ataxia telangiectasia and advanced stage high grade mature B cell malignancies Pediatr Blood Cancer 2014 February 612 360362 There is no consensus regarding the optimal strategy for treating children with AT who develop a hematopoietic malignancy ID: 774821
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Slide1
Pilot study of modified LMB-based therapy for children with ataxia telangiectasia and advanced stage high grade mature B-cell malignancies.Pediatr Blood Cancer. 2014 February ; 61(2): 360–362.
There is no consensus regarding the optimal strategy for treating children with AT who develop a hematopoietic malignancy.
historically, many of these children have been treated with
minimal or modified reduced-intensity therapy
because of concerns regarding tolerance of therapy.
we piloted a curative approach in 5 children with AT who presented with advanced stage (iii, n=2; iv, n=3) B-NHL (diffuse large B-cell lymphoma, n=4;
burkitt
leukemia, n=1) using a modified LMB-based protocol. two achieved sustained
ccr
(one,
ccr
at 6 years; one, pulmonary death after 3 years in
ccr
). two died from toxicity during induction and 1 failed induction with progressive disease.
Slide2Ataxia-telangiectasia and T-Cell Leukemias: No Evidence for Somatic ATM Mutation in Sporadic T-ALL or for Hypermethylation of the ATM-NPAT/E14 Bidirectional Promoter in T-PLL1.Cancer Research 58, 2293-2297, June I. 1998)
A-T3
is a recessive pleiotropic syndrome caused by mutations in
the
ATM
gene (1, 2) located at 1Iq22-q23 (3).
The
risk of
malignancies,
especially
lymphoid
neoplasias
of T-cell origin, is substantially
increased
in A-T
and
was associated previously with
spontaneous chromosomal
instability observed in
A-T.
T-PLL
, an aggressive malignancy with a median age at diagnosis of
69 years
, exhibits
immunophenotypic
and
cytogenetic
similarities to a
T-cell leukemia
seen in A-T
.
In
particular, T-PLL is often associated
with translocations
and inversions of chromosome 14
Slide3Slide4Slide5Pediatr
hematol
oncol
1998 Sep-Oct;15(5):425-9.
Ataxia
telangiectasia associated with B-cell lymphoma: the effect of a half-dose
of
the drugs
administered
according to the acute lymphoblastic leukemia
standard
risk protocol
.
Because
of increased
chemosensitivity
, the treatment of
AT
patients with malignancies
requires
extremely careful planning and caution with respect to the use of
chemotherapy.
The
authors report on a 12-year-old boy with
AT
who developed
B-cell lymphoma
. He
received
a
half-dose of the drugs administered according to the acute lymphoblastic leukemia (ALL) protocol issued by our children's cancer study group (9104 Standard Risk Protocol
, Tokai Pediatric Oncology Study Group).
As
a result, he continues to be in complete remission and free of treatment complications 32 months after the diagnosis of B-cell lymphoma.
J clin immunol 2016 Oct;36(7):667-76.Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center.
We
summarized the clinical characteristics and treatment results of
17 cases with primary immunodeficiency
that developed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL
).
7
patients were diagnosed with
AT,
two with
CVID,
two with selective IgA deficiency, one with
XLP syndrome
, one with
Wiskott
-Aldrich syndrome, one with
EBV related
lymphoproliferative
syndrome, one with interleukin-2-inducible T-cell kinase (ITK) deficiency, and one with lymphoma developing
after ALPS.
7
were diagnosed with HL and
10
with NHL (seven B-cell
, three T-cell
).
The
NHL patients
were started on the
BFM,
POG9317, LMB-96, or R-CHOP treatment
protocols with reduced chemotherapy dosages. HL cases were started on
ABVD
and/or
COPP protocol
, also with modified dosages.
six
of the ten NHL patients have died
. Primary immunodeficiency is a strong predisposing factor for developing lymphoma.
Slide7Annals of Oncology 11 (Suppl I): S141-S145, 2000.Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): Experience from the BFM trials
In three consecutive
multicenter therapy,
trials for pediatric
NHL
(NHL-BFM
), 1569 patients with newly diagnosed
NHL have been
registered between 1986 and
1997.
Nine
patients with
AT
(n
= 5) and NBS
(n
= 4) were
identified.
Results
:
Median age of patients with AT and NBS
at diagnosis
of NHL was nine years.
Diffuse
large B-
cell
lymphoma
,
n =
1
;
ALCL,
n =
1; lymphoblastic T-cell lymphoma,
n
=
1
Stages were: I and II in
3 patients
,
III
in
5
and IV in
1 patient.
All
patients
received
polychemotherapy
according to tumor-entity and stage,
none received radiation.
Dose
reductions according to
individual tolerance
concerned mainly
ethotrexate
, alkylating agents and
epipodophyllotoxines
.
Slide8Annals of Oncology 11 (Suppl I): S141-S145, 2000.Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): Experience from the BFM trials
From
April 1986 to October 1997, 1569 patients up to 18 years of
age with
newly diagnosed NHL or B-ALL were registered in the
NHL-BFM
study center.
Among
these 1569 patients, 9 patients were
suffering from
AT or
NBS.
These
patients were analyzed regarding
clinicopathological
features,
treatment modalities and outcome.
Slide9Annals of Oncology 11 (Suppl I): S141-S145, 2000.Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): Experience from the BFM trials
Therapy and response criteria
Patients
with lymphoblastic
T-cell lymphoma received
ALL type
therapy
consisting of induction, consolidation, re-induction,
and maintenance
therapy as previously described
.
Patients
with
B-cell lymphoma
or anaplastic large-cell lymphoma of either
immunophenotype
received
four to six courses of
polychemotherapy
as
described elsewhere.
Intensity and duration of therapy was stratified according to
stage at
diagnosis and to initial tumor mass, determined by
serum-concentration of
lactate dehydrogenase (LDH
).
In
patients with AT or
NBS, the
study-center recommended to start therapy with reduced
intensity depending
on the physical state of the patient, history of
previous infections
and other ID-related complications
.
Therapy was intensified
during following courses according to tolerance of the
first course
Slide10Slide11Slide12Slide13Slide14T-cell Acute Lymphoblastic Leukemia in a Child With Ataxia-telangiectasia- Case Report
Slide15Modified chop‐chemotherapy plus rituximab for diffuse large B‐cell lymphoma complicating ataxia‐telangiectasia
Chemotherapy was considered and, in order to avoid the severe complications reported in patients with AT treated for cancer (Abadir & Hakamin, 1983), a modified dosage of CHOP was chosen. The patient received: cyclophosphamide 300 mg/m2, doxorubicin 15 mg/m2, vincristine 1 mg/m2 on d 1, prednisone 40 mg/m2/d for 5 d.This treatment was repeated every 3 weeks for eight cycles. On d 2 of each cycle, the addition of Rituximab at a dosage of 375 mg/m2 was made.