Dexamethasone And Leukemia Survival
ironjustice
Dexamethasone-Based Therapy Shows Improvement In
Survival For Children With Acute Lymphoblastic Leukaemia
Article Date: 17 Sep 2009 - 0:00 PDT
A dexamethasone-based treatment reduces the risk of relapse and
improves the cure rate in children with acute lymphoblastic leukaemia
(ALL) without the use of cranial radiation and some routinely used
chemotherapy drugs, thus minimising the risk of unnecessary side-
effects. This highly effective treatment strategy produces results on
a par with the best protocols worldwide. These are the conclusions of
an Article published Online First and in the October edition of The
Lancet Oncology.
Childhood ALL is the most common type of childhood cancer and is
curable in most patients. However, many children with ALL are over-
treated and as such are exposed to unnecessary side-effects. In a
previous study, the ALL-6 protocol (1984-88), the Dutch Childhood
Oncology Group (DCOG) showed that the use of dexamethasone instead of
prednisone and moderately intensive intrathecal chemotherapy instead
of cranial radiation was their most effective treatment protocol to
date. In non-high risk (NHR) patients 5-year event-free survival
reached 83%, but high risk (HR) patients who were on institutional
protocols, had an event-free survival of just 53%.
In this study, the DCOG present the results of the ALL-9 protocol,
which is identical in design to ALL-6 for the NHR group-in order to
confirm the results in a new cohort of patients-while introducing a
new treatment strategy for the HR group with the aim of improving on
the results achieved in ALL-6.
In total, 859 patients with ALL aged 1-18 years were recruited from
eight oncology centres in the Netherlands between January, 1997, and
November, 2004, and followed-up for more than 6 years. Patients were
stratified into two treatment groups-NHR (70%) and HR (30%) by
conventional criteria. Patients in the NHR group were treated with a
basic three-drug induction (dexamethasone, vincristine, and L-
asparaginase) and medium-dose methotrexate (3x2 g/m²). The HR group
received a four-drug induction (as for the NHR group plus four doses
of daunorubicin), consolidation with methotrexate 4x2 g/m², and two
intensification courses before maintenance, which was 109 weeks for
all patients. Triple intrathecal medication was given 13 times in NHR
patients and 15 times in HR patients and 17 times in those with
initial central nervous system involvement. No patient received
cranial irradiation.
Overall, the ALL-9 protocol showed similar event-free survival in the
NHR group and better event-free survival in the HR group compared with
the ALL-6 protocol. The results were also better than the previous
DCOG ALL-7 and ALL-8 protocols.
In the ALL-9 protocol overall event-free survival was 81% compared to
76% in the ALL-6 period. 5-year event-free survival in the NHR group
was 84% in ALL-9 which is similar to 83% reported in ALL-6. Yet, in
the HR group, 5-year event-free survival was 72% in the ALL-9 treated
protocol compared with 53% in the ALL-6 period when they were on
institutional protocols. In addition, overall survival in the ALL-9
protocol was 90% for patients in the NHR group and 78% for HR
patients.
The authors conclude: "The results for NHR patients [70% of all newly
diagnosed patients] were achieved with high cumulative doses of
dexamethasone and vincristine, but without the use of anthracyclines,
etoposide, cyclophosphamide, or cranial irradiation, therefore
minimising the risk of side-effects…The 5-year event-free survival of
72% in the ALL-9 HR group without the use of cranial irradiation and
with limited use of anthracyclines and cyclophosphamide can be
regarded as a favourable result in this group of patients."
Link to article, reflection and reaction
Source
The Lancet Oncology
-------------
"Inhibitory effect of dexamethasone on in vivo erythropoiesis"
"Erythropoietic depression was elicited by cyclophosphamide
administration"
It's curious how these VERY popular drugs .. reduce blood cell count.
Reduce the number of red blood cells.
Somewhat like .. bloodletting.
Enhanced hypoxia-stimulated erythropoietin production in mice with
depression of erythropoiesis induced by hyperoxia.
High Alt Med Biol. 2003 Spring;4(1):73-9.
Bozzini CE, Barceló AC, Conti MI, Martínez MP, Alippi RM.
Department of Physiology, Faculty of Odontology, University of Buenos
Aires, Argentina. ceb...@fisio.odon.uba.ar
Current evidence suggests that a modulatory action on O(2)-dependent
EPO secretion is exerted by the erythroid/precursor cell population
in
the erythropoietic organs through a negative feedback system.
The hypothesis is based on studies of stimulated-EPO secretion
performed in mice in whom the erythropoietic rates were either
enhanced or depressed in the presence of normal plasma EPO half-
lives.
Since erythropoietic depression was elicited by cyclophosphamide
administration, which could have altered EPO production directly, the
aim of the present investigation was to estimate hypoxia-stimulated
EPO secretion in a mouse model of functional depressed erythropoiesis
induced by exposure to normobaric hyperoxia.
Females CF#1 mice aged 70 d were divided into control (C) and
experimental (E) groups.
The former was maintained in plastic cages in a normal environment,
while the latter was placed in an environment of 60% O(2)/40% N(2) in
an 85-dm(3) atmospheric chamber with air flow of 1 L/min.
Erythropoiesis was evaluated by either 24-h RBC-(59)Fe uptake or iron
kinetics performed 3 h after IV injection of a tracer dose of (59)Fe.
Both indexes of the red cell production rate were significantly
depressed in E mice. Plasma disappearance of exogenous EPO in C mice,
as well as in E mice exposed to hyperoxia for 4 d, was estimated by
injecting (125)I-rHuEPO intravenously.
Linear regression analysis indicated that neither the differences
between the slopes of both curves nor the Y-intercepts were
significant.
Hypobaric hypoxemia was used as stimulus for EPO production.
Plasma immuno-EPO titer after a 4-h exposure to hypobaric air was 73%
higher in mice with hyperoxia-induced hypoerythropoiesis than in
control mice with normal erythropoiesis.
Data support the concept that the rate of erythropoiesis, perhaps
through the number of the erythroid progenitor/precursor cell
population, modulates O(2)-dependent EPO secretion.
PMID: 12713714
-------------------
Exp Hematol. 1980 Aug ;8 (7):911-6 16398023 (P,S,G,E,B) Mechanism
underlying the inhibitory effect of dexamethasone on in vivo
erythropoiesis.
[My paper] M J Giglio, R M Alippi, C E Bozzini
Cátedras de Fisiología, Facultad de Odontología, Universidad de
Buenos
Aires, República Argentina.
The time-response curve for RBC-59Fe uptake following i.p. injection
of 5 mg of dexamethasone into normal, non-polycythemic mice, shows a
maximal depression (50% of normal) at 3 days after dexamethasone with
return to almost normal values by 5 days. The effect is dose-related
showing a plateau with doses of dexamethasone above 3 mg. The shape
of
the time-response curve indicates that the more mature cells in the
erythron are not affected by dexamethasone and that the major effect
of the steroid must be on earlier erythroid cells. Intravenous
injection of dexamethasone 33 and 48 h after i.v. injection of
erythropoietin in post-hypoxic polycythemic mice has no effect on the
response to erythropoietin, suggesting that the early and late
erythroblasts develop normally into erythrocytes. Injection of
dexamethasone 13 h after erythropoietin is also ineffective,
suggesting that the final steps of differentiation from
erythropoietin
responsive cells (ERC) to proerythroblasts are not affected. On the
contrary, injection of dexamethasone 1 h after erythropoietin reduces
by 60% the effective erythropoiesis, which can be attributed to a
decrease in differentiation of ERC into proerythroblasts. These
results indicate that the inhibitory action of dexamethasone on
erythropoiesis is exerted on cells of the erythroid line before the
stage of proerythroblast is reached.
Mesh-terms: Animals; Anti-Inflammatory Agents :: administration &
dosage; Cell Differentiation :: drug effects; Cells, Cultured;
Colony-
Forming Units Assay; Dexamethasone :: administration & dosage; Dose-
Response Relationship, Drug; Erythroblasts :: cytology;
Erythroblasts :: physiology; Erythropoiesis :: drug effects;
Erythropoietin :: administration & dosage; Female; Mice; Research
Support, Non-U.S. Gov't;
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