leucemie acuta limfoblastica

8/13/2019 Leucemie acuta limfoblastica

http://slidepdf.com/reader/full/leucemie-acuta-limfoblastica 1/77

NCCN Guidelines Index ALL Table of Contents

Discussion

Version 1.2012, 03/12/12 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN .® ®

NCCN.org

Continue

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) ®

Acute LymphoblasticLeukemiaVersion 1.2012




Discussion


Joseph C. Alvarnas, MD/Co-Chair ‡

† ‡

‡

‡

‡

† Þ

City of Hope ComprehensiveCancer Center

Patrick A. Brown, MD/Co-Chair €The Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins

Patricia Aoun, MD, MPHUNMC Eppley Cancer Center atThe Nebraska Medical Center

Karen Kuhn Ballen, MDMassachusetts General HospitalCancer Center

Naresh Bellam, MD, MPHUniversity of Alabama at Birmingham

Comprehensive Cancer Center William Blum, MDThe Ohio State University ComprehensiveCancer Center - James Cancer Hospitaland Solove Research Institute

Michael W. Boyer, MDHuntsman Cancer Instituteat the University of Utah

Hetty E. Carraway, MDThe Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins

Peter F. Coccia, MD €

UNMC Eppley Cancer Center atThe Nebraska Medical Center

Steven E. Coutre, MDStanford Comprehensive Cancer Center

Jennifer Cultrera, MDH. Lee Moffitt Cancer Center &Research Institute

Lloyd E. Damon, MDUCSF Helen Diller FamilyComprehensive Cancer Center

Daniel J. DeAngelo, MD, PhDDana-Farber Cancer Institute

Dan Douer, MDMemorial Sloan-Kettering Cancer Center

Haydar Frangoul, MD € Vanderbilt-Ingram Cancer Center

Olga Frankfurt, MDRobert H. Lurie Comprehensive Cancer Center of Northwestern University

Salil Goorha, MDUniversity of Tennessee Cancer Institute

‡

‡

† ‡

†

‡

†

Michael M. Millenson, MD

Fox Chase Cancer Center

Susan O’Brien, MDThe University of TexasMD Anderson Cancer Center

Stephen H. Petersdorf, MDFred Hutchinson Cancer ResearchCenter/Seattle Cancer Care Alliance

Arati V. Rao, MDDuke Cancer Institute

Stephanie Terezakis, MD §

‡ Þ

†

† ‡

† Þ

† Þ

† Þ

The Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins

Geoffrey Uy, MDSiteman Cancer Center at Barnes-Jewish Hospital and WashingtonUniversity School of Medicine

Meir Wetzler, MDRoswell Park Cancer Institute

Andrew Zelenetz, MD, PhDMemorial Sloan-Kettering Cancer Center

‡ Hematology/Hematology oncology € Pediatric oncology

Pathology

† Medical oncologyÞ Internal medicine

§ Radiotherapy/Radiation oncology* Writing Committee

Bone marrow transplantation

Continue

NCCN Guidelines Panel Disclosures

NCCN Guidelines Version 1.2012 Panel MembersAcute Lymphoblastic Leukemia

NCCNKristina Gregory, RN, MSNMaoko Naganuma, MSc

*

*

Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM. For personal use only. Not approved for distribution. Copyright © 2012 National Comprehensive Cancer Network, Inc., All Rights Reserved.

http://contents.pdf/

http://www.nccn.org/disclosures/panel_list.asp?ID=180


http://www.nccn.org/disclosures/panel_list.asp?ID=180




Discussion


NCCN Acute Lymphoblastic Leukemia Panel Members

Diagnosis (ALL-1)Workup and Risk Stratification (ALL-2)Ph+ ALL (AYA) Treatment Induction and Consolidation Therapy (ALL-3)Ph+ ALL (Adult) Treatment Induction and Consolidation Therapy (ALL-4)Ph- ALL (AYA) Treatment Induction and Consolidation Therapy (ALL-5)

Ph- ALL (Adult) Treatment Induction and Consolidation Therapy (ALL-6)Surveillance (ALL-7)Relapse/Refractory Disease, Treatment (ALL-7)Typical Immunophenotype by Major ALL Subtypes (ALL-A)Supportive Care (ALL-B)Evaluation and Treatment of Extramedullary Involvement (ALL-C)

Principles of Chemotherapy (ALL-D)Response Criteria (ALL-E)Minimal Residual Disease Assessment (ALL-F)Treatment Options Based on Kinase Domain Mutation Sta tus (ALL-G)BCR-ABL

Clinical Trials:

Categories of Evidence andConsensus:NCCN

believes thatthe best management for any cancer patient is in a clinical trial.Participation in clinical trials isespecially encouraged.

To find clinical trials online at NCCNMember Institutions,

All recommendationsare Category 2A unless otherwisespecified.See

NCCN

click here:nccn.org/clinical_trials/physician.html.

NCCN Categories of Evidenceand Consensus.

The NCCN Guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinicalcircumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network (NCCN ) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCNGuidelines are copyrighted by National Comprehensive Cancer Network . All rights reserved. The NCCN Guidelines and the illustrations herein may notbe reproduced in any form without the express written permission of NCCN. ©2012.

®

® ®

®

NCCN Guidelines Version 1.2012 Table of ContentsAcute Lymphoblastic Leukemia

Printed by oanatrifanescu ion on 7/15/2012 2:16:59 P M. For p ersonal use only. Not appr oved for distribution. Copyright © 2012 National Comprehensive Cancer Network, Inc., All Rights Reserved.


http://www.nccn.org/clinical_trials/physician.html









http://nhl.pdf/



P i d b if i 7/15/2012 2 16 59 PM F l l N d f di ib i C i h © 2012 N i l C h i C N k I All Ri h R d

http://aya.pdf/




Discussion


Note: All recommendations are category 2A unless otherwise indicated.Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

TREATMENT INDUCTION k CONSOLIDATION THERAPY

ALL-3

NCCN Guidelines Version 1.2012Acute Lymphoblastic Leukemia

RISK

STRATIFICATION

Ph+ ALL (AYA)(aged 15-39 y) i,j

Clinical trialor Chemotherapy +tyrosine kinaseinhibitor (TKI)

l

m

Complete

response (CR)n

Less than CR n

Consider monitoring for

minimal residualdisease (MRD) o

Allogeneic HSCT, p if adonor is availableor If allogeneic HSCT is not

available, continuemultiagent chemotherapy+ TKI

lm

Consider post-HSCT TKI m

i

jklmno

Chronological age is a poor surrogate for fitness for therapy. Patients should be evaluated on an individual basis, including for the following factors: end-organ reserve,end-organ dysfunction, and performance status.

For additional considerations in the management of AYA patients with ALL, see the . All ALL treatment regimens include CNS prophylaxis.

.See for use of different TKIs in front-line therapy.

NCCN Guidelines for Adolescent and Young Adult Oncology

See Principles of Chemotherapy (ALL-D)

See Response Criteria (ALL-E).See Minimal Residual Disease Assessment (ALL-F).

Discussion section

p Emerging data suggest that for younger patient (aged 21 y), allogeneic HSCT may not offer an advantage over chemotherapy + TKIs; Schultz KR, Bowman WP, Aledo A, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin

Oncol 2009;27:5175-5181.

See Relapse/RefractoryDisease (ALL-7)

Maintenancetherapy + TKIl m

SeeSurveillance(ALL-7)


Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM. For personal use only. Not approved for distribution. Copyright © 2012 Nationa l Comprehensive Cancer Network, Inc., All Rights Reserved.

Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM For personal use only Not approved for distribution Copyright © 2012 National Comprehensive Cancer Net work Inc All Rights Reserved


http://aya.pdf/

http://aya.pdf/

http://aya.pdf/


http://aya.pdf/

http://senior.pdf/




Discussion



ALL-4


Ph+ ALL(Adult)(aged 40 y)

RISK

STRATIFICATION

Patients < 65years of ageor with nosubstantialcomorbidities

i

Patients 65years of age or withsubstantialcomorbidities

≥

i,q

Clinical trialor TKI +corticosteroidsor

m

ml,r

l

TKI +chemotherapy

CR n

Continue TKI ±corticosteroids

ml

or ml

Continue TKI ±chemotherapy

i

n

o

r


Consider dose modifications appropriate for patient age and performance status.

klm

q

All ALL treatment regimens include CNS prophylaxis..

See for use of different TKIs in front-line therapy.

For additional considerations in the management of senior adult patients with ALL, see the .

See Principles of Chemotherapy (ALL-D)Discussion section

NCCN Guidelines for Senior Adult Oncology



Clinical trialor Chemotherapy+ TKI

lm

CR n

Lessthan CR n

Consider monitoringfor MRD o

Allogeneic HSCT, if adonor is availableor If an allogeneic HSCTdonor is not available,continue multiagentchemotherapy + TKIl,r m

Consider post-HSCT TKI m

See Relapse/RefractoryDisease ALL-7

Maintenancetherapy l m+ TKI



Maintenancetherapy l m+ TKI

Lessthan CR n


See

Surveillance(ALL-7)

Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM. For personal use only. Not approved for distribution. Copyright © 2012 National Comprehensive Cancer Net work, Inc., All Rights Reserved.

Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM For personal use only Not approved for distribution Copyright © 2012 National Co mprehensive Cancer Network Inc All Rights Reserved


http://senior.pdf/

http://senior.pdf/

http://senior.pdf/


http://senior.pdf/

http://aya.pdf/




Discussion



ALL-5


Ph- ALL (AYA)(aged 15-39) i,j

TREATMENT INDUCTION k

Clinical trialor Pediatric-inspiredmultiagentchemotherapy s

RISK

STRATIFICATION

CONSOLIDATION THERA PY

CR n

Lessthan CR n


Continue multiagentchemotherapy (especially MRD-)or

l

Consider allogeneic HSCT if a donor is available (especially MRD+, WBCcount 30 x 10 /L [B lineage] or

50 x 10 /L [T lineage], hypodiploidy,or MLL rearrangement)

t

u

≥

≥

9

9

i

n

o


j

k

l

s

t

For additional considerations in the management of AYA patients with ALL, see the All ALL treatment regimens include CNS prophylaxis.

.

. All regimens include induction/delayed intensification (especially for pediatric-inspired regimens) and maintenance therapy.Benefit with allogeneic HSCT is unclear in this setting.

Data demonstrating the effect of WBC counts on prognosis is less firmly established for adults than for the pediatric population.u

NCCN Guidelines for Adolescent and Young Adult Oncology





Maintenancetherapy l

SeeSurveillance

(ALL-7)


Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM. For personal use only. Not approved for distribution. Copyright © 2012 National Co mprehensive Cancer Network, Inc., All Rights Reserved.

Printed by oanatrifanescu ion on 7/15/2012 2:16:59 PM. For persona l use only . Not approved for distribution. Co pyright © 2012 National Comprehensive Can cer Network, Inc., All Rights Reserved.


http://aya.pdf/

http://aya.pdf/


http://aya.pdf/

http://senior.pdf/




Discussion



ALL-6


RISK

STRATIFICATION

Patients <65years of ageor with nosubstantialcomorbidities

i

Patients 65years of ageor withsubstantialcomorbidities

≥

i,qClinical trialor

or Corticosteroids

Multiagentchemotherapy l

CR n Chemotherapy l



Lessthan CR n

Clinical trialor Multiagent

chemotherapys

CR n

Lessthan CR n





Ph- ALL(Adult)(aged 40 y)

i

n

o


k

l

q

s

t

All ALL treatment regimens include CNS prophylaxis..

For additional considerations in the management of senior adult patients with ALL, see the .. All regimens include induction/delayed intensification (especially for pediatric-inspired regimens) and maintenance therapy.

Benefit with allogeneic HSCT is unclear in this setting.

Data demonstrating the effect of WBC counts on prognosis is less firmly established for adults than for the pediatric population.u


NCCN Guidelines for Senior Adult OncologySee Principles of Chemotherapy (ALL-D)



Continue multiagentchemotherapy (especially MRD-)or

l

Consider allogeneic HSCT if a donor is available (especially MRD+, WBCcount 30 x 10 /L [B lineage] or

50 x 10 /L [T lineage], hypodiploidy,or MLL rearrangement)

t

u

≥

≥

9

9

y p y pp py g p , , g


http://senior.pdf/

http://senior.pdf/

http://senior.pdf/


http://senior.pdf/




http://aya.pdf/

http://aya.pdf/



http://nhl.pdf/


http://pain.pdf/

http://antiemesis.pdf/

http://aml.pdf/

http://aml.pdf/

http://nhl.pdf/

http://infections.pdf/

http://infections.pdf/




Discussion


PRINCIPLES OF CHEMOTHERAPY (1 of 4)

ALL-D1 of 4



*All regimens include CNS prophylaxis with systemic therapy (eg, methotrexate, cytarabine, 6-mercaptopurine) and/or IT therapy (eg, IT methotrexate, IT cytarabine;triple IT therapy with methotrexate, cytarabine, corticosteroid).

**For patients receiving 6-MP, consider testing for TPMT gene polymorphisms, particularly in patients that develop severe neutropenia after starting 6-MP.

Induction Regimens* for Ph-Positive ALLAdult patients aged 40 years:

Pediatric-inspired protocols for AYA patients aged 15-39 years:

Maintenance regimens:

≥

TKIs + hyper-CVAD: imatinib or dasatinib; and hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone,alternating with high-dose methotrexate, and cytarabineTKIs + multiagent chemotherapy: imatinib; and daunorubicin, vincristine, prednisone, and cyclophosphamideTKIs + corticosteroids: imatinib and prednisone (for this study, patients were aged >60 years)Dasatinib

COG AALL-0031 regimen: vincristine, prednisone (or dexamethasone), and asparaginase, with or without daunomycin; or prednisone (or dexamethasone) and asparaginase with or without daunomycin; imatinib added during consolidation blocks

Weekly methotrexate + daily 6-mercaptopurine (6-MP)** + monthly vincristine/prednisone pulses (for 2-3 years)Add TKIs (imatinib or dasatinib) to the above maintenance regimen

1-45,6

78,9

10

References ALL-D 4 of 4

Induction Regimens for Ph-Negative (ALL ALL-D 2 of 4)

Salvage Regimens for Relapsed/Refractory ALL ALL-D 3 of 4






Discussion


Salvage Regimens* for Relapsed/Refractory ALL

Ph-positive ALL:

Ph-negative ALL:

DasatinibNilotinib

Clofarabine

Cytarabine-containing regimensAlkylator combination regimensNelarabine (for T-ALL)

22,2324

252627

28

Augmented hyper-CVAD: hyper-fractionated cyclophosphamide, intensified vincristine, doxorubicin, intensified dexamethasone, andasparaginase; alternating with high-dose methotrexate and cytarabine 29

PRINCIPLES OF CHEMOTHERAPY (3 of 4)

ALL-D3 of 4



*All regimens include CNS prophylaxis with systemic therapy (eg, methotrexate, cytarabine, 6-mercaptopurine) and/or IT therapy (eg, IT methotrexate, IT cytarabine;triple IT therapy with methotrexate, cytarabine, corticosteroid).

References (ALL-D 4 of 4 )

Induction Regimens for Ph-Positive (ALL ALL-D 1 of 4)

Induction Regimens for Ph-Negative (ALL ALL-D 2 of 4)






Discussion

Version 1.2012, 03/12/12 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN .® ® ALL-E



RESPONSE CRITERIA

Response Criteria for Blood and Bone Marrow:

Response Criteria for CNS Disease:

Response Criteria for Mediastinal Disease:

CRNo circulating blasts or extramedullary disease

No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvementTrilineage hematopoiesis (TLH) and <5% blasts

CR with incomplete blood count recovery (CRi)Recovery of platelets but <100,000 or ANC is <1000/microL

Overall response rate (ORR=CR + CRi)

Failure to achieve CR at the end of inductionProgressive disease (PR)

Increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary diseaseRelapsed disease

Reappearance of blasts in the blood or bone marrow (>5%) or in any extramedullary site after a CR

CNS remission: Achievement of CNS-1 status ( ) in a patient with CNS-2 or CNS-3 status at diagnosis.CNS relapse: New development of CNS-3 status or clinical signs of CNS leukemia such as facial nerve palsy, brain/eye involvement, or hypothalamic syndrome.

CR: Complete resolution of mediastinal enlargement by CT.CR Unconfirmed (CRu): Residual mediastinal enlargement that has regressed by >75% in the sum of the product of the greatestperpendicular diameters (SPD).PR: >50% decrease in the SPD of the mediastinal enlargement.PD: >25% increase in the SPD of the mediastinal enlargement.No Response (NR): Failure to qualify for PR or PD.Relapse: Recurrence of mediastinal enlargement after achieving CR or CRu.

Absolute neutrophil count (ANC) >1000/microLPlatelets >100,000/microLNo recurrence for 4 weeks

Refractory disease

see ALL-C






Discussion


TREATMENT OPTIONS BASED ON KINASE DOMAIN MUTATION STATUSBCR-ABL 1

Mutation Treatment Recommendation

T315I HSCT or clinical trial

V299L, T315A, F317L/V/I/C Consider nilotinib rather thandasatinib

Y253H, E255K/V, F359V/C/I Consider dasatinib rather thannilotinib

Any other mutation Consider high-dose imatinib or dasatinib or nilotinib

2

1

2

This research was originally published in Blood. Soverini S, Hochhaus A, Nicolini FE, et al. Bcr-Abl kinase domain mutation analysis in chronic myeloid leukemiapatients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. .© the American Society of Hematology.There are no sufficient data on dose escalation available to indicate if mutations with lower IC values are sensitive to high-dose imatinib.

Blood 2011;118:1208-1215

50

ALL-G








Discussion

NCCN Guidelines Version 1.2012 Acute Lymphoblastic Leukemia

glycol conjugated asparaginase for treatment of children with newlydiagnosed standard risk acute lymphoblastic leukemia: a Children's






Version 1.2012, 03/12/12 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines ® and this illus tration may not be reproduced in any form witho ut the express written permission of NCCN®. REF-16

diagnosed standard-risk acute lymphoblastic leukemia: a Children'sCancer Group study. Blood 2002;99:1986-1994. Available at:http://www.ncbi.nlm.nih.gov/pubmed/11877270 .

198. Wang B, Relling MV, Storm MC, et al. Evaluation of immunologiccrossreaction of antiasparaginase antibodies in acute lymphoblasticleukemia (ALL) and lymphoma patients. Leukemia 2003;17:1583-1588.

Available at: http://www.ncbi.nlm.nih.gov/pubmed/12886246 .

199. Zalewska-Szewczyk B, Gach A, Wyka K, et al. The cross-reactivityof anti-asparaginase antibodies against different L-asparaginasepreparations. Clin Exp Med 2009;9:113-116. Available at:http://www.ncbi.nlm.nih.gov/pubmed/19184328 .

200. Willer A, Gerss J, Konig T, et al. Anti-Escherichia coliasparaginase antibody levels determine the activity of second-linetreatment with pegylated E coli asparaginase: a retrospective analysiswithin the ALL-BFM trials. Blood 2011;118:5774-5782. Available at:

http://www.ncbi.nlm.nih.gov/pubmed/21940824 .201. Vrooman LM, Supko JG, Neuberg DS, et al. Erwinia asparaginaseafter allergy to E. coli asparaginase in children with acute lymphoblasticleukemia. Pediatr Blood Cancer 2010;54:199-205. Available at:http://www.ncbi.nlm.nih.gov/pubmed/19672973 .

202. EUSA Pharma (USA), Inc. Prescribing Information. AsparaginaseErwinia chrysanthemi ERWINAZE™ For Injection, Intramuscular Use.

2011. Available at: http://www.erwinaze.com/pdf/PI_18-Nov2011.pdf . Accessed February 2012.

leucemie acuta limfoblastica

Documents