2010NCCN指南-急性髓性白血病

Continue NCCN Clinical Practice Guidelines in Oncology™ Acute Myeloid Leukemia V.2.2010 www.nccn.org Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® NCCN Acute Myeloid Leukemia Panel Members Margaret R. O’Donnell, MD/Chair ‡ City of Hope Comprehensive Cancer Center Frederick R. Appelbaum, MD † Þ Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Steven E. Coutre, MD Stanford Comprehensive Cancer Center Harry P. Erba, MD, PhD † University of Michigan Comprehensive Cancer Center � � � � ‡ Lloyd E. Damon, MD ‡ UCSF Helen Diller Family Comprehensive Cancer Center ‡ James Foran, MD † University of Alabama at Birmingham Comprehensive Cancer Center Salil Goorha, MD † St. Jude Children's Research Hospital/University of Tennessee Cancer Institute Jeffrey Lancet, MD ‡ † Þ H. Lee Moffitt Cancer Center and Research Institute Lori J. Maness, MD ‡ Þ UNMC Eppley Cancer Center at The Nebraska Medical Center Guido Marcucci, MD † Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University Peter G. Maslak, MD ‡ † Þ Memorial Sloan-Kettering Cancer Center ‡ Þ Joseph O. Moore, MD † Duke Comprehensive Cancer Center � Michael Millenson, MD Fox Chase Cancer Center Farhad Ravandi, MD ‡ The University of Texas M. D. Anderson Cancer Center Vanderbilt-Ingram Cancer Center Paul Shami, MD ‡ Huntsman Cancer Institute at the University of Utah B. Douglas Smith, MD † Þ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Richard M. Stone, MD ‡ Dana-Farber/Brigham and Women’s Cancer Center Stephen Strickland, MD ‡ Martin S. Tallman, MD ‡ Robert H. Lurie Comprehensive Cancer Center of Northwestern University Eunice Wang, MD ‡ Roswell Park Cancer Institute * ‡ Hematology/Hematology oncology † Medical oncology Þ Internal medicine � Bone Marrow Transplantation * Writing Committee Member ContinueNCCN Guidelines Panel Disclosures Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® Table of Contents NCCN Acute Myeloid Leukemia Panel Members Summary of Guidelines Updates Workup and Classification (AML-1 APL, Treatment Induction Guidelines Index Print the Acute Myeloid Leukemia Guideline ) (AML-2 APL, Post-Consolidation Therapy (AML-5) APL, Post-Remission Therapy (AML-6) AML, Treatment Induction Age < 60 y (AML-7 AML, Post-Induction Therapy (Standard-dose cytarabine) Age < 60 y (AML-8 AML, Post-Induction Therapy (High-dose cytarabine) Age < 60 y (AML-9 AML, Treatment Induction Age (AML-11 AML, Post-Induction Therapy (Standard-dose cytarabine) Age (AML-12 AML, Post-Remission Therapy (AML-13) AML, Surveillance (AML-14 AML, Relapse (AML-14 Evaluation and Treatment of CNS Leukemia (AML-A R S B C M (AML-B Supportive Care (AML-C Response Criteria for Acute Myeloid Leukemia (AML-D Monitoring During Therapy (AML-E ) ) ) ) ) ) ) ) ) ) ) ) ) 60 y 60 y isk tatus ased on ytogenetics and olecular Abnormalities � � These 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 these 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 makes no representations nor warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2009. Clinical Trials: Categories of Evidence and Consensus: NCCN The 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, All recommendations are Category 2A unless otherwise specified. See NCCN click here: nccn.org/clinical_trials/physician.html NCCN Categories of Evidence and Consensus For help using these documents, please click here Discussion References Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® Summary of the Guidelines updates UPDATES AML-1 � � � � � � � � CEBPA was added to the recommended molecular markers. “Consider” was removed from the recommendation. Footnote “e” is new to the page, describing the relationship of molecular abnormalities with prognosis and treatment decisions. The recommendation for HLA typing was modified to “except for patients with a major contraindication to HSCT.” A risk stratification based on WBC count, was added to assist with treatment selection for patients able to tolerate anthracyclines. Footnote “i” is new to the page clarifying that therapy-related APL is treated the same as primary APL. Footnote “l” provides the updated reference for the ATRA + arsenic regimen. Dose and schedule were added for the arsenic and ATRA regimen. Footnote “m” is new to the page, listing the option of gemtuzumab for patients with high risk disease at presentation or WBC > 30,000/mcL later during therapy. Footnote “p” is new to the page, providing evaluation and therapy recommendations in the rare event of an induction failure. AML-2 AML-3 AML-4 AML-4 AML-4 � � � � � � � � This is a new page to address the therapy options for patients with high risk disease, as defined by WBC count status. The NA Intergroup, APL 2000, and LPA 2005 regimens are listed as treatment options, in addition to a clinical trial. Footnotes “s”, “t”, and “u” provide references for the regimens. Footnote “r” was added to address patients with a high WBC (> 30,000), consider prophylactic dexamethasone to prevent differentiation syndrome. Footnote “v” was added describing induction failure is related to complications from APL and not disease progression. Also applies to Footnote “w” provides further description regarding the consolidation for the NA Intergroup trial. Footnote “x” was added to provide further guidance regarding the use of high dose cytarabine in consolidation, especially for patients not receiving IT chemotherapy. Footnote “y” was added to caution that dose adjustment of cytarabine may be needed for older patients and patients with renal dysfunction. Also applies to This is a new page to address the therapy options for patients with low risk disease, as defined by WBC count status. The APL 2000 and PETHEMA regimens are listed as treatment options, in addition to a clinical trial. Footnote “t” provides the reference for the regimens. Footnote “z” addresses treatment recommendations for patients who present with low/intermediate risk disease but develop high risk features during induction therapy. Footnote “aa” provides information regarding the NA Intergroup consolidation as compared to APL 2000 or PETHEMA. Footnote “bb” addresses the issue that ATRA may not have a benefit for patients with low risk disease. � � Summary of changes in the 1.2010 version of the Acute Myeloid Leukemia guidelines from the 1.2009 version include: Continued The 2.2010 version of the Acute Myeloid Leukemia guidelines represents the addition of the discussion section correspondent to the changes in the algorithm ( ).MS-1 Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® Summary of the Guidelines updates UPDATES Summary of changes in the 1.2010 version of the Acute Myeloid Leukemia guidelines from the 1.2009 version include: AML-5 AML-7 AML-8 AML-9 AML-12 AML-10 � � � � � � � � � Molecular remission documentation clarified as “after consolidation.” Footnote “ee” was added to provide further description to the role of maintenance therapy. ATRA was added as a possible treatment option in combination with arsenic trioxide. Footnote “hh” was added that references a trial which suggests that the addition of ATRA does not benefit over arsenic alone. Clinical trial was added a treatment option. Doses were listed for idarubicin and daunorubicin. Footnote “oo” is new to the page providing information regarding the daunorubicin dosing and a reference. Footnote “pp” was added describing other published regimens for patients with impaired cardiac function. Footnote “qq” - reference added. Sentence added that there are no data supporting a dose of more than 60 mg of daunorubicin or 12 mg of idarubicin with high-dose cytarabine. � � � � � � � � � � � Treatment recommendations for patients over age 60 are based on performance status. The separate category for patients over 75 was removed. For PS 0-2 with no adverse features and no poor-risk cytogenetics, the following treatment options were added: 5-azacytidine, decitabine, clofarabine. All with a category 2B designation. For PS 0-2 with adverse features, the following treatment options were added: 5-azacytidine, decitabine, clofarabine. All with a category 2B designation. For PS > 2: clinical trial, 5-azacytidine, decitabine were added. 5- azacytidine and decitabine are with a category 2B designation. Footnote “ccc” was modified by adding the following sentence, “The CR rates and 2 yr overall survival in patients between 60 and 65 treated with daunorubicin 90mg/m is also comparable to the outcome for idarubicin 12mg/m ; the higher dose daunorubicin did not benefit patients over age 65.” (Lowenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235-1248).” Footnote “eee” was added to advise that a response may not be evident before 3-4 cycles of treatment with hypomethylating agents. Footnote “fff” was added to highlight that clofarabine should be used in patients with normal renal function. Older patients with a CR, high-dose cytarabine was clarified for patients with “favorable molecular markers.” “Continue low intensity regimens every 4-6 weeks until progression” was added as a treatment option for patients not receiving cytarabine for induction treatment. Footnote “hhh” was added to consider HLA-typing for patients who are deemed strong candidates for allogeneic transplant. Footnote “iii” was added to recommend transplant in first remission, as opposed to holding donor until first relapse. 2 2 AML-6 AML-11 AML-13 and and The follow-up bone marrow was clarified as “7-10 d after induction completed” for standard induction and “7-14 d” for high-dose induction. Footnote “ss” was modified to “alternative donor” search “including cord blood.” � � � � � � � Footnote “ww” now includes “There is controversy regarding allogeneic transplant for FLT3-ITD only mutations in the absence of other poor prognostic features.” Footnote “yy” - reference added. Better-risk status - “maintenance therapy” with a category 2B was added as a treatment option. Treatment-related disease or poor-risk status - 1 to 2 cycles of high dose cytarabine-based consolidation followed by autologous HSCT was added as a treatment option. Footnote “bbb” - an additional statement was added noting that consolidation chemotherapy may be required to maintain remission while a sibling or alternative donor search is in progress. Continued Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® AML-14 AML-B AML-C 1 of 2 � � � � � The timeframe to assess response was changed from 6 months to 12 months. Salvage chemotherapy followed by matched sibling or alternative donor HSCT was added as a treatment option for patients over 60. Footnote “kkk” was added with options for salvage chemotherapy. Footnote “mmm” was added to clarify HSCT should be an option for patients in remission, otherwise it should be in the context of a clinical trial. Footnote “3” was clarified that if high dose cytarabine is used for induction chemotherapy, IT therapy can be deferred until completion of induction, since cytarabine crosses the blood brain barrier. AML-A AML-C 2 of 2 � � � � � Better-risk status: t(15;17) was added to the cytogenetics. Intermediate risk status: “Other abnormalities not listed with better- risk and poor-risk cytogenetics and molecular mutations” was changed to “Other non-defined.” “c-KIT in patients with t(8;21) or inv(16)” was changed to “t(8;21), inv(16), t(16;16): with c-KIT mutation.” Poor-risk status: Footnote “4” was modified to include the sentence “There is controversy as to whether FLT3-TKD mutations carry an equally poor prognosis.” The following was added to the Supportive Care section for AML: Posaconazole has been shown to significantly decrease fungal infections when compared to fluconazole. Outcomes with other azoles, such as voriconazole, echinocandins, or amphotericin B, may produce equivalent results. Azoles should not be given during anthracyline chemotherapy or gemcitabine, since azoles impair drug metabolism and can increase toxicity. Footnote “1” was added as a supporting reference. The following was added to the Supportive Care section for APL: Myeloid growth factors should not be used. �Clinical coagulopathy and overt bleeding: 150 mg/dL was added as the fibrinogen level to maintain with cryoprecipitate and fresh frozen plasma Summary of the Guidelines updates UPDATES Summary of changes in the 1.2010 version of the Acute Myeloid Leukemia guidelines from the 1.2009 version include: Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® 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. DIAGNOSIS Acute leukemia or chloroma a,b,c WORKUP CLASSIFICATION/STAIN ANALYSIS Appropriate therapy for acute lymphoblastic leukemia (ALL) Immunophenotyping (+) for 2 lymphoid markers and (+) for < 2 myeloid markers � g TdT (+) Immunophenotyping (+) for 2 myeloid markers and typically (+) for < 2 lymphoid markers or Myeloperoxidase (+) or Nonspecific esterase (+) or Butyrate esterase (+) � g Acute promyelocytic leukemia (APL) See Treatment Induction (AML-2) Acute myeloid leukemia (AML) See Treatment Induction (AML-7) � � � � � � � � � � � H&P CBC, platelets, differential, chemistry profile PT, PTT, fibrinogen Bone marrow with cytogenetics (mandatory) Immunophenotyping and cytochemistry Cardiac scan if prior cardiac history or prior anthracycline use or clinical symptoms which would raise concern about cardiac function Central venous access device of choice In patients with poor risk features who lack a sibling donor, consider early evaluation for alternative donor search d Evaluation for c-KIT, FLT3-ITD, NPM, and CEBPA mutations Lumbar puncture (LP), if symptomatic (category 2B for asymptomatic) HLA typing (except for patients with a major contraindication to HSCT) e f a b c The WHO classification defines acute leukemia as 20% blasts in the marrow or blood. Ongoing clinical trials for AML and high-risk MDS may continue to use FAB criteria of 30% blasts at least until completion of those trials. AML evolving from MDS (AML-MDS) is often more resistant to cytotoxic chemotherapy than AML which arises without antecedent hematologic disorder and may have a more indolent course. Some clinical trials designed for high-grade MDS may allow enrollment of patients with AML-MDS. Young adults may be eligible for pediatric trials with more intensive induction regimens and transplant options. Patients who present with isolated extramedullary disease (chloroma) should be treated with systemic therapy. Local therapy (surgery/RT) may be used for residual disease. � � AML patients should preferably be managed at experienced leukemia centers where clinical trials may be more available. d e Samples for both techniques should be taken at the time of initial sampling. Prioritization of these two complementary diagnostic procedures is left to the discretion of the pathology departments of the individual institutions. M0 can only be diagnosed by immunophenotyping. The role of immunophenotyping in detecting minimal residual disease is being evaluated. These molecular abnormalities are important for prognostication in a subset of patients (category 2A) and may guide therapeutic intervention (category 2B) ( ). If test is not available at your institution, consult pathology about preserving material from original diagnostic sample for future use at an outside reference lab after full cytogenetic data available. For patients with major neurologic signs or symptoms at diagnosis, appropriate imaging studies should be performed to detect meningeal disease, chloromas, or CNS bleeding. LP should be performed if no mass/lesion detected on imaging study. Screening LP should be considered at first remission for patients with M5 or M4 morphology or WBC > 100,000/mcL at diagnosis. When presented with rare cases not fitting this algorithm, consultation with an experienced hematopathologist is recommended. f g See AML-A See Evaluation and Treatment of CNS leukemia (AML-B). AML-1 Version 2.2010, 12/04/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index AML Table of Contents Discussion, ReferencesAcute Myeloid Leukemia Practice Guidelines in Oncology – v.2.2010NCCN ® 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. CLASSIFICATION TREATMENT INDUCTIONh,k APLh,i,j M3 morphology and (+) for t(15;17) by either cytogenetics or molecular testing; consider possibility of M3 variant h l q Three groups have published large trials with excellent outcomes. However to achieve the expected results, one needs to use th