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NCI CANCERLIT® Search: Therapy of Acute Myeloid Leukemia - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11739161
AU - Kawasaki H; Isoyama K; Eguchi M; Hibi S; Kinukawa N; Kosaka Y; Oda T;
TI -
Oda M; Nishimura S; Imaizumi M; Okamura T; Hongo T; Okawa H; Mizutani S;
Hayashi Y; Tsukimoto I; Kamada N; Ishii E
Superior outcome of infant acute myeloid leukemia with intensive
chemotherapy: results of the Japan Infant Leukemia Study Group.
SO - Blood 2001 Dec 15;98(13):3589-94
AD - Department of Pediatrics, Mie University, Japan.
This study analyzed data on 35 infants with acute myeloid leukemia (AML)
who were treated with intensive chemotherapy between 1995 and 1998 in
Japan. The incidence of boys, younger age (< 6 months old), and
hyperleukocytosis at onset was high in patients with the M4/M5 subtype
(n = 23) in the French-American-British classification, compared with
the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients
with the M4/M5 subtype also showed 11q23 translocations and MLL gene
rearrangements, respectively, whereas only one patient with the
non-M4/M5 subtype had this rearrangement. All 35 patients were treated
with the ANLL91 protocol consisting of etoposide, high-dose cytarabine,
and anthracyclines. Overall survival and the event-free survival (EFS)
rates at 3 years of all patients were 76% (95% confidence interval [CI],
61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no
significant difference between 2 subgroups divided by age, gender,
presence of the MLL gene rearrangements, and white blood cell count at
onset; EFS in patients with the M4/M5 subtype tended to be better than
those with the non-M4/M5 subtype. Although all 6 patients who underwent
allogeneic stem cell transplantation (SCT) have been in complete
remission, no benefit of SCT was confirmed. These findings suggest that
the intensive chemotherapy with the ANLL91 protocol might have been
responsible for the observed good outcome of infant AML, even without
SCT. The presence of the MLL gene rearrangements or the age at onset had
no impact on the outcome of infant AML.
2
UI - 11926186
AU - Loeb DM; Arceci RJ
TI -
Treatment and outcome of infants with acute myeloid leukemia.
SO - Blood 2002 Apr 1;99(7):2626-7
3
UI - 11943160
AU - Hamada M; Nishio K; Doe M; Usuki Y; Tanaka T
TI -
Farnesylpyridinium, an analog of isoprenoid farnesol, induces apoptosis
but suppresses apoptotic body formation in human promyelocytic leukemia
cells.
SO - FEBS Lett 2002 Mar 13;514(2-3):250-4
AD - Department of Bio- and Geoscience, Graduate School of Science, Osaka
City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
1-Farnesylpyridinium (FPy), an analog of isoprenoid farnesol, initially
induced morphological changes similar to those of typical apoptosis in
human leukemia HL-60 cells but FPy-treated cells were characterized by
the absolute absence of final apoptotic events such as fragmentation
into apoptotic bodies. FPy-induced cell death was considered to be
apoptotic on the basis of the induction of DNA fragmentation and the
protection against these events by the coaddition of a pan-caspase
inhibitor. The increase in the cytoplasmic cytochrome c level supported
the possibility that FPy-treated cells should have the ability to
complete the entire apoptotic process ending in cell fragmentation and
apoptotic body formation. At concentrations too low to induce apoptosis,
FPy could suppress the induction of apoptotic body formation in HL-60
cells by typical inducers of apoptosis such as actinomycin D or
anisomycin. FPy exhibited a cytochalasin-like effect on spatial
arrangement of actin filament independent of its apoptosis-inducing
activity.
4
UI - 11960341
AU - Ohnishi K; Yoshida H; Shigeno K; Nakamura S; Fujisawa S; Naito K; Shinjo
TI -
K; Fujita Y; Matsui H; Sahara N; Takeshita A; Satoh H; Terada H; Ohno R
Arsenic trioxide therapy for relapsed or refractory Japanese patients
with acute promyelocytic leukemia: need for careful electrocardiogram
monitoring.
SO - Leukemia 2002 Apr;16(4):617-22
AD - Department of Medicine III, Hamamatsu University School of Medicine,
Handayama, Hamamatsu, Japan.
Recent studies have shown that arsenic trioxide (As(2)O(3)) can induce
complete remission in patients with acute promyelocytic leukemia (APL).
We tested the efficacy and safety of As(2)O(3) for the treatment of
patients with APL who had relapsed from or become refractory to
all-trans retinoic acid (ATRA) and conventional chemotherapy in a
prospective study. As(2)O(3) at a dose of 0.15 mg/kg was administered
until the date of bone marrow remission to a maximum of 60 days. In
patients who achieved complete remission (CR), one additional course of
As(2)O(3) was administered using the same dose for 25 days. Of 14
patients, 11 (78%) achieved CR. Six of 10 patients who achieved CR
showed disappearance of PML-RARalpha transcript by RT-PCR assay. The
duration of As(2)O(3)-induced CR ranged from 4 to 22 months (median, 8
months) at a median follow-up of 17 months. Adverse events included 13
electrocardiogram abnormalities (13 QTc prolongation, eight ventricular
premature contraction, four nonsustained ventricular tachycardia and two
paroxysmal supraventricular tachycardia), seven nausea and vomiting,
four pruritus, three peripheral neuropathy, three fluid retention and
one APL differentiation syndrome. Four patients received antiarrhythmic
agents. Hyperleukocytosis developed in five patients and in three
cytotoxic drugs were necessary. Other adverse events were relatively
mild. As(2)O(3) treatment is effective and relatively safe in relapsed
or refectory patients with APL. Cardiac toxicities in patients with QTc
prolongation should be carefully monitored.
5
UI - 11921023
AU - Bairey O; Kirgner I; Yakobi M; Hamdan A; Ben-Ari Z; Shaklai M
TI -
Clinical severe hepatic venoocclusive disease during induction treatment
of acute monoblastic leukemia managed with defibrotide.
SO - Am J Hematol 2002 Apr;69(4):281-4
AD - Institute of Hematology, Rabin Medical Center, Beilinson Campus, Petah
Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv,
Israel. obairey@post.tau.ac.il
Hepatic venoocclusive disease (VOD) is the most common complication of
cytoreductive therapy used for stem cell transplantation, but it is
rarely encountered during induction treatment of acute leukemia. We
describe a patient in whom severe clinical VOD developed shortly after
induction treatment for acute monoblastic leukemia. Administration of
intravenous defibrotide for 19 days induced complete resolution of the
VOD. Further consolidation treatment was resumed including high-dose
cytosine arabinoside without further complications. Copyright 2002
Wiley-Liss, Inc.
6
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.
7
UI - 11869960
AU - Hernandez P; Martinez G; Losada R; Machin S; Cayado N; Gramatges A
TI -
Cuban experience in the treatment of acute promyelocytic leukemia with
ALL transretinoic acid followed by intensive chemotherapy.
SO - Haematologica 2002 Mar;87(3):ELT14
8
UI - 11952816
AU - Breccia M; Petti MC; D'Elia GM; D'Andrea M; Carmosino I; Alimena G
TI -
Cutaneous pleomorphic T-cell lymphoma coexisting with myelodysplastic
syndrome transforming into acute myeloid leukemia: successful treatment
with a fludarabine-containing regimen.
SO - Eur J Haematol 2002 Jan;68(1):1-3
AD - Department of Cellular Biotechnology and Hematology, University La
Sapienza, Via Benevento 6, Rome, Italy. mbreccia@hotmail.com
The coexistence of a primary myelodysplastic syndrome (MDS) and a T-cell
cutaneous non-Hodgkin's lymphoma is an extremely rare event, which has
so far only been reported in a single instance in the literature. We
describe herein an additional case in which the lymphoid disease was
combined with an MDS at the time of its evolution into acute myeloid
leukemia (AML). Both diseases were successfully treated with a regimen
containing fludarabine. We discuss possible pathogenetic mechanisms and
suggest the use of nonalkylating drugs, such as fludarabine, for the
treatment of this rare association of malignancies usually characterized
by a very poor response to therapy.
9
UI - 11989187
AU - Anderson S; Files J
TI -
Tumor lysis syndrome secondary to Gemtuzumab Ozogamicin in a patient
with acute myelogenous leukemia.
SO - J Miss State Med Assoc 2002 Apr;43(4):105-6
AD - Department of Medicine, University of Mississippi Medical Center, USA.
10
UI - 11001891
AU - Tallman MS; Neuberg D; Bennett JM; Francois CJ; Paietta E; Wiernik PH;
TI -
Dewald G; Cassileth PA; Oken MM; Rowe JM
Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group
experience.
SO - Blood 2000 Oct 1;96(7):2405-11
AD - Northwestern University Medical School, Robert H. Lurie Cancer Center,
Chicago IL, USA. m-tallman@nwu.edu
Acute megakaryocytic leukemia (AMegL) is a rare subtype of acute myeloid
leukemia (AML) evolving from primitive megakaryoblasts. Because of its
rarity and the lack of precise diagnostic criteria in the past, few
series of adults treated with contemporary therapy have been reported.
Twenty among 1649 (1.2%) patients with newly diagnosed AML entered on
Eastern Cooperative Oncology Group (ECOG) trials between 1984 and 1997
were found to have AMegL. The median age was 42.5 years (range 18-70).
Marrow fibrosis, usually extensive, was present in the bone marrow. Of
the 8 patients who had cytogenetic studies performed, abnormalities of
chromosome 3 were the most frequent. The most consistent
immunophenotypic finding was absence of myeloperoxidase in blast cells
from 5 patients. In the most typical 3 cases, the leukemic cells were
positive for one to 2 platelet-specific antigens in addition to lacking
myeloperoxidase or an antigen consistent with a lymphoid leukemia.
Myeloid antigens other than myeloperoxidase and selected T-cell antigens
(CD7 and/or CD2) were frequently expressed. Induction therapy included
an anthracycline and cytarabine in all cases. Complete remission (CR)
was achieved in 10 of 20 patients (50%). Two patients remain alive, one
in CR at 160+ months. Resistant disease was the cause of induction
failure in all but 3 patients. The median CR duration was 10.6 months
(range 1-160+ months). The median survival for all patients was 10.4
months (range 1-160+ months). Although half of the patients achieved CR,
the long-term outcome is extremely poor, primarily attributable to
resistant disease. New therapeutic strategies are needed.
11
UI - 11918543
AU - Au WY; Chim CS; Lie AK; Liang R; Kwong YL
TI -
Combined arsenic trioxide and all-trans retinoic acid treatment for
acute promyelocytic leukaemia recurring from previous relapses
successfully treated using arsenic trioxide.
SO - Br J Haematol 2002 Apr;117(1):130-2
AD - University Department of Medicine, University of Hong Kong, Queen Mary
Hospital, Hong Kong.
The optimal treatment of acute promyelocytic leukaemia (APL) recurring
from relapses successfully treated using arsenic trioxide (As2O3) is
undefined. Three APL patients relapsing from As2O3-induced remission
were studied. Re-treatment with As2O3 failed in one patient in third
relapse, and resulted in morphological but not molecular remission in
another patient. Combination therapy with As2O3 and all-trans retinoic
acid (ATRA), however, resulted in morphological and molecular remission
in all three cases, with a follow-up time ranging from 6 to 16 months.
Our results suggest a synergistic therapeutic effect between As2O3 and
ATRA in APL in advanced relapse.
12
UI - 11918536
AU - Salih HR; Starling GC; Brandl SF; Pelka-Fleischer R; Haferlach T;
TI -
Hiddemann W; Kiener PA; Nuessler V
Differentiation of promyelocytic leukaemia: alterations in Fas
(CD95/Apo-1) and Fas ligand (CD178) expression.
SO - Br J Haematol 2002 Apr;117(1):76-85
AD - Department of Immunology, Inflammation and Pulmonary Diseases,
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, USA.
Helmut.Salih@md.uni-tuebingen.de
The survival of leukaemic blasts contributes to the pathological
mechanism of acute promyelocytic leukaemia (APL). While treatment of APL
using retinoic acid (RA) is a model of differentiation therapy, little
is known about possible effects of this treatment on the Fas/FasL
system. Investigation of APL cells from patients undergoing
differentiation therapy with RA and of promyelocytic HL-60 and
monoblastic U-937 cells cultured with RA revealed a reduction of surface
expression of both Fas and its ligand. Accordingly, the sensitivity of
the cells to anti-Fas-induced apoptosis decreased proportionally and the
reduced expression of FasL resulted in a decreased ability of the
leukaemic cells to induce apoptosis in T cells. Our findings demonstrate
that there are significant changes in Fas and FasL expression during RA
treatment of APL, which probably have consequences for the interaction
between host immune and leukaemia cells, and thus may be involved in the
beneficial effects of differentiation therapy.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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