1 Non Non- Hodgkins Lymphomas Hodgkins Lymphomas Janet H. Van Cleave MSN, ACNP Janet H. Van Cleave MSN, ACNP-CS, AOCN CS, AOCN Acute Care Nurse Practitioner Acute Care Nurse Practitioner The Mount Sinai Medical Center of New York City The Mount Sinai Medical Center of New York City Doctoral Student, Yale University School of Nursing Doctoral Student, Yale University School of Nursing Non Non- Hodgkins Hodgkins Lympoma Lympoma Mr. L. is a 65 year old gentleman Mr. L. is a 65 year old gentleman Has enlarged cervical lymph node Has enlarged cervical lymph node Surgeons remove lymph node Surgeons remove lymph node Pathology shows small lymphocytic Pathology shows small lymphocytic lymphoma lymphoma Doctor recommends to watch and wait Doctor recommends to watch and wait Non Non- Hodgkins Lymphoma Hodgkins Lymphoma Mr. D is a 65 year old Mr. D is a 65 year old Has enlarged cervical lymph node Has enlarged cervical lymph node Surgeons remove lymph node Surgeons remove lymph node Shows Diffuse Large B Shows Diffuse Large B- cell Lymphoma cell Lymphoma Oncologist recommends R Oncologist recommends R- CHOP CHOP chemotherapy chemotherapy Non Non- Hodgkins Lymphomas Hodgkins Lymphomas Why are these two Why are these two patients treated patients treated differently? differently? Normal Maturation of Lymphocytes Normal Maturation of Lymphocytes Differentiation of healthy lymphocytes Differentiation of healthy lymphocytes Stem cells in bone marrow Stem cells in bone marrow Rearrangement of genes to form Rearrangement of genes to form immunoglobulin or T immunoglobulin or T- cell receptors cell receptors Exposure to antigen Exposure to antigen Large proliferating cells Large proliferating cells Hypermutation Hypermutation improves antigen specificity improves antigen specificity Hennessy et al., Lancet Oncology, 2004 Hennessy et al., Lancet Oncology, 2004 Non Non- Hodgkins Lymphoma Hodgkins Lymphoma Differentiation of healthy lymphocytes Differentiation of healthy lymphocytes Lymphocyte differentiation and maturation Lymphocyte differentiation and maturation Antigen profile determines B or T cell Antigen profile determines B or T cell B Cell: CD19, CD20, CD22, CD40, CD45, CD 79a B Cell: CD19, CD20, CD22, CD40, CD45, CD 79a T Cell: CD3, CD4, CD5, CD8, CD 45 T Cell: CD3, CD4, CD5, CD8, CD 45 Hennessy et al., Lancet Oncology, 2004 Hennessy et al., Lancet Oncology, 2004
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NonNon--Hodgkin�s LymphomasHodgkin�s Lymphomas
Janet H. Van Cleave MSN, ACNPJanet H. Van Cleave MSN, ACNP--CS, AOCNCS, AOCNAcute Care Nurse PractitionerAcute Care Nurse Practitioner
The Mount Sinai Medical Center of New York CityThe Mount Sinai Medical Center of New York CityDoctoral Student, Yale University School of Nursing Doctoral Student, Yale University School of Nursing
NonNon--Hodgkin�s Hodgkin�s LympomaLympoma
Mr. L. is a 65 year old gentlemanMr. L. is a 65 year old gentlemanHas enlarged cervical lymph nodeHas enlarged cervical lymph nodeSurgeons remove lymph nodeSurgeons remove lymph nodePathology shows small lymphocytic Pathology shows small lymphocytic lymphomalymphomaDoctor recommends to watch and waitDoctor recommends to watch and wait
NonNon--Hodgkin�s LymphomaHodgkin�s Lymphoma
Mr. D is a 65 year oldMr. D is a 65 year oldHas enlarged cervical lymph nodeHas enlarged cervical lymph nodeSurgeons remove lymph nodeSurgeons remove lymph nodeShows Diffuse Large BShows Diffuse Large B--cell Lymphomacell LymphomaOncologist recommends ROncologist recommends R--CHOP CHOP chemotherapychemotherapy
NonNon--Hodgkin�s LymphomasHodgkin�s Lymphomas
Why are these two Why are these two patients treated patients treated differently?differently?
Normal Maturation of LymphocytesNormal Maturation of Lymphocytes
Differentiation of healthy lymphocytesDifferentiation of healthy lymphocytes�� Stem cells in bone marrowStem cells in bone marrow�� Rearrangement of genes to form Rearrangement of genes to form
immunoglobulin or Timmunoglobulin or T-- cell receptorscell receptors�� Exposure to antigenExposure to antigen
Large proliferating cellsLarge proliferating cellsHypermutationHypermutation improves antigen specificityimproves antigen specificity
Hennessy et al., Lancet Oncology, 2004Hennessy et al., Lancet Oncology, 2004
NonNon--Hodgkin�s LymphomaHodgkin�s Lymphoma
Differentiation of healthy lymphocytesDifferentiation of healthy lymphocytes�� Lymphocyte differentiation and maturation Lymphocyte differentiation and maturation �� Antigen profile determines B or T cellAntigen profile determines B or T cell
B Cell: CD19, CD20, CD22, CD40, CD45, CD 79aB Cell: CD19, CD20, CD22, CD40, CD45, CD 79aT Cell: CD3, CD4, CD5, CD8, CD 45T Cell: CD3, CD4, CD5, CD8, CD 45
Hennessy et al., Lancet Oncology, 2004Hennessy et al., Lancet Oncology, 2004
DeathsDeaths�� Total: 19,410Total: 19,410�� Male: 10,390Male: 10,390�� Female: 9,020Female: 9,020�� 55thth most common cause of cancermost common cause of cancer--related deathsrelated deathsACS Cancer Society, 2004ACS Cancer Society, 2004
EpidemiologyEpidemiology
Slightly greater incidence in caucasian Slightly greater incidence in caucasian populationpopulationSlightly more common in menSlightly more common in menIncidence rises steadily with ageIncidence rises steadily with ageOne of the most common cancers One of the most common cancers between ages 20 and 40between ages 20 and 40Incidence nearly doubled between 1970 Incidence nearly doubled between 1970 and 1990and 1990
Freedman & Nadler (2003)Freedman & Nadler (2003)
Epidemiology and EtiologyEpidemiology and Etiology
Children: Burkitt, lymphoblastic, and Children: Burkitt, lymphoblastic, and diffuse large Bdiffuse large B--cell lymphomacell lymphomaAdult: Diffuse large BAdult: Diffuse large B--cell lymphomascell lymphomasFollicular and small lymphocytic lymphoma Follicular and small lymphocytic lymphoma increase with ageincrease with ageMost cases occur in people over age 50Most cases occur in people over age 50May be associated with immunodeficiencyMay be associated with immunodeficiency
MorphologyMorphologyCytogeneticsCytogenetics�� 7070--90% patients have chromosomal breakpoints90% patients have chromosomal breakpoints�� Translocations more commonTranslocations more common
Cell surface markersCell surface markersMolecular techniquesMolecular techniques�� Immunoglobulin and T cell receptor gene Immunoglobulin and T cell receptor gene
Classification SchemesClassification Schemes�� Evolved over 30 yearsEvolved over 30 years�� BasisBasis
Pattern of lymph node architecturePattern of lymph node architectureCytologic classification of neoplastic cellsCytologic classification of neoplastic cells
Revised European American classification Revised European American classification of lymphoid neoplasms (REAL)of lymphoid neoplasms (REAL)�� MorphologyMorphology�� ImmunophenotypeImmunophenotype�� GenotypeGenotype�� Clinical featuresClinical features
intestinal T cell lymphomaintestinal T cell lymphoma�� Anaplastic large cell lymphomasAnaplastic large cell lymphomasFreedman & Nadler (2003)Freedman & Nadler (2003)
Highly aggressive lymphomasHighly aggressive lymphomas�� Precursor T or B lymphoblastic Precursor T or B lymphoblastic
leukemia/lymphomaleukemia/lymphoma�� Burkitt and BurkittBurkitt and Burkitt--like lymphomalike lymphoma�� Adult TAdult T--cell leukemia/lymphoma (HTLVcell leukemia/lymphoma (HTLV--1+)1+)
Freedman & Nadler (2003)Freedman & Nadler (2003)
Staging: Ann Arbor Staging SystemStaging: Ann Arbor Staging System
Stage I Stage I �� Single lymph node or single Single lymph node or single extralymphatic organ/siteextralymphatic organ/siteStage II Two or more lymph node regions on Stage II Two or more lymph node regions on same side of diaphragm or localized same side of diaphragm or localized involvement of extralymphatic siteinvolvement of extralymphatic siteStage III Involvement on both sides of Stage III Involvement on both sides of diaphragmdiaphragmStage IV Diffuse or disseminated involvement Stage IV Diffuse or disseminated involvement one or more extralymphatic organsone or more extralymphatic organsAJCC Cancer Staging Manual (2002)AJCC Cancer Staging Manual (2002)
Staging Staging Staging in NonStaging in Non--hodgkin�s Lymphomas has less hodgkin�s Lymphomas has less impact on decisionsimpact on decisionsPrognosis depends more on histology and Prognosis depends more on histology and clinical parametersclinical parameters�� AgeAge�� Extranodal diseaseExtranodal disease�� Performance statusPerformance status�� Ann arbor stagingAnn arbor staging�� LDHLDHNCCN (2004)NCCN (2004)
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Adverse Risk FactorsAdverse Risk Factors
Age >60Age >60Serum LDH > 1 X normalSerum LDH > 1 X normalECOG performance status 2ECOG performance status 2--44Ann Arbor Stage III or IVAnn Arbor Stage III or IVExtranodal involvement > 1 siteExtranodal involvement > 1 site
Stage I/IIStage I/II�� Radiation therapyRadiation therapy�� Benefit of chemotherapy in stage I/II indolent NHL Benefit of chemotherapy in stage I/II indolent NHL
Based on Diffuse Large BBased on Diffuse Large B--Cell Lymphoma Cell Lymphoma (DLBCL) guidelines(DLBCL) guidelinesApproximately ~40% cured with induction Approximately ~40% cured with induction chemotherapychemotherapyRR--CHOP standard treatmentCHOP standard treatment�� Radiotherapy in local diseaseRadiotherapy in local disease�� Number of cycles dependent on stage and size of Number of cycles dependent on stage and size of
massesmassesConsider clinical trial for highConsider clinical trial for high--intermediate/high intermediate/high risk categoriesrisk categories
NCCN (2004)NCCN (2004)
Treatment: Aggressive Treatment: Aggressive Lymphomas in Older PatientsLymphomas in Older Patients
Age over 60 in low and lowAge over 60 in low and low--intermediate intermediate risk prognostic group risk prognostic group �� Lower relapseLower relapse--free and overall survival ratesfree and overall survival rates�� ?less intensive regimens?less intensive regimens�� RR--CHOP chemotherapy improved survival CHOP chemotherapy improved survival
Chemotherapy resistant and aggressive diseaseChemotherapy resistant and aggressive diseaseMedian survival 3 Median survival 3 �� 4 years4 yearsNo standard treatmentNo standard treatmentChemotherapy regimens used Chemotherapy regimens used �� RituxanRituxan--CHOP CHOP �� RR--HyperCVADHyperCVAD�� RR--EPOCHEPOCH�� Autologous or allogeneic stem cell transplantation in clinical tAutologous or allogeneic stem cell transplantation in clinical trialrial
Needs further studyNeeds further studyNCCN (2004)NCCN (2004)
Marginal Zone LymphomaMarginal Zone LymphomaHeterogeneous groupHeterogeneous groupGastric versus Gastric versus nongastricnongastricGastric associated with helicobacter pyloriGastric associated with helicobacter pyloriGastric treatmentGastric treatment�� Stage I/II: AntibioticStage I/II: Antibiotic�� Advanced stage: similar to indolent lymphomaAdvanced stage: similar to indolent lymphoma
NongastricNongastric treatmenttreatment�� Stage I/II: Surgery, Radiation therapyStage I/II: Surgery, Radiation therapy�� Advanced: similar to follicular lymphomaAdvanced: similar to follicular lymphomaNCCN (2004)NCCN (2004)
Treatment: High Grade Treatment: High Grade LymphomasLymphomas
Burkitt�s and Burkitt�s Like LymphomaBurkitt�s and Burkitt�s Like Lymphoma�� Intensive short course chemotherapy in clinical trial Intensive short course chemotherapy in clinical trial
setting or combination chemotherapy with alkylating setting or combination chemotherapy with alkylating agents, anthracycline, intrathecal chemotherapy and agents, anthracycline, intrathecal chemotherapy and high dose methotrexatehigh dose methotrexate
Low survival rate with conventional salvage Low survival rate with conventional salvage chemotherapychemotherapyAllogeneic stem cell transplantationAllogeneic stem cell transplantationAutologous stem cell transplantationAutologous stem cell transplantation�� Poor disease free survival in chemo resistant diseasePoor disease free survival in chemo resistant disease�� Poor survival in > 0 IPI prognostic risk factorsPoor survival in > 0 IPI prognostic risk factors
Freedman & Nadler (2003)Freedman & Nadler (2003)
New Therapeutic ApproachesNew Therapeutic Approaches
New Therapeutic ApproachesNew Therapeutic Approaches
Dose dense chemotherapy (biweekly Dose dense chemotherapy (biweekly CHOP) in aggressive lymphoma age> 60 CHOP) in aggressive lymphoma age> 60 years with GCSF supportyears with GCSF support�� Improved 5 year eventImproved 5 year event--free and overall free and overall
New Therapeutic ApproachesNew Therapeutic Approaches
Patients aged 18 to 60 years with good Patients aged 18 to 60 years with good prognosis aggressive lymphomas w/ prognosis aggressive lymphomas w/ GCSF supportGCSF support�� CHOP chemotherapy with etoposide achieved CHOP chemotherapy with etoposide achieved
RituximabRituximab�� ChimericChimeric IgG1 anti CD20 monoclonal IgG1 anti CD20 monoclonal
antibodyantibody�� First monoclonal antibody approved by FDAFirst monoclonal antibody approved by FDA�� Proposed mechanisms of actionProposed mechanisms of action
AntibodyAntibody--dependent cellular dependent cellular cytotoxicitycytotoxicityComplementComplement--mediated mediated cytotoxicitycytotoxicityInduction of apoptosisInduction of apoptosisRecruitment of Recruitment of effectoreffector cellscellsCytokinesCytokines
Newer usesNewer uses�� Combine with various chemotherapeutic Combine with various chemotherapeutic
agentsagents�� Combination uses in transplantation regimensCombination uses in transplantation regimens�� Use with other Use with other immunomodulatoryimmunomodulatory agentsagents
ChesonCheson, Seminars in Oncology, 2002, Seminars in Oncology, 2002
DosimetricDosimetric dosedoseNext week Next week dosimetricdosimetric dose followed by dose followed by tositumomabtositumomabOverall response rate 65% c/w 28% for last prior Overall response rate 65% c/w 28% for last prior chemochemoHematologic toxicitiesHematologic toxicitiesEvaluated in clinical trials for transplant settingEvaluated in clinical trials for transplant setting
ChesonCheson, Seminars in Oncology, 2002, Seminars in Oncology, 2002
[[ZevalinZevalin])])IndiumIndium--labeled tracer dose for labeled tracer dose for dosimetrydosimetryOverall response rate 74% in patients refractory to Overall response rate 74% in patients refractory to rituximabrituximabGrade IV neutropenia and thrombocytopenia in Grade IV neutropenia and thrombocytopenia in 35% and 9% patients35% and 9% patientsIneligible if > 25% bone marrow invasionIneligible if > 25% bone marrow invasion
ChesonCheson 2002;2002; Hennessy et al., 2004Hennessy et al., 2004
Other monoclonal antibodiesOther monoclonal antibodies�� Alemtuzumab/CampathAlemtuzumab/Campath--1H1H
Targets CD52Targets CD52Present on most B and T lymphocytesPresent on most B and T lymphocytesApproved for CLL patients Approved for CLL patients pretx�dpretx�d w/ w/ fludarabinefludarabine
�� EpratuzumabEpratuzumabAnti CD22Anti CD22
�� Aplizumab/Hu1d10Aplizumab/Hu1d10Directed against HLADirected against HLA--DRDR
IdiotypeIdiotype markers present on all lymphoma cellsmarkers present on all lymphoma cells�� Tumor cells harvestedTumor cells harvested�� Tumor sequence identified by PCRTumor sequence identified by PCR�� Gene clonedGene cloned�� TransfectedTransfected into mammalian cellsinto mammalian cells�� Produced for vaccineProduced for vaccine�� Ongoing trialsOngoing trials�� Investigating methods to enhance the immune Investigating methods to enhance the immune
responseresponseVoseVose et al 2002et al 2002
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SummarySummary
NonNon--Hodgkin�s Lymphoma is a diagnosis Hodgkin�s Lymphoma is a diagnosis comprising different types of diseasescomprising different types of diseasesLow grade lymphoma has longer average Low grade lymphoma has longer average survival but decreased response to survival but decreased response to chemotherapychemotherapyAggressive lymphoma has greater Aggressive lymphoma has greater response to chemotherapy but shorter response to chemotherapy but shorter average survivalaverage survival
SummarySummary
Diffuse large BDiffuse large B--cell lymphoma is the most cell lymphoma is the most common aggressive lymphoma and most common aggressive lymphoma and most common subtype of NHLcommon subtype of NHLFirst line treatment for diffuse large BFirst line treatment for diffuse large B--cell cell lymphoma is Rlymphoma is R--CHOP chemotherapyCHOP chemotherapyApproximately 40% can patients w/ diffuse Approximately 40% can patients w/ diffuse large Blarge B--cell lymphoma can be cured with cell lymphoma can be cured with chemotherapychemotherapy
Nursing Implications: RNursing Implications: R--CHOPCHOPGenerally outpatient chemotherapy except for coGenerally outpatient chemotherapy except for co--morbid conditions or concern for risk for tumor lysis morbid conditions or concern for risk for tumor lysis syndrome in setting of bulky diseasesyndrome in setting of bulky diseaseAssess patient for adequate vascular access in setting Assess patient for adequate vascular access in setting of strong vesicantsof strong vesicantsEvaluate cardiac left ventricular ejection fraction prior Evaluate cardiac left ventricular ejection fraction prior to initiating chemotherapyto initiating chemotherapyEvaluate for need for hematological growth factor Evaluate for need for hematological growth factor supportsupportUse with caution in setting of liver dysfunctionUse with caution in setting of liver dysfunction
Fischer et al (2003), Chu & DeVita, Jr. (2003), Pfreundschuh et Fischer et al (2003), Chu & DeVita, Jr. (2003), Pfreundschuh et al (2004)al (2004)
Why did one patient receive Why did one patient receive chemotherapy and the other patient chemotherapy and the other patient
did not receive chemotherapy?did not receive chemotherapy?
Why did the doctor Why did the doctor recommend recommend chemotherapy Mr. D chemotherapy Mr. D (aggressive (aggressive lymphoma) and none lymphoma) and none for Mr. L (indolent for Mr. L (indolent lymphoma)? lymphoma)?
Watch and wait for Watch and wait for asymptomatic asymptomatic indolent lymphomaindolent lymphomaChemotherapy Chemotherapy aggressive lymphomaaggressive lymphoma
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Thank YouThank You
Mount Sinai Medical Mount Sinai Medical CenterCenter�� Thomas Smith RNThomas Smith RN�� Takao Takao OhnumaOhnuma MDMD
