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 Table of Contents  
CLINICAL GUIDELINE
Year : 2019  |  Volume : 7  |  Issue : 3  |  Page : 231-233

Primary mediastinal large B-Cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up


1 Department of Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Central Region, Riyadh, Saudi Arabia
2 Department of Adult Hematology and BMT, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
3 Oncology Institute, John Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
4 Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
5 Department of Oncology, King Faisal Specialist Hospital and Research Centre, Jeddah; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
6 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences; Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, Jeddah, Saudi Arabia
7 Adult Hematology and Stem Cell Transplantation Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia
8 Medical Oncology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia; Clinical Oncology Department, Cairo University, Giza, Egypt

Date of Submission25-Mar-2019
Date of Decision12-May-2019
Date of Acceptance23-Jul-2019
Date of Web Publication28-Aug-2019

Correspondence Address:
Dr. Mubarak Al-Mansour
Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, PO Box 9515, Jeddah 21423
Saudi Arabia
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DOI: 10.4103/sjmms.sjmms_106_19

PMID: 31543751

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How to cite this article:
Alhejazi A, Motabi I, Sagheir A, Alzahrani M, Dada R, Al-Mansour M, Alhashmi H, Kandil M. Primary mediastinal large B-Cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up. Saudi J Med Med Sci 2019;7:231-3

How to cite this URL:
Alhejazi A, Motabi I, Sagheir A, Alzahrani M, Dada R, Al-Mansour M, Alhashmi H, Kandil M. Primary mediastinal large B-Cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up. Saudi J Med Med Sci [serial online] 2019 [cited 2019 Nov 22];7:231-3. Available from: http://www.sjmms.net/text.asp?2019/7/3/231/265641




  Introduction Top


Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL), accounting for 6%–10% of the cases. PMBL typically presents in women during the third to fourth decade of life.[1] However, its incidence in Saudi Arabia is yet unknown.


  Methods Top


A committee comprising experts in hematology and medical oncology was established under the supervision of the Saudi Lymphoma Group and in collaboration with the Saudi Oncology Society. For collecting evidence, a literature search was carried out with relevant keywords using online database search engines such as PubMed/Medline, Web of Science and Scopus. In addition, expert opinion was considered when necessary. The levels of evidence used in developing this guideline were as follows:

  • Evidence level (EL)-1 (highest), evidence from Phase III randomized trials or meta-analyses
  • EL-2 (intermediate), evidence from well-designed Phase II trials or Phase III trials with limitations
  • EL-3 (low), evidence from retrospective or observational studies/reports and/or expert opinion.


This easy-to-follow grading system is convenient for readers to understand and allows an accurate assessment of the guideline's applicability in individual patients.[2]

1. PATHOLOGIC DIAGNOSIS

1.1. The preferred method for establishing the diagnosis of PMBL is surgical biopsy either by excision of the involved lymph node or, if not possible, by mediastinoscopy or thoracoscopy (EL-3)[3],[4]

1.2. Fine needle aspirates or core biopsies may be non-diagnostic because of inadequate sample or presence of extensive necrosis, fibrosis or crush artifacts

1.3. PMBL usually arises from the thymus. This is composed of large cells with pale cytoplasm, variable nuclear features, Reed–Sternberg-like cells and sclerosis that may raise suspicion of Hodgkin lymphoma [5],[6],[7]

1.4. The tumor cells express B-cell antigens such as CD19, CD20, CD22, CD79a and CD45 and weak CD30 in >80% of cases.[1],[8],[9] These cells also frequently express other markers of Reed–Sternberg cells such as IRF4/MUM1.[10] Regarding the oncogenic abnormalities, a gain in chromosome 9p24 is seen in up to 75% of the cases. Immunoglobulin genes are rearranged but BCL-2, BCL-6 and MYC are rare or uncommon.[3],[9],[11]

2. DIAGNOSIS AND WORK-UP (EL-3)

2.1. Pathology review is essential for all potential cases

2.2. Evaluations should include complete history (i.e., age, gender; comorbidities; B-symptoms; Eastern Cooperative Oncology Group performance status; hepatitis or human immunodeficiency virus risk factors; medications; allergy to contrast media or drugs as well as social and family history) and physical examination (i.e., of lymph nodes, Waldeyer's ring, spleen, liver and skin)

2.3. Laboratory evaluations of all patients should include complete blood count (CBC) with differential count, liver and renal function test as well as routine blood chemistry including lactate dehydrogenase, electrolytes and calcium

2.4. Hepatitis serology tests (hepatitis B and C viruses) should be carried out

2.5. Computed tomography (CT) scan of neck and chest, abdomen and pelvis (CAP) should be performed in all cases

2.6. Bone marrow biopsy is recommended for staging

2.6. Cardiac function should be assessed by echocardiogram because pleural and pericardial effusions are common at presentation

2.7. Pregnancy test should be done for women of childbearing age

2.8. Although PET/CT is not part of the initial staging work up, it is a useful tool and surrogate test to guide the need for consolidation radiotherapy after six cycles of chemotherapy

2.9. Clinical staging should be based on the Lugano modification of Ann Arbor staging system.[12]

3. MANAGEMENT

3.1. Currently, there is no standard therapy for PMBL. In terms of radiotherapy use, there are concerns regarding its long-term toxicity, especially in young patients. Additional concerns are the optimal type and duration of chemoimmunotherapy and risk of relapse

3.2. Six cycles of CHOP-R 21 is the preferable chemotherapy for DLBCL at all stages of PMBL (EL-2)[13],[14]

3.3. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab) can be used for patients who wish to avoid radiation therapy, such as those aged <30 years and women with disease requiring irradiation of the breast tissue (EL-2)[15]

3.4. Management of patients with relapse is as follows:

3.4.1. Restaging is required including blood work, CT of neck and CAP as well as bone marrow biopsy

3.4.2. For all patients aged <60 years, management includes salvage chemotherapy with R-ESHAP (rituximab, etoposide, methylprednisolone, high-dose cytarabine and cisplatin) or R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) for a maximum of three cycles followed by high-dose chemotherapy and autologous stem cell transplant (EL-2)[16],[17]

3.4.3. Patients who are not transplant candidates could be treated with conventional chemotherapy, such as ESHAP and GDP, and with involved-field radiation therapy for symptomatic sites

3.4.4. Pembrolizumab can be used for patients who have relapsed after two or more prior lines of therapy (EL-3).[18]

4. FOLLOW UP (EL-3)

4.1. Every 3 months for 2 years, then every 6 months for 3 years, and then annually

4.2. History and physical examination should be documented in every visit

4.3. CBC with differential count, erythrocyte sedimentation rate and liver function test should be requested in every visit

4.4. Thyroid-stimulating hormone test should be carried out at least once annually if the patient had received radiotherapy to the neck

4.5. CT of neck and CAP is required every 6–12 months for first 2 years, and then based on the clinical presentation

4.6. Chest X-ray should be performed at each visit in the first 2 years, and then every other visit, especially for patients who previously had intrathoracic disease

4.7. Mammogram is required who received chest radiotherapy, beginning 10 years after diagnosis of lymphoma or when aged 40 years, whichever comes first

4.8. Annual influenza immunization is recommended.[19]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Swerdlow SH. Update on the WHO classification of malignant lymphomas. Pathology 2014;46:S2.  Back to cited text no. 1
    
2.
Jazieh AR, Saudi Lung Cancer Guidelines Committee. The lung cancer management guidelines 2012. J Infect Public Health 2012;5 Suppl 1:S4-10.  Back to cited text no. 2
    
3.
Martelli M, Ferreri A, Di Rocco A, Ansuinelli M, Johnson PW. Primary mediastinal large B-cell lymphoma. Crit Rev Oncol Hematol 2017;113:318-27.  Back to cited text no. 3
    
4.
Johnson PW, Davies AJ. Primary mediastinal B-cell lymphoma. Hematology Am Soc Hematol Educ Program 2008; 1349-58.  Back to cited text no. 4
    
5.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (IARC WHO Classification of Tumours). Revised 4th Edition. Lyon: International Agency for Research on Cancer; 2017.  Back to cited text no. 5
    
6.
Addis BJ, Isaacson PG. Large cell lymphoma of the mediastinum: A B-cell tumour of probable thymic origin. Histopathology 1986;10:379-90.  Back to cited text no. 6
    
7.
Lamarre L, Jacobson JO, Aisenberg AC, Harris NL. Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases. Am J Surg Pathol 1989;13:730-9.  Back to cited text no. 7
    
8.
Harris NL. Shades of gray between large B-cell lymphomas and Hodgkin lymphomas: Differential diagnosis and biological implications. Mod Pathol 2013;26 Suppl 1:S57-70.  Back to cited text no. 8
    
9.
Pileri SA, Gaidano G, Zinzani PL, Falini B, Gaulard P, Zucca E, et al. Primary mediastinal B-cell lymphoma: High frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins. Am J Pathol 2003;162:243-53.  Back to cited text no. 9
    
10.
De Mello CA, De Andrade VP, De Lima VC, Carvalho AL, Soares FA. Prognostic impact of MUM1 expression by immunohistochemistry on primary mediastinal large B-cell lymphoma. Leuk Lymphoma 2011;52:1495-503.  Back to cited text no. 10
    
11.
de Leval L, Ferry JA, Falini B, Shipp M, Harris NL. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: Evidence for derivation from germinal center B cells? Am J Surg Pathol 2001;25:1277-82.  Back to cited text no. 11
    
12.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol 2014;32:3059-68.  Back to cited text no. 12
    
13.
Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera international trial (MInT) group. Lancet Oncol 2011;12:1013-22.  Back to cited text no. 13
    
14.
Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: A phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 2013;381:1817-26.  Back to cited text no. 14
    
15.
Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 2013;368:1408-16.  Back to cited text no. 15
    
16.
Popat U, Przepiork D, Champlin R, Pugh W, Amin K, Mehra R, et al. High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: Mediastinal localization predicts for a favorable outcome. J Clin Oncol 1998;16:63-9.  Back to cited text no. 16
    
17.
Kuruvilla J, Pintilie M, Tsang R, Nagy T, Keating A, Crump M. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma 2008;49:1329-36.  Back to cited text no. 17
    
18.
Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood 2017;130:267-70.  Back to cited text no. 18
    
19.
Pedrazzoli P, Baldanti F, Donatelli I, Castrucci MR, Puglisi F, Silvestris N, et al. Vaccination for seasonal influenza in patients with cancer: Recommendations of the Italian Society of Medical Oncology (AIOM). Ann Oncol 2014;25:1243-7.  Back to cited text no. 19
    




 

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