Diffuse large B cell lymphoma medical therapy: Difference between revisions

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===Chemotherapy===
===Chemotherapy===
Main treatment of Choice for DLBCL. [[Chemotherapy]] is administered intravenously and people receiving chemotherapy commonly have a ([[peripherally inserted central catheter]]) in their arm near the elbow or a surgically implanted medical port. It is most effective when it is administered multiple times over a period of months (e.g. every 3 weeks, over 6 to 8 cycles). Different regimens of Chemotherapy with different durations/Cycles are used depending on the stage of disease, age of patient  and prognsotic index. In general  
Main treatment of Choice for DLBCL. [[Chemotherapy]] is administered intravenously and people receiving chemotherapy commonly have a ([[peripherally inserted central catheter]]) in their arm near the elbow or a surgically implanted medical port. It is most effective when it is administered multiple times over a period of months (e.g. every 3 weeks, over 6 to 8 cycles). Different regimens of Chemotherapy with different durations/Cycles are used depending on the stage of disease, age of patient  and prognsotic index. In general  
*Patients with limited stage disease receive 3 cycles of therapy
*Patients with limited stage disease receive 3 cycles of therapy
*Patients with extensive disease 6 or 8 cycles of chemotherapy. In the United States, 6 cycles is the preferred approach rather than 8 cycles.
*Patients with extensive disease 6 or 8 cycles of chemotherapy. In the United States, 6 cycles is the preferred approach rather than 8 cycles.
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[[Radiation]] is often added in the treatment. It is used commonly after completing 3 cycles of treatment in limited stage disease. In extensive disease, after 6-8 cycles of chemotherapy, radiation can be used at the end of the treatment to areas of bulky involvement. Radiation therapy alone is not an effective treatment for this disease
[[Radiation]] is often added in the treatment. It is used commonly after completing 3 cycles of treatment in limited stage disease. In extensive disease, after 6-8 cycles of chemotherapy, radiation can be used at the end of the treatment to areas of bulky involvement. Radiation therapy alone is not an effective treatment for this disease


=== Stem Cell Transplantation ===
===Stem Cell Transplantation===
High dose Chemotherapy coupled with stem cell transplantation is sometimes used to treat patients whose disease is refractory or relapsed following initial chemotherapy. Most common is [[Autologous stem cell transplant]]  in which patients receive their own stem cells. Other option is [[Allogenic stem cell transplant]] in which patient will receive stem cells from a [[donor]]
High dose Chemotherapy coupled with stem cell transplantation is sometimes used to treat patients whose disease is refractory or relapsed following initial chemotherapy. Most common is [[Autologous stem cell transplant]]  in which patients receive their own stem cells. Other option is [[Allogenic stem cell transplant]] in which patient will receive stem cells from a [[donor]]


=== Regimens of Chemotherapy ===
===Regimens of Chemotherapy===
'''1) R-CHOP'''
'''1) R-CHOP'''
*Standard treatment is CHOP-R, also referred to as ''R-CHOP'', an improved form of [[CHOP]] with the addition of [[rituximab]] (Rituxan), which has increased the rates of complete responses for Diffuse large B cell lymphoma patients, particularly elderly patients.<ref name="pmid17105812">{{cite journal |doi=10.1182/blood-2006-08-038257 |pmid=17105812 |title=The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP |journal=Blood |volume=109 |issue=5 |pages=1857–61 |year=2007 |last1=Sehn |first1=L. H. |last2=Berry |first2=B. |last3=Chhanabhai |first3=M. |last4=Fitzgerald |first4=C. |last5=Gill |first5=K. |last6=Hoskins |first6=P. |last7=Klasa |first7=R. |last8=Savage |first8=K. J. |last9=Shenkier |first9=T. |last10=Sutherland |first10=J. |last11=Gascoyne |first11=R. D. |last12=Connors |first12=J. M. }}</ref><ref name="pmid27980306">{{cite journal| author=Miyazaki K| title=Treatment of Diffuse Large B-Cell Lymphoma. | journal=J Clin Exp Hematop | year= 2016 | volume= 56 | issue= 2 | pages= 79-88 | pmid=27980306 | doi=10.3960/jslrt.56.79 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27980306  }} </ref><ref name="cornelllymphoma">http://cornell-lymphoma.com/tag/dlbcl/{{full|date=April 2015}}</ref>
*Standard treatment is CHOP-R, also referred to as ''R-CHOP'', an improved form of [[CHOP]] with the addition of [[rituximab]] (Rituxan), which has increased the rates of complete responses for Diffuse large B cell lymphoma patients, particularly elderly patients.<ref name="pmid17105812">{{cite journal |doi=10.1182/blood-2006-08-038257 |pmid=17105812 |title=The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP |journal=Blood |volume=109 |issue=5 |pages=1857–61 |year=2007 |last1=Sehn |first1=L. H. |last2=Berry |first2=B. |last3=Chhanabhai |first3=M. |last4=Fitzgerald |first4=C. |last5=Gill |first5=K. |last6=Hoskins |first6=P. |last7=Klasa |first7=R. |last8=Savage |first8=K. J. |last9=Shenkier |first9=T. |last10=Sutherland |first10=J. |last11=Gascoyne |first11=R. D. |last12=Connors |first12=J. M. }}</ref><ref name="pmid27980306">{{cite journal| author=Miyazaki K| title=Treatment of Diffuse Large B-Cell Lymphoma. | journal=J Clin Exp Hematop | year= 2016 | volume= 56 | issue= 2 | pages= 79-88 | pmid=27980306 | doi=10.3960/jslrt.56.79 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27980306  }} </ref><ref name="cornelllymphoma">http://cornell-lymphoma.com/tag/dlbcl/{{full|date=April 2015}}</ref>
R-CHOP is a combination of one monoclonal antibody, 3 chemotherapy drugs and one steroid:<ref>{{cite journal |first1=Charles M. |last1=Farber |first2=Randy C. |last2=Axelrod |title=The Clinical and Economic Value of Rituximab for the Treatment of Hematologic Malignancies |journal=Contemporary Oncology |volume=3 |issue=1|year=2011 |url=http://www.onclive.com/publications/contemporary-oncology/2011/spring-2011/the-clinical-and-economic-value-of-rituximab-for-the-treatment-of-hematologic-malignancies}}</ref>
R-CHOP is a combination of one monoclonal antibody, 3 chemotherapy drugs and one steroid:<ref>{{cite journal |first1=Charles M. |last1=Farber |first2=Randy C. |last2=Axelrod |title=The Clinical and Economic Value of Rituximab for the Treatment of Hematologic Malignancies |journal=Contemporary Oncology |volume=3 |issue=1|year=2011 |url=http://www.onclive.com/publications/contemporary-oncology/2011/spring-2011/the-clinical-and-economic-value-of-rituximab-for-the-treatment-of-hematologic-malignancies}}</ref>
*[[Rituximab]] (Rituxan)  
 
*[[Cyclophosphamide]] (Cytoxan)  
*[[Rituximab]] (Rituxan)
*[[Doxorubicin]] (Hydroxydaunorubicin)  
*[[Cyclophosphamide]] (Cytoxan)
*[[Vincristine]] (Oncovin)  
*[[Doxorubicin]] (Hydroxydaunorubicin)
*[[Prednisone]]  
*[[Vincristine]] (Oncovin)
*[[Prednisone]]
 
'''2) R-ACVBP'''
'''2) R-ACVBP'''


Alternate Intensive immmunochemotherapy, which is a combination of:
Alternate Intensive immmunochemotherapy that is preferred in patients with an age-adjusted [[IPI]] score of 1. However, its clinically significant toxic [[Adverse effect (medicine)|adverse effects]] have limited its use. It is a combination of:
* Rituximab
 
* Doxorubicin
*[[Rituximab]]
* Cyclophosphamide
*[[Doxorubicin]]
* Vindesine
*[[Cyclophosphamide]]
* Bleomycin
*[[Vindesine]]
* Prednisone
*[[Bleomycin]]
*[[Prednisone]]
 
'''3) R-CHOEP'''
'''3) R-CHOEP'''
* Rituximab
* Cyclophosphamide
* Doxorubicin
* Vincristine
* etoposide
* Prednisolone


=== Age Based Treatment Approach: ===
*[[Rituximab]]
*[[Cyclophosphamide]]
*[[Doxorubicin]]
*[[Vincristine]]
*[[etoposide]]
*Prednisolone
 
<br />
===Age Based Treatment Approach:===


=== <u>'''Age less than or equal to 60 years'''</u>: ===
===Limited-Stage Disease (stage I or II disease, non-bulky and localized) with Age Younger Than 60 Years and Low IPI ( 0 )===


==== Non-Bulky Disease with aaPI Low ( 0 ) ====
*This represents about 30% of patients
* Six Cycles of R-CHOP given every 21 days<ref>Pfreundschuh M, Kuhnt E, Trumper L et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-celllymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011; 12: 1013–1022</ref>
*Those patients often have low-risk clinical features and a favorable outcome
* Radiotherapy Consolidation treatment has no proven benefit in patients with non bulky disease  
*Four Cycles of [[R-CHOP regimen|R-CHOP]] are enough<ref name="pmid33657296">{{cite journal| author=Sehn LH, Salles G| title=Diffuse Large B-Cell Lymphoma. | journal=N Engl J Med | year= 2021 | volume= 384 | issue= 9 | pages= 842-858 | pmid=33657296 | doi=10.1056/NEJMra2027612 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33657296  }}</ref>
*[[Radiation therapy|Radiotherapy]] [[Consolidation (medicine)|Consolidation]] treatment has no proven benefit in patients with non-bulky disease. It may cause late [[relapses]] and second [[Cancer|cancers]] <br />


==== non Bulky with aaPI Low-Intermediate risk ( 1 ) OR aaPI Low ( 0 ) with Bulky Disease ====
=== Patients Who Are Not Candidate For Standard Therapy  ===
* Six Cycles of R-CHOP given every 21 days plus Radiotherapy is recommended along with chemotherapy in this group
* Alteranative treatment can include intensive immunochemotherapy with [[R-ACVBP]]( Dose intensive Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin and Prednisone) with subsequent [[consolidation therapy]] and can improve survival. Radiotherapy is not recommended in this regimen<ref name="pmid22118442">{{cite journal| author=Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O et al.| title=Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. | journal=Lancet | year= 2011 | volume= 378 | issue= 9806 | pages= 1858-67 | pmid=22118442 | doi=10.1016/S0140-6736(11)61040-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22118442  }} </ref>.


==== Intermediate High risk or High Risk ( > or equal to 2 ) ====
* This represents about 20 to 25% of patients who are not candidates for the standard treatment such as [[R-CHOP regimen|R-CHOP]]
* No current standard therapy
* The etiology is poor fitness due to advanced [[Ageing|age]], [[heart disease]], or coexisting medical conditions
* Inclusion in Clinical Trial is recommended
* A detailed [[geriatric]] [[Assessment and Plan|assessment]] or simple functional testing can be helpful to recognize patients for whom a modified approach is required
* Eight cycles of R-CHOP given every 21 days is most frequently used therapy
* Patients with low [[functional status]] may benefit from dose-reduced regimens of [[R-CHOP regimen|R-CHOP]], such as [[R-mini-CHOP]]
* Intensive treatment with [[R-ACVBP]] or [[R-CHOEP-14 regimen|R-CHOEP]] is also used sometimes<ref name="pmid21546499">{{cite journal| author=Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G et al.| title=Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. | journal=Haematologica | year= 2011 | volume= 96 | issue= 8 | pages= 1136-43 | pmid=21546499 | doi=10.3324/haematol.2010.038109 | pmc=3148907 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21546499  }} </ref>
* To reduce the [[Adverse effect (medicine)|adverse effects]], a short prephase of [[glucocorticoids]], with or without [[vincristine]] can be useful for that purpose
* If there is a [[contraindication]] to [[anthracycline]], replacement with [[gemcitabine]] or [[etoposide]] is an option  <br />
 
=== Central Nervous System Prophylaxis ===
 
* [[Central nervous system]] (CNS) [[Recurrence quantification analysis|recurrence]] occurs in 3 to 5% of patients, with median survival of less than 6 months
* Risk factors:
* CNS-IPI risk model including the five IPI risk factors in addition to [[Kidney|renal]] or [[Adrenal gland|adrenal]] involvement, stratifies patients into risk categories, with 12% of patients having a high risk of CNS recurrence
* Double [[Gene expression|expression]] of [[MYCBP2|MYC]] and [[BCL2-like 1|BCL2]]
* ABC subtype
* [[Testicular]] involvement at the time of presentation
* The role of [[CNS]] prophylaxis is still [[controversial]]
* The use of [[Prophylaxis|prophylactic]] [[intrathecal]] [[chemotherapy]] is no longer recommended for [[Diffuse large B cell lymphoma|DLBCL]]  <br />
 
====non Bulky with aaPI Low-Intermediate risk ( 1 ) OR aaPI Low ( 0 ) with Bulky Disease====
 
*Six Cycles of R-CHOP given every 21 days plus Radiotherapy is recommended along with chemotherapy in this group
*Alteranative treatment can include intensive immunochemotherapy with [[R-ACVBP]]( Dose intensive Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin and Prednisone) with subsequent [[consolidation therapy]] and can improve survival. Radiotherapy is not recommended in this regimen<ref name="pmid22118442">{{cite journal| author=Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O et al.| title=Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. | journal=Lancet | year= 2011 | volume= 378 | issue= 9806 | pages= 1858-67 | pmid=22118442 | doi=10.1016/S0140-6736(11)61040-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22118442  }} </ref>.
 
====Intermediate High risk or High Risk ( > or equal to 2 )====
 
*No current standard therapy
*Inclusion in Clinical Trial is recommended
*Eight cycles of R-CHOP given every 21 days is most frequently used therapy
*Intensive treatment with [[R-ACVBP]] or [[R-CHOEP-14 regimen|R-CHOEP]] is also used sometimes<ref name="pmid21546499">{{cite journal| author=Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G et al.| title=Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. | journal=Haematologica | year= 2011 | volume= 96 | issue= 8 | pages= 1136-43 | pmid=21546499 | doi=10.3324/haematol.2010.038109 | pmc=3148907 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21546499 }} </ref>
 
===<u>Age 60-80 years</u>===
 
*Detailed Geriatric assessment should be done to assess co-morbidities and functional decline to decide upon the treatment of choice<ref name="pmid25491101">{{cite journal| author=Morrison VA, Hamlin P, Soubeyran P, Stauder R, Wadhwa P, Aapro M et al.| title=Diffuse large B-cell lymphoma in the elderly: impact of prognosis, comorbidities, geriatric assessment, and supportive care on clinical practice. An International Society of Geriatric Oncology (SIOG) expert position paper. | journal=J Geriatr Oncol | year= 2015 | volume= 6 | issue= 2 | pages= 141-52 | pmid=25491101 | doi=10.1016/j.jgo.2014.11.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25491101  }} </ref>
*Current Standard treatment is R-CHOP and include 8 Doses of Rituximab given every 21 days with 6-8 cycles of Combination Chemotherapy with CHOP<ref name="pmid20548096">{{cite journal| author=Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S et al.| title=Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. | journal=Blood | year= 2010 | volume= 116 | issue= 12 | pages= 2040-5 | pmid=20548096 | doi=10.1182/blood-2010-03-276246 | pmc=2951853 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20548096  }} </ref>
*Radiotherapy can improve outcome in patients in this age group with bulky disease<ref name="pmid24493716">{{cite journal| author=Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C et al.| title=Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. | journal=J Clin Oncol | year= 2014 | volume= 32 | issue= 11 | pages= 1112-8 | pmid=24493716 | doi=10.1200/JCO.2013.51.4505 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24493716 }} </ref>


=== <u>Age 60-80 years</u> ===
* Detailed Geriatric assessment should be done to assess co-morbidities and functional decline to decide upon the treatment of choice<ref name="pmid25491101">{{cite journal| author=Morrison VA, Hamlin P, Soubeyran P, Stauder R, Wadhwa P, Aapro M et al.| title=Diffuse large B-cell lymphoma in the elderly: impact of prognosis, comorbidities, geriatric assessment, and supportive care on clinical practice. An International Society of Geriatric Oncology (SIOG) expert position paper. | journal=J Geriatr Oncol | year= 2015 | volume= 6 | issue= 2 | pages= 141-52 | pmid=25491101 | doi=10.1016/j.jgo.2014.11.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25491101  }} </ref>
* Current Standard treatment is R-CHOP and include 8 Doses of Rituximab given every 21 days with 6-8 cycles of Combination Chemotherapy with CHOP<ref name="pmid20548096">{{cite journal| author=Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S et al.| title=Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. | journal=Blood | year= 2010 | volume= 116 | issue= 12 | pages= 2040-5 | pmid=20548096 | doi=10.1182/blood-2010-03-276246 | pmc=2951853 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20548096  }} </ref>
* Radiotherapy can improve outcome in patients in this age group with bulky disease<ref name="pmid24493716">{{cite journal| author=Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C et al.| title=Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. | journal=J Clin Oncol | year= 2014 | volume= 32 | issue= 11 | pages= 1112-8 | pmid=24493716 | doi=10.1200/JCO.2013.51.4505 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24493716  }} </ref>
A new development is obtaining a [[PET scan]] after completing two cycles of chemotherapy, to help make further decisions after chemotherapy.
A new development is obtaining a [[PET scan]] after completing two cycles of chemotherapy, to help make further decisions after chemotherapy.


=== <u>Age more than 80 years</u> ===
===<u>Age more than 80 years</u>===
* The elderly are usually unable to tolerate therapy well. Multiple lower intensity regimens have been attempted in this age group<ref>{{cite journal |doi=10.1080/10428190600799946 |pmid=17071492 |title=CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma |journal=Leukemia & Lymphoma |volume=47 |issue=10 |pages=2174–80 |year=2006 |last1=Zaja |first1=F. |last2=Tomadini |first2=V. |last3=Zaccaria |first3=A. |last4=Lenoci |first4=M. |last5=Battista |first5=M. |last6=Molinari |first6=A. L. |last7=Fabbri |first7=A. |last8=Battista |first8=R. |last9=Cabras |first9=M. G. |last10=Gallamini |first10=A. |last11=Fanin |first11=R. }}</ref>
 
* Attenuated Chemotherapy also known as [[R mini-CHOP]] is used and is associate with improved outcome in these patients<ref name="pmid21482186">{{cite journal| author=Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S et al.| title=Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. | journal=Lancet Oncol | year= 2011 | volume= 12 | issue= 5 | pages= 460-8 | pmid=21482186 | doi=10.1016/S1470-2045(11)70069-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21482186  }} </ref>
*The elderly are usually unable to tolerate therapy well. Multiple lower intensity regimens have been attempted in this age group<ref>{{cite journal |doi=10.1080/10428190600799946 |pmid=17071492 |title=CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma |journal=Leukemia & Lymphoma |volume=47 |issue=10 |pages=2174–80 |year=2006 |last1=Zaja |first1=F. |last2=Tomadini |first2=V. |last3=Zaccaria |first3=A. |last4=Lenoci |first4=M. |last5=Battista |first5=M. |last6=Molinari |first6=A. L. |last7=Fabbri |first7=A. |last8=Battista |first8=R. |last9=Cabras |first9=M. G. |last10=Gallamini |first10=A. |last11=Fanin |first11=R. }}</ref>
* In Patients with Cardiac Dysfunction, Doxorubicin can be replaced with other chemotherapeutic agents like [[Etoposide]], [[Gemcitabine]] or [[Liposomal doxorubicin]]<ref name="pmid24220559">{{cite journal| author=Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P et al.| title=De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. | journal=J Clin Oncol | year= 2014 | volume= 32 | issue= 4 | pages= 282-7 | pmid=24220559 | doi=10.1200/JCO.2013.49.7586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24220559  }} </ref>
*Attenuated Chemotherapy also known as [[R mini-CHOP]] is used and is associate with improved outcome in these patients<ref name="pmid21482186">{{cite journal| author=Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S et al.| title=Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. | journal=Lancet Oncol | year= 2011 | volume= 12 | issue= 5 | pages= 460-8 | pmid=21482186 | doi=10.1016/S1470-2045(11)70069-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21482186  }} </ref>
*In Patients with Cardiac Dysfunction, Doxorubicin can be replaced with other chemotherapeutic agents like [[Etoposide]], [[Gemcitabine]] or [[Liposomal doxorubicin]]<ref name="pmid24220559">{{cite journal| author=Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P et al.| title=De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. | journal=J Clin Oncol | year= 2014 | volume= 32 | issue= 4 | pages= 282-7 | pmid=24220559 | doi=10.1200/JCO.2013.49.7586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24220559  }} </ref>


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3)Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anila Hussain, MD [2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

The optimal therapy for diffuse large B cell lymphoma depends on the stage at diagnosis,age, IPI (International Prognostic Index) and aaIPI (Age adjusted International Prognostic index). The predominant therapy for diffuse large B cell lymphoma is chemotherapy. Adjunctive radiotherapy may be required. Inclusion in a clinical trial is recommended when available.

Medical Therapy

Chemotherapy

Main treatment of Choice for DLBCL. Chemotherapy is administered intravenously and people receiving chemotherapy commonly have a (peripherally inserted central catheter) in their arm near the elbow or a surgically implanted medical port. It is most effective when it is administered multiple times over a period of months (e.g. every 3 weeks, over 6 to 8 cycles). Different regimens of Chemotherapy with different durations/Cycles are used depending on the stage of disease, age of patient and prognsotic index. In general

  • Patients with limited stage disease receive 3 cycles of therapy
  • Patients with extensive disease 6 or 8 cycles of chemotherapy. In the United States, 6 cycles is the preferred approach rather than 8 cycles.

Radiation therapy

Radiation is often added in the treatment. It is used commonly after completing 3 cycles of treatment in limited stage disease. In extensive disease, after 6-8 cycles of chemotherapy, radiation can be used at the end of the treatment to areas of bulky involvement. Radiation therapy alone is not an effective treatment for this disease

Stem Cell Transplantation

High dose Chemotherapy coupled with stem cell transplantation is sometimes used to treat patients whose disease is refractory or relapsed following initial chemotherapy. Most common is Autologous stem cell transplant in which patients receive their own stem cells. Other option is Allogenic stem cell transplant in which patient will receive stem cells from a donor

Regimens of Chemotherapy

1) R-CHOP

  • Standard treatment is CHOP-R, also referred to as R-CHOP, an improved form of CHOP with the addition of rituximab (Rituxan), which has increased the rates of complete responses for Diffuse large B cell lymphoma patients, particularly elderly patients.[1][2][3]

R-CHOP is a combination of one monoclonal antibody, 3 chemotherapy drugs and one steroid:[4]

2) R-ACVBP

Alternate Intensive immmunochemotherapy that is preferred in patients with an age-adjusted IPI score of 1. However, its clinically significant toxic adverse effects have limited its use. It is a combination of:

3) R-CHOEP


Age Based Treatment Approach:

Limited-Stage Disease (stage I or II disease, non-bulky and localized) with Age Younger Than 60 Years and Low IPI ( 0 )

  • This represents about 30% of patients
  • Those patients often have low-risk clinical features and a favorable outcome
  • Four Cycles of R-CHOP are enough[5]
  • Radiotherapy Consolidation treatment has no proven benefit in patients with non-bulky disease. It may cause late relapses and second cancers

Patients Who Are Not Candidate For Standard Therapy

Central Nervous System Prophylaxis

non Bulky with aaPI Low-Intermediate risk ( 1 ) OR aaPI Low ( 0 ) with Bulky Disease

  • Six Cycles of R-CHOP given every 21 days plus Radiotherapy is recommended along with chemotherapy in this group
  • Alteranative treatment can include intensive immunochemotherapy with R-ACVBP( Dose intensive Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin and Prednisone) with subsequent consolidation therapy and can improve survival. Radiotherapy is not recommended in this regimen[6].

Intermediate High risk or High Risk ( > or equal to 2 )

  • No current standard therapy
  • Inclusion in Clinical Trial is recommended
  • Eight cycles of R-CHOP given every 21 days is most frequently used therapy
  • Intensive treatment with R-ACVBP or R-CHOEP is also used sometimes[7]

Age 60-80 years

  • Detailed Geriatric assessment should be done to assess co-morbidities and functional decline to decide upon the treatment of choice[8]
  • Current Standard treatment is R-CHOP and include 8 Doses of Rituximab given every 21 days with 6-8 cycles of Combination Chemotherapy with CHOP[9]
  • Radiotherapy can improve outcome in patients in this age group with bulky disease[10]

A new development is obtaining a PET scan after completing two cycles of chemotherapy, to help make further decisions after chemotherapy.

Age more than 80 years

  • The elderly are usually unable to tolerate therapy well. Multiple lower intensity regimens have been attempted in this age group[11]
  • Attenuated Chemotherapy also known as R mini-CHOP is used and is associate with improved outcome in these patients[12]
  • In Patients with Cardiac Dysfunction, Doxorubicin can be replaced with other chemotherapeutic agents like Etoposide, Gemcitabine or Liposomal doxorubicin[13]

.

References

  1. ↑ Sehn, L. H.; Berry, B.; Chhanabhai, M.; Fitzgerald, C.; Gill, K.; Hoskins, P.; Klasa, R.; Savage, K. J.; Shenkier, T.; Sutherland, J.; Gascoyne, R. D.; Connors, J. M. (2007). "The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP". Blood. 109 (5): 1857–61. doi:10.1182/blood-2006-08-038257. PMID 17105812.
  2. ↑ Miyazaki K (2016). "Treatment of Diffuse Large B-Cell Lymphoma". J Clin Exp Hematop. 56 (2): 79–88. doi:10.3960/jslrt.56.79. PMID 27980306.
  3. ↑ http://cornell-lymphoma.com/tag/dlbcl/[full citation needed]
  4. ↑ Farber, Charles M.; Axelrod, Randy C. (2011). "The Clinical and Economic Value of Rituximab for the Treatment of Hematologic Malignancies". Contemporary Oncology. 3 (1).
  5. ↑ Sehn LH, Salles G (2021). "Diffuse Large B-Cell Lymphoma". N Engl J Med. 384 (9): 842–858. doi:10.1056/NEJMra2027612. PMID 33657296 Check |pmid= value (help).
  6. ↑ Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O; et al. (2011). "Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial". Lancet. 378 (9806): 1858–67. doi:10.1016/S0140-6736(11)61040-4. PMID 22118442.
  7. ↑ Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G; et al. (2011). "Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA". Haematologica. 96 (8): 1136–43. doi:10.3324/haematol.2010.038109. PMC 3148907. PMID 21546499.
  8. ↑ Morrison VA, Hamlin P, Soubeyran P, Stauder R, Wadhwa P, Aapro M; et al. (2015). "Diffuse large B-cell lymphoma in the elderly: impact of prognosis, comorbidities, geriatric assessment, and supportive care on clinical practice. An International Society of Geriatric Oncology (SIOG) expert position paper". J Geriatr Oncol. 6 (2): 141–52. doi:10.1016/j.jgo.2014.11.004. PMID 25491101.
  9. ↑ Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S; et al. (2010). "Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte". Blood. 116 (12): 2040–5. doi:10.1182/blood-2010-03-276246. PMC 2951853. PMID 20548096.
  10. ↑ Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C; et al. (2014). "Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma". J Clin Oncol. 32 (11): 1112–8. doi:10.1200/JCO.2013.51.4505. PMID 24493716.
  11. ↑ Zaja, F.; Tomadini, V.; Zaccaria, A.; Lenoci, M.; Battista, M.; Molinari, A. L.; Fabbri, A.; Battista, R.; Cabras, M. G.; Gallamini, A.; Fanin, R. (2006). "CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma". Leukemia & Lymphoma. 47 (10): 2174–80. doi:10.1080/10428190600799946. PMID 17071492.
  12. ↑ Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S; et al. (2011). "Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial". Lancet Oncol. 12 (5): 460–8. doi:10.1016/S1470-2045(11)70069-9. PMID 21482186.
  13. ↑ Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P; et al. (2014). "De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial". J Clin Oncol. 32 (4): 282–7. doi:10.1200/JCO.2013.49.7586. PMID 24220559.


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