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(2016.V3)NCCN临床实践指南：非霍奇金淋巴瘤(1)

2022-01-07 来源：赴品旅游

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Non-Hodgkin’sLymphomas

Version 3.2016

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Version 3.2016, 05/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

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NCCN Guidelines Index

NHL Table of Contents

NCCN Guidelines Version 3.2016 Panel Members

Non-Hodgkin’s Lymphomas

Memorial Sloan Kettering Cancer Center

* Andrew D. Zelenetz, MD, PhD/Chair † Þ

Nancy Lee Harris, MD ≠

Massachusetts General Hospital Cancer Center Francisco Hernandez-Ilizaliturri, MD † Roswell Park Cancer Institute Richard T. Hoppe, MD § Stanford Cancer Institute

Memorial Sloan Kettering Cancer Center Mark S. Kaminski, MD † University of Michigan

Comprehensive Cancer Center Christopher R. Kelsey, MD § Duke Cancer Institute Youn H. Kim, MD ϖ † Stanford Cancer Institute Susan Krivacic, MPAff ¥ Consultant

Ann S. LaCasce, MD †

Dana-Farber/Brigham and Women’s Cancer Center Matthew Lunning, DO Þ

Fred & Pamela Buffett Cancer Center

Michael G Martin, MD †

St. Jude Children’s Research Hospital/

University of Tennessee Health Science Center Auayporn Nademanee, MD † ‡ ξ

City of Hope Comprehensive Cancer Center

Discussion

Leo I. Gordon, MD/Co-Vice Chair ‡ ξ * Robert H. Lurie Comprehensive Cancer

Pierluigi Porcu, MD ‡ Þ †

The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance Rachel Rabinovitch, MD §

University of Colorado Cancer Center Nishitha Reddy, MD ‡ ξ

Vanderbilt-Ingram Cancer Center Erin Reid, MD ‡ ξ

UC San Diego Moores Cancer Center Kenneth Roberts, MD §

Yale Cancer Center/Smilow Cancer Hospital Ayman A. Saad, MD ‡ ξ

University of Alabama at Birmingham Comprehensive Cancer Center Lubomir Sokol, MD, PhD † ‡ Þ § ξ Moffitt Cancer Center

Lode J. Swinnen, MB, ChB ‡ ξ

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Julie M. Vose, MD, MBA ‡ ξ

Fred & Pamela Buffett Cancer Center Memorial Sloan Kettering Cancer Center

Center of Northwestern University

* Oliver Press, MD, PhD † ‡

G. Wierda, MD, PhD/Co-Vice Chair † ‡ The * William

University of Texas

MD Anderson Cancer Center

* Jeremy S. Abramson, MD † ‡

* Steven M. Horwitz, MD † Þ

Massachusetts General Hospital Cancer Center Ranjana H. Advani, MD † Stanford Cancer Institute

* C. Babis Andreadis, MD, MSCE ‡ †

UCSF Helen Diller Family

Comprehensive Cancer Center Nancy Bartlett, MD †

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

John C. Byrd, MD ‡ Þ ξ

The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute Luis E. Fayad, MD ‡ Þ † The University of Texas

MD Anderson Cancer Center Richard I. Fisher, MD ‡ † Fox Chase Cancer Center Martha J. Glenn, MD † ‡ Þ ξ Huntsman Cancer Institute at the University of Utah

* Joachim Yahalom, MD §

* Thomas M. Habermann, MD ‡ ξ Mayo Clinic Cancer Center

NCCN Guidelines Panel Disclosures

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NCCN Mary Dwyer, MS Hema Sundar, PhD

Version 3.2016, 05/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. ®

NCCN gratefully acknowledges Dr. Elise A. Olsen

for participating in the update of the Primary Cutaneous B-Cell Lymphomas and MycosisFungoides/Sézary Syndrome guidelines.

† Medical oncology Þ Internal medicine ‡ Hematology/Hematology oncology ϖDermatology §Radiotherapy/Radiation oncology ¥ Patient advocacy ξ Bone marrow transplantation * Discussion Writing Committee ≠Pathology Member guide.medlive.cn

NCCN Guidelines Index

NHL Table of Contents

NCCN Guidelines Version 3.2016 Table of Contents

Non-Hodgkin’s Lymphomas

NCCN Non-Hodgkin’s Lymphoma Panel Members

Summary of the Guidelines Updates

Chronic Lymphocytic Leukemia/

Small Lymphocytic Lymphoma (CSLL-1) Follicular Lymphoma (FOLL-1)

Marginal Zone Lymphomas (MZL-1)

Gastric MALT Lymphoma (MALT-1)

Nongastric MALT Lymphoma (NGMLT-1) Nodal Marginal Zone Lymphoma (NODE-1) Splenic Marginal Zone Lymphoma (SPLN-1) Mantle Cell Lymphoma (MANT-1)

Diffuse Large B-Cell Lymphoma (BCEL-1)

Burkitt Lymphoma (BURK-1)

Lymphoblastic Lymphoma (BLAST-1)

AIDS-Related B-Cell Lymphomas (AIDS-1)

Hairy Cell Leukemia (HCL-1)

Primary Cutaneous B-Cell Lymphomas (CUTB-1) Peripheral T-Cell Lymphomas (TCEL-1)

Mycosis Fungoides/Sezary Syndrome (MFSS-1) Primary Cutaneous CD30+ T-Cell Lymphoproliferative

Disorders (PCTLD-1)

T-Cell Large Granular Lymphocytic Leukemia (LGLL-1) Adult T-Cell Leukemia/Lymphoma (ATLL-1) T-Cell Prolymphocytic Leukemia (TPLL-1)

Extranodal NK/T-Cell Lymphoma, nasal type (NKTL-1) Post-Transplant Lymphoproliferative Disorders (PTLD-1) Castleman’s Disease (CD-1)

Use of Immunophenotyping/

Genetic Testing in Differential

Diagnosis of Mature B-Cell and

NK/T-Cell Neoplasms (NHODG-A)

Supportive Care for NHL (NHODG-B)

Lugano Response Criteria for Non-Hodgkin’s Lymphoma (NHODG-C)

Principles of Radiation Therapy

(NHODG-D)

Special Considerations for the Use

of Small-Molecule Inhibitors Classification and Staging (ST-1)

(Ibrutinib and Idelalisib) (NHODG-E)

Primary CNS Lymphoma (See NCCN Guidelines for CNS) Waldenström’s Macroglobulinemia/Lymphoplasmacytic Lymphoma (See NCCN Guidelines for WM/LPL)

Clinical Trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. To find clinical trials online at NCCN Member Institutions, click here: nccn.org/clinical_trials/physician.html. NCCN Categories of Evidence and Consensus: All recommendations are category 2A unless otherwise specified. See NCCN Categories of Evidence and Consensus. Discussion

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 clinical circumstances 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 NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2016.

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NCCN Guidelines Index

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NCCN Guidelines Version 3.2016 Updates

Non-Hodgkin’s Lymphomas

• CLL with del(17p)/TP53 mutation:

_Relapsed/refractory therapy

Discussion

Updates in Version 3.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2016 include:

CSLL-D 3 of 7

◊◊Venetoclax was added as an option with a category 2A designation.

CSLL-F

• A new page titled, \"Venetoclax: Recommended TLS Prophylaxis and Monitoring Based on Tumor Burden\" was added.

Updates in Version 2.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 1.2016 include:

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma CSLL-D 4 of 7 CSLL-D 1 of 7 • CLL with del(11q): • Frail patient, significant comorbidity _First-line therapy, Age ≥70 y and younger patients with significant _\"Ibrutinib\" was added with a category 1 designation. comorbidities • CLL without del(11q) or del(17p)/TP53 mutation: ◊◊\"Ibrutinib\" was added with a category 1 designation.

_First-line therapy, Age ≥70 y and younger patients with significant

CSLL-D 5 of 7 comorbidities

• CLL with del(11q): ◊◊\"Ibrutinib\" was added with a category 1 designation.

_Second-line extended dosing, \"Ofatumumab maintenance (for complete CSLL-D 2 of 7 or partial response after relapsed or refractory therapy)\" was added • CLL without del(11q) or del(17p)/TP53 mutation: with a category 2B designation. _Second-line extended dosing, \"Ofatumumab maintenance (for complete

or partial response after relapsed or refractory therapy)\" was added Diffuse Large B-Cell Lymphoma BCEL-3 with a category 2B designation.

• Footnotes \"

CSLL-D 3 of 7 _Footnote \"n\" was revised, For patients who cannot tolerate anthracyclines, See BCEL-C for regimens used in for patients with • CLL with del(17p)/TP53 mutation:

_Second-line extended dosing, \"Ofatumumab maintenance (for complete

or partial response after relapsed or refractory therapy)\" was added with a category 2B designation.

poor left ventricular function and patients >80 years of age with comorbidities.\"

_Footnote \"r\" was revised, \"Based on current clinical trials, RCHOP is preferable due to reduced toxicities, but other comparable

anthracycline-based regimens are also acceptable (see BCEL-C).\"

Discussion MS-1 • The Diffuse Large B-Cell Lymphoma section of the discussion was updated to reflect the changes in the algorithm.

Continued on next page

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NCCN Guidelines Version 3.2016 Updates

Non-Hodgkin’s Lymphomas

• Suggested treatment regimen references were updated throughout the

guidelines.

• Diagnosis, Essential, the bullet for \"Adequate immunophenotyping to establish diagnosis\" was revised by changing \"or\" to \"with or without\" as follows for IHC and flow cytometry: _IHC panel: with or without

_Cell surface marker analysis by flow cytometry:

• Diagnosis, \"karyotype\" replaced \"cytogenetics\" throughout the guidelines as appropriate.

Discussion

Updates in Version 1.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2015 include:

CSLL-5 Global changes • Page was extensively reorganized.

• The algorithm for del(11q) (previously page CSLL-7) was removed and is now included with the algorithm for del(17p)/mut TP53. \"With or without deletion of del(11q)\" was added to the title and is used as a decision point along the algorithm.

• After relapsed CLL with indication for treatment, the text was revised, \"Reevaluate FISH and karyotype, if del(17p), see CSLL-6.\"

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma General • For deletion of 17p, \"mutation TP53\" was added throughout.

CSLL-1 • Essential

_2nd bullet, 3rd sub-bullet, \"CD200 and LEF1 may be useful to distinguish from MCL\" was added.

• Informative for prognostic and/or therapy determination

_2nd bullet was revised: \"CpG-stimulated metaphase karyotype stimulated cytogenetics for complex karyotype\" • After Indication present for patients with adequate funtional status _1st bullet was revised: \"Evaluate FISH and karyotype.\"

CSLL-3

CSLL-6

• Page was extensively reorganized. • First-line therapy

_1st sub-bullet was revised, “17p deletion/mutation TP53 is associated with low response rates with chemoimmunotherapy if there is no standard _treatment, clinical trial is recommended.” • Response to therepy

_After response, the algorithm was separated by \"complex karyotype present\" and \"complex karyotype not present.\"

◊◊After complex karyotype present, the option for \"consider allogeneic stem cell transplant\" was added with \"Clinical trial\" and \"Observe.\" • Footnotes

_Footnote \"q\" was added: \"CPG-stimulated karyotype is useful to identify high-risk patients, particularly for bruton tyrosine kinase (BTK) inhibitor therapy.\"

_Footnote \"t\" was added: \"For patients with complex karyotype (≥3 abnormalities) in remission after BTK-inhibitor therapy, consider discussion of allogeneic transplant although data available do not support this as highly effective (Jaglowski Br J Haematol Br J Haematol 2012;159:82-87).

CSLL-C 2 of 2

• A link for special considerations related to small molecule inhibitors was added.

Continued on next page

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Non-Hodgkin’s Lymphomas

Discussion

Updates in Version 1.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2015 include:

CSLL-D 1 of 7 CSLL-D 5 of 7 • CLL without del(11q) or del(17p)/TP53 mutation: • CLL with del(11q):

_Relapsed/refractory therapy, Age ≥70 and younger patients with significant _First-line therapy, Age ≥70 y and younger patients with significant

comorbidities comorbidities

◊◊Idelalisib + rituximab was changed from a category 2A to a category ◊◊“Cladribine” was removed as a recommendation along with the

1 recommendation. corresponding footnote, \"In rare circumstances of CNS disease,

cladribine is potentially useful.\" ◊◊Idelalisib monotherapy was listed separately and is a category • Footnote 2A recommendation. _Footnote “c” was revised: “Autoimmune hemolytic anemia (AIHA) should ◊◊Bendamustine ± rituximab was moved as the first option under not preclude the use of combination therapy containing fludarabine and chemoimmunotherapy.

patients should be observed carefully. Avoid fludarabine in patients with _Relapsed/refractory therapy, Age <70 y without significant comorbidities

◊◊Idelalisib + rituximab was changed from a category 2A to a category active AIHA or history of fludarabine-associated AIHA.” Revision made

1 recommendation. for all CSLL-D pages.

◊◊Idelalisib monotherapy was listed separately and is a category CSLL-D 2 of 7 2A recommendation. • CLL without del(11q) or del(17p)/TP53 mutation: _Relapsed/refractory therapy, Age ≥70 y and younger patients with CSLL-E

• The response definition for PR-L was added to the table along with the significant comorbidities

◊◊Idelalisib + rituximab was changed from a category 2A to a category cooresponding reference, \"Cheson BD, Byrd JC, Rai KR, et al. Novel 1 recommendation. targeted agents and the need to refine clinical end points in chronic ◊◊Idelalisib monotherapy was listed separately and is a category lymphocytic leukemia. J Clin Oncol 2012;30:2820-2822.”

2A recommendation.

◊◊Bendamustine ± rituximab was moved as the first option under chemoimmunotherapy. Continued on next page _Relapsed/refractory therapy, Age <70 y without significant comorbidities

◊◊Idelalisib + rituximab was changed from a category 2A to a category 1 recommendation.

◊◊Idelalisib monotherapy was listed separately and is a category 2A recommendation.

CSLL-D 3 of 7

• CLL with del(17p)/TP53 mutation: _Relapsed/refractory therapy

◊◊Idelalisib + rituximab was changed from a category 2A to a category 1 recommendation.

◊◊Idelalisib monotherapy was listed separately and is a category 2A recommendation.

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Non-Hodgkin’s Lymphomas

Discussion

Updates in Version 1.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2015 include:

FOLL-6 Follicular Lymphoma • Histologic transformation to diffuse large B-cell lymphoma

FOLL-1 _Multiple prior therapies,

• Footnotes

◊◊For chemotherapy ± rituximab, \"± ISRT\" was added.

_Footnote “e” was revised as, “In young patients with localized disease

_For minimal or no prior chemotherapy,

that lack BCL2 rearrangement expression or t(14;18)...\"

◊◊ For PR, “Consider ISRT” was added. _Footnote \"f\" was added: \"FL with 1p36 deletions have a predominant

diffuse pattern in inguinal nodes, large localized mass, CD23+, typically FOLL-B 1 of 3

grade 1-2 and have a good prognosis.\"

• Second-line Consolidation or Extended Dosing

_Footnote \"g\" was added: \"Lymphomas with IRF4 translocations are

_“Obinutuzumab maintenance for rituximab refractory disease (category 2B) usually DLBCL but occasionally are purely FL grade 3B and often

(1 g every 8 wks for total of 12 doses)\" was added.

DLBCL with FL grade 3B. Patients typically present with Waldeyer’s ring

• Footnote was removed, \"First-line consolidation with radioimmunotherapy involvement and are often children/young adults. The tumor is locally

or extended dosing of rituximab after bendamustine + rituximab has not aggressive but responds well to chemotherapy +/- RT. These lymphomas

been studied.\" do not have a BCL2 rearrangement and should not be treated as low-

grade FL.\" Gastric MALT Lymphoma MALT-1 FOLL-2

• Workup

• Workup, Essential

_9th bullet,\"...and/or PET-CT scan (especially if ISRT anticipated)\" was _9th bullet was revised by adding, \"(PET-CT scan essential if RT for stage

added. I, II disease planned).”

Nongastric MALT Lymphoma

FOLL-3

NGMLT-1 • Footnote

• Workup

_Footnote \"k\" was modified as, \"Observation may be appropriate in _“PET-CT scan” was moved from Useful in Selected Cases to Essential and circumstances where potential toxicity of involved-site RT (ISRT) combined with the following bullet as, \"Chest/abdominal/pelvic CT with outweighs potential clinical benefit and pediatric follicular lymphoma.\" contrast of diagnostic quality and/or PET-CT scan.\" (Also for NODE-1 and

SPLN-1)

FOLL-4 • Stage II bulky, III, IV: NGMLT-2

_The heading \"Initial therapy\" was changed to \"Initial Managment.\" • The stage \"extranodal (multiple sites)\" was removed.

• The following footnotes were removed: • The stage \"Stage III, IV: extranodal disease and multiple nodal sites\" was

_\"Consider appropriate clinical trials for patients on observation.\" revised to say \"Stage IV\" only.

_\"Given incurability with conventional therapy, consider investigational _The inital therapy for Stage IV has been clarified as,

therapy as first line of treatment.\" ◊◊ ISRT or Observation in selected cases or Manage per advanced-stage FL (FOLL-4) FOLL-5 • Footnote • Footnote was removed, \"Clinical trials may involve novel agents, _Footnote \"l\" was revised: \"Observation may be considered for patients regimens, or transplantation.\" whose diagnostic biopsy was excisional, or involved-field RT or systemic treatment where RT could result in significant comorbidity.\" _Footnote was removed, \"DLBCL coexistent with MALT cell lymphoma is managed as DLBCL. See NCCN Guidelines for Diffuse Large B-Cell Lymphoma (BCEL-1).\" Continued on next page

UPDATES Version 3.2016, 05/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

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Non-Hodgkin’s Lymphomas

Discussion

Updates in Version 1.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2015 include: Mantle Cell Lymphoma • Footnotes MANT-1 _Footnote was removed: \"These regimens include first-line consolidation • Diagnosis, Useful Under Certain Circumstances with high-dose therapy and autologous stem cell rescue (HDT/ASCR).

_Bullet was removed: \"Molecular analysis to detect: antigen receptor gene _Footnote was removed: \"Typically patients will receive an aggressive rearrangements; CCND1 rearrangements\" induction regimen prior to consolidation; however, less aggressive

_1st bullet was revised: \"LEF1 may help distinguish from variant CLL; SOX11 or IGHV sequencing may be useful for determination of indolent MCL; may also help in diagnosis of CCND1- MCL.\" _3rd bullet: \"Cytogenetics\" was changed to \"karyotype.\"

_4th bullet was added: \"Cell surface marker analysis by flow cytometry: CD200.\" • Workup

_“PET-CT scan” was moved from Useful Under Certain Circumstances to Essential and combined with the following bullet as, \"Chest/abdominal/ pelvic CT with contrast of diagnostic quality and/or PET-CT scan.\" • Footnote

_Footnote \"c\" was revised: \"Ki-67 proliferation fraction of <30% in lymph nodes is associated with a more favorable prognosis. However, it is not used to guide treatment.\"

regimens followed by consolidation with high-dose therapy may also result in a good long-term outcome.\"

MANT-3

• Stage II bulky, III, IV was extensively revised with a separation between \"Aggressive\" and \"Indolent.\"

_For aggressive, the algorithm was clarified for both \"Candidate for HDT/ ASCR\" and \"Not candidate for HDT/ASCR\"

_For indolent, a definition was added, \"(SOX11- [IGHV mutated], leukemic non-nodal CLL-like with splenomegaly, low tumor burden, Ki-67

proliferation fraction <30%)\" along with a treatment of \"Observation.\"

Diffuse Large B-Cell Lymphoma BCEL-1 • Diagnosis, Useful Under Certain Circumstances _1st sub-bullet, IHC panel, \"SOX11\" was added.

_2nd bullet was revised as, \"Karyotype or FISH: MYC, BCL2, BCL6 rearrangements t(14;18),t(3;v), t(8;14), t(8;v).\" • Footnotes

_Footnote \"a\" was revised by removing,\" These cases would be

appropriate to evaluate for MYC, BCL2, and BCL6 rearrangements.\" _Footnote \"e\" was changed to, \"Cases with double expression of MYC and either BCL2 or BCL6 by IHC having a GCB-like immunophenotype should undergo FISH testing for MYC, BCL2, and BCL6 rearrangement.\" from \"There are no established guidelines to select DLBCL

patients to investigate for double-hit lymphomas. Standard of care is not established for DLBCL with t(14;18) with concurrent MYC rearrangements.\"

MANT-A 1 of 3

• For Less aggressive therapy,

_The information about maintenance rituximab was removed from each option since it is under first-line consolidation.

_\"Cladribine + rituximab\" was changed from a category 2A to a category 2B recommendation.

• First-line consolidation was separated by transplant eligible and not transplant eligible

_For first-line consolidation, candidate for HDT/ASCR, \"± rituximab

maintenance\" was added to \"High-dose therapy with autologous stem cell rescue.\"

_For first-line consolidation, Not a candidate for HDT/ASCR, \"rituximab maintenance (category 1 following RCHOP)\" was added.

BCEL-2 • Workup:

_Essential, \"Chest/abdominal/pelvic CT with contrast of diagnostic quality and/or PET-CT scan\" was changed to \"PET-CT scan ± chest/ abdominal/pelvic CT with contrast of diagnostic quality.\" _Useful in Selected Cases, “Lumbar puncture” bullet was revised as, \"...if paranasal sinus, testicular, epidural, bone marrow with large cell lymphoma, HIV lymphoma, or ≥2 extranodal sites and elevated LDH if have 4–6 factors according to prognostic model, HIV lymphoma,

testicular, double expressor lymphoma” with a link to BCEL-A 2 of 2.\"

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Non-Hodgkin’s Lymphomas

Discussion

Updates in Version 1.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2015 include:

BCEL-3 BCEL-B 3 of 3 • Stage I, II, the category 1 designation was added to RCHOP x 3 cycles + RT for • Double hit lymphoma page is new to the guidelines. nonbulky disease and removed from RCHOP x 6 cycles ± RT for bulky disease.\" BCEL-C 1 of 4 • Footnote \"k\" was revised as, \"In selected cases (paranasal sinus, testicular, • First-line Therapy for Patients with Poor Left Ventricular Function or epidural, bone marrow with large cell lymphoma, HIV lymphoma, kidney or Very Frail

adrenal gland involvement, concurrent expression of MYC and BCL2 protein, or _\"RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and ≥2 extranodal sites and elevated LDH 4–6 factors according to prognostic model, prednisolone)\" was added. HIV lymphoma, testicular, double hit lymphoma)...\" _\"RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, • Footnote \"p\" was added, \"If RT is not used, interim staging after 3–4 cycles of prednisone)\" was removed. RCHOP is appropriate to confirm response.\" • Patients >80 Years of Age with Comorbidities

_\"RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and

BCEL-4 prednisolone)\" was added. • After End-of-Treatment Response, for both PR and NR or PD, \"RT in select • Footnotes patients who are not candidates for chemotherapy\" was added as an option. ◊◊Footnote \"b\" was added, \"In RCHOP-14 and RCHOP 21, may 2(Also added to BCEL-5) consider increasing dose of rituximab to 500 mg/m in men >60 y.\" • Footnotes ◊◊Footnote \"e\" was added, \"There are limited data for treatment of _Footnote \"t\" was revised: \"Repeat biopsy should be strongly considered if in early stage disease with these regimens; however, short course PET positive prior to additional therapy. If biopsy negative, follow PET-negative chemotherapy + RT for Stage I-II disease is practiced at NCCN guideline.\" (Also for BCEL-5) member institutions.\" _Footnote “w” was revised: “The optimum timing of repeat end-of-treatment BCEL-C 2 of 4

PET-CT is unknown; however, waiting a minimum of 8 weeks after RT to repeat • Second-line and Subsequent Therapy (non-candidates for high-dose PET-CT scan is suggested.\" therapy)

_For \"Lenalidomide ± rituximab,\" the qualifier \"non-GCB DLBCL\" was

BCEL-A added. • \"Stage-Adjusted IPI” was added. AIDS-Related B-cell Lymphomas BCEL-B 1 of 3 AIDS-1 • Primary Mediastinal Large B-Cell Lymphoma • Diagnosis _The first-line therapy options were organized in \"order of preference.\" _Bullet was removed from Useful Under Certain Circumstances \"Additional immunohistochemical studies to establish lymphoma BCEL-B 2 of 3 subtype DLBCL, Burkitt, Plasmablastic, Primary effusion • Grey Zone Lymphoma (intermediate between DLBCL and classical HL) lymphoma (PEL): CD10, BCL2, Ki-67, BCL6, CD138, CD30 for PEL, _Clinical presentation, 2nd bullet was added: \"Non-mediastinal grey zone KSHV LANA-1\" and appropriate text was added to 3rd bullet under lymphoma is more likely compared to mediastinal cases to occur in older Essential. individuals and typically have higher risk features, more advanced-stage AIDS-3 disease, and higher IPI.\" • Footnote \"f\" was revised: \"... (paranasal sinus, testicular, epidural, _Immunophenotype, 3rd bullet was revised: \"EBV - (<20% of cases +)\"

bone marrow with large cell lymphoma, EBER positivity, or ≥2 _Prognosis and Treatment,

extranodal sites and elevated LDH) (4–6 factors according to ◊◊2nd bullet was revised, \"While there is no consensus on the treatment,

aggressive large B-cell lymphoma [or Hodgkin type] regimens are preferred prognostic model, HIV lymphoma, testicular, double hit lymphoma) have been proposed.\" See Prognostic Model to Assess the Risk of CNS Disease (BCEL-A ◊◊4th bullet, last sentence was revised: \"If localized disease, then ± RT RT is 2 of 2).\" preferred . Hairy Cell Leukemia ◊◊5th bullet was added: \"There is no ostensible difference in outcome between HCL-1 mediastinal and non-mediastinal grey zone lymphoma.\"

• Diagnosis, \"IHC for mutant BRAF\" was moved to Essential. _Reference 4 was added.

Continued on next page UPDATES Version 3.2016, 05/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

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NCCN Guidelines Version 3.2016 Updates

Updates in Version 1.2016 of the NCCN Guidelines for Non-Hodgkin’s Lymphomas from Version 2.2015 include:

Primary Cutaneous B-Cell Lymphomas Mycosis Fungoides/Sezary Syndrome

CUTB-2 MFSS-1 • Initial therapy • Diagnosis, Essential

_Solitary/regional and Generalized disease, _1st bullet, a new sub-bullet was added, \"Multiple biopsies may ◊◊After response, \"Observe\" was added. be necessary to capture the pathologic variability of disease at

• Footnote “i” was revised from “Local RT is not preferred for relapsed disease” diagnosis.”

to \"Local RT is the preferred initial treatment, but not necessarily the preferred • Footnote \"a\" was added, \"Presence of transformation or areas of treatment for relapse.\" folliculotropicism may have important implications for selection of

therapy and outcome and should be included in pathology reports.\"

Peripheral T-Cell Lymphomas

MFSS-2

TCEL-1

• Workup, Useful in Selected Cases

• Footnotes _1st bullet was revised: \"Bone marrow biopsy (not required for staging _Footnote \"a\" was revised by removing the following sentence, \"Molecular but used to document visceral disease in those suspected to have diagnosis for T-cell receptor rearrangements should be done in most marrow involvement including B2 blood involvement and in patients circumstances to confirm clonality.\" with unexplained hematologic abnormality.\" _Footnote \"d\" was added, \"Primary cutaneuous peripheral T-cell lymphomas _2nd bullet was revised, \"Biopsy (FNA is often inadequate) of are very heterogeous and the optimal management may not be along these suspicious lymph nodes for identical clones (recommend assessment guidelines.\" of clonality for all but particularly NCI LN 2-3) or suspected

extracutaneous sites.\"

TCEL-B 1 of 5 _3rd bullet was revised: \"Rebiopsy skin if suspicious of large cell • First-line Therapy:

transformation.\"

_ALCL, ALK+ histology

MFSS-3

◊◊CHOEP-21 was modified by removing \"21.\" • B0 was revised by adding, \"...or <250/mcL are atypical (Sezary) cells or

<15% CD4+/CD26- or CD4+/CD7- cells.\" TCEL-B 2 of 5

• Second-line therapy and subsequent therapy was separated into 3 groups and MFSS-5

• Stage IA, primary treatment, \"If histologic evidence of folliculotropic organized by preferred and alternate agents/regimens for both intention to

or large-cell transformed MF\" was removed along with corresponding transplant and no intention to transplant. The 3 groups are as follows and the

sub-bullet, \"Consider primary treatment for Stage IIB (See MFSS-6).\" list for preferred and alternative are in alphabetical order.

• Footnotes _PTCL-NOS and EATL

_AITL _Footnote \"o\" was added: \"In rare cases of confirmed unilesional MF,

_ALCL RT has been shown to provide long-term remission.\"

_Footnote \"q\" was added: \"In patients with folliculotropism or • For PTCL-NOS, EATL, AITL and ALCL

_Belinostat was changed from a category 2B to category 2A recommendation. histologic large-cell transformed MF, skin disease may be less

_Dose-adjusted EPOCH was removed. responsive to topical therapies.\"

• Second-line Therapy (intention to transplant) and Subsequent Therapy MFSS-6

_Alternative regimens, \"gemcitabine\" and \"lenalidomide\" and \"GND • Stage IB-IIA, primary treatment for If histologic evidence of (gemcitabine, vinorelbine, liposomal doxorubicin)\" were added to folliculotropic or large-cell transformed MF, \"In selected cases\" was

added to \"consider primary treatment for Stage IIB\" with a footnote, appropriate subtypes.

\"Histologic evidence of folliculotropic or large-cell transformed MF is • Second-line Therapy (no intention to transplant) and Subsequent Therapy

associated with higher risk of disease progression.\"

_Alternative single agents, \"lenalidomide\" was added to appropriate subtypes. Continued on next page

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Non-Hodgkin’s Lymphomas

Discussion

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