Pilot study of modified LMB-based therapy for children with - PowerPoint Presentation

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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.

Ataxia-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

Pediatr

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.

Annals 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

.

Annals 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.

Annals 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

T-cell Acute Lymphoblastic Leukemia in a Child With Ataxia-telangiectasia- Case Report

Modified 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.