Lymphoma: Clinical Lymphoma: Clinical CasesCases

Tanya Repka, MD, FACPTanya Repka, MD, FACP

St. Luke’s Cancer CenterSt. Luke’s Cancer Centertrepka@slhduluth.comtrepka@slhduluth.com

Lymphomas

• Predominant primary organ involvement is lymphatic tissues instead of bone marrow.

• Clonal disorder--(provable by surface markers, Ig gene or T cell receptor gene rearrangement)

• Two main types: Hodgkin's (HD) and Non-Hodgkin's (NHL).

Lymphoma ClassificationLymphoma Classification

Hodgkin’s LymphomaHodgkin’s Lymphoma Malignant Cell is Reed-Sternberg CellMalignant Cell is Reed-Sternberg Cell Now recognized as a B-cellNow recognized as a B-cell Bulk of “tumor” is reactive tissueBulk of “tumor” is reactive tissue Spreads contiguously from node to nodeSpreads contiguously from node to node

• • Non-Hodgkin'sNon-Hodgkin's Localization depends on cell of originLocalization depends on cell of origin Spreads hematogenouslySpreads hematogenously

B.S. Case Study B.S. Case Study

24 year old woman presented to primary 24 year old woman presented to primary care c/o enlarged node right neck and care c/o enlarged node right neck and feversfevers

Placed on antibiotics x 2 weeksPlaced on antibiotics x 2 weeks On return to primary MD, no change in On return to primary MD, no change in

neck nodeneck node Referred to OncologyReferred to Oncology

B.S. Case StudyB.S. Case Study

ROS ROS 5 pound weight loss (125#), and night sweats5 pound weight loss (125#), and night sweats

PEPE 2.5 cm rubbery right posterior cervical node 2.5 cm rubbery right posterior cervical node

and 2 cm right supraclavicular node, ?axillary and 2 cm right supraclavicular node, ?axillary node(s) node(s)

Skin: multiple excoriations on arms and legsSkin: multiple excoriations on arms and legs

B.S. Case StudyB.S. Case Study

Referred to surgeryReferred to surgery FNA done in surgeons office, path FNA done in surgeons office, path

“suspicious for, but not diagnostic of, “suspicious for, but not diagnostic of, Hodgkin’s Disease”Hodgkin’s Disease”

Open biopsy “ classical nodular sclerosing Open biopsy “ classical nodular sclerosing Hodgkin’s Disease”Hodgkin’s Disease”

Lymphoma StagingLymphoma Staging Physical ExamPhysical Exam Performance statusPerformance status B symptomsB symptoms

• 10% wt loss, night sweats, fever10% wt loss, night sweats, fever CBC, diff, plts, LDH, Uric acid, CMPCBC, diff, plts, LDH, Uric acid, CMP Chest/abd/pelvis CT (chest xray) Chest/abd/pelvis CT (chest xray) PET scanPET scan Bilateral BM bx or unilateral (1-2cm) + aspBilateral BM bx or unilateral (1-2cm) + asp EF (MUGA or ECHO)EF (MUGA or ECHO) 2 microglobulin2 microglobulin Hepatitis B testing Hepatitis B testing

Thomas Hodgkin, M.D 1798-1866

“…between thirty and forty years of age, stout made, and not lean, had been affected with swelling of the glands…….

“17 year old white boy, who presented with the Chief Complaint of swelling of the neck…..”

Age Distribution in Hodgkin’s Lymphoma

Classification of HLClassification of HLWorld Health Organization World Health Organization

(WHO)(WHO)

Nodular lymphocyte predominantNodular lymphocyte predominant Classical HLClassical HL

Lymphocyte-rich classicalLymphocyte-rich classical Nodular sclerosis (grades I and II)Nodular sclerosis (grades I and II) Mixed cellularityMixed cellularity Lymphocyte depletedLymphocyte depleted

Therapy of HLTherapy of HL

Highly curable with chemotherapy and/or Highly curable with chemotherapy and/or radiationradiation

Therapy determined principally by stageTherapy determined principally by stage Localized disease can be treated with local Localized disease can be treated with local

therapy: XRTtherapy: XRT Widespread disease treated with systemic Widespread disease treated with systemic

therapy: chemotherapytherapy: chemotherapy Bulky localized disease: chemotherapy f/b Bulky localized disease: chemotherapy f/b

radiation therapyradiation therapy

Staging of lymphoma

• Stage I Single nodal group

• Stage II Multiple nodal groups

• Stage III Nodal groups on both sides of diaphragm

• Stage IV Marrow or CNS Involvement

Stages of HL

A = asymptomatic

B = symptoms (fever, night sweats, weight loss)

Long-term Follow-up of MOPP Treated Patients

B.S. Case studyB.S. Case study

CT/PETCT/PET Uptake in right neck, right axillaUptake in right neck, right axilla

Bone marrow:Bone marrow: No involvement No involvement

Stage IIStage II Combination chemotherapy recommendedCombination chemotherapy recommended

B.S. Case studyB.S. Case study

4 cycles of ABVD4 cycles of ABVD (Adriamycin, bleomycin, vinblastine, (Adriamycin, bleomycin, vinblastine,

dacarbazine)dacarbazine) CT/PET negative after 4 cyclesCT/PET negative after 4 cycles Pruritis resolves with first cyclePruritis resolves with first cycle Additional 2 cycles Additional 2 cycles Observe vs IFRT (prognostic factors)Observe vs IFRT (prognostic factors)

Late Effects of Therapy

Late Effects of TherapyLate Effects of Therapy

Second malignancySecond malignancy Solid tumors (risk continues to increase Solid tumors (risk continues to increase

beyond 15 years)beyond 15 years)• Lung cancer most common (1/3 of all Lung cancer most common (1/3 of all

second cancers)second cancers)• Breast cancerBreast cancer

Secondary leukemia (rare beyond 10-15 years)Secondary leukemia (rare beyond 10-15 years)

Late Effects of TherapyLate Effects of Therapy Cardiac mortality Cardiac mortality

Distant third cause of death after HL and second malignanciesDistant third cause of death after HL and second malignancies Most common is acute MI secondary to CADMost common is acute MI secondary to CAD Associated with mediastinal XRTAssociated with mediastinal XRT

Infectious mortalityInfectious mortality HypogammaglobulinemiaHypogammaglobulinemia

PulmonaryPulmonary Ranges from acute interstitial pneumonitis to chronic lung Ranges from acute interstitial pneumonitis to chronic lung

injuryinjury May be gaining in significance in patients treated in recent May be gaining in significance in patients treated in recent

years due to increasing use of bleomycin containing years due to increasing use of bleomycin containing regimens, especially when combined with mediastinal XRTregimens, especially when combined with mediastinal XRT

Significant complication in transplant patientsSignificant complication in transplant patients

M.F. Case StudyM.F. Case Study

50 year old man referred to Oncology by primary 50 year old man referred to Oncology by primary carecare

Clinical presentation:Clinical presentation: C/o abdominal problems x several yearsC/o abdominal problems x several years Sought attention of 1° care in 10/05 with c/o epigastric Sought attention of 1° care in 10/05 with c/o epigastric

pain, Rx: Protonixpain, Rx: Protonix May ‘06: Continued pain and burping, gallbladder u/s May ‘06: Continued pain and burping, gallbladder u/s

revealed an abdominal massrevealed an abdominal mass CT scan several very large masses in abdomen, felt CT scan several very large masses in abdomen, felt

to be adenopathy, left hydronephrosis/hydroureterto be adenopathy, left hydronephrosis/hydroureter

M.F. Case StudyM.F. Case Study

ROSROS MF………..MF……….. 20-25% weight loss over the past year, night 20-25% weight loss over the past year, night

sweats x 6 months, no fever (but does not sweats x 6 months, no fever (but does not take temps), nausea x 6 monthstake temps), nausea x 6 months

Social history: works at grain elevator for Social history: works at grain elevator for many years, at least 25 pack year history, many years, at least 25 pack year history, drinks 4-5 beers/daydrinks 4-5 beers/day

M.F. Case StudyM.F. Case Study

5/24/06, CT guided FNA of retroperitoneal 5/24/06, CT guided FNA of retroperitoneal massmass

Path: malignant lymphoma B cell type, Path: malignant lymphoma B cell type, most were small lymphocytes c/w low most were small lymphocytes c/w low grade lymphoma, but non-specific. Flow grade lymphoma, but non-specific. Flow cytometry not helpful: B cell lymphomacytometry not helpful: B cell lymphoma

? Treatment? Treatment

M.F. Case StudyM.F. Case Study

6/9/06 Laparascopic intraabdominal small 6/9/06 Laparascopic intraabdominal small bowel mesenteric mass biopsybowel mesenteric mass biopsy

Path: Malignant lymphoma, B-cell Path: Malignant lymphoma, B-cell phenotype (comprising about 35-40%) phenotype (comprising about 35-40%) arising in a background of follicular arising in a background of follicular lymphoma, grade 1 (comprising lymphoma, grade 1 (comprising approximately 60-65%)approximately 60-65%)

Non-Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma (NHL)(NHL)

Classified by morphologic/molecular Classified by morphologic/molecular featuresfeatures Dozens of specific types (blame the Dozens of specific types (blame the

pathologists)pathologists) Scheme revised every few years (ditto)Scheme revised every few years (ditto)

Most commonly of B-cell origin, but may be Most commonly of B-cell origin, but may be from T-cell originfrom T-cell origin

Non-Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma (NHL)(NHL)

Traditionally classified in a few broad Traditionally classified in a few broad clinical categories (by “treating physicians”clinical categories (by “treating physicians” Low grade; eg, follicular lymphomasLow grade; eg, follicular lymphomas Intermediate grade; e.g., diffuse large cellIntermediate grade; e.g., diffuse large cell Aggressive; e.g., Burkitt’sAggressive; e.g., Burkitt’s

Spread hematogenouslySpread hematogenously Usually widespread at diagnosisUsually widespread at diagnosis

Classification of NHLClassification of NHLWorld Health Organization World Health Organization

(WHO)(WHO) Mature B-cell neoplasmsMature B-cell neoplasms

Follicular Follicular Mantle cellMantle cell Diffuse large cellDiffuse large cell Burkitt’sBurkitt’s

Mature T-cell neoplasmsMature T-cell neoplasms Mycosis fungoidesMycosis fungoides Peripheral T-cellPeripheral T-cell Anaplastic large cellAnaplastic large cell

Histologic Subtypes of NHLHistologic Subtypes of NHL

Sandlund JT et al. NEJM 1996;334:1288.

NHL OutcomesNHL Outcomes

Determined by cell typeDetermined by cell type Low grade-indolent but incurableLow grade-indolent but incurable

• Follicular/small lymphocyticFollicular/small lymphocytic Intermediate/aggressive-rapidly lethal but Intermediate/aggressive-rapidly lethal but

curablecurable• Diffuse large cell/Burkitt’sDiffuse large cell/Burkitt’s

Therapy determined by cell typeTherapy determined by cell type Indolent gets indolent therapy Indolent gets indolent therapy Intermediate/aggressive gets aggressive Intermediate/aggressive gets aggressive

therapytherapy

Therapy of Indolent NHLTherapy of Indolent NHL• Don’t treat unless forced toDon’t treat unless forced to

-Cytopenias, “B”-symptoms-Cytopenias, “B”-symptoms

• As little therapy as possibleAs little therapy as possible-Monoclonal antibody therapy (Rituximab – anti -Monoclonal antibody therapy (Rituximab – anti

CD20) or mild alkylators often achieve remissionsCD20) or mild alkylators often achieve remissions

• Survival measured in years to decadesSurvival measured in years to decades-Some never need therapy-Some never need therapy

Non-Hodgkin's Therapy

Aggressive lymphoma therapy Treat at diagnosis for cure Combination cytotoxics

• Previously *multiple agents* (PromaceCytobom, Previously *multiple agents* (PromaceCytobom, COPBLAM, mBACOD, MBACOD, VACOP-B, etc)COPBLAM, mBACOD, MBACOD, VACOP-B, etc)

Now R-CHOPNow R-CHOPXRT if localized

Targeted therapies Rituximab: anti-CD-20

Stem cell transplant (auto/allo) Allows more aggressive therapy If allogeneic get immune attack as well

M.F. Case StudyM.F. Case Study

Combination chemotherapyCombination chemotherapy R-CHOP x 3 cyclesR-CHOP x 3 cycles

CT scan: Dramatic decrease in the size of CT scan: Dramatic decrease in the size of the retrocrural mass, also significant the retrocrural mass, also significant decrease in the size of the retroperitoneal decrease in the size of the retroperitoneal mass, initially over 12 cm, now 6 cmmass, initially over 12 cm, now 6 cm

Combination chemotherapyCombination chemotherapy R-CHOP x 3 cyclesR-CHOP x 3 cycles

M.F. Case StudyM.F. Case Study

CT/PET after 6 cycles: Improvement but still CT/PET after 6 cycles: Improvement but still with PET showing minimal hyperactivitywith PET showing minimal hyperactivity

2 additional cycles of R-CHOP2 additional cycles of R-CHOP Referral to University for consideration of stem Referral to University for consideration of stem

cell transplantcell transplant U recommended allogeneic sibling U recommended allogeneic sibling

hematopoietic stem cell transplant, U felt auto hematopoietic stem cell transplant, U felt auto transplant had less chance of relapse but with transplant had less chance of relapse but with higher morbidity/mortalityhigher morbidity/mortality

MF has 7 siblings, 3 were HLA compatibleMF has 7 siblings, 3 were HLA compatible

M.F. Case StudyM.F. Case Study

During BMT w/u he was found to have During BMT w/u he was found to have decreased renal function (bulky NHL) and decreased renal function (bulky NHL) and moderately reduced EF (Adria)moderately reduced EF (Adria)

Non-myeloablative peripheral blood (G-Non-myeloablative peripheral blood (G-CSF primed) stem cell sibling transplant CSF primed) stem cell sibling transplant recommendedrecommended

M.F. Case StudyM.F. Case Study

After preparatory regimen received his After preparatory regimen received his brother’s stem cells on 2/22 and 2/23/07brother’s stem cells on 2/22 and 2/23/07

Post-transplant course complicated by Post-transplant course complicated by CMV viremia, renal insufficiency 2° CSA, CMV viremia, renal insufficiency 2° CSA, acute skin GVHD, laparoscopic acute skin GVHD, laparoscopic cholecystectomy, and chronic gut GVHDcholecystectomy, and chronic gut GVHD

Key Difference Between HD and NHL

Hodgkin's spreads through lymphatics. Therapy determined by stage

Non-Hodgkin's spreads through blood. Therapy determined by cell type