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{{Diffuse large B cell lymphoma}}
{{Diffuse large B cell lymphoma}}


{{CMG}}
{{CMG}}; {{AE}} {{AHS}} {{AS}}  


==Overview==
==Overview==
Several subtypes of diffuse large B cell lymphoma have been identified, each having a different clinical presentation and prognosis. The IPI (INTERNTIONAL PROGNOSTIC INDEX) score is used in prognosis in clinical practice.
The prognosis of [[diffuse large B cell lymphoma]] ([[Diffuse large B cell lymphoma|DLBCL]]) depends on the [[Stage fright|stage]] of the disease. [[Diffuse large B cell lymphoma]] is associated with a 5 year survival rate ranging from 70% to more than 90% among children. There are several [[Biology|biologic]] factors a that are associated with the outcomes in patients with [[Diffuse large B cell lymphoma|DLBCL]]
==Prognosis==
==Prognosis==
Several subtypes of diffuse large B cell lymphoma have been identified, each having a different clinical presentation and prognosis. However, the usual treatment for each of these is [[chemotherapy]], often in combination with an antibody targeted at the tumour cells.The IPI score is used in prognosis in clinical practice.<ref>{{cite journal |doi=10.1056/NEJM199309303291402 |pmid=8141877 |title=A Predictive Model for Aggressive Non-Hodgkin's Lymphoma |journal=New England Journal of Medicine |volume=329 |issue=14 |pages=987–94 |year=1993 }}</ref>
Several subtypes of [[diffuse large B cell lymphoma]] have been identified, each having a different clinical presentation and [[prognosis]]. However, the usual treatment for each of these is [[chemotherapy]], often in combination with an [[antibody]] targeted at the [[tumor cells]]. The IPI (International Prognostic Index) score is used in prognosis in clinical practice.<ref>{{cite journal |doi=10.1056/NEJM199309303291402 |pmid=8141877 |title=A Predictive Model for Aggressive Non-Hodgkin's Lymphoma |journal=New England Journal of Medicine |volume=329 |issue=14 |pages=987–94 |year=1993 }}</ref><ref>Diffuse large B-cell lymphoma (DLBCL):ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up Annals of Oncology 26(Supplement 5):v116–v125,2015 doi:10.1093/annonc/mdv304</ref>
*Through these treatments, more than half of patients with diffuse large B cell lymphoma can be cured,<ref name="Akyurek2011">{{cite journal |doi=10.1002/cncr.27396 |pmid=22213394 |title=Prognostic significance ofMYC,BCL2, andBCL6rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab |journal=Cancer |volume=118 |issue=17 |pages=4173–83 |year=2012 |last1=Akyurek |first1=Nalan |last2=Uner |first2=Aysegul |last3=Benekli |first3=Mustafa |last4=Barista |first4=Ibrahim }}</ref> and overall survival for older adults at five years is around 58%.<ref name="Feugier2005">{{cite journal |doi=10.1200/JCO.2005.09.131 |pmid=15867204 |title=Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients with Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'Adulte |journal=Journal of Clinical Oncology |volume=23 |issue=18 |pages=4117–26 |year=2005 |last1=Feugier |first1=P. |last2=Van Hoof |first2=A |last3=Sebban |first3=C |last4=Solal-Celigny |first4=P |last5=Bouabdallah |first5=R |last6=Fermé |first6=C |last7=Christian |first7=B |last8=Lepage |first8=E |last9=Tilly |first9=H |last10=Morschhauser |first10=F |last11=Gaulard |first11=P |last12=Salles |first12=G |last13=Bosly |first13=A |last14=Gisselbrecht |first14=C |last15=Reyes |first15=F |last16=Coiffier |first16=B }}</ref>
 
{| class="wikitable"
! colspan="4" |INTERNATIONAL PROGNOSTIC INDEX (IPI)
|-
! colspan="2" |Interantional Prognostic Index
!
!Estimated 3 year Overall Survival (95% CI)
|-
| rowspan="5" |Risk Factors
| colspan="2" |Age >60 years
| rowspan="5" |
|-
| colspan="2" |Serum LDH >Normal
|-
| colspan="2" |Stage III-IV
|-
| colspan="2" |Performance Status 2-4
|-
| colspan="2" |Extranodal Sites >1
|-
|Risk categories
|Low
|0-1
|91(89-94)
|-
|
|Low Intermediate
|2
|81(73-86)
|-
|
|High Intermediate
|3
|65(58-73)
|-
|
|High
|4-5
|59(49-69)
|-
| colspan="4" |'''AGE ADJUSTED INTERNATIONAL PROGNOSTIC INDEX  (aaIPI) In Patients < or equal to 60 years'''
|-
| rowspan="3" |Risk Factors
| colspan="2" |Serum LDH >Normal
| rowspan="3" |
|-
| colspan="2" |Stage III-IV
|-
| colspan="2" |Performance Status 2-4
|-
|Risk Categories
|Low
|0
|98(96-100)
|-
|
|Low Intermediate
|1
|92(87-95)
|-
|
|High Intermediate
|2
| rowspan="2" |75(66-82)
|-
|
|High
|3
|}
 
*Through the treatments, more than half of patients with diffuse large B cell lymphoma can be cured<ref name="Akyurek2011">{{cite journal |doi=10.1002/cncr.27396 |pmid=22213394 |title=Prognostic significance ofMYC,BCL2, andBCL6rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab |journal=Cancer |volume=118 |issue=17 |pages=4173–83 |year=2012 |last1=Akyurek |first1=Nalan |last2=Uner |first2=Aysegul |last3=Benekli |first3=Mustafa |last4=Barista |first4=Ibrahim }}</ref> and overall survival for older adults at five years is around 58%.<ref name="Feugier2005">{{cite journal |doi=10.1200/JCO.2005.09.131 |pmid=15867204 |title=Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients with Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'Adulte |journal=Journal of Clinical Oncology |volume=23 |issue=18 |pages=4117–26 |year=2005 |last1=Feugier |first1=P. |last2=Van Hoof |first2=A |last3=Sebban |first3=C |last4=Solal-Celigny |first4=P |last5=Bouabdallah |first5=R |last6=Fermé |first6=C |last7=Christian |first7=B |last8=Lepage |first8=E |last9=Tilly |first9=H |last10=Morschhauser |first10=F |last11=Gaulard |first11=P |last12=Salles |first12=G |last13=Bosly |first13=A |last14=Gisselbrecht |first14=C |last15=Reyes |first15=F |last16=Coiffier |first16=B }}</ref>
*For children with diffuse large B-cell lymphomas, most studies have found 5-year survival rates ranging from about 70% to more than 90%.<ref name="cancer.org">http://www.cancer.org/Cancer/Non-HodgkinLymphomainChildren/OverviewGuide/non-hodgkin-lymphoma-in-children-overview-survival-rates{{full|date=April 2015}}</ref>
*For children with diffuse large B-cell lymphomas, most studies have found 5-year survival rates ranging from about 70% to more than 90%.<ref name="cancer.org">http://www.cancer.org/Cancer/Non-HodgkinLymphomainChildren/OverviewGuide/non-hodgkin-lymphoma-in-children-overview-survival-rates{{full|date=April 2015}}</ref>
*The Germinal-center subtype has the best prognosis, with 66.6% of treated patients surviving more than five years.<ref name="asco">http://abstract.asco.org/AbstView_114_99225.html{{full|date=April 2015}}{{dead link|date=April 2015}}</ref>
*The Germinal-center subtype has the best prognosis, with 66.6% of treated patients surviving more than five years.<ref name="asco">http://abstract.asco.org/AbstView_114_99225.html{{full|date=April 2015}}{{dead link|date=April 2015}}</ref>
*[[Lenalidomide]] has been recently shown to improve outcomes in the Non-germinal center subtype.<ref>{{cite journal |doi=10.1200/JCO.2014.55.5714 |pmid=25135992 |title=Lenalidomide Combined with R-CHOP Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study |journal=Journal of Clinical Oncology |volume=33 |issue=3 |pages=251–7 |year=2014 |last1=Nowakowski |first1=G. S. |last2=Laplant |first2=B. |last3=Macon |first3=W. R. |last4=Reeder |first4=C. B. |last5=Foran |first5=J. M. |last6=Nelson |first6=G. D. |last7=Thompson |first7=C. A. |last8=Rivera |first8=C. E. |last9=Inwards |first9=D. J. |last10=Micallef |first10=I. N. |last11=Johnston |first11=P. B. |last12=Porrata |first12=L. F. |last13=Ansell |first13=S. M. |last14=Gascoyne |first14=R. D. |last15=Habermann |first15=T. M. |last16=Witzig |first16=T. E. }}</ref>
*[[Lenalidomide]] has been recently shown to improve outcomes in the Non-germinal center subtype.<ref>{{cite journal |doi=10.1200/JCO.2014.55.5714 |pmid=25135992 |title=Lenalidomide Combined with R-CHOP Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study |journal=Journal of Clinical Oncology |volume=33 |issue=3 |pages=251–7 |year=2014 |last1=Nowakowski |first1=G. S. |last2=Laplant |first2=B. |last3=Macon |first3=W. R. |last4=Reeder |first4=C. B. |last5=Foran |first5=J. M. |last6=Nelson |first6=G. D. |last7=Thompson |first7=C. A. |last8=Rivera |first8=C. E. |last9=Inwards |first9=D. J. |last10=Micallef |first10=I. N. |last11=Johnston |first11=P. B. |last12=Porrata |first12=L. F. |last13=Ansell |first13=S. M. |last14=Gascoyne |first14=R. D. |last15=Habermann |first15=T. M. |last16=Witzig |first16=T. E. }}</ref>


INTERNTIONAL PROGNOSTIC INDEX <ref>{{cite web | title = Non-Hodgkin's Lymphomas (NCCN.org) | url = http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf }}</ref>
=== Biologic Factors Associated with Outcomes in Patients with DLBCL<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> ===
*ALL PATIENTS:
 
:*Serum LDH > normal
==== Cell-of-origin molecular classification ====
:*Performance status 2-4
 
:*Stage III or IV
* Various technologies ([[gene]] [[Array comparative genomic hybridization|array]], [[Digital Imaging and Communications in Medicine|digital]] [[Gene expression|expression]] [[profiling]], multiplex [[Reverse transcription polymerase chain reaction|RT-PCR]]–based methods)
:*Extranodal involvement >1 site
 
* [[ABC]] subtype is associated with poor [[prognosis]]
 
* ABC subtype may be associated with an increased risk of [[CNS]] [[relapse]]
 
==== Cell-of-origin IHC-based algorithms ====
 
* Various [[IHC]]-based [[Algorithm|algorithms]] to assign [[molecular]] subtype; most commonly the Hans [[Algorithm (medical)|algorithm]]
 
* Non-GCB subtype is associated with poor prognosis, although this is not confirmed in some studies
 
* Dichotomizes patients into GC and non-GCB subgroups and represents an approximation of [[molecular]] subtype as assessed by [[GEP]]


*INTERNATIONAL INDEX,
==== Double- or triple-hit rearrangement involving MYC and either BCL2 or BCL6 or both ====
*ALL PATIENTS
:* Low                0 or 1
:* Low intermediate    2
:* High intermediate    3
:* High              4 or 5


AGE-ADJUSTED INTERNATIONAL PROGNOSTIC INDEX
* [[Fluorescence in situ hybridization|FISH]] is used primarily in clinical practice; the use of break-apart probes is recommended; GEP-based assays may identify additional cases with double-hit signature undetected by [[Fluorescence in situ hybridization|FISH]] with similar [[Biological|biologic]] features and outcome
*PATIENTS <60 YEARS
* Double- or triple-hit cases are associated with poor [[prognosis]]; poor prognosis may be limited to cases in which the [[MYCBPAP (gene)|MYC]] [[Chromosomal translocation|translocation]] partner is an [[immunoglobulin]] [[gene]] locus
:*Stage III or IV
* Now classified by the [[World Health Organization|WHO]] as [[High-grade lymphoma|high-grade]] [[B-cell lymphoma]] with [[MYCBPAP (gene)|MYC]] and [[BCL2-like 1 (gene)|BCL2]] and/or [[BCL6]] rearrangements; majority of cases are GCB subtype; may benefit from more intensive therapies
:*Serum LDH > normal
:*Performance status 2-4


*INTERNATIONAL INDEX,  
==== MYC and BCL2 protein expression ====
*PATIENTS < 60 YEARS
 
:*Low/intermediate      1
* IHC measurement to estimate the percentage of cells expressing [[MYCBP|MYC]] or [[BCL2-like 1 (gene)|BCL2]] protein or both; 40% cutoff [[Threshold Limit Value|threshold]] for [[MYCBP|MYC]] and 50% for [[BCL2-like 1|BCL2]]
:*High/intermediate    2
* Double [[Gene expression|expression]] of [[MYCBP2|MYC]] and [[BCL2-like 1 (gene)|BCL2]] or expression of BCL2 alone is associated with worse prognosis
:*High                  3
* May have [[Prognosis|prognostic]] significance mainly in GCB-type [[Diffuse large B cell lymphoma|DLBCL]]; MYC-BCL2 double [[Expression of programmed death ligand-1 in donor hearts regulates chronic allograft rejection|expression]] may be associated with an increased risk of [[CNS]] [[relapse]]
 
==== Proliferation index ====
 
* IHC measurement of proliferation marker Ki67; no established cutoff threshold
* Higher [[proliferation]] may be associated with poorer [[prognosis]], although it has not consistently been shown to be an independent [[Prognosis|prognostic]] marker
* High [[proliferation]] rate (>80%) may increase suspicion that patient has [[High-grade lymphoma|high-grade]] [[B-cell lymphoma]] (with or without double- or triple-hit rearrangements)
 
==== TP53 ====
 
* [[Polymerase chain reaction|PCR]], [[NGS]], or gene array for detection of [[mutation]] or [[Deletion (genetics)|deletion]] of [[TP53]]
* [[TP53]] [[Mutation|mutations]] in the [[DNA-binding domain]] are associated with [[poor]] [[prognosis]]
* May [[Cluster (epidemiology)|cluster]] with a genetic subset of [[Diffuse large B cell lymphoma|DLBCL]]
 
==== CDKN2A ====
 
* Gene array, [[Fluorescence in situ hybridization|FISH]], or [[Polymerase chain reaction|PCR]] for detection of deletion of the [[CDKN2A]] locus or loss of the [[9p21]] region
* [[Deletion (genetics)|Deletion]] of the [[CDKN2A]] locus or loss of the 9p21 is associated with poor prognosis
* May [[Cluster (epidemiology)|cluster]] with some genetic subsets of [[Diffuse large B cell lymphoma|DLBCL]]
 
==== MHC class II ====
 
* IHC measurement of partial or complete loss of [[MHC class II]] [[Gene expression|expression]]
* Loss of [[Gene expression|expression]] of [[MHC class II]] may be associated with a poor [[prognosis]] (more frequent in non-GCB subtype)
* Primarily observed in primary [[mediastinal]] [[B-cell lymphoma]] and in tumors with [[EZH2]] [[Mutation|mutations]]
 
==== Lymphocyte count and lymphocyte:monocyte ratio ====
 
* Measured in [[peripheral blood]]; low [[lymphocyte]] count (<1×109/liter) or low lymphocyte:monocyte ratio (various cutoff [[thresholds]])
* Low [[lymphocyte]] count or low lymphocyte:monocyte ratio is associated with poor [[prognosis]]
* May have [[implications]] for immune-based therapies
 
==== Host genetics ====
 
* [[Single nucleotide polymorphism|Single]] [[nucleotide]] variation in 5q23.2 or 6q21 ([[Polymerase chain reaction|PCR]] or single [[nucleotide]] [[polymorphism]] array)
* [[Single-nucleotide polymorphism|Single]] [[nucleotide]] variation in 5q23.2 or 6q21 is associated with poor [[prognosis]]
* Further [[Investigational Device Exemption|investigation]] is needed
 
==Complications==
[[Complication (medicine)|Complications]] can be disease associated or treatment related. some of the complications included are<ref>{{Cite journal
| author = [[Yun Hwa Jung]], [[In Sook Woo]] & [[Chi Wha Han]]
| title = Clinical characteristics and outcomes in diffuse large B cell lymphoma patients aged 70 years and older: a single-center experience with a literature review
| journal = [[The Korean journal of internal medicine]]
| volume = 30
| issue = 5
| pages = 684–693
| year = 2015
| month = September
| doi = 10.3904/kjim.2015.30.5.684
| pmid = 26354063
}}</ref>:
 
*[[Infection]] (most commonly [[Pneumonia]] or [[Sepsis]]), that can lead to [[multiorgan failure]]
*[[Hepatic Failure]] (treatment Related)
*[[Gastrointestinal bleeding|Gastrointestinal Bleeding]] (disease-related)
*Disease [[Progression]] leading to [[Death-associated protein 6|death]]


==References==
==References==
{{reflist|2}}
{{reflist|2}}
 
[[Category:Needs content]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Types of cancer]]

Latest revision as of 06:10, 17 April 2021

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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 prognosis of diffuse large B cell lymphoma (DLBCL) depends on the stage of the disease. Diffuse large B cell lymphoma is associated with a 5 year survival rate ranging from 70% to more than 90% among children. There are several biologic factors a that are associated with the outcomes in patients with DLBCL

Prognosis

Several subtypes of diffuse large B cell lymphoma have been identified, each having a different clinical presentation and prognosis. However, the usual treatment for each of these is chemotherapy, often in combination with an antibody targeted at the tumor cells. The IPI (International Prognostic Index) score is used in prognosis in clinical practice.[1][2]

INTERNATIONAL PROGNOSTIC INDEX (IPI)
Interantional Prognostic Index Estimated 3 year Overall Survival (95% CI)
Risk Factors Age >60 years
Serum LDH >Normal
Stage III-IV
Performance Status 2-4
Extranodal Sites >1
Risk categories Low 0-1 91(89-94)
Low Intermediate 2 81(73-86)
High Intermediate 3 65(58-73)
High 4-5 59(49-69)
AGE ADJUSTED INTERNATIONAL PROGNOSTIC INDEX (aaIPI) In Patients < or equal to 60 years
Risk Factors Serum LDH >Normal
Stage III-IV
Performance Status 2-4
Risk Categories Low 0 98(96-100)
Low Intermediate 1 92(87-95)
High Intermediate 2 75(66-82)
High 3
  • Through the treatments, more than half of patients with diffuse large B cell lymphoma can be cured[3] and overall survival for older adults at five years is around 58%.[4]
  • For children with diffuse large B-cell lymphomas, most studies have found 5-year survival rates ranging from about 70% to more than 90%.[5]
  • The Germinal-center subtype has the best prognosis, with 66.6% of treated patients surviving more than five years.[6]
  • Lenalidomide has been recently shown to improve outcomes in the Non-germinal center subtype.[7]

Biologic Factors Associated with Outcomes in Patients with DLBCL[8]

Cell-of-origin molecular classification

  • ABC subtype may be associated with an increased risk of CNS relapse

Cell-of-origin IHC-based algorithms

  • Non-GCB subtype is associated with poor prognosis, although this is not confirmed in some studies
  • Dichotomizes patients into GC and non-GCB subgroups and represents an approximation of molecular subtype as assessed by GEP

Double- or triple-hit rearrangement involving MYC and either BCL2 or BCL6 or both

  • FISH is used primarily in clinical practice; the use of break-apart probes is recommended; GEP-based assays may identify additional cases with double-hit signature undetected by FISH with similar biologic features and outcome
  • Double- or triple-hit cases are associated with poor prognosis; poor prognosis may be limited to cases in which the MYC translocation partner is an immunoglobulin gene locus
  • Now classified by the WHO as high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; majority of cases are GCB subtype; may benefit from more intensive therapies

MYC and BCL2 protein expression

  • IHC measurement to estimate the percentage of cells expressing MYC or BCL2 protein or both; 40% cutoff threshold for MYC and 50% for BCL2
  • Double expression of MYC and BCL2 or expression of BCL2 alone is associated with worse prognosis
  • May have prognostic significance mainly in GCB-type DLBCL; MYC-BCL2 double expression may be associated with an increased risk of CNS relapse

Proliferation index

  • IHC measurement of proliferation marker Ki67; no established cutoff threshold
  • Higher proliferation may be associated with poorer prognosis, although it has not consistently been shown to be an independent prognostic marker
  • High proliferation rate (>80%) may increase suspicion that patient has high-grade B-cell lymphoma (with or without double- or triple-hit rearrangements)

TP53

CDKN2A

  • Gene array, FISH, or PCR for detection of deletion of the CDKN2A locus or loss of the 9p21 region
  • Deletion of the CDKN2A locus or loss of the 9p21 is associated with poor prognosis
  • May cluster with some genetic subsets of DLBCL

MHC class II

Lymphocyte count and lymphocyte:monocyte ratio

Host genetics

Complications

Complications can be disease associated or treatment related. some of the complications included are[9]:

References

  1. ↑ "A Predictive Model for Aggressive Non-Hodgkin's Lymphoma". New England Journal of Medicine. 329 (14): 987–94. 1993. doi:10.1056/NEJM199309303291402. PMID 8141877.
  2. ↑ Diffuse large B-cell lymphoma (DLBCL):ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up Annals of Oncology 26(Supplement 5):v116–v125,2015 doi:10.1093/annonc/mdv304
  3. ↑ Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim (2012). "Prognostic significance ofMYC,BCL2, andBCL6rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab". Cancer. 118 (17): 4173–83. doi:10.1002/cncr.27396. PMID 22213394.
  4. ↑ Feugier, P.; Van Hoof, A; Sebban, C; Solal-Celigny, P; Bouabdallah, R; Fermé, C; Christian, B; Lepage, E; Tilly, H; Morschhauser, F; Gaulard, P; Salles, G; Bosly, A; Gisselbrecht, C; Reyes, F; Coiffier, B (2005). "Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients with Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'Adulte". Journal of Clinical Oncology. 23 (18): 4117–26. doi:10.1200/JCO.2005.09.131. PMID 15867204.
  5. ↑ http://www.cancer.org/Cancer/Non-HodgkinLymphomainChildren/OverviewGuide/non-hodgkin-lymphoma-in-children-overview-survival-rates[full citation needed]
  6. ↑ http://abstract.asco.org/AbstView_114_99225.html[full citation needed][dead link]
  7. ↑ Nowakowski, G. S.; Laplant, B.; Macon, W. R.; Reeder, C. B.; Foran, J. M.; Nelson, G. D.; Thompson, C. A.; Rivera, C. E.; Inwards, D. J.; Micallef, I. N.; Johnston, P. B.; Porrata, L. F.; Ansell, S. M.; Gascoyne, R. D.; Habermann, T. M.; Witzig, T. E. (2014). "Lenalidomide Combined with R-CHOP Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study". Journal of Clinical Oncology. 33 (3): 251–7. doi:10.1200/JCO.2014.55.5714. PMID 25135992.
  8. ↑ 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).
  9. ↑ Yun Hwa Jung, In Sook Woo & Chi Wha Han (2015). "Clinical characteristics and outcomes in diffuse large B cell lymphoma patients aged 70 years and older: a single-center experience with a literature review". The Korean journal of internal medicine. 30 (5): 684–693. doi:10.3904/kjim.2015.30.5.684. PMID 26354063. Unknown parameter |month= ignored (help)


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