- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer Center
NCI CANCERLIT® Search: Therapy of Acute Myeloid Leukemia - January 2002
National Cancer Institute®
Last Modified: January 1, 2002
Table of Contents
1
UI - 11452409
AU - Biagi E; Rovelli A; De Lorenzo P; Uderzo C
TI -
Autologous hematopoietic stem cell transplantation (AHSCT) as
consolidation therapy for childhood acute myelogenous leukemia in 1st
complete remission.
SO - Pediatr Hematol Oncol 2001 Jul-Aug;18(5):359-62
2
UI - 11488854
AU - Hui CH; Bardy P; Hughes T; Horvath N; To LB
TI -
Successful salvage of RAEB/AML relapsing early post allograft with
FLAG-Ida conditioned mini-allograft: a report of two cases.
SO - Clin Lab Haematol 2001 Apr;23(2):135-8
AD - Clinical Haematology & Bone Marrow Transplant Unit, Royal Adelaide
Hospital, Adelaide, SA 5000, Australia. chi-hung.hui@imvs.sa.gov.au
Management options are often limited for patients with AML or high grade
myelodysplasia (MDS) relapsing within a year of allogeneic
transplantation. We report, in two such patients, the use of
re-induction with FLAG-Ida chemotherapy, followed by the infusion of
GCSF-mobilized blood stem cells from the same HLA-matched donor. Both
patients achieved durable complete remissions with good quality of life
and longer disease-free survival than after the first myeloablative
allografts. This mini-allograft approach offers a practical,
well-tolerated salvage and a potentially curative treatment for relapsed
AML/high grade MDS patients failing a first conventional myeloablative
allogeneic transplants.
3
UI - 11503549
AU - Koh LP; Goh YT; Teoh G; Tan P
TI -
Treatment of acute promyelocytic leukaemia using a combination of
all-trans retinoic acid and chemotherapy.
SO - Ann Acad Med Singapore 2001 Jul;30(4):401-8
AD - Department of Haematology, Singapore General Hospital, 1 Hospital Drive,
Singapore 169608.
INTRODUCTION: The combination of all-trans retinoic acid (ATRA) with
chemotherapy has improved the outcome of acute promyelocytic leukaemia
(APL). Effective induction as well as maintenance therapy for APL can be
achieved using this combination of anti-leukaemic agents. MATERIALS AND
METHODS: Twenty-four consecutive patients with newly-diagnosed APL were
treated with ATRA daily together with either daunorubicin or idarubicin.
Therapy with ATRA was continued until complete remission (CR) was
achieved; thereafter, patients were treated with 2 cycles of an
anthracycline-based consolidation chemotherapy (either daunorubicin or
idarubicin). Maintenance therapy was achieved using 5 alternating cycles
of low-dose methotrexate (MTX) plus 6-mercaptopurine (6MP) followed by
ATRA alone. RESULTS: Twenty-three out of 24 patients (96%) completed
induction therapy and achieved haematological CR (HCR) as well as
molecular remission (MR); however, 1 patient (5%) died from retinoic
acid syndrome. Twenty-one out of 23 evaluable patients (91%) completed
consolidation chemotherapy, and 2 patients (10%) died, 1 from
neutropenic sepsis and the other from relapse following non-compliance
to therapy. All 21 surviving patients in the present study received
maintenance chemotherapy and are still in HCR and MR at a median
follow-up of 23 months. The estimated actuarial 2-year overall survival
(OS) and event-free survival (EFS) rates were both 84% +/- 9%.
CONCLUSION: The combination of ATRA with an anthracycline is an
effective remission-induction therapy for newly-diagnosed APL.
Maintenance therapy using alternating cycles of MTX plus 6MP followed by
ATRA alone is effective in maintaining CR and MR as well as prolonging
the survival of patients with APL.
4
UI - 11571506
AU - Urbano-Ispizua A; Brunet S; Solano C; Moraleda JM; Rovira M; Zuazu J; de
TI -
La Rubia J; Bargay J; Caballero D; Diez-Martin JL; Ojeda E; Perez de
Oteiza JP; Ferra C; Espigado I; Alegre A; de La Serna J; Torres P; Riu
C; Odriozola J; Rozman C; Sierra J; Garcia-Conde J; Montserrat E;
Spanish Group of Allo-PBT
Allogeneic transplantation of CD34+-selected cells from peripheral blood
in patients with myeloid malignancies in early phase: a case control
comparison with unmodified peripheral blood transplantation.
SO - Bone Marrow Transplant 2001 Aug;28(4):349-54
AD - Depatment of Hematology, Hospital Clinic, University of Barcelona,
Spain.
An allogeneic transplantation of CD34(+)-selected cells from peripheral
blood (allo-PBT/CD34(+)) from HLA-identical sibling donors was performed
in 50 adult patients with acute myeloid leukemia in first complete
remission (AML CR1) (n = 29), myelodysplastic syndrome (MDS) (n = 4), or
chronic myeloid leukemia in first chronic phase (CML CP1) (n = 17).
Clinical results were compared to a concurrent group of 50 patients
transplanted with unmodified peripheral blood progenitor cells
(allo-PBT), matched for age, diagnosis, and disease stage. The median
follow-up period was 29 months (range 1-69). The actuarial probability
of developing acute GVHD clinical grade II to IV was 16% (95%CI: 6-26)
for the allo-PBT/CD34(+) group and 41% (95%CI: 29-57) for the allo-PBT
group (P = 0.002). The actuarial probability of developing extensive
chronic GVHD was 22% (95%CI: 8-36) for the allo-PBT/CD34(+) group and
47% (95%CI: 31-63) for the allo-PBT group (P = 0.02). Recipients of
allo-PBT/CD34(+) had less toxicity associated with the transplant and
better Karnofsky index at the last follow-up. For AML/MDS patients, the
actuarial probability of disease-free survival (DFS) for recipients of
allo-PBT/CD34(+) and allo-PBT was 65% (95%CI: 45-85) vs43% (95%CI:
28-58) (P = 0.05), respectively. These data provide a rationale for a
randomised trial of allo-PBT/CD34(+) vs allo-PBT in AML/MDS patients in
early stage of the disease.
5
UI - 11571508
AU - Meloni G; Proia A; Capria S; Romano A; Trape G; Trisolini SM; Vignetti
TI -
M; Mandelli F
Obesity and autologous stem cell transplantation in acute myeloid
leukemia.
SO - Bone Marrow Transplant 2001 Aug;28(4):365-7
AD - Department of Biotecnologie Cellulari ed Ematologia, University La
Sapienza, Roma, Italy.
In the bone marrow transplant setting, several authors hypothesized that
severely overweight patients are at increased risk of transplant-related
toxicity, but different definitions of obesity, different body weight
groupings and heterogeneous samples of patients were analyzed. To
overcome these limitations, we retrospectively considered a homogeneous
group of 54 patients (median age 36.5 years), with a diagnosis of de
novo acute myeloid leukemia (AML), autografted in first complete
remission (CR) with the Bu-Cy2 conditioning regimen, dosed on actual
body weight. Patients were classified into three groups (obese,
non-obese, underweight) using body mass index (BMI = kg/m(2)); for each
group we analyzed transplant-related toxicity and mortality, overall
survival and disease-free survival (OS/DFS). In spite of the relatively
small number of patients, in our results high BMI appears a predictive
factor for an increase of treatment-related toxicity and mortality.
Moreover, 30 (55%) patients are currently alive in continuous CR, and
after a median follow-up of 76.5 months (range 14-137) statistically
significant differences in OS and DFS were detected between obese and
non-obese groups (P = 0.012 and 0.021, respectively). Our study suggests
that obesity may represent an independent risk factor for autograft in
AML and further investigations are warranted.
6
UI - 11571518
AU - Au WY; Lie AK; Lee CK; Ma SK; Wan TS; Shek TW; Liang R; Kwong YL
TI -
Late onset post-transplantation lymphoproliferative disease of recipient
origin following cytogenetic relapse and occult autologous
haematopoietic regeneration after allogeneic bone marrow transplantation
for acute myeloid leukaemia.
SO - Bone Marrow Transplant 2001 Aug;28(4):417-9
AD - Department of Medicine, Queen Mary Hospital, Hong Kong.
A post-transplantation lymphoproliferative disease (PTLD) of recipient
origin was identified in one of 376 consecutive cases of allogeneic bone
marrow transplantation (BMT). This occurred in a 36-year-old woman who
received an allogeneic BMT for acute myeloid leukaemia in relapse. At 15
months after BMT, recipient haematopietic and leukaemic cells were found
in the bone marrow, which disappeared on withdrawal of
immunosuppression. However, severe graft-versus-host disease (GVHD)
necessitated the continuation of immunosuppression, leading to the
occurrence of PTLD in the liver and lung 12 months afterwards.
Fluorescence in situ hybridisation showed that the neoplastic cells were
of recipient origin. Although the PTLD also responded completely to
withdrawal of immunosuppression, the patient finally died from the
complications of GVHD. This case of late onset PTLD post-BMT showed
features similar to those in solid organ transplantation, in that the
tumour was of recipient origin and responded well to the withdrawal of
immunosuppression. Of further interest is that recipient lymphoid
regeneration had accompanied autologous haematopoietic regeneration and
become a target for subsequent neoplastic transformation.
7
UI - 11568900
AU - Loeb DM; Bowers DC; Civin CI; Friedman AD
TI -
Intensive timed sequential remission induction chemotherapy with
high-dose cytarabine for childhood acute myeloid leukemia.
SO - Med Pediatr Oncol 2001 Oct;37(4):365-71
AD - Division of Pediatric Oncology, Johns Hopkins University, 1650 Orleans
Street, Baltimore, MD 21231, USA.
BACKGROUND: Timed sequential chemotherapy and high-dose cytarabine
(cytosine arabinoside, Ara-C; HDAC) are both effective treatments for
acute myeloid leukemia (AML). We review our institutional experience
with timed sequential induction chemotherapy consisting of
daunorubicin/Ara-C/-thioguanine (DAT) or idarubicin/Ara-C/-thioguanine
(IAT) followed on day 14 by HDAC regardless of the degree of marrow
aplasia for children with newly diagnosed AML. PROCEDURE: Children
presenting with newly diagnosed AML were treated with induction
chemotherapy consisting of idarubicin (12 mg/m/day on days 1-3 or
daunorubicin at 45 mg/m(2)/day for the first five patients), Ara-C (100
mg/m(2)/day by continuous infusion on days 1-7), and thioguanine (100
mg/m(2)/day on days 1-7). HDAC (1 g/m(2)/dose every 12 hr for 10 doses)
was administered beginning on day 14, regardless of the results of bone
marrow examination. RESULTS: Thirteen children received timed sequential
HDAC. Only one child received HDAC later than Day 18. Eleven of the
children achieved a complete remission. All patients experienced grade 4
hematologic toxicity, and all had fever as well. There were 11 children
with documented infections. Ten had grade 3 or 4 GI toxicity. One
patient died of sepsis. CONCLUSIONS: HDAC administered as a part of
timed sequential therapy yields an excellent remission induction rate
with manageable toxicity. Copyright 2001 Wiley-Liss, Inc.
8
UI - 11574763
AU - Hanel M; Friedrichsen K; Hanel A; Herbst R; Morgner A; Neser S;
TI -
Nicklisch M; Teich M; Ehninger G; Fiedler F
Mito-flag as salvage therapy for relapsed and refractory acute myeloid
leukemia.
SO - Onkologie 2001 Aug;24(4):356-60
AD - Abteilung Hamatologie, Klinik fur Innere Medizin III/Kuchwald, Klinikum
Chemnitz gGmbH, Chemnitz.
BACKGROUND: This study was performed to examine the feasibility and
toxicity of the combination of mitoxantrone, fludarabine, cytarabine as
bolus (B) or continuous infusion (CI) and granulocyte- colony
stimulating factor (G-CSF) in patients with recurrent and refractory
acute myeloid leukemia (AML). PATIENTS AND METHODS: 29 patients with
relapsed (n =17) or refractory (n =12) AML were treated with the
Mito-FLAG protocol consisting of mitoxantrone (7 mg/m(2), days 1/3/5),
fludarabine (15mg/m(2), every 12 h, days 1-5), cytarabine (Ara-C) as
bolus infusion (1000 mg/m(2) over 1 h, every 12 h, days 1-5) (n =15) or
as continuous infusion (100-150 mg/m(2) over 24 h, days 1-5) (n =14),
and G-CSF (5 mgr;g/ kg/day, day 0 until a neutrophile count of 0.5
x10(9)/l). RESULTS: 17 patients (59%) and 1 patient (3%) achieved
complete remission (CR) and partial remission (PR), respectively; thus
the overall response rate was 62%. Following Mito-FLAG, 5 patients with
CR underwent high-dose therapy (HDT) with allogeneic (n = 2) or
autologous (n = 3) stem cell transplantation (SCT).With a median
follow-up of 28 (range 6-54) months, 4 transplanted patients are alive
in CR (n = 2) or in relapse (n = 2). The median duration of event-free
survival (EFS) and overall survival (OS) was 3.2 and 6.8 months, and
probabilities of EFS and OS after 1 year were 14 and 34%, respectively.
The 1-year rates for EFS and OS in this group were 18 and 53%,
respectively. Median duration of WHO grade 4 granulocytopenia and
thrombocytopenia was 20 and 23 days, respectively. Nonhematological side
effects were moderate, predominantly reaching WHO grades 1-2.
Neutropenic fever was seen in 85% of courses, with a median duration of
4 (1-38) days. Four patients (14%) suffered an early death because of
aplasia (n = 2), pneumonia (n =1) or progressive AML (1 nonresponding
patient). CONCLUSIONS: Our data suggest that the Mito-FLAG protocol is
feasible and can be safely performed with both schedules of Ara-C. In
this study the regimens have shown high efficacy and acceptable toxicity
in patients with relapsed or refractory AML. We currently examine the
importance of bolus versus continuous infusion of Ara-C as part of the
Mito-FLAG regimen in a prospective randomized multicenter trial.
Copyright 2001 S. Karger GmbH, Freiburg
9
UI - 11584711
AU - Wedding U; Hoffken K
TI -
[Therapy of acute myeloid leukemia in the elderly patient]
SO - Z Gerontol Geriatr 2001 Aug;34(4):269-76
AD - Klinik fur Innere Medizin II Hamatologie, Onkologie, Endokrinologie,
Stoffwechselerkrankungen Friedrich-Schiller-Universitat Erlanger Allee
101 07747 Jena, Germany. ulrich.wedding@med.uni-jena.de
Incidence and mortality rates of acute myeloid leukemia (AML) increase
exponentially with advancing age. AML diagnosed in elderly patients
differs from that diagnosed in younger patients. But not only
disease-specific differences are important. Treating elderly patients
with AML age-associated differences in the patients general
presentation, such as physiological changes in organ function, decreased
ability to react to stress, dependence in activities of daily living,
existence of other morbidities (co-morbidity), the need to take drugs
for those diseases and the reduced life expectancy can force alterations
in the disease management. Clinical trials for the treatment of AML have
been excluding elderly patients for years. Even trials accepting elderly
patients with AML did select the group of otherwise healthy elderly
patients for participation in the trial. Thus the data for AML
management in elderly patients do not reflect the whole group of elderly
patients with AML. If the patient is treated with curative intention,
therapy of choice is the so-called 3 + 7 protocol for induction of
complete remission, followed by a consolidation therapy and in some
cases by maintenance therapy. In some situations, especially in very old
patients, a palliative intention to treatment is favored. There are no
generally accepted criteria to measure treatment benefit in this setting
nor established chemotherapy protocols for this situation. Further
trials for elderly patients with AML have to offer treatment options for
the whole group of patients and have to determine what treatment
approach is the best for which individual patient.
10
UI - 11588026
AU - de Witte T; Suciu S; Verhoef G; Labar B; Archimbaud E; Aul C; Selleslag
TI -
D; Ferrant A; Wijermans P; Mandelli F; Amadori S; Jehn U; Muus P;
Boogaerts M; Zittoun R; Gratwohl A; Zwierzina H; Hagemeijer A; Willemze
R
Intensive chemotherapy followed by allogeneic or autologous stem cell
transplantation for patients with myelodysplastic syndromes (MDSs) and
acute myeloid leukemia following MDS.
SO - Blood 2001 Oct 15;98(8):2326-31
AD - University Medical Center St Radboud, Nijmegen, The Netherlands.
t.dewitte@hemat.azn.nl
This study investigated the feasibility of allogeneic (alloSCT) and
autologous stem cell transplantation (ASCT) as postconsolidation therapy
for patients with myelodysplastic syndromes (MDSs) or acute myeloid
leukemia after MDS. Patients with a histocompatible sibling were
candidates for alloSCT and the remaining patients for ASCT.
Remission-induction therapy consisted of 1 or 2 courses with idarubicin,
cytarabine, and etoposide, followed by one intensive consolidation
course with cytarabine and mitoxantrone. Initially, bone marrow cells
were used for ASCT. Subsequently, mobilized blood stem cells were used
in an attempt to shorten posttransplantation hypoplasia. With a median
follow-up of 3.6 years the 184 evaluable patients showed a 4-year
survival rate of 26% and a median survival of 13 months. The
remission-induction chemotherapy induced complete remission (CR) in 100
patients (54%). The 4-year disease-free survival (DFS) rate was 29% and
the median DFS was 12 months. Twenty-eight of 39 patients (72%) with a
donor were allografted in CR-1, including 2 patients who underwent
transplantation in CR-1 without a consolidation course. Thirty-six of 59
patients (61%) without a donor received ASCT in CR-1. The 4-year DFS
rates in the group of patients with or without a donor were 31% and 27%,
respectively. The 4-year survival rates from CR were 36% and 33%,
respectively. This large prospective study shows the feasibility of both
alloSCT and ASCT. This treatment approach leads to a relatively high
remission rate, and the majority of patients in remission received the
SCT in CR-1. The ongoing study investigates whether this approach is
better than treatment with chemotherapy only.
11
UI - 11601256
AU - Shang X; Yin H; Lu A; Zhang L
TI -
Application of recombinant human granulocyte colony stimulating factor
in children with acute myeloid leukemia.
SO - Chin Med J (Engl) 1999 Jul;112(7):620-2
AD - Department of Pediatrics, Second Hospital, Beijing Medical University,
Beijing 100044, China.
OBJECTIVE: To evaluate the effect of recombinant human granulocyte
colony stimulating factor (rhG-CSF) on accelerating neutrophil recovery
and decrease fatal infections for childhood acute myeloid leukemia
enrolled into our study and 15 were newly diagnosed. All were treated
with high dose chemotherapy combined with rhG-CSF. RESULTS: Of 15 newly
diagnosed patients, 13 achieved complete remission (CR) after one course
of therapy and 2 achieved CR after two courses of therapy. For newly
diagnosed patients, the durations of absolute neutrophil counts (ANC) <
0.5 x 10(9)/L were 5 days and 10 days in rhG-CSF group and control group
respectively (P < 0.05). The incidences of infection of these two groups
were 40% and 60% respectively (P < 0.05). As for patients who received
intensive therapy, the durations of ANC < 0.5 x 10(9)/L were 5 days and
8 days in rhG-CSF group and control group, respectively (P < 0.05), and
the incidences of infection were 25% and 44.4% respectively (P < 0.05).
CONCLUSIONS: The application of rhG-CSF in children with AML after
chemotherapy may hasten the hematopoietic recovery. The duration of
neutropenia was shortened by 3-4 days, and the incidence of fatal
infection was reduced. rhG-CSF does not stimulate AML growth in vivo.
12
UI - 11604554
AU - Tomita N; Kanamori H; Fujita H; Maruta A; Naitoh A; Nakamura S; Ota Y;
TI -
Nozue N; Kihara M; Ishigatsubo Y
Granulomatous tubulointerstitial nephritis induced by all-trans retinoic
acid.
SO - Anticancer Drugs 2001 Sep;12(8):677-80
AD - Department of Hematology , Fujieda Municipal General Hospital, Shizuoka,
426-8677, Japan. cavalier@ch-yamate.dienet.com
We report the first case of granulomatous tubulointerstitial nephritis
induced by all-trans retinoic acid (ATRA) in a patient with acute
promyelocytic leukemia (APL). Acute renal failure during treatment with
ATRA has been previously reported as a part of an ATRA syndrome or a
thrombotic complication of a hypercoagulable state. This case indicates
an alternative mechanism of acute renal failure occurring during ATRA
therapy.
13
UI - 11600603
AU - Specchia G; Lo Coco F; Vignetti M; Avvisati G; Fazi P; Albano F; Di
TI -
Raimondo F; Martino B; Ferrara F; Selleri C; Liso V; Mandelli F
Extramedullary involvement at relapse in acute promyelocytic leukemia
patients treated or not with all-trans retinoic acid: a report by the
Gruppo Italiano Malattie Ematologiche dell'Adulto.
SO - J Clin Oncol 2001 Oct 15;19(20):4023-8
AD - Department of Hematology, University of Bari, Bari, Italy.
emadhba@cimedoc.uniba.it
PURPOSE: Recent reports of extramedullary disease (EMD) at recurrence in
acute promyelocytic leukemia (APL) have raised increasing concern about
a possible role of retinoic acid (RA) therapy. PATIENTS AND METHODS: We
analyzed the risk of developing EMD localization at relapse in APL
patients enrolled onto two consecutive studies of the Gruppo Italiano
Malattie Ematologiche dell'Adulto. The studies investigated chemotherapy
alone (LAP0389) versus RA plus chemotherapy (AIDA). RESULTS: When all
relapse types were taken into account, 94 (51%) of 184 patients and 131
(18%) of 740 patients who attained hematologic remission underwent
relapse in the LAP0389 and AIDA studies, respectively (P < .0001). EMD
localization was documented in five (5%) of 94 and 16 (12%) of 131
patients (P = .08). Hematologic and/or molecular relapse was diagnosed
concomitantly in all but two patients with EMD in the AIDA study. For
patients in the LAP0389 and AIDA series, the probability of EMD
localization of any type at relapse was 3% and 4.5%, respectively (P =
.79), while the probability of CNS involvement was 0.6% and 2% (P =
.28). No significant differences were found with regard to mean WBC
count and promyelocytic leukemia/retinoic acid receptor-alpha junction
type in comparisons of patients with EMD and hematologic relapse.
CONCLUSION: APL patients receiving all-trans retinoic acid in addition
to chemotherapy have no increased risk of developing EMD at relapse as
compared with those treated with chemotherapy alone.
14
UI - 11602915
AU - Lengfelder E; Hehlmann R; Buchner T
TI -
[Current therapeutic concept of acute promyelocytic leukemia]
SO - Dtsch Med Wochenschr 2001 Sep 28;126(39):1073-9
AD - III. Medizinische Universitatsklinik Mannheim, Universitat Heidelberg,
Germany.
15
UI - 11673686
AU - Marie JP
TI -
Drug resistance in hematologic malignancies.
SO - Curr Opin Oncol 2001 Nov;13(6):463-9
AD - Department of Hematology and Medical Oncology, University Paris 6,
Paris, France. jean-pierre.marie@htd.ap-hop-paris.fr
Drug resistance eventually occurs in most hematologic malignancies
treated with chemotherapy. The mechanisms responsible for drug
resistance include expression of transporters of xenobiotics of the
adenosine triphosphate-binding cassette protein superfamily
(P-glycoprotein, multidrug resistance associated proteins, breast cancer
resistance protein), modifications of enzymes like deoxycytidine kinase,
and defects in chemotherapy-induced apoptosis. The efforts to overcome
this drug resistance have been focused, thus far, on modulation of
P-glycoprotein. Several compounds were manufactured for this purpose,
and phase III trials of PSC833, one of the most potent P-glycoprotein
inhibitors, are completed. The emergence of modulators with several
adenosine triphosphate-binding cassette protein targets, like GG120918
(inhibiting P-glycoprotein and breast cancer resistance protein) and
VX710 (inhibiting P-glycoprotein and multidrug resistance associated
protein 1), are of clinical interest in malignancies often expressing
several efflux pumps simultaneously. Another approach is the use of
"furtive" drugs like liposomal or nanoparticular anthracyclines.
16
UI - 11673694
AU - Sievers EL; Linenberger M
TI -
Mylotarg: antibody-targeted chemotherapy comes of age.
SO - Curr Opin Oncol 2001 Nov;13(6):522-7
AD - Clinical Research Division, Fred Hutchinson Cancer Research Center,
Seattle, Washington 98109-1024, USA. esievers@fhcrc.org
Mylotarg (gemtuzumab ozogamicin, CMA-676; Wyeth-Ayerst Laboratories,
Philadelphia, PA) recently was approved by the US Food and Drug
Administration for the treatment of patients with CD33-positive acute
myeloid leukemia in first relapse, age 60 years or older, who are not
considered candidates for other types of cytotoxic chemotherapy. In
combined phase II studies of 142 patients with CD33-positive acute
myeloid leukemia in first relapse, Mylotarg monotherapy was associated
with a 30% overall response rate. Although treated patients had
relatively high incidences of myelosuppression, hyperbilirubinemia, and
elevated hepatic transaminases, the incidences of severe mucositis and
infections were low compared with what might be expected in association
with conventional chemotherapeutic treatment. Preliminary data in
pediatric patients also suggest that the immunoconjugate is reasonably
well tolerated. Studies of Mylotarg in combination with anthracycline,
cytarabine, and agents that inhibit P-glycoprotein are underway.
17
UI - 11681409
AU - Visani G; Buonamici S; Malagola M; Isidori A; Piccaluga PP; Martinelli
TI -
G; Ottaviani E; Grafone T; Baccarani M; Tura S
Pulsed ATRA as single therapy restores long-term remission in
PML-RARalpha-positive acute promyelocytic leukemia patients: real time
quantification of minimal residual disease. A pilot study.
SO - Leukemia 2001 Nov;15(11):1696-700
AD - Department of Hematology, Azienda Ospedale San Salvatore, Pesaro, Italy.
All-trans retinoic acid (ATRA), alone or combined with chemotherapy
(CHT) is widely used to induce complete remission (CR) in newly
diagnosed acute promyelocytic leukemia (APL). If used alone, ATRA
results in a substantial proportion of CRs. To maintain remission
further, ATRA is commonly used with cycles of CHT, frequently followed
by autologous (auto) or allogeneic (allo) stem cell transplantation
(SCT), as early reports have shown that the continuous administration of
ATRA as single therapy almost invariably leads to relapse in a short
period of time (months). Pharmacokinetic studies have shown that induced
resistance to ATRA is frequently suppressed by the intermittent use of
the drug. In this study we applied an intermittent therapeutic protocol
with ATRA in five APL patients who were either molecularly refractory
after combined ATRA/CHT treatment, or relapsed, or at diagnosis, but not
eligible for the combination treatment because of previous toxicity.
They were treated with ATRA (45 mg/m2/day) for 21 days. The treatment
was then prolonged continuously for 1 week every 2 weeks. Molecular
analysis was performed by qualitative and quantitative reverse
transcription-polymerase chain reaction (RT-PCR). All patients obtained
molecular remission, as assessed by qualitative RT-PCR, in a median of 3
months (range 1-15). Quantitative RT-PCR confirmed these data, showing a
progressive reduction (1 or 2 logs) to a 'negligible quantity' of
PML-RARalpha fusion transcript (ratio PML-RARalpha/ABL x 10(4) ABL <
10(-1)) in all but one patient treated with pulsed ATRA therapy. These
data were confirmed with qualitative and quantitative RT-PCR. After a
median follow-up of 17 months from the start of ATRA therapy, 4/5
patients (80%) are in continuous complete molecular remission. To our
knowledge, this is the first clinical observation that intermittent ATRA
therapy (without chemotherapy) is effective not only in inducing but
also in maintaining long-term molecular remission in APL patients. This
approach could therefore be effective, if confirmed in larger series, in
relapsed/refractory patients unsuitable for high-dose therapy and SCT;
it may be proposed as induction therapy for selected older APL patients
if considered not to be eligible for combined ATRA/CHT due to inadequate
performance status or concurrent disease.
18
UI - 11684284
AU - Koistinen P; Siitonen T; Mantymaa P; Savolainen ER
TI -
p53 and redox state in etoposide-induced acute myeloblastic leukemia
cell death.
SO - Leuk Res 2001 Dec;25(12):1099-105
AD - Department of Internal Medicine, University of Oulu, Kajaanintie 50,
FIN-90220 Oulu, Finland. pirjo.koistinen@ppshp.fi
We investigated whether p53, being a redox-sensitive protein, has a role
in the responsiveness of AML cells to etoposide. Two subclones of the
OCI/AML-2 cell line, the etoposide-sensitive (ES) and the
etoposide-resistant (ER), were used as models. Sensitivity to etoposide
was measured by trypan blue and annexin V assays. Etoposide-induced
peroxide formation was associated with the induction of cell death.
Evident expression of mutated p53 was observed in both subclones in
basal growth conditions as analysed by Western blotting and flow
cytometry. After etoposide exposure for up to 24 hours, some nuclear
accumulation of p53 was observed in the ER subclone, as analysed by
Western blotting. The conformation of p53, however, was not changed from
mutated toward wild-type during exposure in either of the subclones as
analysed by flow cytometry. In conclusion, etoposide-induced change in
cellular redox state was associated with apoptosis, but was not a
sufficient stimulus for p53 to make its conformation active. Thus,
mutated p53 seems to have no role in etoposide-induced apoptosis.
19
UI - 11704841
AU - de The H; Chelbi-Alix MK
TI -
APL, a model disease for cancer therapies?
SO - Oncogene 2001 Oct 29;20(49):7136-9
AD - CNRS UPR 9051 Hopital St. Louis 1, avenue C. Vellefaux 75475 Paris Cedex
10, France.
20
UI - 11704842
AU - Degos L; Wang ZY
TI -
All trans retinoic acid in acute promyelocytic leukemia.
SO - Oncogene 2001 Oct 29;20(49):7140-5
AD - Institut Universitaire d'Hematologie, Saint Louis Hospital (AP-HP) 1,
avenue Claude Vellefaux, 75010 Paris, France. degos@chu-stlouis.fr
All trans retinoic acid (ATRA) is able to induce complete remission (CR)
in almost all patients with acute promyelocytic leukemia (APL) through
in vivo differentiation of APL blasts. However, it cannot eliminate the
leukemic clone and to be effective must be used in combination with
anthracycline-based chemotherapy. Experience accumulated over the last
10 years has clearly shown that the combination of ATRA and chemotherapy
gives better survival in newly diagnosed APL than chemotherapy alone
because of fewer relapses and a higher CR rate experienced by these
patients. It is also strongly suggested that maintenance treatment with
ATRA, and possibly in combination with low-dose chemotherapy, can
further reduce the incidence of relapse. Overall, more than 90% of
patients with newly diagnosed APL can achieve CR and about 75% can be
cured by the combination of ATRA and chemotherapy.
21
UI - 11722411
AU - Petti MC; Pinazzi MB; Diverio D; Romano A; Petrucci MT; De Santis S;
TI -
Meloni G; Tafuri A; Mandelli F; Lo Coco F
Prolonged molecular remission in advanced acute promyelocytic leukaemia
after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676).
SO - Br J Haematol 2001 Oct;115(1):63-5
AD - Department of Cellular Biotechnology and Haematology, University La
Sapienza, Roma, Italy.
We report a patient with acute promyelocytic leukaemia (APL) who
received two doses of gemtuzumab ozogamicin for advanced disease.
Previous treatments included front-line all-trans retinoic acid and
anthracyclines, polychemotherapy consolidation, salvage chemotherapy for
the first relapse followed by autologous stem cell transplantation
(ASCT), arsenic trioxide for the second relapse followed by a second
ASCT and then high-dose methotrexate for more advanced systemic disease
with central nervous system involvement. The patient achieved prolonged
haematological and molecular remission after monotherapy with gemtuzumab
ozogamicin given at the time of the third relapse.
22
UI - 11713460
AU - Trebo MM; Mann G; Gadner H
TI -
And the sun keeps shining.
SO - J Pediatr 2001 Nov;139(5):753
AD - Children 5 Cancer Research Institute, St Anna Kinderspital,
Kinderspitalgasse, 61090, Vienna, Austria.
23
UI - 11719356
AU - List AF; Kopecky KJ; Willman CL; Head DR; Persons DL; Slovak ML; Dorr R;
TI -
Karanes C; Hynes HE; Doroshow JH; Shurafa M; Appelbaum FR
Benefit of cyclosporine modulation of drug resistance in patients with
poor-risk acute myeloid leukemia: a Southwest Oncology Group study.
SO - Blood 2001 Dec 1;98(12):3212-20
AD - Southwest Oncology Group, Operations Office, 14980 Omicron Dr, San
Antonio, TX, USA. alist@azcc.arizona.edu
Cyclosporine A (CsA) inhibits P-glycoprotein (Pgp)-mediated cellular
export of anthracyclines at clinically achievable concentrations. This
randomized controlled trial was performed to test the benefit of CsA
addition to treatment with cytarabine and daunorubicin (DNR) in patients
with poor-risk acute myeloid leukemia (AML). A total of 226 patients
were randomly assigned to sequential treatment with cytarabine and
infusional DNR with or without intravenous CsA. Remitting patients
received one course of consolidation chemotherapy that included DNR with
or without CsA as assigned during induction. Addition of CsA
significantly reduced the frequency of resistance to induction
chemotherapy (31% versus 47%, P =.0077). Whereas the rate of complete
remission was not significantly improved (39% versus 33%, P =.14),
relapse-free survival (34% versus 9% at 2 years, P =.031) and overall
survival (22% versus 12%, P =.046) were significantly increased with
CsA. The effect of CsA on survival was greatest in patients with
moderate or bright Pgp expression (median 12 months with CsA versus 4
months for controls) compared to patients with absent or low Pgp
expression (median 6 months in both arms). The frequency of induction
deaths was 15% with CsA and 18% in controls. Steady-state serum
concentrations of DNR (P =.0089) and daunorubicinol (P <.0001) were
significantly higher in CsA-treated patients. Survival (P =.0003) and
induction response (P =.028) improved with increasing DNR concentration
in CsA-treated patients but not in controls, suggesting a targeted
interaction by CsA to enhance anthracycline cytotoxicity. These results
indicate that addition of CsA to an induction and consolidation regimen
containing infusional DNR significantly reduces resistance to DNR,
prolongs the duration of remission, and improves overall survival in
patients with poor-risk AML.
24
UI - 11719375
AU - Montagna D; Maccario R; Locatelli F; Rosti V; Yang Y; Farness P; Moretta
TI -
A; Comoli P; Montini E; Vitiello A
Ex vivo priming for long-term maintenance of antileukemia human
cytotoxic T cells suggests a general procedure for adoptive
immunotherapy.
SO - Blood 2001 Dec 1;98(12):3359-66
AD - BMT Laboratory and BMT Units, Department of Pediatrics, Laboratory of
Organ Transplantation, IRCCS Policlinico San Matteo, University of
Pavia, Italy.
Adoptive cellular immunotherapy has proven to be a successful approach
in preventing and curing cytomegalovirus infection and Epstein-Barr
virus-associated lymphomas after bone marrow transplantation.
Translation of this approach for preventing leukemia relapse after bone
marrow transplantation might require ex vivo priming and long-term
maintenance of leukemia blast-specific T cells. To accomplish this goal,
procedures were optimized for the in vitro priming of naive CD8 using
dendritic cells activated by CD40 ligation, interleukin-12 (IL-12), and
IL-7. Using T lymphocytes and dendritic cells obtained from HLA-matched
allogeneic bone marrow transplantation donors and leukemia blasts as a
source of tumor antigens, anti-acute myeloid leukemia cytotoxic T
lymphocytes (CTLs) were induced. In these experiments, it was found that
though it is possible to induce CTLs using immature dendritic cells,
IL-12, and IL-7, obtaining long-term CTLs requires the presence of CD4 T
cells in the priming phase. Using this approach, long-term antileukemia
CTL lines could be generated from 4 of 4 bone marrow donors. Because
this procedure does not require definition of the target antigen and
because it selects responding cells from a virgin T-cell repertoire, its
general application is suggested in adoptive immunotherapy and in the
definition of tumor rejection antigens.
25
UI - 11732869
AU - Voog E; Le QH; Philip I; Benetaib B; Michallet M; Fiere D; Thomas X
TI -
Autologous transplantation in acute myeloid leukemia: peripheral blood
stem cell harvest after mobilization in steady state by granulocyte
colony-stimulating factor alone.
SO - Ann Hematol 2001 Oct;80(10):584-91
AD - Service d'Hematologie, Hjpital E. Herriot, Lyon, France.
In order to determine whether granulocyte colony-stimulating factor
(G-CSF) alone initiated during steady state was able to mobilize
peripheral blood stem cells (PBSC) in acute myeloid leukemia (AML) and
to assess predictive factors for engraftment after autologous PBSC
transplantation, we studied 49 successive adult AML patients for whom
1998. G-CSF was used as priming agent and was initiated at least 4 weeks
after the last day of chemotherapy, while neutrophil count was >0.5 x
10(9)/l and platelet count was >30 x 10(9)/l. A median of three
aphereses was performed resulting in a median collection of 14.8 x 10(8)
nucleated cells/kg containing 7.7 x 10(8) mononuclear cells/kg, 47.1 x
10(4) CFU-GM/kg, and 3.8 x 10(6) CD34+ cells/kg. A significant
correlation was observed between nucleated cell, mononuclear cell, and
CFU-GM yields, while no correlation was found with CD34+ cell yield.
Recruitment was not significantly different in patients with CD34+
leukemic cells at the time of initial diagnosis when compared to that of
those presenting with CD34- blastic cells. Thirty-three patients
actually underwent transplantation. Reasons for not autografting were
inadequate stem cell harvest (ten patients), early relapse (two
patients), prolonged neutropenia (one patient), organ failure (two
patients), or patient refusal (one patient). Median time to achieve a
neutrophil count greater than 0.5 x 10(9)/l and platelet count >50 x
10(9)/l untransfused was 13 and 36 days, respectively. A predictive
factor for a shorter period neutropenia and a shorter thrombopenia was a
higher count of harvested nucleated cells (p < 0.01 and p = 0.02,
respectively). A higher count of harvested cells was also a predictive
factor for less red cell and platelet transfusions (p=0.03 and p=0.02,
respectively). The number of CD34+ harvested PBSC was not predictive for
engraftment. We conclude that PBSC mobilization with G-CSF alone
initiated in steady state is a feasible, safe, and suitable procedure
for harvesting cells in sight of autologous transplantation in adult
acute myeloid leukemia.
26
UI - 11694116
AU - Barbey JT; Soignet S
TI -
Prolongation of the QT interval and ventricular tachycardia in patients
treated with arsenic trioxide for acute promyelocytic leukemia.
SO - Ann Intern Med 2001 Nov 6;135(9):842-3
27
UI - 11713382
AU - Keung YK; Morgan D; Cobos E
TI -
Cocaine-contaminated allogeneic bone marrow transplantation.
SO - Acta Haematol 2001;106(3):136-7
AD - Department of Internal Medicine, Texas Tech University Health Sciences
Center, Lubbock, Tex., USA. ykeung@wfubmc.edu
Should a person with history of drug addiction be categorically denied
as a bone marrow donor? The answer to the question is controversial. We
report a case of allogeneic bone marrow transplantation for refractory
acute myeloid leukemia preceded by essential thrombocythemia. The donor
used cocaine and marijuana the night before the bone marrow harvest.
Copyright 2001 S. Karger AG, Basel
28
UI - 11418363
AU - Anonymous
TI -
Spanish contributions to management of acute promyelocytic leukemia.
SO - Haematologica 2001 Jun;86(6):561-2
29
UI - 11525581
AU - Rule S; Poirer V; Singer C
TI -
Management of acute myeloid leukaemia. A regional audit in the south and
west of the United Kingdom.
SO - Clin Med 2001 Jul-Aug;1(4):313-6
AD - Department of Haematology, Derriford Hospital, Plymouth, Devon.
simon.rule@phnt.swest.nhs.uk
In a retrospective audit data were collected on all 231 patients from 26
hospitals diagnosed with AML in the south and west region of the UK in
1996. Their median age at diagnosis was 67 years. Sixty one percent
(142/231) of patients were treated with chemotherapy; most of the rest
received blood product support only; and 7% (15) had no treatment at
all. Sixty eight percent of patients aged under 60 years were treated in
a clinical trial compared with 24% of patients over 60. The major
reasons given for not entering patients in a trial were ineligibility in
the younger cohort and poor performance status in the older group.
Twenty elderly patients (12.5%) refused to be entered in a trial. In an
unselected cohort of patients with AML the accrual into clinical trials
is impressively high for patients under 60 years. However, this is a
disease of the elderly and comparable enrolment is not seen with elderly
patients despite being managed by the same haematologists. If the
percentage of patients entered into trials is to be defined as a quality
standard, then it is important for those trials to be relevant to the
population being treated.
30
UI - 2031969
AU - Willemze R; Fibbe WE; Kluin-Nelemans JC; Falkenburg JH; Richel DJ;
TI -
Peters WG; den Ottolander GJ; Brand A; Zwaan FE
Bone marrow transplantation or chemotherapy as post-remission treatment
of adult acute myelogenous leukemia.
SO - Ann Hematol 1991 Feb-Mar;62(2-3):59-63
AD - Department of Hematology, Leiden University Medical Center, The
Netherlands.
We compared three consolidation regimens in patients with acute
myelogenous leukemia in first remission. Thirty-four patients received
only intensive consolidation chemotherapy (SIC); 28 patients were
scheduled to undergo an autologous bone marrow transplant (auto-BMT) and
44 patients an allogeneic BMT (allo-BMT). Twenty-seven of them were
referred in first remission for allo-BMT. Nineteen patients achieved a
complete remission after salvage treatment. All other patients obtained
a remission after one or two courses of a standard combination of
cytosine arabinoside and daunorubicin. Except for the patients who were
referred in remission, all patients received intermediate dose cytosine
arabinoside and amsacrine as a first consolidation treatment. The median
ages of the three groups were 48 (SIC), 39 (auto-BMT) and 33 years
(allo-BMT). Two patients relapsed before auto-BMT and 1 before allo-BMT.
The median interval from the date of complete remission to the auto- or
allo-BMT was 3 months. In total, 80% of the patients of the SIC group
relapsed, compared to 50% of the patients belonging to the auto-BMT
group and 35% of the 44 patients who were scheduled to receive an
allo-BMT. The overall median disease-free survival was 14 months, 30% of
the patients being
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
