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NCI CANCERLIT® Search: Therapy of Acute Myeloid Leukemia - October 2002
National Cancer Institute®
Last Modified: October 1, 2002
- Introduction.
- Established practice in the treatment of patients with acute promyleocytic leukemia and the introduction of arsenic trioxide as a
- Quality of life through rehabilitation at end of life.
- Bone marrow reticulin fibrosis at diagnosis in promyelocytic leukaemia treated with all-trans retinoic acid has no adverse prognosis.
- Clinical use of oral contraceptives administered vaginally: a case report.
- ATRA syndrome with extensive organ infiltration.
- Economic analysis of filgrastim use for patients with acute myeloid leukaemia in the UK: a comparison of collection methods of resource use
- Faith, identity, and leukemia: when blood products are not an option.
- Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in
- Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment
- How long can we give interleukin-2? Clinical and immunological evaluation of AML patients after 10 or more years of IL2 administration.
- Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for
- [Experimental bases of the in vitro treatment of leukemic bone marrow by a derivative of cyclophosphamide: ASTA Z 7557]
- Retinoic acid and acute promyelocytic leukemia: a model of targetting treatment for human cancer.
Table of Contents
1
UI - 12012314
AU - Tallman MS
TI -
Introduction.
SO - Semin Hematol 2002 Apr;39(2 Suppl 1):1-2
AD - Division of Hematology/Oncology, Northwestern University Medical School,
Chicago, IL 60611, USA.
2
UI - 12012316
AU - Dombret H; Fenaux P; Soignet SL; Tallman MS
TI -
Established practice in the treatment of patients with acute
promyleocytic leukemia and the introduction of arsenic trioxide as a
novel therapy.
SO - Semin Hematol 2002 Apr;39(2 Suppl 1):8-13
AD - Department of Hematology, Hopital Saint Louis, Paris, France.
First-line therapy for patients with newly diagnosed acute promyelocytic
leukemia (APL) has been established in a series of randomized clinical
trials. Remission induction and consolidation are based on the
differentiation agent, all-trans retinoic acid (ATRA), and
anthracycline-based chemotherapy. Maintenance therapy is also based on
ATRA and may involve additional chemotherapy. Established protocols are
associated with a high rate of complete responses (CRs) (87% to 97%),
and long-term follow-up has indicated a 4-year disease-free survival of
greater than 60%. Therapy for patients who relapse or are refractory to
ATRA-based regimens is not standardized and there is a need for new
approaches. Arsenic trioxide (ATO) has recently been licensed for use in
patients with relapsed/refractory APL. Controlled clinical trials have
indicated that ATO is associated with a CR rate of 87% in this
population. This agent has a manageable toxicity profile and presents a
welcome option for patients with relapsed disease for whom other, more
debilitating therapies are unsuitable. Several prognostic factors have
been defined in patients with APL, and it is possible that novel
treatments such as ATO should be differentially applied to specific
prognostic groups. Copyright 2002, Elsevier Science (USA). All rights
reserved.
3
UI - 12100101
AU - Wolfe SL
TI -
Quality of life through rehabilitation at end of life.
SO - Cancer Pract 2002 Jul-Aug;10(4):174-8
AD - Oncology Nurse, Rehabilitation Liaison, HealthSouth Mountain View,
Regional Rehabilitation Hospital, Morgantown, West Virginia, USA.
4
UI - 12187033
AU - Losada R; Cabrera H; Hernandez P; Hernandez C; Menendez A; Mesa J;
TI -
Plascencia A; Ramon L; Agramonte O; Espinosa E
Bone marrow reticulin fibrosis at diagnosis in promyelocytic leukaemia
treated with all-trans retinoic acid has no adverse prognosis.
SO - Acta Haematol 2002;108(2):111-2
AD - Instituto de Hematologia e Inmunologia, La Habana, Cuba.
ihidir@hemato.sld.cu
5
UI - 2806624
AU - Sullivan-Nelson M; Kuller JA; Zacur HA
TI -
Clinical use of oral contraceptives administered vaginally: a case
report.
SO - Fertil Steril 1989 Nov;52(5):864-6
AD - Department of Gynecology and Obstetrics, Johns Hopkins University School
of Medicine, Baltimore, Maryland 21205.
6
UI - 12221682
AU - Kakkar N; Dhameja N; Jasmina; Das A; Radotra BD; Varma S
TI -
ATRA syndrome with extensive organ infiltration.
SO - Am J Hematol 2002 Sep;71(1):62-4
7
UI - 12162755
AU - Standaert B; Goldstone J; Lu ZJ; Erder MH; Yin JL
TI -
Economic analysis of filgrastim use for patients with acute myeloid
leukaemia in the UK: a comparison of collection methods of resource use
data.
SO - Pharmacoeconomics 2002;20(10):665-74
AD - Department of Health Economics, Amgen Inc., Thousand Oaks, California,
USA.
BACKGROUND: A clinical trial of patients with de novo acute myeloid
leukaemia (AML) showed that haematopoietic support with filgrastim
(granulocyte colony-stimulating factor, G-CSF) following induction and
consolidation chemotherapy accelerated recovery from neutropenia. The
clinical benefits included reductions in infections, anti-infective
therapy and length of hospital stay. OBJECTIVE: The objective of this
economic analysis is 2-fold. First, it aims to determine if the observed
clinical benefits from the use of filgrastim would lead to cost savings
from the perspective of a healthcare institution in the UK. Second, the
analysis compares the results of two methods on collection of resource
use data. DESIGN: A retrospective cost-minimisation analysis was
undertaken based on the clinical results of all UK patients enrolled in
the trial. Two cost models were developed: a model based only on the
medical resource use collected in the case report forms (the CRF model);
and a model based on all medical resources collected from patient
medical files (the PF Model). Treatment costs of AML between filgrastim
and the placebo arm were compared for the first induction cycle as well
as the first induction and the first consolidation cycles combined.
Results from the two models were compared. SETTING AND PATIENTS: The CRF
model was applied to two samples of patients: all UK patients (n = 82)
and patients enrolled at one centre [the Manchester Royal Infirmary
(MRI) (n = 30)], whereas the PF model was applied to the MRI patient
sample only. RESULTS: For all UK patients, using the CRF model, the
filgrastim-treated arm produced cost savings of 747 pounds sterling
(9.0%) and 2135 pounds sterling (14.4%) [1998 values] per patient in the
first induction cycle and in the induction and consolidation cycles
combined, respectively. For the patients at MRI the CRF model resulted
in cost savings with filgrastim of 177 pounds sterling (2.2%) and 414
pounds sterling (3.2%) per patient respectively. Using the PF model the
savings at MRI were 910 pounds sterling (8.6%) and 1285 pounds sterling
(8.0%) per patient, respectively. CONCLUSION: Use of filgrastim in the
treatment of AML in the UK may result in net cost savings. A
retrospective analysis using total resources obtained through patient
files produced higher cost savings estimates than that obtained by
resources noted in the CRFs. The models based on PF resource data may be
more reliable because they are more comprehensive. However, the cost
estimates in this study may have been impacted by sample size, site
characteristics, disease and treatment settings. Therefore, further
evaluation on the methods for collecting resource use data in larger,
multicentred studies is warranted.
8
UI - 12185299
AU - Knuti KA; Amrein PC; Chabner BA; Lynch TJ Jr; Penson RT
TI -
Faith, identity, and leukemia: when blood products are not an option.
SO - Oncologist 2002;7(4):371-80
AD - Department of Medicine, Division of Hematology-Oncology, Massachusetts
General Hospital, Boston, Massachusetts, USA.
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient
at Massachusetts General Hospital, founded the Kenneth B. Schwartz
Center. The Schwartz Center is a non-profit organization dedicated to
supporting and advancing compassionate health care delivery, which
provides hope to the patient, support to caregivers, and sustenance to
the healing process. The center sponsors the Schwartz Center Rounds, a
monthly multidisciplinary forum where caregivers reflect on important
psychosocial issues faced by patients, their families, and their
caregivers and gain insight and support from fellow staff members. When
a competent adult patient refuses lifesaving treatment for religious or
personal reasons, caregivers have a legal obligation to respect this
decision. A patient's refusal of treatment adds particular challenges to
the delivery of compassionate care. The case of a 50-year-old Jehovah's
Witness with acute myelocytic leukemia who declined blood product
support is presented. Respecting her religious beliefs during
chemotherapy required balancing risk and benefit, watching her suffer
while unable to intervene with what the staff saw as simple treatment,
and eventually undertaking a complicated grief process. Jehovah's
Witness beliefs regarding blood products are reviewed. Caregiver roles
and responsibilities are discussed in the context of psychosocial,
legal, familial, and ethical issues.
9
UI - 12200391
AU - Martino R; Caballero MD; Simon JA; Canals C; Solano C; Urbano-Ispizua A;
TI -
Bargay J; Leon A; Sarra J; Sanz GF; Moraleda JM; Brunet S; San Miguel J;
Sierra J; AML and alloPBSCT Subcommittees of the Spanish Group for
Hematopoietic Transplantation
Evidence for a graft-versus-leukemia effect after allogeneic peripheral
blood stem cell transplantation with reduced-intensity conditioning in
acute myelogenous leukemia and myelodysplastic syndromes.
SO - Blood 2002 Sep 15;100(6):2243-5
AD - Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau,
Av Sant Antoni Maria Claret, 167 08025 Barcelona, Spain.
rmartino@hsp.santpau.es
We report the results of a prospective study of a reduced-intensity
conditioning (RIC) regimen followed by allogeneic peripheral blood stem
cell transplantation (PBSCT) from an HLA-identical sibling in 37
patients with acute myeloid leukemia (AML; n = 17) or myelodysplastic
syndrome (MDS; n = 20). The median age was 57 years, and 22 (59%) were
beyond the early phase of their disease. The incidence of grade II to IV
acute graft-versus-host disease (GVHD) was 19% (5% grade III-IV), and
the 1-year incidence of chronic extensive GVHD was 46%. With a median
follow-up of 297 days (355 days in 24 survivors), the 1-year probability
of transplant-related mortality was 5%, and the 1-year progression-free
survival was 66%. The 1-year incidence of disease progression in
patients with and without GVHD was 13% (95% CI, 4%-34%) and 58% (95% CI,
36%-96%), respectively (P =.008). These results suggest that a
graft-versus-leukemia effect plays a crucial role in reducing the risk
of relapse after a RIC allograft in AML and MDS.
10
UI - 12357347
AU - Grimwade D; Lo Coco F
TI -
Acute promyelocytic leukemia: a model for the role of molecular
diagnosis and residual disease monitoring in directing treatment
approach in acute myeloid leukemia.
SO - Leukemia 2002 Oct;16(10):1959-73
AD - Division of Medical and Molecular Genetics, Guy's, King's and St Thomas'
School of Medicine, London, UK.
Acute promyelocytic leukemia (APL) is characterized by a number of
features that underpin the need for rapid and accurate diagnosis and
demand a highly specific treatment approach. These include the
potentially devastating coagulopathy, sensitivity to anthracycline-based
chemotherapy regimens, as well as unique responses to all-trans retinoic
acid and arsenic trioxide that have revolutionized therapy over the last
decade. The chromosomal translocation t(15;17) which generates the
PML-RARalpha fusion gene has long been considered the diagnostic
hallmark of APL; however, this abnormality is not detected in
approximately 10% cases with successful karyotype analysis. In the
majority of these cases, the PML-RARalpha fusion gene is still formed,
resulting from insertion events or more complex rearrangements. These
cases share the beneficial response to retinoids and favorable prognosis
of those with documented t(15;17), underscoring the clinical relevance
of molecular analyses in diagnostic refinement. In other cases of
t(15;17) negative APL, various chromosomal rearrangements involving
17q21 have been documented leading to fusion of RARalpha to alternative
partners, namely PLZF, NPM, NuMA and STAT5b. The nature of the fusion
partner has a significant bearing upon disease characteristics,
including sensitivity to retinoids and arsenic trioxide. APL has
provided an exciting treatment model for other forms of AML whereby
therapeutic approach is directed towards cytogenetically and molecularly
defined subgroups and further modified according to response as
determined by minimal residual disease (MRD) monitoring. Recent studies
suggest that rigorous MRD monitoring, coupled with pre-emptive therapy
at the point of molecular relapse improves survival in the relatively
small subgroup of PML-RARalpha positive patients with 'poor risk'
disease. Advent of 'real-time' quantitative RT-PCR technology seems set
to yield further improvements in the predictive value of MRD assessment,
achieve more rapid sample throughput and facilitate inter- and
intra-laboratory standardization, thereby enabling more reliable
comparison of data between international trial groups.
11
UI - 12357352
AU - Meloni G; Trisolini SM; Capria S; Torelli GF; Baldacci E; Torromeo C;
TI -
Valesini G; Mandelli F
How long can we give interleukin-2? Clinical and immunological
evaluation of AML patients after 10 or more years of IL2 administration.
SO - Leukemia 2002 Oct;16(10):2016-8
AD - Department of Biotecnologie Cellulari ed Ematologia, University La
Sapienza, Rome, Italy.
We have treated 20 patients, affected by acute myelogenous leukemia in
advanced phase of the disease, with intravenous high-dose recombinant
interleukin-2 (IL2) as induction treatment, achieving a complete
remission (CR) in 11/20 of patients (55%). All CR patients were planned
to receive a maintenance program with lower subcutaneous doses of IL2
until relapse. Currently, 5/11 patients are alive in continuous complete
remission with a minimum follow-up of 9 years from IL2 induction. In the
aim to investigate the treatment's side-effects during or after
prolonged IL2 therapy, we decided to submit these patients to a clinical
and immunological evaluation. Four patients have been evaluated as one,
who independently stopped IL2 after 6 years, refused the check-up. No
organ-specific treatment sequelae that may decrease the quality of life
or may be life-threatening were found, concerning renal, liver and
cardiovascular function. Endocrine abnormalities were detected in three
patients, the most serious being a severe hypothyroidism, which prompted
cessation of IL2 maintenance after 6 years and required thyroid
supplementation treatment. Immunological studies were carried out prior
to the last IL2 cycle and showed high levels of CD3-positive T cells
expressing the IL2 receptor alpha chain (CD25), both in the peripheral
blood and in the bone marrow. Our study shows that low-dose IL2 can be
given for a prolonged period of time without serious organ-specific late
sequelae and with a good quality of life.
12
UI - 12377965
AU - Crews KR; Gandhi V; Srivastava DK; Razzouk BI; Tong X; Behm FG; Plunkett
TI -
W; Raimondi SC; Pui CH; Rubnitz JE; Stewart CF; Ribeiro RC
Interim comparison of a continuous infusion versus a short daily
infusion of cytarabine given in combination with cladribine for
pediatric acute myeloid leukemia.
SO - J Clin Oncol 2002 Oct 15;20(20):4217-24
AD - Department of Pharmaceutical Sciences, St Jude Children's Research
Hospital, Memphis, TN 38105, USA. kristine.rews@stjude.org
PURPOSE: To identify the optimal schedule for infusion of cytarabine
(ara-C) given with cladribine (2-CdA) to pediatric patients with acute
myeloid leukemia (AML), and to compare the effects of the two schedules
on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic
cells. PATIENTS AND METHODS: Forty-nine pediatric patients with newly
diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and
2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as
either a 2-hour daily infusion (arm A) or a continuous infusion (arm B).
Cellular pharmacokinetics were studied on days 1 and 2. All patients
then received two courses of remission induction chemotherapy with
daunorubicin, ara-C, and etoposide (DAV). RESULTS: Thirty-two percent of
patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered
complete remission (P =.045) after ara-C and 2-CdA therapy.
Coadministration of 2-CdA increased the intracellular concentration of
ara-CTP in 20 of 36 patients, although we found no statistically
significant difference between the treatment arms in this effect (P
=.63). The incidence of toxicity did not differ significantly between
the two treatment arms (P =.53). After two courses of DAV, the rate of
complete remission was 91% in arm A and 96% in arm B (P =.58).
CONCLUSION: Intracellular accumulation of ara-CTP is increased when
2-CdA is given with ara-C, but no schedule-dependent differences in this
effect were seen. The combination of 2-CdA and ara-C seems to be
effective therapy for pediatric AML.
13
UI - 3928107
AU - Douay L; Gorin NC; Mary JY; Duhamel G
TI -
[Experimental bases of the in vitro treatment of leukemic bone marrow by
a derivative of cyclophosphamide: ASTA Z 7557]
SO - C R Acad Sci III 1985;301(6):303-8
The authors report their experience with the ASTA Z 7557, a derivative
of cyclophosphamide, for the in vitro treatment of leukemic bone
marrows. They determined the sensitivity of human leukemic progenitors
(CFU-L, n = 9) and normal progenitors studied in semi-solid media
cultures (CFU-GM, n = 37; BFU-e, n = 11) and in long term marrow culture
(pre-CFU-GM n = 41). Data establish: The inhibition of the in vitro
proliferation of CFU-L by ASTA Z 7557. The similar sensitivity of CFU-L
and normal CFU-GM. The respect, at doses toxic on CFU-L and CFU-GM, of
more primitive stem cells, capable of self-renewing and the existence of
correlation between the intensiveness of treatment and the regeneration
capacity of CFU-GM; therefore, they defined a maximum tolerable dose
which spares 5 +/- 5% CFU-GM (DL 95) after treatment. The existence of a
wide range susceptibility from patient to patient which requires the
determination of the DL 95 for each individual patient.
14
UI - 7697468
AU - Chen Z; Chen SJ; Wang ZY
TI -
Retinoic acid and acute promyelocytic leukemia: a model of targetting
treatment for human cancer.
SO - C R Acad Sci III 1994 Dec;317(12):1135-41
AD - Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Second
Medical University, P.R. China.
Acute promyelocytic leukemia (APL) is the first example among the human
malignancies that responds to differentiation therapy, in that complete
remission (CR) can be achieved in up to 90% of patients by using a
differentiation inducer, all-trans retinoic acid (ATRA). The specific
chromosomal translocation t(15;17) in APL has been shown to fuse the
gene for the retinoic acid receptor alpha (RAR alpha) with a chromosome
15q locus, PML. Alterations to the RAR alpha and the PML gene structures
in the t(15;17) have been characterized and used as specific molecular
marker for diagnosis of the disease. PML/RAR alpha antagonizes wild-type
PML and RXR and could block the differentiation pathways mediated by
these two regulators. A variant translocation t(11;17) has also been
discovered in a subset of APL which fuses RAR alpha to a new gene, PLZF
on chromosome 11q23. Both PML/RAR alpha and PLZF/RAR alpha display the
"dominant negative" effect on the wild-type RAR/RXR. However, t(11;17)
APL patients differ from t(15;17) APL in that they respond poorly to
ATRA. Morphologically defined APL cases which however do not have
PML/RAR alpha generally show no response to ATRA. Recently it has been
shown that PML/RAR alpha can be modulated directly by ATRA. All these
data support the idea that PML/RAR alpha is a specific target of ATRA
which can overcome the differentiation block imposed by PML/RAR alpha.
The ATRA treatment of APL thus further reinforces the concept 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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