HODGKIN S LYMPHOMA (HODGKIN S DISEASE) LYMPHOMAS GENERAL One f the mst curable and treatable malignancy Diverse grup f disrders Lymphma bilgy and management has led t several majr breakthrughs in cancer treatments Lymphma incidence is increasing Abut 79,000 new cases with 20,000 deaths frm lymphma in 2013 per ACS estimate HODGKIN S LYMPHOMA (HODGKIN S DISEASE) GENERAL Abut 10% f ttal lymphid neplasms B cell neplasm Characteristic cell is Sternberg Reed cell Disease spread is generally cntiguus Explratry lapartmy and splenectmy are n lnger used fr staging Over 75% f cases are ptentially cured INCIDENCE In United states f America: Abut 9200 cases annually (2013 estimate) Abut 1180 deaths annually(2013 estimate) RISK FACTORS AND ETIOLOGY Etilgy is unknwn Risk f HD is increased 3 fld in peple with histry f infectius mnnuclesis Risk is increased in AIDS mre extra ndal site invlvement and aggressive disease with pr utcmes In bne marrw transplant patients Increased incidence in wd wrkers, farmer and meat prcessrs N clear cut envirnmental factrs indentified. Assciatin with EB virus Risk f HD is increased 3 fld in peple with histry f infectius mnnuclesis PATHOGENESIS Abut half f Hdgkin ndes shw evidence f EBV DNA in Stenberg reed cells genme Summarized By Dr. Harmesh Naik 2013 update 1 P a g e
Nt all Hdgkin s cases are EBV psitive. PREVENTION STRATEGY Unknwn SCREENING Nt available SYMPTOMS / SIGNS Seen in yung patients Pain less lymphadenpathy Splenmegaly Fever, drenching night seats, weight lss, pruritus Pain in ndal area after alchl cnsumptin DIAGNOSIS Requires bipsy: Large atypical lymphblast surrunded by an infiltrate f inflammatry and accessry cells Sternberg Reed cells HISTOLOGY Sternberg Reed cells express CD 15 and CD 30 WHO classificatin: Classical Hdgkin s lymphma 95% f all cases Ndular sclersis: Abut 60% f classical Hdgkin s lymphma Anterir mediastinal mass at presentatin Mixed cellularity mre cmmn in men Abut 20% f classical Hdgkin s lymphma EBV genmic DNA seen in 60-70% f this subtype - Disseminated disease is mre cmmn Lymphcyte rich classic Hdgkin s lymphma Mre cmmn in elderly men and present at early stage Cells have feature similar t mantle cells Late relapses are less cmmn but mre cmmnly fatal when ccurs Lymphcyte depleted Less than 5% cases Mre cmmn in elder men and with HIV infectin Higher incidence f abdminal adenpathy, marrw invlvement and hepatsplenmegaly Ndular Lymphcyte predminant Hdgkin s lymphma -Abut 5% f ttal cases Large neplastic B cells (ppcrn cells)- negative fr CD 15 and CD 30 Typically seen in men with lcalized adenpathy stages I r II and slw prgressin and prlnged survival Summarized By Dr. Harmesh Naik 2013 update 2 P a g e
STAGING SYSTEM Ann Arbr staging Stage I: Invlvement f single lymph nde regin r lymphid structue Stage II: Invlvement f tw r mre lymph nde regins cnfined t same side f diaphragm Stage III: Invlvement f tw r mre lymph nde regins n bth sides f diaphargm Stage IV: Dissemintated disease (marrw, liver etc) Substages: A: Absence f B symtms; B: Presence f B symtms (fever ver 37*C n tw cassins nt related t infectin. unintended lss f mre than 10% bdy wieght within six mnths, drenching night sweats) E: Extra ndal site invlvement by direct extensin f a nde STAGING WORK UP AND OTHER TESTING Histry and physical examinatin Excisinal lymph nde bipsy with histlgy and immune phentype CBC diff, Liver enzyme testing, LDH, Sed rate Chest x-ray r CT chest CT abdmen and pelvis PET scan Bne marrw aspiratin and bipsy (if advanced stage r B symptms) Fertility preservatin evaluatin if applicable Pulmnary functin testing Cardiac ejectin fractin tests HIV testing Vaccinatin if splenectmy is planned r splenic RT is given PROGNOSTIC FACTORS: Internatinal prgnstic Scre (IPS) Age ver 45 years Male sex Stage 4 disease Serum albumin belw 4 Hemglbin belw 10.5 WBC ver 15000, Lymphcytes less than 600 r lymphcyte cunts less than 8% 5 year survival; Three r mre factrs: 55% Up t tw factrs: 74% IPS is nt perfect FDG PET scan after tw cycles f ABVD might be superir predictr than IPS FDG PET scan in Hdgkin s disease Summarized By Dr. Harmesh Naik 2013 update 3 P a g e
Used fr Initial staging T assess respnse t treatment T evaluate residual masses T predict risk f relapse after cmpletin f treatment Malignant cells ften cmprise nly a part f tumr mass s cnventinal imaging has limitatin in assessing respnse and residual disease size reductin is nt accurate predictr f respnse PET is functinal imaging tl TREATMENT Curable in majrity f patients despite advanced stage Cmbinatin chemtherapy is standard f care fr Classical Hdgkin s disease Number f curses f chemtherapy varies with stage Invlved field raditherapy is used fllwing shrt curse f chemtherapy in early stage Hdgkin s disease Rle f raditherapy is underging re-evaluatin. Invlved field raditherapy is cmmnly used in Lymphcyte predminant subtype which typically presents in lcalized stage THREE PROGNOSTIC GROUPING Early favrable Early unfavrable Late r advanced stage Early favrable Stage IA and IIA nn bulky favrable Shrt curse f chemtherapy (2-4 cycles ) fllwed by invlved field radiatin therapy (20 Gy) Cure rate f 90-95% Early unfavrable Stage I and II with bulky disease / Bulky disease : Mre than 10 cm size r mre than ne third f trans-thracic diameter Sed rate ver 50 Mre than three disease sites B symptms Extra ndal disease Six cycles f chemtherapy fllwed by invlved field Radiatin Augmented regimen Stanfrd V r BEACOPP is used by sme Advanced disease Stage III and IV Unfavrable features up t 30% are at risk f death ABVD is standard f care in United States Rle f cnslidatin RT in patients with stage III and IV disease remain cntrversial ABVD is mre effective and less txic than MOPP Full dse administratin withut delay, dse reductin r grwth factr is necessary t ptimize cure rates Summarized By Dr. Harmesh Naik 2013 update 4 P a g e
Stanfrd V and BEACOPP regimens are designed t reduce cumulative txicity f several drugs and t imprve utcmes BEACOPP regimen is used mre cmmnly in Eurpe Stanfrd V and BEACOPP regimens are awaiting cmparisns t ABVD MOPP: Develped in 1960s Rarely used nw - because f txicity Increased risk f acute myelid leukemia in survivrs RELAPSED HODGKIN S LYMPHOMA 10-20% patient d nt achieve CR r PR Anther 15-30% relapse after initial CR Treatment: Initial RT alne ABVD results in lng term disease free survival in 50-80% Initial ABVD Salvage secnd line regimens (ICE, CHLVPP r Gemcitabine based) are used 15% 5 year disease free survival High dse therapy and stem cell transplant Cnsidered standard fr patient with relapse wh remains sensitive t chemtherapy (in secnd CR) 5 year relapse free survival is 20-50% based n prgnstic factrs Likelihd f successful transplant is higher if ABVD was used as frnt line therapy rather than BEACOPP Rle f stem cell transplant in first CR remains cntrversial and nt yet prven Ndular Lymphcyte predminant Hdgkin s lymphma - treatment Early stage / lcalized Ndular Lymphcyte predminant Hdgkin s lymphma Invlved field RT is used fr early stage lcal disease Late relapses are cmmn Relapse/Recurrence after lcal RT: Can be treated with additinal RT (if utside radiatin field) r Single agent Rituximab (70-100% Respnse rate) Or with cmbinatin ABVD Disseminated Ndular Lymphcyte predminant Hdgkin s lymphma Generally it is treated with ABVD. Rituxan has been used successfully as well in sme situatins. SPECIAL SITUATIONS Residual masses after treatment Many patients with mediastinal and retr-peritneal disease have residual masses In many cases residual mass represents fibrsis PET scan can help differentiate between active tumr and fibrsis Regenerating thymus Regenerating thymus in yung patients may create cnfusin because f increasing size f mediastinal mass thymus can be psitive n PET scan Careful assessment is necessary in this situatin FOLLOW UP Summarized By Dr. Harmesh Naik 2013 update 5 P a g e
Purpse f lng term fllw up: T mnitr fr relapse T mnitr fr late effects f treatment T mnitr fr new primary cancer Late effects f treatment Myel-dysplasia RT alne r ABVD alne are generally assciated with lw risk Treatment related secndary leukemia ABVD: less than 1% risk f leukemia Secndary diffuse nn Hdgkin s lymphma : rate f 4-5% at 10 years Secndary cancers Slid tumr risk 2% at 10 years and 13% at 19 years abut 22% at 25 years RT is assciated with increased risk f breast cancer, lung cancer, sft tissue sarcma, melanma in irradiated fields Slid tumr risk after RT: 1% per year in smkers, 0.5% per year in nn smkers Breast cancers are ften bilateral start breast cancer and mammgram early Hypthyridism is cmmn after mantle filed RT seen in tw thirds Premature crnary artery disease risk is increased with Dxrubicin and mediastinal RT Pulmnary txicity is seen after Blemycin and mantle field RT Infertility: MOPP/ alkylatrs almst always cause lng term infertility ABVD has lw risk f lng term infertility Mdern RT may reduce risk f lng term txicity Aviding alkylatrs may reduce risk f late txicity PROGNOSIS Overall prgnsis is gd with treatment See abve under treatment sectin SAMPLE QUESTIONS Summarized By Dr. Harmesh Naik 2013 update 6 P a g e