38%), P =
0.068). In this elderly high risk population, the toxicity was very
high: 19% in arm A and 26% in arm B died during treatment. CONCLUSION:
Alternating regimen did not improve outcome, was less efficient and more
toxic.
26
UI - 11978140
AU - Apisarnthanarax N; Talpur R; Duvic M
TI -
Treatment of cutaneous T cell lymphoma: current status and future
directions.
SO - Am J Clin Dermatol 2002;3(3):193-215
AD - Division of Internal Medicine, Department of Dermatology, University of
Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX
77030, USA.
The treatment of cutaneous T cell lymphoma (CTCL), which includes
mycosis fungoides and Sezary syndrome, has been in a state of continual
change over recent decades, as new therapies are constantly emerging in
the search for more effective treatments for the disease. However,
prognosis and survival of patients with CTCL remains dependent upon
overall clinical stage (stage IA-IVB) at presentation, as well as
response to therapy. Past therapies have been limited by toxicity or the
lack of consistently durable responses, and few treatments have been
shown to actually alter survival, especially in the late stages of
disease. Even aggressive chemotherapy has not been shown to improve
overall survival compared to conservative sequential therapy in advanced
disease, and adds the risk of immunosuppressive complications. Over the
last decade, extracorporeal photopheresis has been the only single
treatment that has been shown to improve survival in patients with
Sezary syndrome, although its true efficacy and place in combination
therapy remain unclear. Much of the focus of current research has been
on combinations of skin-directed therapies and biological response
modifiers, which improve response rates. The results of various trials
over the years have also brought into favor the use of post-remission
maintenance therapy with topical corticosteroids, topical
mechlorethamine (nitrogen mustard), interferon-alpha, or phototherapy to
prevent disease relapse. Recent novel developments in CTCL therapy
include oral bexarotene, a retinoid X receptor-selective retinoid that
has activity in all stages of CTCL, and the topical gel formulation of
bexarotene, which plays a role in treating localized lesions. US Food
and Drug Administration (FDA)-approved, oral systemic bexarotene has the
advantage of a 48% overall response rate at a dosage of 300 mg/m(2)/day,
and avoids immunosuppression and risk of central line and
catheter-related infectious complications that are associated with other
systemic therapies. Monitoring of triglycerides and use of concomitant
lipid-lowering agents and thyroid replacement is required in most
patients. Also recently FDA-approved, denileukin diftitox is the first
of a novel class of fusion toxin proteins and is selective for
interleukin-2R (CD25+) T cells, targeting the malignant T cell clones in
CTCL. Denileukin diftitox is associated with capillary leak syndrome in
20 to 30% of patients, which may be ameliorated by hydration and
corticosteroids. Higher response rates are possible by combining
bexarotene with "statin" drugs and active CTCL therapies. Studies are
being conducted on combining bexarotene and denileukin diftitox with
other modalities. Biological response modifier therapies that are in
current or future investigational trials include topical tazarotene,
pegylated interferon, interleukin-2, and interleukin-12. At the
forefront of systemic chemotherapy development, pegylated liposomal
doxorubicin, gemcitabine, and pentostatin appear to have the greatest
potential for success in CTCL therapy. Bone marrow transplantation,
which is currently limited by the risk of graft-versus-host disease,
offers the greatest potential for disease cure. Further developments for
CTCL may include more selective immunomodulatory agents, vaccines, and
monoclonal antibodies.
27
UI - 12008655
AU - Aksentijevich I; Flinn IW
TI -
Monoclonal antibody therapy with autologous peripheral blood stem cell
transplantation for non-Hodgkin's lymphoma.
SO - Cancer Control 2002 Mar-Apr;9(2):99-105
AD - Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
BACKGROUND: With the introduction of novel monoclonal antibody products
into the clinic, significant new strategies are being developed to
improve upon existing treatment for non-Hodgkin's lymphoma. METHODS:
Monoclonal antibodies are being used alone, in combination with
chemotherapy, or as adjuncts to autologous bone marrow transplantation
for the purpose of purging bone marrow of neoplastic cells. RESULTS:
Monoclonal antibodies when used in vivo in conjunction with autologous
bone marrow transplantation have been relatively well tolerated. Results
from several trials seem to demonstrate a therapeutic benefit for the
use of such combinations. CONCLUSIONS: Before these agents can be
included in standard bone marrow transplantation regimen, long-term
survival outcomes need to be obtained from randomized trials. We review
the results from recent trials using monoclonal antibodies in
conjunction with autologous stem cell transplantation for the treatment
of non-Hodgkin's lymphoma.
28
UI - 11929754
AU - Wilson WH; Grossbard ML; Pittaluga S; Cole D; Pearson D; Drbohlav N;
TI -
Steinberg SM; Little RF; Janik J; Gutierrez M; Raffeld M; Staudt L;
Cheson BD; Longo DL; Harris N; Jaffe ES; Chabner BA; Wittes R; Balis F
Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a
pharmacodynamic approach with high efficacy.
SO - Blood 2002 Apr 15;99(8):2685-93
AD - Center for Cancer Research, National Cancer Institute, Bethesda, MD
20892, USA.
We hypothesized that incremental improvements in the
cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy
regimen through optimization of drug selection, schedule, and
pharmacokinetics would improve outcome in patients with large B-cell
lymphomas. A prospective multi-institutional study of administration of
etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of
cyclophosphamide and oral prednisone (EPOCH therapy) was done in 50
patients with previously untreated large B-cell lymphomas. The doses of
etoposide, doxorubicin, and cyclophosphamide were adjusted 20% each
cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L.
The median age of the patients was 46 years (range, 20-88 years); 24%
were older than 60 years; and 44% were at high-intermediate or high risk
according to International Prognostic Index (IPI) criteria. There was a
complete response in 92% of patients, and at the median follow-up time
of 62 months, the progression-free survival (PFS) and overall survival
(OS) rates were 70% and 73%, respectively. Neither IPI risk factors nor
the index itself was associated with response, PFS, or OS. Doses were
escalated in 58% of cycles, and toxicity levels were tolerable.
Significant inverse correlations were observed between dose intensity
and age for all adjusted agents, and drug clearance of doxorubicin and
free etoposide was also inversely correlated with age (r = -0.54 and
P(2) =.08 and r = -0.45 and P(2) =.034, respectively). Free-etoposide
clearance increased significantly during successive cycles (P(2) =.015).
Lymphomas with proliferation of at least 80% had somewhat lower
progression and those expressing bcl-2 had significantly higher
progression (P(2) =.04). Expression of bcl-2 may discriminate the
recently described activated B-like from germinal-center B-like
large-cell lymphomas and provide important pathobiologic and prognostic
information. Dose-adjusted EPOCH may produce more cell kill than
CHOP-based regimens. Dynamic dose adjustment may overcome inadequate
drug concentrations, particularly in younger patients, and compensate
for increased
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