Revision as of 12:41, 29 October 2022

0 regimens on this page 0 variants on this page

Guidelines

"How I Treat"

2011: Lamy T, Loughran TP Jr. How I treat LGL leukemia. Blood. 2011 Mar 10;117(10):2764-74. link to original article link to PMC article PubMed

NCCN

NCCN Guidelines - T-cell Lymphomas - contains information about T-cell Large Granular Lymphocytic Leukemia

Initial therapy

Cyclophosphamide monotherapy

Regimen

Study	Evidence
Bareau et al. 2010	Retrospective

These are retrospective series, of which Bareau et al. 2010 is representative. The most common dose reported is 100 mg PO once per day; some authors mentions co-administration of steroids but details are not supplied.

Immunosuppressive therapy

Cyclophosphamide (Cytoxan) 50 to 100 mg PO once per day

Lamy et al. 2011 recommends that patients who are responding are continued on treatment for 6 to 12 months; patients who do not respond within 4 months of therapy are discontinued

References

Retrospective: Go RS, Li CY, Tefferi A, Phyliky RL. Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. Blood. 2001 Jul 15;98(2):483-5. link to original article PubMed
Retrospective: Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, Schleinitz N, Tournilhac O, Roussel M, Fest T, Lamy T. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica. 2010 Sep;95(9):1534-41. link to original article link to PMC article PubMed content property of HemOnc.org
Retrospective: Moignet A, Hasanali Z, Zambello R, Pavan L, Bareau B, Tournilhac O, Roussel M, Fest T, Awwad A, Baab K, Semenzato G, Houot R, Loughran TP Jr, Lamy T. Cyclophosphamide as a first-line therapy in LGL leukemia. Leukemia. 2014 May;28(5):1134-6. Epub 2013 Nov 27. link to original article link to PMC article PubMed

Methotrexate & Prednisone

Regimen

Study	Evidence
Loughran et al. 2014 (ECOG E5998)	Phase 2

Immunosuppressive therapy

Methotrexate (MTX) 10 mg/m²/day PO in divided doses once per day on days 1, 8, 15, 22
- Details not described in ECOG E5998; Lamy et al. 2011 divides the 10 mg/m² methotrexate dose into 5 mg/m² in the morning and 5 mg/m² in the evening
Prednisone (Sterapred) 1 mg/kg PO once per day for 30 days, then tapered off over 24 days (details not described)

28-day cycles

Subsequent treatment

Patients with PR: continue up to one year
Patients with CR: continue for one month past documented CR
Non-responders were transitioned to cyclophosphamide & prednisone

References

ECOG E5998: Loughran TP Jr, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, Hasanali Z, Bennett JM, Lazarus HM, Litzow MR, Evens AM, Mustjoki S, Tallman MS. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015 Apr;29(4):886-94. Epub 2014 Sep 13. link to original article contains dosing details in manuscript link to PMC article PubMed

Relapsed or refractory

Cyclophosphamide & Prednisone

Regimen

Study	Evidence	Efficacy
Loughran et al. 2014 (ECOG E5998)	Phase 2	ORR: 64% (95% CI, 35-87)

Note: Patients with PR continue up to one year; patients with CR continue for one month past documented CR.

Preceding treatment

Methotrexate & prednisone, with treatment failure

Immunosuppressive therapy

Cyclophosphamide (Cytoxan) 100 mg PO once per day
Prednisone (Sterapred) 1 mg/kg PO once per day for 30 days, then tapered off over 24 days (details not described)

28-day cycles (see note)

References

ECOG E5998: Loughran TP Jr, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, Hasanali Z, Bennett JM, Lazarus HM, Litzow MR, Evens AM, Mustjoki S, Tallman MS. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015 Apr;29(4):886-94. Epub 2014 Sep 13. link to original article contains dosing details in manuscript link to PMC article PubMed

Difference between revisions of "Staging page"

Revision as of 12:41, 29 October 2022

Contents

Guidelines

"How I Treat"

NCCN

Initial therapy

Cyclophosphamide monotherapy

Regimen

Immunosuppressive therapy

References

Methotrexate & Prednisone

Regimen

Immunosuppressive therapy

Subsequent treatment

References

Relapsed or refractory

Cyclophosphamide & Prednisone

Regimen

Preceding treatment

Immunosuppressive therapy

References

Navigation menu

Search

@@ Line 11: / Line 11: @@
 {{TOC limit|limit=3}}
 =Guidelines=
-==[http://www.esmo.org/ ESMO]==
-*'''2015:''' d'Amore et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Peripheral-T-Cell-Lymphomas Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 =="How I Treat"==
-* Tse E, Kwong YL. How I treat NK/T-cell lymphomas. Blood. 2013 Jun 20;121(25):4997-5005. Epub 2013 May 7. [http://www.bloodjournal.org/content/121/25/4997.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23652805 PubMed]
+*'''2011:''' Lamy T, Loughran TP Jr. How I treat LGL leukemia. Blood. 2011 Mar 10;117(10):2764-74. [http://www.bloodjournal.org/content/117/10/2764.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062292/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21190991 PubMed]
 ==[https://www.nccn.org/ NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas]
+*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas] - contains information about T-cell Large Granular Lymphocytic Leukemia
-=Untreated=
+=Initial therapy=
-==Cisplatin & RT {{#subobject:544d0b|Regimen=1}}==
+==Cyclophosphamide monotherapy {{#subobject:464f08|Regimen=1}}==
-Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:550baf|Variant=1}}===
+===Regimen {{#subobject:78c71b|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 33%"|Study
+!style="width: 25%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2009.23.8592 Kim et al. 2009 (CISL 2004-10-08)]
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#e0ecf4" |ORR: 83%
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-====Radiotherapy====
-*Concurrent [[External_beam_radiotherapy|radiation therapy]] to the primary tumor, 1.8 to 2 Gy fractions (median total dose: 40 Gy), given 5 times per week.
-'''4-week course'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#VIPD|VIPD]] consolidation, 3 to 5 weeks after the last dose of cisplatin
-</div></div>
-===References===
-#'''CISL 2004-10-08:''' Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS; Consortium for Improving Survival of Lymphoma. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed,  stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009 Dec 10;27(35):6027-32. [https://doi.org/10.1200/jco.2009.23.8592 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19884539 PubMed] NCT00418535
-==DEP & RT {{#subobject:d8a9eb|Regimen=1}}==
-DEP & RT: '''<u>D</u>'''examethasone, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:f93f37|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1111/ejh.12405 Tsai et al. 2014 (T1405)]
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#e0ecf4" |ORR: 81%
-|-
-|}
-''Dosing details not available in the abstract.''
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]]
-====Chemotherapy====
-*[[Etoposide (Vepesid)]]
-*[[Cisplatin (Platinol)]]
-'''28-day cycle for 2 cycles'''
-====Radiotherapy====
-*Concurrent [[External_beam_radiotherapy|radiation therapy]] to the primary tumor, 50.4 Gy in 28 fractions
-'''5.5-week course'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#VIPD|VIPD]] consolidation
-</div></div>
-===References===
-#'''T1405:''' Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015 Feb;94(2):130-7. Epub 2014 Oct 10. [https://doi.org/10.1111/ejh.12405 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24957163 PubMed] NCT00292695
-==DeVIC & RT {{#subobject:4b25e6|Regimen=1}}==
-DeVIC & RT: '''<u>De</u>'''xamethasone, '''<u>V</u>'''P-16 (Etoposide), '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:74ecfd|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2009.23.8295 Yamaguchi et al. 2009 (JCOG0211)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930955/ Bareau et al. 2010]
-|style="background-color:#91cf61"|Phase 2
+|style="background-color:#ffffbe"|Retrospective
-| style="background-color:#e0ecf4" |ORR: 81%
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''These are retrospective series, of which Bareau et al. 2010 is representative. The most common dose reported is 100 mg PO once per day; some authors mentions co-administration of steroids but details are not supplied.''
-====Glucocorticoid therapy, Dose Level I====
+====Immunosuppressive therapy====
-*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 3
+*[[Cyclophosphamide (Cytoxan)]] 50 to 100 mg PO once per day
-====Chemotherapy, Dose Level I====
+'''Lamy et al. 2011 recommends that patients who are responding are continued on treatment for 6 to 12 months; patients who do not respond within 4 months of therapy are discontinued'''
-*[[Etoposide (Vepesid)]] 67 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 3
-*[[Ifosfamide (Ifex)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
-*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup> IV over 30 minutes once on day 1
-====Glucocorticoid therapy, Dose Level II====
-*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 3
-====Chemotherapy, Dose Level II====
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 3
-*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
-*[[Carboplatin (Paraplatin)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day 1
-====Supportive therapy====
-*[[Filgrastim (Neupogen)]] (dose/route/schedule not specified) started for WBC count less than 2 x 10<sup>9</sup>/L or ANC less than 1000/uL; discontinued if WBC count greater than 5 x 10<sup>9</sup>/L.
-'''21-day cycle for 3 cycles'''
-====Radiotherapy====
-''Started simultaneously with the beginning of cycle 1 of chemotherapy''
-*Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following stage-based criteria:
-**Stage IE disease: 2 Gy fractions x 25 fractions (total dose: 50 Gy)
-**Stage IIE disease: 1.8 Gy fractions x 28 fractions (total dose: 50.4 Gy)
-'''5- to 6-week course'''
 </div></div>
 ===References===
-# '''JCOG0211:''' Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Ohshima K, Matsuno Y, Terauchi T, Nawano S, Ishikura S, Kagami Y, Hotta T, Oshimi K. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009 Nov 20;27(33):5594-600. [https://doi.org/10.1200/jco.2009.23.8295 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19805668 PubMed]
+# '''Retrospective:''' Go RS, Li CY, Tefferi A, Phyliky RL. Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. Blood. 2001 Jul 15;98(2):483-5. [http://www.bloodjournal.org/content/98/2/483.long link to original article] [https://pubmed.ncbi.nlm.nih.gov?term=11435321 PubMed]
-## '''Update:''' Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Hotta T, Tsukasaki K, Oshimi K. Concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: an updated analysis of the Japan clinical oncology group study JCOG0211. J Clin Oncol. 2012 Nov 10;30(32):4044-6. Epub 2012 Oct 8. [https://doi.org/10.1200/jco.2012.45.6541 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23045573 PubMed]
+# '''Retrospective:''' Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, Schleinitz N, Tournilhac O, Roussel M, Fest T, Lamy T. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica. 2010 Sep;95(9):1534-41. [http://www.haematologica.org/content/95/9/1534.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930955/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20378561 PubMed] content property of [http://hemonc.org HemOnc.org]
-==GELOX/RT {{#subobject:e51517|Regimen=1}}==
+# '''Retrospective:''' Moignet A, Hasanali Z, Zambello R, Pavan L, Bareau B, Tournilhac O, Roussel M, Fest T, Awwad A, Baab K, Semenzato G, Houot R, Loughran TP Jr, Lamy T. Cyclophosphamide as a first-line therapy in LGL leukemia. Leukemia. 2014 May;28(5):1134-6. Epub 2013 Nov 27. [https://doi.org/10.1038/leu.2013.359 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017255/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24280867 PubMed]
-GELOX/RT: '''<u>G</u>'''emcitabine, '''<u>L</u>'''-asparaginase, '''<u>O</u>'''xaliplatin, alternating with '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+==Methotrexate & Prednisone {{#subobject:9c0e17|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:ed4bb8|Variant=1}}===
+===Regimen {{#subobject:3bbb5|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1002/cncr.27752 Wang et al. 2012]
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#f7fcfd" |ORR: 96%
-|-
-|}
-''Note: total number of chemotherapy cycles was limited to 6.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, part 1====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 1 to 7
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for at least 2 cycles, followed by:'''
-====Radiotherapy====
-*[[External_beam_radiotherapy|IFRT]] to 56 Gy in 28 fractions, 5 fractions per week
-'''5.5-week course, followed within one week by:'''
-====Chemotherapy, part 2====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 1 to 7
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for up to 4 cycles'''
-</div></div>
-===References===
-# Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. Epub 2012 Jul 18. [https://doi.org/10.1002/cncr.27752 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22811078 PubMed]
-==LVP "Sandwich" {{#subobject:b50432|Regimen=1}}==
-LVP: '''<u>L</u>'''-asparaginase, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisolone
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:5a27c1|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1002/cncr.26629 Jiang et al. 2011]
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#e0ecf4" |ORR: 84%
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, part 1====
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
-====Glucocorticoid therapy, part 1====
-*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
-'''21-day cycle for 2 cycles, followed by:'''
-====Radiotherapy====
-*[[External beam radiotherapy]] to the nasal cavity and surrounding sinuses, 56 Gy in 28 fractions, once per day, five days per week
-'''5.5-week course, followed in one week by:'''
-====Chemotherapy, part 2====
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
-====Glucocorticoid therapy, part 2====
-*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
-'''21-day cycle for up to 4 cycles'''
-</div></div>
-===References===
-# Jiang M, Zhang H, Jiang Y, Yang Q, Xie L, Liu W, Zhang W, Ji X, Li P, Chen N, Zhao S, Wang F, Zou L. Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012 Jul 1;118(13):3294-301. Epub 2011 Dec 2. [https://doi.org/10.1002/cncr.26629 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22139825 PubMed]
-==MESA/RT {{#subobject:54b89d|Regimen=1}}==
-MESA/RT: '''<u>M</u>'''ethotrexate, '''<u>E</u>'''toposide, '''<u>S</u>'''teroid (dexamethasone), PEG-'''<u>A</u>'''-sparaginase alternating with '''<u>R</u>'''adiation '''<u>T</u>'''therapy
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:f98dcf|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763273/ Liang et al. 2016]
-|style="background-color:#91cf61"|Phase 2
-|style="background-color:#e0ecf4"|ORR: 87%
-|-
-|}
-''Note: this regimen also incorporates radiation, see text for details.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, part 1====
-*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
-*[[Pegaspargase (Oncaspar)]] 2500 IU/m<sup>2</sup> IM once on day 5
-====Glucocorticoid therapy, part 1====
-*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> IV once per day on days 2 to 5
-'''21-day cycle for at least 3 cycles, followed by:'''
-====Radiotherapy====
-*[[External_beam_radiotherapy|Radiation therapy]], 45 to 50 Gy in 25 fractions
-'''One course, followed by:'''
-====Chemotherapy, part 2====
-*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
-*[[Pegaspargase (Oncaspar)]] 2500 IU/m<sup>2</sup> IM once on day 5
-====Glucocorticoid therapy, part 1====
-*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> IV once per day on days 2 to 5
-'''21-day cycle for a maximum of 7 cycles'''
-</div></div>
-===References===
-# Liang R, Gao GX, Chen JP, Wang JS, Wang XM, Zeng Y, Bai QX, Zhang T, Yang L, Dong BX, Gu HT, Shu MM, Hao CX, Wang JH, Zhang N, Chen XQ. A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China. Hematol Oncol. 2017 Dec;35(4):619-629. Epub 2016 Oct 10. [https://doi.org/10.1002/hon.2325 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763273/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27723108 PubMed]
-==SMILE {{#subobject:eaf2e1|Regimen=1}}==
-SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:cfe666|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2011.35.6287 Yamaguchi et al. 2011]
-|style="background-color:#91cf61"|Phase 2
-|style="background-color:#e0ecf4"|ORR: 79%
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 2 to 4
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1
-*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 2 to 4
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 8, 10, 12, 14, 16, 18, 20
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 15 mg IV or PO every 6 hours on days 2 to 4, beginning 30 hours after completion of [[Methotrexate (MTX)]]
-*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV three times per day on days 2 to 4; first dose given together with [[Ifosfamide (Ifex)]], second dose given at 4 hours after start of [[Ifosfamide (Ifex)]], and third dose given 8 hours after start of [[Ifosfamide (Ifex)]]
-*[[Filgrastim (Neupogen)]] (dose not specified) IV or SC once per day, starting on day 6, given until WBC count greater than 5 x 10<sup>9</sup>/L
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] prophylaxis recommended
-'''28-day cycle for 2 cycles'''
-''After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.''
-</div></div>
-===References===
-# '''Phase 1:''' Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. [https://doi.org/10.1111/j.1349-7006.2008.00768.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18294294 PubMed] content property of [http://hemonc.org HemOnc.org]
-# Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R; NK-Cell Tumor Study Group. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011 Nov 20;29(33):4410-6. Epub 2011 Oct 11. [https://doi.org/10.1200/jco.2011.35.6287 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990393 PubMed]
-=Consolidation after upfront therapy=
-==VIPD {{#subobject:1de775|Regimen=1}}==
-VIPD: '''<u>V</u>'''P-16 (Etoposide), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin), '''<u>D</u>'''examethasone
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:76171b|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 !style="width: 25%"|Study
 !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/jco.2009.23.8592 Kim et al. 2009 (CISL 2004-10-08)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377298/ Loughran et al. 2014 (ECOG E5998)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|[https://doi.org/10.1111/ejh.12405 Tsai et al. 2014 (T1405)]
 |style="background-color:#91cf61"|Phase 2
 |-
 |}
-''Details here are from CISL 2004-10-08.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*CISL 2004-10-08: [[#Cisplatin_.26_RT|Cisplatin & concurrent RT]]
-*T1405: [[#DEP_.26_RT|DEP & concurrent RT]]
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Immunosuppressive therapy====
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 to 3
+*[[Methotrexate (MTX)]] 10 mg/m<sup>2</sup>/day PO in divided doses once per day on days 1, 8, 15, 22
-*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
+**Details not described in ECOG E5998; Lamy et al. 2011 divides the 10 mg/m<sup>2</sup> methotrexate dose into 5 mg/m<sup>2</sup> in the morning and 5 mg/m<sup>2</sup> in the evening
-*[[Cisplatin (Platinol)]] 33 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
+*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day for 30 days, then tapered off over 24 days (details not described)
-====Glucocorticoid therapy====
+'''28-day cycles'''
-*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 1 to 4
-====Supportive therapy====
-*[[Mesna (Mesnex)]] 240 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 3
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] given for grade 3 or 4 neutropenia
-'''21-day cycle for up to 3 cycles'''
-</div></div>
-===References===
-# '''CISL 2004-10-08:''' Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS; Consortium for Improving Survival of Lymphoma. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed,  stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009 Dec 10;27(35):6027-32. [https://doi.org/10.1200/jco.2009.23.8592 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19884539 PubMed] NCT00418535
-#'''T1405:''' Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015 Feb;94(2):130-7. Epub 2014 Oct 10. [https://doi.org/10.1111/ejh.12405 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24957163 PubMed] NCT00292695
-=Relapsed or refractory=
-==AspaMetDex {{#subobject:407753|Regimen=1}}==
-AspaMetDex: '''<u>Aspa</u>'''raginase, '''<u>Met</u>'''hotrexate, '''<u>Dex</u>'''amethasone
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:305a48|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[http://www.bloodjournal.org/content/117/6/1834.long Jaccard et al. 2011 (I05009)]
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#e0ecf4" |ORR: 78%
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IM once per day on days 2, 4, 6, 8
-*[[Methotrexate (MTX)]] by the following age-based criteria:
-**Age up to 70: 3000 mg/m<sup>2</sup> (route not specified) once on day 1
-**Older than 70: 2000 mg/m<sup>2</sup> (route not specified) once on day 1
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]] by the following age-based criteria:
-**Age up to 70: 40 mg PO once per day on days 1 to 4
-**Older than 70: 20 mg PO once per day on days 1 to 4
-====Supportive therapy====
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/route/schedule not specified) prophylaxis, discontinued during [[Methotrexate (MTX)]] administration
-*[[Valacyclovir (Valtrex)]] (dose/route/schedule not specified) prophylaxis
-*For [[Methotrexate (MTX)]]: alkaline hydration and [[Folinic acid (Leucovorin)]] rescue (dose/route/schedule not specified)
-'''21-day cycle for 3 cycles'''
 </div>
 <div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*See paper for details about further treatment
+*Patients with PR: continue up to one year
+*Patients with CR: continue for one month past documented CR
+*Non-responders were transitioned to [[#Cyclophosphamide_.26_Prednisone|cyclophosphamide & prednisone]]
 </div></div>
 ===References===
-# '''I05009:''' Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O; GELA; GOELAMS. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011 Feb 10;117(6):1834-9. [http://www.bloodjournal.org/content/117/6/1834.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21123825 PubMed] NCT00283985
+# '''ECOG E5998:''' Loughran TP Jr, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, Hasanali Z, Bennett JM, Lazarus HM, Litzow MR, Evens AM, Mustjoki S, Tallman MS. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015 Apr;29(4):886-94. Epub 2014 Sep 13. [https://doi.org/10.1038/leu.2014.298 link to original article]  '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377298/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25306898 PubMed]
-==AspaMetDex (Erwinaze) {{#subobject:402253|Regimen=1}}==
+=Relapsed or refractory=
-AspaMetDex: '''<u>Aspa</u>'''raginase, '''<u>Met</u>'''hotrexate, '''<u>Dex</u>'''amethasone
+==Cyclophosphamide & Prednisone {{#subobject:3cfd6b|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:308gy8|Variant=1}}===
+===Regimen {{#subobject:c27546|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
@@ Line 333: / Line 71: @@
 !style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[http://www.bloodjournal.org/content/117/6/1834.long Jaccard et al. 2011 (I05009)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377298/ Loughran et al. 2014 (ECOG E5998)]
 |style="background-color:#91cf61"|Phase 2
-| style="background-color:#e0ecf4" |ORR: 78%
+|ORR: 64% (95% CI, 35-87)
 |-
 |}
-''Note: this regimen is for patients with allergies to asparaginase.''
+''Note: Patients with PR continue up to one year; patients with CR continue for one month past documented CR.''
-<div class="toccolours" style="background-color:#b3e2cd">
+<div class="toccolours" style="background-color:#cbd5e8">
-====Chemotherapy====
+====Preceding treatment====
-*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 20,000 units/m<sup>2</sup> IM once per day on days 2, 4, 6, 8
+*[[#Methotrexate_.26_Prednisone|Methotrexate & prednisone]], with treatment failure
-*[[Methotrexate (MTX)]] by the following age-based criteria:
-**Age up to 70: 3000 mg/m<sup>2</sup> (route not specified) once on day 1
-**Older than 70: 2000 mg/m<sup>2</sup> (route not specified) once on day 1
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]] by the following age-based criteria:
-**Age up to 70: 40 mg PO once per day on days 1 to 4
-**Older than 70: 20 mg PO once per day on days 1 to 4
-====Supportive therapy====
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/route/schedule not specified) prophylaxis, discontinued during [[Methotrexate (MTX)]] administration
-*[[Valacyclovir (Valtrex)]] (dose/route/schedule not specified) prophylaxis
-*For [[Methotrexate (MTX)]]: alkaline hydration and [[Folinic acid (Leucovorin)]] rescue (dose/route/schedule not specified)
-'''21-day cycle for 3 cycles'''
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*See paper for details about further treatment
-</div></div>
-===References===
-# '''I05009:''' Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O; GELA; GOELAMS. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011 Feb 10;117(6):1834-9. [http://www.bloodjournal.org/content/117/6/1834.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21123825 PubMed] NCT00283985
-==L-Asparaginase, Vincristine, Prednisolone {{#subobject:1ba9b6|Regimen=1}}==
-LVP: '''<u>L</u>'''-asparaginase, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisolone
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:651a7|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1007/bf02983387 Yong et al. 2003]
-|style="background-color:#ffffbe"|Phase 2, <20 patients
-| style="background-color:#e0ecf4" |ORR: 83%
-|-
-|}
-''Regimen details are from a review article; original article is not available through PubMed''
-====Chemotherapy====
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
-====Glucocorticoid therapy====
-*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
-</div></div>
-===References===
-# Yong W, Zheng W, Zhang Y, Zhu J, Wei Y, Zhu D, Li J. L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol. 2003 Aug;78(2):163-7. [https://doi.org/10.1007/bf02983387 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12953813 PubMed]
-==SMILE {{#subobject:924b1a|Regimen=1}}==
-SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:aa2ac|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2011.35.6287 Yamaguchi et al. 2011]
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#e0ecf4" |ORR: 79%
-|-
-|}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Glucocorticoid therapy====
+====Immunosuppressive therapy====
-*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 2 to 4
+*[[Cyclophosphamide (Cytoxan)]] 100 mg PO once per day
-====Chemotherapy====
+*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day for 30 days, then tapered off over 24 days (details not described)
-*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1
+'''28-day cycles (see note)'''
-*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 2 to 4
-*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV once per day on days 8, 10, 12, 14, 16, 18, 20
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 15 mg IV or PO every 6 hours on days 2 to 4, beginning 30 hours after completion of [[Methotrexate (MTX)]]
-*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV three times per day on days 2 to 4; first dose given together with [[Ifosfamide (Ifex)]], second dose given at 4 hours after start of [[Ifosfamide (Ifex)]], and third dose given 8 hours after start of [[Ifosfamide (Ifex)]]
-*[[Filgrastim (Neupogen)]] (dose not specified) IV or SC once per day, starting on day 6, given until WBC count greater than 5 x 10<sup>9</sup>/L
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] prophylaxis recommended
-'''28-day cycle for 2 cycles'''
-''After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.''
 </div></div>
 ===References===
-# '''Phase 1:''' Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. [https://doi.org/10.1111/j.1349-7006.2008.00768.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18294294 PubMed] content property of [http://hemonc.org HemOnc.org]
+# '''ECOG E5998:''' Loughran TP Jr, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, Hasanali Z, Bennett JM, Lazarus HM, Litzow MR, Evens AM, Mustjoki S, Tallman MS. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015 Apr;29(4):886-94. Epub 2014 Sep 13. [https://doi.org/10.1038/leu.2014.298 link to original article]  '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377298/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25306898 PubMed]
-# Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R; NK-Cell Tumor Study Group. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011 Nov 20;29(33):4410-6. Epub 2011 Oct 11. [https://doi.org/10.1200/jco.2011.35.6287 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990393 PubMed]
+[[Category:Large granular lymphocytic leukemia regimens]]
-[[Category:Extranodal NK- and T-cell lymphoma, nasal type regimens]]
 [[Category:Disease-specific pages]]
 [[Category:T-cell lymphomas]]