Mediastinal gray-zone lymphoma

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Tarsheen Sethi, MD, MSCI
Yale University
New Haven, CT

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Note: Mediastinal gray-zone lymphome (MGZL) is considered intermediate between primary mediastinal B-cell lymphoma (PMBL) and nodular sclerosis Hodgkin lymphoma (NSHL). Given that it is treated more similarly to the non-Hodgkin lymphoma, it is included here.



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DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)


Study Evidence
Wilson et al. 2014 (NCI 93-C-0133MGZL) Phase 2

Note: this should be considered a substudy under the master protocol NCI 93-C-0133.

Targeted therapy

  • Rituximab (Rituxan) 375 mg/m2 IV once per cycle or 1 day before the start of EPOCH (depending on reference)


Glucocorticoid therapy

Supportive medications

21-day cycle for 6 to 8 cycles


  • Start cycle 1 as described above.
  • Obtain CBCs twice per week for nadir measurements.
  • If nadir ANC greater than 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • If nadir ANC less than 500/uL on 1 or 2 measurements, use same doses as last cycle.
  • If nadir ANC less than 500/uL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • And/or if nadir platelet count less than 25 x 109/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
  • Can start new cycle every 21 days if ANC greater than 1000/uL and platelets greater than 100 x 109/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.


  1. NCI 93-C-0133: Wilson WH, Pittaluga S, Nicolae A, Camphausen K, Shovlin M, Steinberg SM, Roschewski M, Staudt LM, Jaffe ES, Dunleavy K. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014 Sep 4;124(10):1563-9. Epub 2014 Jul 14. link to original article contains protocol link to PMC article PubMed

Relapsed or refractory

Brentuximab vedotin monotherapy

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Study Evidence
Jacobsen et al. 2015 (SGN35-012) Phase 2, <20 pts in this subgroup

This regimen was evaluated in patients with CD30+ non-Hodgkin lymphoma, as determined by immunohistochemistry.

Antibody-drug conjugate therapy

21-day cycles


  1. SGN35-012: Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. link to original article contains verified protocol PubMed NCT01421667