Table of Contents
1
UI - 10944137
AU - Haioun C; Lepage E; Gisselbrecht C; Salles G; Coiffier B; Brice P; Bosly
TI -
A; Morel P; Nouvel C; Tilly H; Lederlin P; Sebban C; Briere J; Gaulard
P; Reyes F
Survival benefit of high-dose therapy in poor-risk aggressive
non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2
protocol--a groupe d'Etude des lymphomes de l'Adulte study.
SO - J Clin Oncol 2000 Aug;18(16):3025-30
AD - Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP),
Creteil, France. corinne.haioun@hmn.ap-hop-paris.fr
PURPOSE: To present the final analysis, with a median follow-up of 8
years, of the LNH87-2 randomized study, which compares consolidative
sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and
cytarabine) with high-dose therapy (HDT) using cyclophosphamide,
carmustine, and etoposide (CBV regimen) followed by stem-cell
transplantation in patients with aggressive non-Hodgkin's lymphoma in
first complete remission after induction, focusing on high/intermediate-
and high-risk patients identified by the age-adjusted international
prognostic index. PATIENTS AND METHODS: Among the 916 eligible patients,
451 presented with two (n = 318) or three (n = 133) risk factors. After
reaching complete remission to induction therapy, 236 of these higher
risk patients were assessable for the consolidation phase, with 125
patients in the HDT arm and 111 in the sequential chemotherapy arm.
RESULTS: Among these 451 higher risk patients, 277 (61%) achieved
complete remission after induction treatment. In the population of 236
randomized patients, HDT was superior to sequential chemotherapy, with
8-year disease-free survival rates of 55% (95% confidence interval [CI],
46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P =.02; relative
risk, 1.56). The 8-year survival rate was significantly superior in the
HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential
chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk,
1.51). CONCLUSION: On the basis of the final analysis of this
prospectively treated series of patients, retrospectively analyzed on
the basis of the International Prognostic Index, we hypothesize that HDT
benefits patients at higher risk who achieve complete remission after
induction treatment.
2
UI - 11148572
AU - Vaccher E; Spina M; di Gennaro G; Talamini R; Nasti G; Schioppa O;
TI -
Vultaggio G; Tirelli U
Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone
chemotherapy plus highly active antiretroviral therapy in patients with
human immunodeficiency virus-related, non-Hodgkin lymphoma.
SO - Cancer 2001 Jan 1;91(1):155-63
AD - Division of Medical Oncology A, National Cancer Institute, Aviano,
Italy.
BACKGROUND: The feasibility and efficacy of concomitant chemotherapy and
highly active antiretroviral therapy (HAART) is still unknown in
patients with human immunodeficiency virus (HIV)-related malignancies.
To evaluate the impact of chemotherapy plus HAART on the clinical course
of patients with HIV-related, systemic, non-Hodgkin lymphoma (HIV-NHL),
the authors compared retrospectively a group of 24 patients with HIV-NHL
who were treated with the cyclophosphamide, doxorubicin, vincristine,
and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80
patients who were treated with CHOP chemotherapy or a CHOP-like regimen
(i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with
vincristine plus bleomycin) without receiving antiretroviral therapy.
METHODS: All patients were enrolled in two sequential trials performed
Antiretroviral regimens consisted of two reverse transcriptase
inhibitors and one protease inhibitor. RESULTS: The two treatment groups
were well matched with regard to patient demographics, NHL
characteristics, HIV status, and treatment, i.e., the number of cycles
and chemotherapy dose. The response rates were similar between the two
groups. Severe anemia (Grade 3-4 according to the World Health
Organization criteria) was significantly greater in the patients who
received CHOP-HAART compared with the patients who received CHOP alone
(33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between
the two groups, but colony stimulating factor support was significantly
greater in the CHOP-HAART group than in the control group (92% vs. 66%,
respectively; P = 0.03). Seventeen percent of CHOP-HAART patients
developed severe autonomic neurotoxicity, whereas none of the CHOP
patients developed neurotoxicity (P = 0.002). At similar median
follow-up, opportunistic infection (OI) rates and mortality were
significantly lower in the CHOP-HAART patients than in the CHOP patients
(18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P =
0.001). The median survival for CHOP-HAART patients was not reached,
whereas the medial survival of CHOP patients was 7 months (P = 0.03).
CONCLUSIONS: The combination of CHOP plus HAART is feasible and may
reduce the morbidity from OIs in HIV-NHL patients. However, careful
attention must be directed to cross toxicity and possible
pharmacokinetic interactions between antiretroviral and antineoplastic
drugs. The impact of the combined chemotherapy plus HAART treatment on
patient survival needs urgently to be evaluated in prospective studies.
Copyright 2001 American Cancer Society.
3
UI - 11148559
AU - Hsu C; Chen CL; Chen LT; Liu HT; Chen YC; Jan CM; Liu CS; Cheng AL
TI -
Comparison of MALT and non-MALT primary large cell lymphoma of the
stomach: does histologic evidence of MALT affect chemotherapy response?
SO - Cancer 2001 Jan 1;91(1):49-56
AD - Department of Oncology, National Taiwan University Hospital, Taipei,
Taiwan.
BACKGROUND: Although the clinicopathologic features of low grade gastric
MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have
been well delineated, the significance of identifying histologic
evidence of MALT origin in a primary high grade gastric lymphoma is less
clear. The authors sought to address this issue and, in particular, to
clarify if MALT and non-MALT primary large cell gastric lymphoma might
have a different response to systemic chemotherapy. METHODS: The authors
reviewed the pathologic specimens of all patients who had a diagnosis of
primary large cell lymphoma of the stomach and who had been treated
primarily by systemic chemotherapy in our institutions January 1,
1988-December 31, 1998. The patients were divided into two groups by
experienced hematopathologists, based on the presence or absence of
histologic features suggestive of MALToma, including typical
lymphoepithelial lesions and infiltration of characteristic
centrocyte-like cells. Disease staging was done according to the
AJCC/UICC system with Musshoff modification. The median number of
gastric biopsies for each patient was 7 (range, 1-21). RESULTS:
Seventeen patients with and 26 patients without histologic evidence of
MALToma were identified. Clinical features were similar between the two
groups except that a greater proportion of patients without evidence of
MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%,
P = 0.01). The median duration of follow-up for the 43 patients was 46.5
months (range, 17-124 mos). All patients received standard systemic
chemotherapy including anthracyclines or anthracenedione. The response
rate was 88.2% for patients with evidence of MALToma and 57.7% for those
without (P = 0.03). The 5-year overall survival rate was 80.5% for
patients with evidence of MALToma and 48.9% for those without (P =
0.02). Multivariate analysis indicated that response to chemotherapy,
disease stage (Stage I and II-1 vs. Stage II-2, III, and IV), and the
presence of MALToma features were independent prognostic factors for
overall survival. CONCLUSION: The results of this relatively small study
series suggested that the presence of histologic features of MALToma in
patients with primary large cell gastric lymphoma might have been
associated with a better response to systemic chemotherapy and a better
prognosis. Further studies to consolidate this conclusion are necessary.
Copyright 2001 American Cancer Society.
4
UI - 11251023
AU - Kennedy RD; Cuthbert RG; Kettle PJ; Morris TC
TI -
Survival benefit of high-dose therapy in poor-risk aggressive
non-Hodgkin's lymphoma: concerns about omissions in the data presented.
SO - J Clin Oncol 2001 Mar 15;19(6):1884
5
UI - 11401189
AU - Smith AL; Haider K; Schachtner JM; Mathur S; Vanorden R; Gentile TC
TI -
Fatal hemolysis after high-dose etoposide: is benzyl alcohol to blame?
SO - Pharmacotherapy 2001 Jun;21(6):764-6
AD - Department of Pharmacy, State University of New York, Syracuse, USA.
A 53-year-old African-American man with relapsed non-Hodgkin's lymphoma
developed seizures and respiratory arrest 2 hours after an infusion of
high-dose etoposide in preparation for an autologous bone marrow
transplant. Laboratory tests revealed both rapid hemolysis and severe
metabolic acidosis. The patient died the following day. Based on
toxicities observed, we suspect that our patient possessed an ethnic
polymorphism of the enzyme alcohol dehydrogenase. Further research is
required to determine the relationship between the benzyl alcohol
metabolic rate and toxicity and genetic polymorphisms of alcohol
dehydrogenase in African-Americans.
6
UI - 11432625
AU - Borchmann P; Schnell R; Knippertz R; Staak JO; Camboni GM; Bernareggi A;
TI -
Hubel K; Staib P; Schulz A; Diehl V; Engert A
Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or
refractory non-Hodgkin's lymphoma.
SO - Ann Oncol 2001 May;12(5):661-7
AD - Klinik I fur Innere Medizin der Universitat Koln, Germany.
BACKGROUND: BBR 2778 is a novel aza-anthracenedione showing no
cardiotoxicity and superior activity compared to doxorubicin and
mitoxantrone in animal models. Objectives of this phase I study included
the determination of the maximum tolerated dose (MTD), the dose limiting
toxicity (DLT), clinical pharmacokinetics (PK), and antitumor activity.
Patients with relapsed or refractory, advanced non-Hodgkin's lymphoma
were included. PATIENTS AND METHODS: Patients were treated with a q1w x
3 schedule on the basis of a modified Fibonacci dose escalation method.
Seven groups with a total of twenty-six patients were treated at dosages
of 5, 10, 16.5, 25, 34, 56 or 84 mg/m2/w, respectively. RESULTS: DLT was
observed on the seventh dose level with neutropenia WHO grade 4 in three
of six patients. Pharmacokinetic analysis showed a large volume of
distribution (13.5-17.5 l/kg), a high plasma clearance (0.65-1.74
l/h/kg) and a long elimination half-life (14.7-31.9 h). Tumor response
included three complete remissions and two partial remissions.
CONCLUSIONS: Neutropenia is the DLT of the new aza-anthracenedione BBR
2778. The recommend dose is 84 mg/m2 in a q1w x 3 schedule. PK data are
consistent with a linear kinetic of BBR 2778 comparable to mitoxantrone.
This new drug shows promising activity in intensively pretreated
patients with relapsed or refractory NHL. Based on this results, phase
II studies with this new compound are underway.
7
UI - 11418315
AU - Wiseman GA; White CA; Sparks RB; Erwin WD; Podoloff DA; Lamonica D;
TI -
Bartlett NL; Parker JA; Dunn WL; Spies SM; Belanger R; Witzig TE; Leigh
BR
Biodistribution and dosimetry results from a phase III prospectively
randomized controlled trial of Zevalin radioimmunotherapy for low-grade,
follicular, or transformed B-cell non-Hodgkin's lymphoma.
SO - Crit Rev Oncol Hematol 2001 Jul-Aug;39(1-2):181-94
AD - Mayo Clinic and Foundation, Division of Nuclear Medicine, Charlton
Building 1-223, 200 First Street S.W., Rochester, MN 55905, USA.
gwiseman@mayo.edu
Radiation dosimetry studies were performed in patients with
non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium
ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively
randomized multicenter trial. The trial was designed to evaluate the
efficacy and safety of 90Y Zevalin radioimmunotherapy compared to
rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed
or refractory low-grade, follicular, or transformed NHL. An important
secondary objective was to determine if radiation dosimetry prior to 90Y
Zevalin administration is required for safe treatment in this patient
population. METHODS: Patients randomized into the Zevalin arm were given
a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab
tiuxetan) on Day 0, evaluated with dosimetry, and then administered a
therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both
Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to
clear peripheral B-cells and improve Zevalin biodistribution. Following
administration of (111)In Zevalin, serial anterior and posterior
whole-body scans were acquired and blood samples were obtained.
Residence times for 90Y were estimated for major organs, and the
MIRDOSE3 computer software program was used to calculate organ-specific
and total body radiation absorbed dose. Patients randomized into the
rituximab arm received a standard course of rituximab immunotherapy (375
mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient
interim analysis, the overall response rate was 80% for Zevalin vs. 44%
for rituximab. For all patients with Zevalin dosimetry data (N=72),
radiation absorbed doses were estimated to be below the protocol-defined
upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The
median estimated radiation absorbed doses were 71 cGy to red marrow
(range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver
(range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to
kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy).
Toxicity was primarily hematologic, transient, and reversible. The
severity of hematologic nadir did not correlate with estimates of
effective half-life (half-life) or residence time of 90Y in blood, or
radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y
Zevalin administered to NHL patients at non-myeloablative maximum
tolerated doses delivers acceptable radiation absorbed doses to
uninvolved organs. Lack of correlation between dosimetric or
pharmacokinetic parameters and the severity of hematologic nadir suggest
that hematologic toxicity is more dependent on bone marrow reserve in
this heavily pre-treated population. Based on these findings, it is safe
to administer 90Y Zevalin in this defined patient population without
pre-treatment (111)In-based radiation dosimetry.
8
UI - 11418316
AU - Goldenberg DM
TI -
The role of radiolabeled antibodies in the treatment of non-Hodgkin's
lymphoma: the coming of age of radioimmunotherapy.
SO - Crit Rev Oncol Hematol 2001 Jul-Aug;39(1-2):195-201
AD - Garden State Cancer Center, Center for Molecular Medicine and
Immunology, 520 Belleville Avenue, Belleville, NJ 07109, USA.
dmg.gscancer@att.net
This review summarizes the current clinical status of radioimmunotherapy
(RAIT) in the treatment of patients with non-Hodgkin's lymphoma (NHL),
as a prototype of the advances of RAIT in the management of cancer. Four
radiolabeled antibody products are progressing towards commercialization
for the RAIT of NHL: 131I-tositumomab (Bexxar), 90Y-ibritumomab
tiuxetan, 90Y-epratuzumab (hLL2), and 131I-Lym-1. All except epratuzumab
are murine monoclonal antibodies (Mabs) labeled with an isotope, except
that ibritumomab (Zevalin) adds chimeric rituximab to the product,
whereas epratuzumab is solely a humanized Mab. Bexxar and Zevalin target
CD20, epratuzumab binds to CD22, and Lym-1 reacts with HLA-DR. Clinical
studies have shown that all four antibody products can be safe and
efficacious. Bexxar has been shown to induce responses that are
relatively better than the prior chemotherapy, and has also been shown
to be effective in combination with chemotherapy as a frontline therapy
of low-grade and transformed NHL. However, since it is a fully murine
Mab, it did show a approximately 60% HAMA rate in untreated patients.
Zevalin has been found to be more effective than rituximab, its naked
chimeric Mab counterpart, as well as in chemotherapy-relapsed low-grade
NHL patients. Both radiolabeled epratuzumab and Lym-1 have shown
efficacy in patients who have failed chemotherapy, either with low-grade
or aggressive forms of NHL. It appears that Bexxar and Zevalin will be
the first two radiolabeled antibodies that may be available for
widespread use in the U.S., and will mark the final introduction of RAIT
as an approved cancer treatment modality. Future studies will help
define the role of these RAIT products in the management of NHL,
especially as part of a multimodal therapy of this disease.
9
UI - 11467381
AU - Kawamura T; Koga S; Okamoto M; Kanno T; Iwamura H
TI -
Results of combined-modality therapy for primary and secondary malignant
lymphoma of the central nervous system (CNS).
SO - Radiat Med 2001 May-Jun;19(3):145-9
AD - Department of Radiology, Fujita Health University School of Medicine,
Toyoake, Aichi, Japan.
PURPOSE: We consider that whatever the vital prognosis of secondary CNS
lymphoma (SCNSL), its local control is as serious as that of primary CNS
lymphoma (PCNSL). In this study, both the treatment outcomes and local
control of patients with SCNSL and PCNSL were compared, with the aim of
improving the treatment of SCNSL. MATERIALS AND METHODS: This study
included 11 patients with PCNSL and 14 with SCNSL treated from January
and received systemic chemotherapy. All SCNSL patients received systemic
chemotherapy, and eight also received intrathecal anticancer drug
infusion. Nine PCNSL patients and 11 SCNSL patients underwent
whole-brain radiation therapy with 4-MV photons. Among the SCNSL
patients, three patients underwent localized-brain irradiation and two
patients also received whole-spine irradiation. RESULTS: Five-year
survival rates were 34% for PCNSL and 33% for SCNSL. In SCNSL, survival
times after CNS involvement were very short, irrespective of treatment.
One-year local control rates after CNS irradiation were 38% for PCNSL
and 14% for SCNSL. Recurrence was mainly found in the cranial region, in
seven of 11 PCNSL patients and 10 of 14 SCNSL patients. CONCLUSIONS:
Patients with SCNSL had a poor prognosis, and local control in them was
more problematic than in patients with PCNSL. It is necessary to develop
new combined modality therapy for patients with SCNSL,including the
participation of a radiation oncologist, before the disease becomes
progressive.
10
UI - 11488114
AU - Alcaide Matas F; Garcia Munoz-Najar A; Menchen Trujillo BJ; Campano Cruz
TI -
I; Fernandez Monge C; Sanchez-Bustos Cobaleda F; Quadros Borrajo M;
Garrote Nieto E; Sierra Garcia A
[Conservatively treated primary lymphoma of the rectum]
SO - Rev Esp Enferm Dig 2001 May;93(5):335-6
11
UI - 11497233
AU - Sarris AH; Romaguera J; Hagemeister FB; Rodriguez MA; McLaughlin P; Pro
TI -
B; Younes A; Mesina O; Cabanillas F; Medeiros LJ; Samuels B
Irinotecan in relapsed or refractory non-Hodgkin's lymphoma.
SO - Oncology (Huntingt) 2001 Jul;15(7 Suppl 8):53-6
AD - Department of Lymphoma and Myeloma, The University of Texas, M. D.
Anderson Cancer Center, Houston 77030, USA. asarris@mail.mdanderson.org
Irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a
broad spectrum of antitumor clinical activity. Various schedules and
doses have been studied, and major complications were delayed diarrhea
and myelosuppression. We explored the activity of irinotecan in patients
with relapsed or refractory non-Hodgkin's lymphoma, using a 3-week
schedule of administration. Eligible patients had histologically proven
relapse, had received no more than two previous regimens, were > or = 15
years and < or = 75 years old, had normal renal function, neutrophil
count > 1,500/microL, platelet count > 100,000/microL, and no human
immunodeficiency virus infection or central nervous system involvement.
Patients were treated with irinotecan 300 mg/m2 i.v. every 21 days with
intensive loperamide management of diarrhea. Responders received up to
six treatment cycles. Of 25 patients registered so far, 22 are evaluable
for response. The median age was 67 years (range: 25 to 74 years) and 11
were male. The median number of previous regimens was 2 (range: 1 to 4
regimens), and 16 patients had disease that was refractory to their last
regimen. Serum lactate dehydrogenase level was high in 75%, and
beta2-microglobulin was > 3.0 mg/L in 26% of patients. Responses were
seen in 8 of 22 (36%) patients with non-Hodgkin's lymphoma. Response
rates were 40% for indolent, 0% for mantle cell, 45% for relapsed
aggressive, and 33% for refractory aggressive lymphomas. Grade 3/4
toxicities included myelosuppression, neutropenic fever, and delayed
diarrhea. Irinotecan appears active and relatively well tolerated in
patients with relapsed aggressive non-Hodgkin's lymphoma. Accrual to
this study is continuing for better determination of the response rate
in all histologic subtypes of non-Hodgkin's lymphoma.
12
UI - 11508931
AU - Solal-Celigny P
TI -
Rituximab as first-line monotherapy in low-grade follicular lymphoma
with a low tumor burden.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S11-4
AD - Centre Jean Bernard, Le Mans, France. p.solal-celigny@noos.fr
Patients with follicular lymphoma and a low tumor burden have a median
overall survival of more than 10 years. Toxic conventional chemotherapy
regimens are inappropriate in these patients, as they do not improve
overall survival and the patients do not require palliation of symptoms.
However, as most of these patients will ultimately die of their
lymphoma, new therapies, with curative intent, are required. Rituximab
is a human-mouse chimeric monoclonal antibody that has shown efficacy in
patients with non-Hodgkin's lymphoma (NHL). The benign tolerability
profile of rituximab makes it a suitable candidate for first-line
treatment of follicular NHL patients with a low tumor burden. In a trial
of 49 patients, 73% achieved a clinical response (26% complete response)
with rituximab treatment. Molecular studies showed that 57% of patients
achieved molecular remission (clearance of the bcl-2 molecular
translocation from the blood, evaluated by polymerase chain reaction),
62% of these remaining bcl-2- for at least 1 year. There was a good
correlation between molecular and clinical responses, with patients
failing to achieve a molecular response at higher risk of disease
progression. Rituximab monotherapy is therefore an effective and
well-tolerated treatment for patients with low-grade lymphoma and a low
tumor burden.
13
UI - 11508932
AU - Czuczman MS
TI -
Combination chemotherapy and rituximab.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S15-9
AD - Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
myron.czuczman@roswellpark.org
Rituximab is a human-mouse chimeric monoclonal antibody that has
demonstrated efficacy against non-Hodgkin's lymphoma (NHL). There is a
powerful rationale for combining rituximab treatment with
chemotherapeutic agents that have also shown efficacy in NHL, since the
mechanisms of action are distinct and there is also evidence that
rituximab may sensitize chemoresistant tumor cells to the actions of
cytotoxic drugs. A study of rituximab plus cyclophosphamide,
doxorubicin, vincristine and prednisone (CHOP) chemoimmunotherapy has
been carried out in 40 patients with low-grade NHL. In the 35 patients
who completed the study, the overall response rate was 100%, with 63%
achieving a complete response. Median time to progression has not yet
been reached at 47.2+ months. Molecular analysis (polymerase chain
reaction) showed that CHOP plus rituximab (unlike CHOP alone) could
completely clear blood and bone marrow of cells containing the bcl-2
gene translocation, a molecular marker of NHL cells. Rituximab can
therefore add to the efficacy of CHOP without significantly increasing
toxicity. A further study is underway to determine whether similar
efficacy with less overall toxicity can be achieved using rituximab in
combination with fludarabine.
14
UI - 11508933
AU - Schmitz N
TI -
Rituximab in autologous stem cell transplantation for follicular
lymphoma.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S21-4
AD - Second Department of Internal Medicine, Christian-Albrechts-University,
Kiel, Germany. n.schmitz@med2.uni-kiel.de
Contamination of stem cell harvests with residual tumor cells is a
significant problem hampering the success of autologous peripheral blood
stem cell transplantation in non-Hodgkin's lymphoma (NHL). Techniques
have therefore been introduced to attempt to remove these cells, either
in vivo, prior to harvesting, or ex vivo, before reinfusion into the
patient. Rituximab is a human-mouse chimeric anti-CD20 monoclonal
antibody that has been administered to patients prior to stem cell
harvesting, to purge the blood of residual malignant cells. Clinical
studies have shown that rituximab is safe to use during stem cell
mobilization since administration did not adversely affect the yield of
CD34+ stem cells or the functional capability of these progenitors.
Rituximab was also effective in purging stem cell harvests of malignant
cells. Translocation of the bcl-2 gene was found in a significantly
smaller proportion of stem cell harvests from patients who had received
a purging infusion of rituximab than controls. Rituximab may also be
useful as salvage therapy following post-transplant relapse or as
maintenance therapy for patients in remission. Prospective randomized
trials will ultimately define the role of rituximab in the autologous
transplantation setting.
15
UI - 11508934
AU - Linch D
TI -
Current treatment of follicular and low-grade non-Hodgkin's lymphoma.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S5-9
AD - Department of Haematology, Royal Free and University College Medical
School, London, UK. d.linch@ucl.ac.uk
Patients with low-grade non-Hodgkin's lymphoma (NHL) have a median
survival of 4-8 years from diagnosis and a cause-specific survival of
about 10 years. Radiotherapy can be curative in a small proportion of
patients with very localized disease, but the majority of patients have
advanced disease at diagnosis and it is not clear that any current
therapy is curative in this situation. While in many instances patients
with high-grade NHL are cured by chemotherapy, those with low-grade NHL,
despite impressive response rates, almost invariably relapse. A
'watch-and-wait' strategy can therefore delay the onset of chemotherapy
by 2-3 years, without affecting survival. Results with autologous stem
cell transplantation have been similarly disappointing to date.
Rituximab is a human-mouse chimeric monoclonal antibody that represents
a novel approach to treatment of low-grade NHL, targeting malignant
cells without the side effects associated with chemotherapy. A pivotal
study has demonstrated a response rate of 56% in relapsed or refractory
low-grade NHL. The relatively benign side-effect profile means rituximab
can be used early in the disease process, and in combination with
chemotherapeutic regimens and autologous transplantation. Ongoing and
future studies will define the optimal role of rituximab in treatment of
low-grade NHL.
16
UI - 11512599
AU - Dowling AJ; Prince HM; Wirth A; Wolf M; Januszewicz EH; Juneja S;
TI -
Seymour JF; Gates P; Smith JG
High-dose therapy and autologous transplantation for lymphoma: The Peter
MacCallum Cancer Institute experience.
SO - Intern Med J 2001 Jul;31(5):279-89
AD - Department of Medical Oncology, St Vincent's Hospital, Melbourne,
Victoria, Australia.
BACKGROUND: High-dose therapy (HDT) with autologous bone marrow or blood
cell transplantation for the treatment of lymphoma commenced at Peter
MacCallum Cancer Institute in 1986. AIM: To examine the patient
characteristics and outcomes of patients with non-Hodgkin's lymphoma
(NHL) and Hodgkin's disease (HD) treated with HDT and autologous
transplantation at our Institute in the first 10 years of the service
(1986-95). METHODS: A retrospective analysis was performed examining
patient characteristics, prior chemotherapy regimens, pretransplant
disease status, HDT regimen, source of stem cells, time for
haematopoietic recovery, complications of transplantation, response
rates, overall survival (OS) and progression-free survival (PFS).
RESULTS: Sixty-seven patients with NHL were treated with an estimated
5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate
of 34% (95% CI 21-44%). Factors independently predictive of an
unfavourable PFS on multivariate analyses were presence of
constitutional symptoms at transplant (P < 0.002) and
chemotherapy-resistant disease at transplant (P = 0.02). Twenty-three
patients with HD were treated with a 5-year predicted OS rate of 74%
(95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%). There was no
difference in PFS for HD patients who relapsed either within 12 months
of completion of front-line therapy or after this time (P= 0.5). The
transplant-related mortality for the entire cohort was 17%, with a
progressive decrease over time. CONCLUSION: HDT with autologous
transplantation achieves durable PFS and OS in patients with lymphoma.
Improved patient selection, therapy modifications according to
prognostic factors and ongoing improvements in supportive care should
improve outcomes further.
17
UI - 11544694
AU - Laine K; Valavaara R; Rouru J
TI -
[Drug interaction behind the toxicity of chemotherapy]
SO - Duodecim 1998;114(11):1128-30
AD - TYKS:n kliinisen farmakologian yksikko 20520 Turku. karlai@utu.fi
18
UI - 11527816
AU - Perez CL; Rudoy S
TI -
Anti-CD20 monoclonal antibody treatment of human herpesvirus
8-associated, body cavity-based lymphoma with an unusual phenotype in a
human immunodeficiency virus-negative patient.
SO - Clin Diagn Lab Immunol 2001 Sep;8(5):993-6
AD - Departamento Virologia, Instituto Nacional de Enfermedades
Infecciosas-ANLIS Dr. Carlos G. Malbran, Av. Velez Sasrsfield 563
(1281), Buenos Aires, Argentina. Cperez@anlis.gov.ar
Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus,
is a gammaherpesvirus first detected in Kaposi's sarcoma tumor cells and
subsequently in primary effusion lymphoma (PEL) tumor cells and
peripheral blood mononuclear cells from PEL patients. PEL has been
recognized as an individual nosologic entity based on its distinctive
features and consistent association with HHV-8 infection. PEL is an
unusual form of body cavity-based B-cell lymphoma (BCBL). It occurs
predominantly in human immunodeficiency virus (HIV)-positive patients
but occasionally also in elderly HIV-negative patients. We describe a
case of PEL, with ascites, bilateral pleural effusions, and a small
axillary lymphadenopathy, in a 72-year-old HIV-negative man. PCR
performed on a lymph node specimen and in liquid effusion was positive
for HHV-8 and negative for Epstein-Barr virus. The immunophenotype of
the neoplastic cells was B CD19+ CD20+ CD22+ with coexpression of CD10
and CD23 and with clonal kappa light chain rearrangement. The patient
was treated with Rituximab, a chimeric (human-mouse) anti-CD20
monoclonal antibody. Thirteen months later, the patient continued in
clinical remission. This is the first report of an HHV-8-associated BCBL
in an HIV-negative patient in Argentina.
19
UI - 11564066
AU - Di Gaetano N; Xiao Y; Erba E; Bassan R; Rambaldi A; Golay J; Introna M
TI -
Synergism between fludarabine and rituximab revealed in a follicular
lymphoma cell line resistant to the cytotoxic activity of either drug
alone.
SO - Br J Haematol 2001 Sep;114(4):800-9
AD - Laboratory of Molecular Immunohaematology and Department of Oncology,
Istituto Ricerche Farmacologiche Mario Negri, via Eritrea 62, 20157
Milan, Italy.
We have shown previously that the anti-CD20 chimaeric monoclonal
antibody rituximab exerts its effects on neoplastic B-lymphoma cell
lines in part via complement-dependent cytotoxicity. In addition,
membrane expression levels of complement inhibitory proteins CD55 and
CD59 play a role in determining susceptibility to lysis. We have
identified one t(14;18)-positive human B-cell non Hodgkin's lymphoma
cell line (Karpas 422) that is resistant to rituximab and complement and
used it for subsequent studies on the possible interaction between this
novel therapeutic agent and established antineoplastic drugs. We have
exposed Karpas to several chemotherapeutic agents (doxorubicin,
idarubicin, cisplatin, taxol) for different time periods and
subsequently exposed the cells to rituximab and human complement. The
combination of these drugs with rituximab induced an additive cytotoxic
effect. In contrast, exposure to fludarabine (1 microg/ml for 48-72 h)
showed a synergistic effect, with cell lysis increasing from 10% to 20%
using fludarabine or rituximab and complement alone to about 70% with
both cytotoxic agents. Analysis of the mechanism for this synergistic
effect showed that fludarabine downmodulates the membrane expression of
CD55 (from 96% to 55% positive cells) without significantly altering
CD20 levels. Northern analysis demonstrated that fludarabine induced a
general downmodulation of steady state mRNA levels with no change in
transcription rate detected in run-off assays. The study of the effect
of fludarabine and rituximab in six freshly isolated B-cell chronic
lymphocytic leukaemia (B-CLL) samples showed that, in most cases,
fludarabine has an additive cytotoxic activity with rituximab and
complement. This report gives a rational support for clinical studies
with combinations of drugs, including monoclonal antibodies and
fludarabine.
20
UI - 11583015
AU - Ribeiro JM; Lucas M; Palhano MJ; Victorino RM
TI -
Remission of a high-grade gastric mucosa associated lymphoid tissue
(MALT) lymphoma following Helicobacter pylori eradication and highly
active antiretroviral therapy in a patient with AIDS.
SO - Am J Med 2001 Sep;111(4):328-9
21
UI - 11593318
AU - Gutierrez-Delgado F; Maloney DG; Press OW; Golden J; Holmberg LA;
TI -
Maziarz RT; Hooper H; Buckner CD; Appelbaum FR; Bensinger WI
Autologous stem cell transplantation for non-Hodgkin's lymphoma:
comparison of radiation-based and chemotherapy-only preparative
regimens.
SO - Bone Marrow Transplant 2001 Sep;28(5):455-61
AD - The Fred Hutchinson Cancer Research Center, 1100 Fairview Av North
D5-390, Seattle, WA 98109, USA.
The aim of this study was to compare toxicity and efficacy of total body
irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) vs
busulfan, melphalan and thiotepa (Bu/Mel/T) in patients receiving
autologous stem cell infusion (ASCI) for malignant lymphoma (NHL).
with TBI/CY/E (n = 221) or Bu/Mel/T (n = 130) followed by ASCI. Patients
in first, or second remission, first responding or untreated relapse
were defined as having less advanced disease before transplantation. The
median follow-up was 5 years (range 1-9) and 3.5 years (1-6) for
patients receiving TBI/CY/E and Bu/Mel/T, respectively. The cumulative
probabilities of survival, event-free survival (EFS) and relapse at 5
years were 44%, 32%, 49% following TBI/CY/E and 42%, 34% and 42%
following Bu/Mel/T. The probability of EFS at 5 years for patients who
had prior dose-limiting radiation (n = 59) was 32% after Bu/Mel/T
therapy. Transplant-related mortality was 16% for TBI/CY/E and 21% for
Bu/Mel/T. In univariate and multivariate analyses, more advanced disease
status was associated with poor outcome (TBI/CY/E: RR 0.70, CI 0.50 to
0.97 P = 0.04; Bu/Mel/T: RR 0.61, CI 0.39 to 0.97 P = 0.03). No
significant differences in toxicities and outcomes were observed between
these two regimens despite the inclusion of patients who had received
dose-limiting irradiation in the Bu/Mel/T regimen.
22
UI - 11584710
AU - Spath-Schwalbe E
TI -
[Treatment of malignant non-Hodgkin's lymphomas in elderly patients]
SO - Z Gerontol Geriatr 2001 Aug;34(4):263-8
AD - Krankenhaus Spandau 2, Abteilung fur Innere Medizin Neue Bergstrasse 6
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