Marginal zone lymphoma

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21 regimens on this page
22 variants on this page


Untreated, randomized data

Note: Untreated in this context implies chemotherapy-naive. Some patients in the following studies, especially those with gastric MALT, received H. pylori eradication therapy or radiation prior to chemotherapy.

BR

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BR: Bendamustine, Rituximab

Regimen

Study Evidence Comparator Efficacy
Flinn et al. 2014 (BRIGHT) Phase III R-CHOP
R-CVP 		Equivalent RR

Supportive medications:

  • Antiemetics, antipyretics, and antibiotics according to local standard of care
  • Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

28-day cycle x up to 8 cycles

References

  1. Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains verified protocol PubMed

Chlorambucil (Leukeran)

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Regimen #1

Study Evidence Comparator Efficacy
Leblond et al. 2012 (WM1) Phase III Fludarabine Decreased PFS

Supportive medications:

28-day cycles x up to 12 cycles

Regimen #2

Study Evidence Comparator Efficacy
Zucca et al. 2013 (IELSG-19) Phase III Chlorambucil & Rituximab Decreased EFS

Induction phase

42-day course of therapy

Stable disease & responders -> consolidation phase

28-day cycles x up to 4 cycles

References

  1. Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains verified protocol PubMed
  2. Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. link to original article contains verified protocol PubMed

Chlorambucil & Rituximab

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Regimen

Study Evidence Comparator Efficacy
Zucca et al. 2013 (IELSG-19) Phase III Chlorambucil Increased EFS

Induction phase

Stable disease & responders -> consolidation phase

28-day cycles x up to 4 cycles

References

  1. Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. link to original article contains verified protocol PubMed

Fludarabine (Fludara)

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Regimen

Study Evidence Comparator Efficacy
Leblond et al. 2012 (WM1) Phase III Chlorambucil Increased PFS
  • Fludarabine (Fludara) 40 mg/m2 (30 mg/m2 per day if older than 75 years old) PO once per day on days 1 to 5

Supportive medications:

28-day cycles x up to 6 cycles

References

  1. Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains verified protocol PubMed

R-CHOP

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: R-CHOP-21, CHOP-R

Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)

Regimen

Study Evidence Comparator Efficacy
Flinn et al. 2014 (BRIGHT) Phase III, <20 in this arm BR
R-CVP 		Equivalent RR

Supportive medications:

21-day cycle x up to 8 cycles

References

  1. Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains verified protocol PubMed

R-CVP

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R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

Study Evidence Comparator Efficacy
Flinn et al. 2014 (BRIGHT) Phase III, <20 in this arm BR
R-CHOP 		Equivalent RR

Supportive medications:

21-day cycle x up to 8 cycles

References

  1. Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains verified protocol PubMed

Untreated, non-randomized or retrospective data

Note: Untreated in this context implies chemotherapy-naive. Some patients in the following studies, especially those with gastric MALT, received H. pylori eradication therapy or radiation prior to chemotherapy.

Bortezomib (Velcade)

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Regimen

Study Evidence
Troch et al. 2009 Phase II

Supportive medications:

21-day cycles x up to 8 cycles

References

  1. Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. Epub 2009 Mar 31. link to original article contains verified protocol PubMed

Cladribine (Leustatin)

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Study Evidence
Jäger et al. 2002 Phase II

Regimen

Dose reductions:

  • "In case of a persisting nadir of the WBCs = 4.0 × 10^9/L (or neutrophils = 1.5 × 10^9/L) and/or the platelets = 100 × 10^9/L, the next treatment cycle was delayed by 1 week until achieving normal values and then treatment was administered at a reduced dose of 0.1 mg/kg body weight."

Supportive medications:

  • Not described

28-day cycles x 4 to 6 cycles

References

  1. Jäger G, Neumeister P, Brezinschek R, Hinterleitner T, Fiebiger W, Penz M, Neumann HJ, Mlineritsch B, DeSantis M, Quehenberger F, Chott A, Beham-Schmid C, Höfler G, Linkesch W, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol. 2002 Sep 15;20(18):3872-7. link to original article contains verified protocol PubMed

Cladribine & Rituximab

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Study Evidence
Troch et al. 2012 Phase II

Regimen

Supportive medications:

21-day cycles up to 6 cycles

References

  1. Troch M, Kiesewetter B, Willenbacher W, Willenbacher E, Zebisch A, Linkesch W, Fridrik M, Müllauer L, Greil R, Raderer M. Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie. Haematologica. 2013 Feb;98(2):264-8. Epub 2012 Sep 14. link to original article contains verified protocol PubMed

Fludarabine & Rituximab

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Regimen

Study Evidence
Salar et al. 2009 Phase II
  • Fludarabine (Fludara) 25 mg/m2 IV (or 40 mg/m2 PO) once per day on days 1 to 5
    • Patients with gastric lymphoma received the cycle 1 dose intravenously to guarantee drug absorption
  • Rituximab (Rituxan) 375 mg/m2 IV once on day 1

Dose reductions:

    • Patients >70 years old could receive Fludarabine (Fludara) at the above dose, but only once per day on days 1 to 3

Supportive medications:

28-day cycles for 4-6 cycles

References

  1. Salar A, Domingo-Domenech E, Estany C, Canales MA, Gallardo F, Servitje O, Fraile G, Montalbán C. Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Cancer. 2009 Nov 15;115(22):5210-7. link to orginal article contains verified protocol PubMed

Ibritumomab tiuxetan (Zevalin)

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Regimen

Study Evidence
Samaniego et al. 2014 Phase II, <20 patients reported

Dose reductions:

One course of therapy

References

  1. Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. link to original article contains verified protocol PubMed

Lenalidomide (Revlimid)

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Regimen

Study Evidence
Kiesewetter et al. 2012 Phase II, <20 patients reported

Supportive medications:

28-day cycle x up to 6 cycles

References

  1. Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica. 2013 Mar;98(3):353-6. doi: 10.3324/haematol.2012.065995. Epub 2012 Aug 16. link to orginal article contains verified protocol PubMed

Lenalidomide & Rituximab

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Regimen

Study Evidence
Fowler et al. 2014 Phase II

28-day cycles up to 12 cycles

References

  1. Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. link to original article contains protocol PubMed

MCP

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MCP: Mitoxantrone, Chlorambucil, Prednisolone

Regimen

Study Evidence
Wöhrer et al. 2003 Retrospective

28-day cycles x up to 8 cycles

References

  1. Retrospective: Wöhrer S, Drach J, Hejna M, Scheithauer W, Dirisamer A, Püspök A, Chott A, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP). Ann Oncol. 2003 Dec;14(12):1758-61. link to orginal article contains verified protocol PubMed

PCR

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PCR: Pentostatin, Cyclophosphamide, Rituximab

Regimen

Study Evidence
Samaniego et al. 2015 Phase II, <20 patients in this subgroup

Supportive medications:

21-day cycle x 6 cycles

References

  1. Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. link to original article contains verified protocol PubMed

Rituximab (Rituxan)

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Regimen

Study Evidence
Conconi et al. 2003 Phase II
Martinelli et al. 2005 Phase II

References

  1. Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. link to orginal article contains protocol PubMed content property of HemOnc.org
  2. Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. link to original article contains protocol PubMed

Relapsed/refractory, non-randomized or retrospective data

Bendamustine (Treanda)

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Regimen

Study Evidence
Kahl et al. 2010 Phase II, <20 patients reported

21-day cycle x 6 to 8 cycles

References

  1. Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a Multicenter Study. Cancer. 2010 Jan 1;116(1):106-14. link to original article contains verified protocol PubMed

Bortezomib (Velcade)

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Regimen #1

Study Evidence
Conconi et al. 2011 Phase II

Supportive medications:

  • No routine growth factors, antibiotic, or antiviral prophylaxis was given

21-day cycles x up to 6 cycles

Regimen #2

Study Evidence
Troch et al. 2009 Phase II

Supportive medications:

21-day cycles x up to 8 cycles

References

  1. Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. Epub 2009 Mar 31. link to original article contains verified protocol PubMed
  2. Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJ, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E; International Extranodal Lymphoma Study Group (IELSG). Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol. 2011 Mar;22(3):689-95. link to original article contains verified protocol PubMed

BR

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BR: Bendamustine, Rituximab

Regimen

Study Evidence
Rummel et al. 2005 Phase II, <20 patients reported

Pre-treatment phase

Cycle 1 is started 7 days after the first dose of rituximab

Main regimen=

28-day cycles x 5 cycles

References

  1. Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains protocol PubMed

Cladribine & Rituximab

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Regimen

Study Evidence
Troch et al. 2012 Phase II, <20 patients reported

Supportive medications:

21-day cycles up to 6 cycles

References

  1. Troch M, Kiesewetter B, Willenbacher W, Willenbacher E, Zebisch A, Linkesch W, Fridrik M, Müllauer L, Greil R, Raderer M. Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie. Haematologica. 2013 Feb;98(2):264-8. Epub 2012 Sep 14. link to original article contains verified protocol PubMed

Clarithromycin (Biaxin)

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Regimen

Study Evidence
Ferreri et al. 2015 (HD-K) Phase II

21-day cycle x 4 cycles

References

  1. Ferreri AJ, Sassone M, Kiesewetter B, Govi S, Scarfò L, Donadoni G, Raderer M. High-dose clarithromycin is an active monotherapy for patients with relapsed/refractory extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT): the HD-K phase II trial. Ann Oncol. 2015 Aug;26(8):1760-5. Epub 2015 May 1. link to original article contains verified protocol PubMed

Idelalisib (Zydelig)

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Regimen,

Study Evidence
Gopal et al. 2014 (DELTA) Phase II, <20 patients in this subgroup

Continued until progression, death, or unacceptable toxicity

References

  1. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma. N Engl J Med. 2014 Jan 22. link to original article contains verified protocol PubMed
    1. Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). ASH Annual Meeting 2014, Abstract 1708 link to abstract

Lenalidomide (Revlimid)

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Regimen

Study Evidence
Kiesewetter et al. 2012 Phase II, <20 patients reported

Supportive medications:

28-day cycle x up to 6 cycles

References

  1. Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica. 2013 Mar;98(3):353-6. doi: 10.3324/haematol.2012.065995. Epub 2012 Aug 16. link to orginal article contains verified protocol PubMed

Rituximab (Rituxan)

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Regimen

Study Evidence
Conconi et al. 2003 Phase II
Martinelli et al. 2005 Phase II

References

  1. Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. link to orginal article contains protocol PubMed
  2. Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. link to original article contains protocol PubMed
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