promyelocytic leukemia | Treatment of adult Promyélocytaires acute leukemias

Treatment of adult Promyélocytaires acute leukemias

Summary
Acute promyelocytic leukemia (LAP) accounts for about 8% of adult myéloblastiques acute leukemias. It is characterized by a chromosomal translocation T (15; 17), a strong hemorrhagic tendency to diagnosis and sensitivity to agents that induce differentiation of leukemic blasts, such as all-trans-retinoic acid (ATRA) or arsenic. The combinations of chemotherapy and ATRA have significantly improved the results with a relapse rate which is now reduced to around 15%. Arsenic is for the time being used to treat relapses, successfully, allowing hematopoietic stem cell transplants to be performed in a second complete remission. Other agents also have very high efficacy in the LAP, making this long-dreaded acute leukemia one of the subtypes for which the therapeutic arsenal and the results of the treatments are the most satisfying.

Keywords
Acute promyelocytic leukemia treatment ATRA Arsenic Treating of adult acute promyelocytic leukaemia
Abstract
Acute promyelocytic leukaemia (APL) accounts for approximately 8% of all acute myeloid leukemias (AML) in adults. APL is characterized by a t (15; 17) chromosomal translocation, a strong tendency for bleeding at diagnosis, and a sensitivity to those agents that induce a differentiation of leukaemia blasts such as all-trans retinoic acid (ATRA) or arsenic. Combined ATRA and chemotherapy have significantly improved patient outcome, with a rate of relapse that has been reduced to approximately 15%. Today, arsenic is being used successfully to treat relapsed patients; Its high efficacy allows undertaking haematopoietic stem cell transplantation and achieving second full remission. Other new agents also exhibit high efficacy in APL, which makes this type of AML, considered fearsome for long, a subset for which there are a lot of therapeutic options and satisfactory therapeutic outcome.

Keywords
Acute promyelocytic leukaemia Therapy ATRA Arsenic


Treatment of Adult
Acute promyelocytic
Leukaemia

Abstract: Acute promyelocytic leukaemia
(APL) accounts for approximately
8% of all acute myeloid
Leukemias (AML) in adults. APL is
Characterized by a t (15; 17) chromosomal
Translocation, a strong tendency
For bleeding at diagnosis, and
A sensitivity to those agents that
Induce a differentiation of leukaemia
Blasts such as all transtinoic acid
(ATRA) or arsenic. Combined ATRA
and chemotherapy have significantly
Improved patient outcome, with a
Rate of relapse that has been reduced
To approximately 15%. Today, Arsenic
is being used successfully to treat
Patients Its high efficacy
Allows undertaking haematopoietic
Stem cell transplantation and achieving
Second full remission. Other New
Agents also exhibit high efficacy in
Which makes this type of AML,
Considered fearsome for long, a subset
For which there are a lot of
Therapeutic options and satisfactory
Therapeutic outcome.
Keywords: Acute promyelocytic
Leukaemia – Therapy – ATRA –
Arsenic
Re ´ sume ´: La leuce ´ mie Acute ¨ promye ´
Locytaire (LAP) represents ´ about
8% of Leuce ´ Mies acute ¨ s
Clam ´ loblastiques of the adult. It is
Characterized ´ rise by a translocation
Chromosome T (15; 17), A
Strong trend He ´ Morragique
Diagnosis and ´ sensitivity to
Agents inducing a diffe ´ differentiation
´ Leuce blasts, such as
All-trans-er acid ´ tinoı ¨ as (ATRA)
or arsenic. The combinations of
Chimiothe ´ Therapy and ATRA have allowed
´ to improve significantly
The ´ results with a rate of
Relapse which is now re ´
Around 15%. Arsenic is
Currently uses ´ to process
relapses, with success, allowing
of re ´ to carry out cell transplants
Strains he ´ Matopoı ¨ e ´ Ticks
Second ´ mission.
Other agents pre ´ feel e ´ Also
A very high ´ efficiency in
The LAP, making this leuce ´ mie
Acute ¨, long dreads ´ E, one of the
Subtypes for which the Arsenal the ´-
´ and the results of the treatment
Are the most satisfying.
Key words ´ s: Leuce ´ mie ¨ promye ´
Locytaire – Treatment – ATRA –
ArsenicIntroduction
Leuce ´ mie ¨ promye ´ locytaire
(LAP) represents a subtype of ´
Leuce ´ mie ¨ clam ´ loblastique
(LAM), identifies ´ in the classification
English-American-British (LAM-3)
As well as in the classification
Who. Relatively rare in
The child and in the subject age ´, this
Leuce ´ mie Acute ¨ represent ´ about
8% of the adult's LAM. Its main
Characterized ´ characteristics are:
-A significant association
With clotting disorders
And Fibrinolysis, a source of
He ´ Morragique syndrome sometimes
Deadly, especially in the forms
Variants (LAM-3v) and/or Hyperleucocytaires
;
– The pre-´ presence of a translocation
Chromosome e ´ equilibrium ´ E, the
T (15; 17) (Q22; q21), which is responsible for
In the great majority ´
Cases of the production of a
Prote ´ oncoge ´ Fusion ine
PML-RARa (there are very few
Translocation variants that involve
Always the GE ' Nerar coding
For the RE ´ alpha receptor to the acid
Re ´ tinoı ¨ that);
– ´ Sensitivity to agents
Inducing a diff ´ differentiation of
´ Leuce blasts, such as
The All-Trance acid ´ Tinoı ¨ that (ATRA)
Or arsenic, allowing both
A rate of re-´ mission (RC)
´ Leve ´, even in monothe ´ therapy.
First line treatment
E ´ Establishment of treatment
De Re ´ fe ´
A chimiothe ´ therapy associating a
Anthracycline and Cytosine arabinoside
(Ara-C) has been, for more than
30 years, the treatment of re ´ FE ´
of LAM and has long been ´
The only treatment of LAP that are
Particularly sensitive to
Anthracyclines [2]. The role of Ara-C
In the LAP however seems
Be more marginal than in the
Other LAM. In addition to its largest
´ sensitivity to anthracyclines, the
LAP pre ´ feels, compared to
Other LAM, the ´ peculiarity of a
Progressive disappearance of the
Blastose me ´ dullaire under Anthracyclines.
It is ´ to find,
A month after the ´ goal of the
Treatment, a number still
E ´ leve ´ from Blastes me ´ dullaires,
Without this signing a ´ failure,
He ´ Hematology Oncology (2008) 10:290 – 294
© Springer 2008
DOI 10.1007/s10269-008-0884-5
Oncology
290
Unlike other LAM. These
Tardivesdeblastes persistence are
Often associates ´ with signs of
Diffe ´ differentiation Promye ´ locytes
Abnormal. In total, before
The ATRA and trioxide
Arsenic (ATO), a chimiothe ´ therapy
Antimitotic with
Significant doses of anthracyclines
(with or without Ara-C), combines ´ E
To a massive platelet support
During the induction phase, allowed
To get an RC in pre's
80% of cases [13] and to limit the
Initial ´ mortality binds ´ to the coagulopathy.This treatment allowed
A ' 35% of patients to have a
Re ´ mission extends ´ E, which is known
That it is GE ´ ne ´ usually e ´ equivalent
In a GUE ´ Rison, the relapses
After five years e ´ so rare (< 2%).
Les re ´ tinoı ¨ des ´ definitively
Proves ´ the ´ possibility of dealing with
Leuce ´ mies by inducing the diff ´-
Differentiation, De's 1985, by a collaboration
Between the St. Louis Hospital
In Paris and the Institute of He ´ Hematology of
Shanghai [8.12]. The latter put, the
First, treat, in 1987, patients
Infected with LAP by ATRA and get
RC. However, it should be noted that
On the one hand, patients treat ´
ATRA alone relapsed almost
All after obtaining an RC if they
were not receiving other treatments
(Especially the Chimiothe ´
Therapy antimitotic) and that,
On the other hand, we observed fre ´ frequently
A rapid increase in
Leukocytes, associates ´ with signs
Clinics, re ´ retention
Hydrosode ´ E, pulmonary infiltrates,
E ´ panchements Weeping and
PE ´ ricardiques, which can lead to
´ ("ATRA syndrome", secondarily
´ names ´ syndrome
Activation Leukocyte ") [5].
These findings have brought ´ to
Propose the introduction of Chimiothe ´
Antimitotic in Association
ATRA [11], or after the
An RC obtained by ATRA,
FAC ¸ on pre ´ early in case of Leukocytosis,
´ to avoid the occurrence of the
Leukocyte activation syndrome.
The first Test ´, Mene ´
In the group Franc ¸ ais des LAP
(APL test 91), compared a treatment
Classic by AnthracyclinesAra-C
(An induction Cure and two
Consolidation treatments) at the same
Treatment, but pre ´ this ´ of ´ by a
Induction by ATRA until obtained
of the RC [14]. This last arm
´ to reduce the re-
Leuce ´ and re ´ significantly reduce the
The risk of
50 is about 25%.
Subsequently, the APL 93 test (which
E ´ was worth the introduction pre ´ early or
The ATRA as well as the place
Maintenance treatment) will show
On the one hand, that the rate of
Relapse e ´ ´ if the chimiothe ´
Therapy e ´ was introduced by FAC ¸ on pre ´-
Early in induction treatment
(In practice after three days
On the other hand, that a ATRA treatment
Maintenance by discontinuous ATRA
Or chimiothe ´ Therapy continues
By 6-MP + MTX could re ´ reduce the
relapses, with an additive effect of
Two modalities ´. In total, the ´ results
of this test as well as other
Essays Coope ´ Imperatives International,
Re ´ alise ´ s according to dryer ´ Mas close
[23.28], have shown that
The introduction pre ´ early of a treatment
By Anthracyclines-Ara-C
Combines ´ with ATRA, followed by cures
Consolidation and then an interview
Combining chimiothe ´ Therapy a ' low
Continuous dose and discontinuous ATRA,
90% RC Rates and
Relapses in the order of 15%, a
Gue ´ Rison in the order of 75%
could be obtained.
of ´ bats re ´ cents and current around
of LAP Processing
Role of the Aracytine and impact

of Anthracyclines
The MD Anderson Cancer ´ Team
Center of Houston (E ´ United States) [10]
First, followed by the groups
Italian and Spanish, a de ´ shows ´
In non-randomized tests ´
Treatment based only on
An Association of Anthracycline
(idarubicin) and ATRA, followed by a
Maintenance treatment, allowed
To obtain ´ similar results
While re-´ing the ´ toxicity of the
Chimiothe ´ therapy [1]. However
The Europe ´ test in APL 2000 [1]
Randomisait the Ara-C induction in
More than one treatment by anthracyclines
(daunorubicin) and ATRA a
To be Arre ´ pre ´
of a significant relapse surplus
In the arm without Ara-C, putting
The ´ IDE that the Ara-C e ´ was
Useless in the processing of LAP.
It must, however, be noted that
Cumulative doses of Anthracyclines
E ´ were Supe ´ in the
Spanish and Italian essays, compare ´
Es to those uses ´ es in the test
Europe ´ in. A RE ´ hundred analysis
Of the Spanish tests (without
ARA-C) and Europe ´ Ens (with Ara-c) a
Finally allowed to show that
In the standard forms of risk,
That is to say no hyperleucocytaires,
The addition of Ara-C seemed useless
and e ´ was more clam ´ lotoxique.
On the other hand, in the forms
Hyperleucocytaires (recalling
That in the LAP, the Hyperleucocytaires forms
Are ´ finished by a
Rate of GB Supe ´ to 10 000/mm3
,
´ ending a group of LAP
At the highest risk of relapse),
The addition of Ara-C allowed
Re ´ reduce the incidence of relapses
(2 versus 16%).
The role of arsenic in LAP
First line
The ´ doctors of Harbin in Manchuria
Have used ´ the first
Arsenic in patients with
of LAP's 1970. Very quickly, an effect
Spectacular Product A E ´ te ´ notes ´
In the LAP in relapse after
Treatment by ATRA Associates ´ with the
Chimiothe ´ Therapy, in the EXPE ´ experiences
Chinese [25], and then in Europe and
To the United States ´. In addition, the analyses
Se ´ quentielles by RT-PCR of disease
Re ´ residual showed that the
Arsenic trioxide only E ´ was able
Only to induce a re ´ mission
Mole ´ Ordinatespoint What the ATRA is
GE ´ does not ´ incapable, placing ¸ the
Mole ´ cule like treatment the
More effective in monothe ´ therapy [19].
However, in the absence of consolidation,
Patients were relapsing to
New. These ´ results led
Aude ´ Development Enpreme
approaches the ´ Rapeutiques news,
Without chemo-the ´ therapy: the trioxide
Arsenic may be associated with ´
ATRA, even in some
Expe ´ experiences, uses ´ in monothe ´ therapy.
These approaches have ´ ´ particularly
´ develops ´ es in.