Managing lymphoma in small animal practice
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Managing Lymphoma in Small Animal Practice. Wendy Blount, DVM. Lymphoma. aka lymphosarcoma (LSA) Other than euthanasia in shelters, cancer is the #1 killer of dogs LSA most common cancer in dogs & cats Most common cause of hypercalcemia in dogs and cats 30% of cats with cancer have lymphoma

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Managing Lymphoma in Small Animal Practice

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Managing lymphoma in small animal practice

Managing Lymphoma in Small Animal Practice

Wendy Blount, DVM


Lymphoma

Lymphoma

  • aka lymphosarcoma (LSA)

  • Other than euthanasia in shelters, cancer is the #1 killer of dogs

  • LSA most common cancer in dogs & cats

  • Most common cause of hypercalcemia in dogs and cats

    • 30% of cats with cancer have lymphoma

    • 24% of dogs with cancer have lymphoma

  • Most common spinal cord tumor in the cat

  • Most common brain tumor in the cat

  • Most common nasal tumor in the cat

  • Most common liver tumor in the cat


Lymphoma1

Lymphoma

Juan Carlos Garza – Houston TX

x


Etiology

Etiology

  • GI lymphoma can be preceded by IBD in cats

  • Helicobacter spp increase risk of GI adenocarcinoma in people, and are often present in gastric LSA histopath in cats

  • FeLV predisposes to LSA in cats

  • Lymphoma respects age less than other tumors


Clinical signs

Clinical Signs

Vary tremendously by tumor location

Multicentric lymphoma most common

  • Multiple painless enlarged lymph nodes, hepatomegaly, splenomegaly in dogs

  • Enlarged mesenteric lymph node, hepatomegaly, splenomegaly in cats

  • Fever

  • Other locations

    Ocular lymphoma

  • Third eyelid or conjunctival mass in cats

    • rapidly enlarges

  • Anterior or posterior uveal infiltrates and/or uveitis


Clinical signs1

Clinical Signs


Clinical signs2

Clinical Signs


Clinical signs3

Clinical Signs


Clinical signs4

Clinical Signs


Clinical signs5

Clinical Signs


Clinical signs6

Clinical Signs


Clinical signs7

Clinical Signs


Clinical signs8

Clinical Signs

Vary tremendously by tumor location

  • GI lymphoma (focal or diffuse)

    • Vomiting, diarrhea, steatorrhea, melena

    • Hematochezia, mucoid feces, tenesmus

    • Mass on rectal palpation

    • Anorexia, weight loss, lethargy

    • Abdominal pain or effusion

    • Palpable abdominal mass, thickened loops of bowel

    • Pallor, anemia if GI bleeding

    • Icterus if obstruction of bile duct


Clinical signs9

Clinical Signs

Nasal lymphoma

  • Unilateral or bilateral nasal discharge

  • Epistaxis, Sneezing

  • Dyspnea, stertor, nasal stridor

  • Facial distortion and ocular discharge

  • Intermediate to large cells


Clinical signs10

Clinical Signs

Nasal lymphoma

  • Unilateral or bilateral nasal discharge

  • Epistaxis, Sneezing

  • Dyspnea, stertor, nasal stridor

  • Facial distortion and ocular discharge

  • Intermediate to large cells


Clinical signs11

Clinical Signs

Nasal lymphoma

  • Unilateral or bilateral nasal discharge

  • Epistaxis, Sneezing

  • Dyspnea, stertor, nasal stridor

  • Facial distortion and ocular discharge

  • Intermediate to large cells

  • Neurologic signs if invasion of the cribriform plate – anterior forebrain

    • Seizures

    • Behavioral changes, obtunded, head pressing

    • Blindness, circling

    • CP deficits worst in rear


Clinical signs12

Clinical Signs

Spinal cord lymphoma

  • Extramedullary tumor

  • Onset chronic or acute

  • More common in cats than dogs

  • Localized severe spinal pain

    • Extramedullary tumors seem to be more painful than medullary

    • More pain receptors in these areas

  • LMN signs (flaccid weakness) 2 vertebrae caudal to the area of spinal pain

  • UMN signs (spastic paresis) caudal to that

  • Usually part of multifocal disease

  • Younger cats, up to 2 years of age

  • Difficult to diagnose, CSF often not diagnostic


Clinical signs13

Clinical Signs

Brain lymphoma

  • Symptoms caused by

    • Displacement of brain tissue

    • Disruption of blood brain barrier

    • Disruption of CSF and blood flow

  • Seizures the most common symptom in dogs (cerebral)

    • Lethargy, weight loss, obtunded

    • Circling, behavior changes, head pressing

    • Contralateral CP deficits worse in rear

  • Head tilt and ataxia in cats (caudal brain stem)

  • Brain herniation in the late stages

    • Coma, dilated pupils, death


Clinical signs14

Clinical Signs

Acute Lymphoblastic Leukemia (ALL)

  • Usually non-specific signs

  • May have coagulopathy of thrombocytopenia

    • Petechiae

    • Epistaxis, bleeding from the gums

    • Primary hemostasis disorder

  • Often part of multicentric disease

  • Usually “atypical cells” in circulation, but not always

    • “Aleukemic leukemia”

    • Cytopenias prompt bone marrow sample


Clinical signs15

Clinical Signs

Lymphomatoid granulomatosis

  • aka eosinophilic pulmonary granulomatosis

  • aka lymphoid granulomatosis

  • aka lymphoproliferative angitis

  • aka granulomatosis

  • Destructive angitis in the lungs

  • Atypical T-cell lymphoma

  • History of treated heartworm disease

  • May progress to lymphoma

  • Symptoms of pneumonitis


  • Clinical signs16

    Clinical Signs

    Renal lymphoma (feline)

    • Bilateral large, bumpy kidneys

    • The many signs of renal failure

      Mediastinal lymphoma (feline)

    • Dyspnea, coughing

    • Regurgitation

    • Horner’s Syndrome

      Hepatic lymphoma

    • Marked hepatomegaly, liver failure

    • Large cell in dogs, small cell in cats


    Clinical signs17

    Clinical Signs

    Cutaneous lymphoma

    • Usually diffuse in the dog

      • Intense pruritis, resistant to treatment

      • Sometimes follows atopy

    • Two forms in cats

      • Epitheliotropic – diffuse

        • “Mycosis fungoides”

        • Intradermal nests of 5-10 cells

        • Usually large but sometimes small T cells

      • Non-epitheliotropic

        • Large B cells deeper in the dermis


    Managing lymphoma in small animal practice

    x

    x


    Clinical signs18

    Clinical Signs

    CBC

    • Neutrophilia if gross disease

    • Lymphocytosis

      • atypical lymphocytes if ALL

      • May not have atypia with CLL

    • Anemia

      • Anemia of chronic inflammatory disease

        • Mild nonregenerative anemia

      • Iron deficiency anemia if GI bleeding

        • Regenerative or non-regenerative

    • Pancytopenia if leukemia is present


    Clinical signs19

    Clinical Signs

    Panel

    • Hypercalcemia

    • Elevated ALT, SAP, GGT if hepatic LSA

    • Icterus – GI, hepatic, pancreatic LSA

    • Low albumin

      • PLE due to intestinal LSA

      • GI bleeding due to GI LSA

    • High globulins – B cell lymphoma

    • Low globulins – GI bleeding due to GI LSA

    • High BUN

      • Pre-renal - dehydration

      • Pre-renal - GI bleeding due to GI LSA

      • Feline - renal LSA


    Clinical signs20

    Clinical Signs

    Panel - icterus with normal liver enzymes

    • A unique presentation in the cat

    • Differential diagnosis:

      • Pancreatitis – elevated fPLI

      • Lymphoma – cytology or histopathology

      • FIP – histopathology or diagnostic trifecta

        • Lymphopenia <1500/ul

        • Titer 1:160 or greater

        • Globulins >5.1 g/dl

        • Positive predictive value 89%

        • Negative predictive value 99%

        • Histopath and fluid analysis supportive

        • Fluid analysis chart


    Clinical signs21

    Clinical Signs

    Abdominal Imaging (rads)

    • Abdominal mass – gut or lymph node

    • Hepatomegaly, splenomegaly

    • Gut obstruction

    • Abdominal effusion

      • Chyle or modified transudate

    • Thickened gut wall (muscularis)

    • Pneumoperitoneum if GI perforation

    • Mucosal craters

    • Soft tissue calcification if hypercalcemia

    • Bilateral renomegaly in cats


    Clinical signs22

    Clinical Signs

    Bilateral renomegaly in cats


    Clinical signs23

    Clinical Signs

    Cat with mid-abdominal mass and ascites


    Clinical signs24

    Clinical Signs

    Hepatosplenomegaly due to multicentric lymphoma in a dog


    Clinical signs25

    Clinical Signs

    Abdominal Imaging (US)

    • Enlarged mediastinal lymph node

    • Hepatomegaly

      • Hypoechoic focal to multifocal lesions

      • Generalized hypo- or hyper-echogenicity

      • Normal to nodular hepatic sonogram

    • Splenomegaly

      • Nodular to diffuse

      • hyper or hypoechoic


    Clinical signs26

    Clinical Signs

    Lila

    • 1.5 year old female Rottweiler

    • Acute onset of abdominal pain and tachypnea

    • Has not eaten for 2 days, no vomiting, mucus in the stool

    • Abdominal splinting on palpation

    • Fever – 103.8F

    • CBC, panel – NSAF

    • cPLI – abnormal (>400)

    • Fecal float negative

    • No response to treatment with IV fluids and antibiotics for 2 days (began vomiting)


    Clinical signs27

    Clinical Signs


    Clinical signs28

    Clinical Signs

    Ileus and abdominal effusion


    Clinical signs29

    Clinical Signs

    Lila

    • Abd US declined due to financial limitations

    • Elected diagnostic surgery

    • Generalized peritonitis, serosanguinous abdominal fluid

    • No obstruction or foreign body

    • Fluid analysis

      • Modified transudate

      • Neoplastic very large lymphoid cells

      • Cytology says “suspicious of lymphoma”

    • Histopathology of mesenteric lymph node confirms large cell lymphoma


    Clinical signs30

    Clinical Signs

    Lila

    • Responded to chemo within a few days

    • Remission 6 months

    • End – recurrence of initial clinical signs

      Owner failed to “pay as she went” as promised, and never paid her balance of >$1,500


    Clinical signs31

    Clinical Signs

    Abdominal Imaging (US)

    • Abdominal effusion

    • Soft tissue calcification if hypercalcemia

    • GI lesions

      • Gut obstruction – dilated fluid filled bowel

      • Thickened gut wall (muscularis)

      • Obliteration of gut layers

      • Pneumoperitoneum if GI perforation

      • Mucosal craters

      • Decreased motility


    Clinical signs32

    Clinical Signs

    Renal lymphoma in a cat


    Clinical signs33

    Clinical Signs

    Renal lymphoma in a cat


    Clinical signs34

    Clinical Signs

    gastric lymphoma in a cat with ascites


    Clinical signs35

    Clinical Signs

    Abdominal effusion and infiltrated omentum in a cat


    Clinical signs36

    Clinical Signs

    Hypoechoic liver - lymphoma


    Clinical signs37

    Clinical Signs

    Hyperechroic liver - lymphoma


    Clinical signs38

    Clinical Signs

    Stomach & duodenum in a dog with lymphoma


    Managing lymphoma in small animal practice

    x

    x

    x

    x


    Clinical signs39

    Clinical Signs

    Thoracic Imaging (rads)

    • Enlarged perihilar lymph nodes

    • Interstitial nodular pattern

    • Enlarged sternal lymph node

    • Mediastinal mass

    • Pleural effusion

    • Soft tissue calcification if hypercalcemia

    • Lymphoid granulomatosis

      • Soft tissue masses in the lungs

      • Interstitial to alveolar pattern

      • Enlarged lymph nodes

      • Pleural effusion


    Clinical signs40

    Clinical Signs


    Clinical signs41

    Clinical Signs

    Enlarged

    mediastinal lymph

    nodes and

    chylothorax

    in a cat with LSA


    Clinical signs42

    Clinical Signs

    Enlarged mediastinal, sternal and perihilar lymph nodes in a dog with LSA


    Clinical signs43

    Clinical Signs


    Clinical signs44

    Clinical Signs

    Interstitial pulmonary nodules in a dog with lymphoma, enlarged lymph nodes


    Clinical signs45

    Clinical Signs

    Pleural effusion in a dog with lymphoma


    Clinical signs46

    Clinical Signs

    ECG

    • VPCs if splenic mass

    • Possible arrhythmia if hypercalcemia

      • Prolonged PR interval (>0.14sec)

        • 1st degree AV block

      • 2nd degree AV block

        • P wave not followed by QRS

      • Ventricular fibrillation if severe

        • Calcium (>18)


    Hypercalcemia of malignancy

    Hypercalcemia of Malignancy

    aka Pseudohyperparathyroidism

    aka HHM (humoral hypercalcemia of malignancy)

    • HHM is most common cause of hypercalcemia in the dog and cat

      • 67% of dogs with hyperCa have cancer

      • 33% of cats with hyperCa have cancer

    • Dogs with HHM most often have

      • Anal sac adenocarcinoma

      • LSA

      • multiple myeloma

    • Cats with HHM most often have LSA or SCC


    Hypercalcemia of malignancy1

    Hypercalcemia of Malignancy

    • 90% of dogs with anal sac tumors have HHM

      • >50% are hypercalcemic at diagnosis

    • 10-35% of dogs with LSA have HHM

    • 15-20% of dogs with multiple myeloma have HHM

    • Cats with LSA and HHM are most likely to have cranial mediastinal lymphoma

    • >90% of dogs with LSA and HHM have enlarged lymph nodes


    Hypercalcemia of malignancy2

    Hypercalcemia of Malignancy

    • Some tumors release PTH-rp

      • Parathyroid hormone related protein

    • Stimulates osteoclastic bone resorption

    • Increases renal tubular reabsorption of calcium

    • Made in low amounts by normal tissues

      • Thought to regulate calcium transport during gestation and lactation

    • Other humoral factors are involved in HHM

    • Bony invasion can contribute to HHM


    Hypercalcemia of malignancy3

    Hypercalcemia of Malignancy

    • Clinical Signs of HHM

      • PU-PD

      • Weakness, lethargy

      • Anorexia, weight loss

      • Vomiting, diarrhea


    Hypercalcemia of malignancy4

    Hypercalcemia of Malignancy

    Diagnosis

    • Rule out lab artifact

      • Fasting prevents lipemia

      • No hemolysis

    • Confirm hypercalcemia is real

      • Ionized calcium

      • Follow reference lab handling guidelines

      • Altered by temperature, pH and CO2

    • Look for tumors

      • Rectal exam, LN palpation, imaging, CBC

      • Sample bone marrow if cytopenias

    • Send PTH, PTHrp and iCa++ to Michigan


    Hypercalcemia of malignancy5

    Hypercalcemia of Malignancy

    Diagnosis

    • If concurrent azotemia, it can be difficult to distinguish HHM from renal hypercalcemia

      • Hypercalcemia can cause nephrotoxicity

    • Marked azotemia and mild hypercalcemia is more consistent with renal disease

    • Marked hypercalcemia with mild azotemia is consistent with HHM

    • Phosphorus often high with renal disease

    • Phosphorus often low with HHM

    • iCa++ high with HHM

    • iCa++ normal to low with renal failure


    Hypercalcemia of malignancy6

    Hypercalcemia of Malignancy

    Differential Diagnosis Hypercalcemia

    • H = Hyperparathyroidism (1°, 3°, hyperplasia), HHM, houseplants, hyperthyroid (cats)

    • A = Addison's disease, aluminum toxicity, vitamin A

    • R = Renal disease, raisins/grapes (dogs)

    • D = Vitamin D toxicosis (granulomatous dz), drugs, Dovonex, dehydration, diet

    • I = Idiopathic (cats), infectious, inflammatory

    • O = Osteolytic (osteomyelitis, immobilization, local osteolytic hypercalcemia, bone infarct)

    • N = Neoplasia (HHM and LOH), nutritional

    • S = Spurious, schistosomiasis, salts of calcium, supplements


    Hypercalcemia of malignancy7

    Hypercalcemia of Malignancy

    Differential Diagnosis Hypercalcemia

    Diagnostic Chart

    • 16 conditions and 10 blood parameters

      Treatment Algorhythm

    • Clinically ill with high iCa++

    • Chronic hypercalcemia without illness

    • Idiopathic hypercalcemia in cats


    Diagnosis

    Diagnosis

    Cytology

    • Avoid sampling the submandibular lymph nodes, as they are most prone to inflammation

    • Use “core technique” – needle only with no attached syringe for aspiration, then attach 10-12cc syringe full of air to squirt onto slide

    • Vertical pull apart, as lymphoid cells are fragile

    • Horizontal smears destroy the cells (“smudge cells”)


    Managing lymphoma in small animal practice

    x

    x

    x


    Diagnosis1

    Diagnosis

    Cytology

    • Normal lymph node

      • Mostly small lymphocytes

        • Smooth chromatin, scant cytoplasm, no prominent nucleoli

        • 1-1.5x size of RBC

      • Fewer intermediate & large lymphocytes

      • Occasional neutrophil, macrophage, plasma cell, mast cell

      • But pyramid of maturation is conserved

    • Reactive lymph node

      • Can have many blasts

      • Many cell types present


    Diagnosis2

    Diagnosis

    Cytology

    • >80% lymphoblasts = large cell lymphoma

      • 3-5x size of RBC

      • More abundant cytoplasm, round to slightly cleaved nucleus, pale chromatin, prominent nucleoli

    • Small cell lymphoma

      • Other cells are largely missing

      • Not many intermediate or large lymphocytes

      • Difficult cytologic diagnosis (often need histopath)


    Diagnosis3

    Diagnosis

    Cytology - cats

    • Immunoblastic lymphoid hyperplasia

    • Aka atypical follicular lymphoid hyperplasia

      • Peripheral LN hyperplasia in a young cat is more likely to be this than lymphoma

      • Associated with FIV or FeLV positive

      • Pyramid of maturation preserved

      • Very large immunoblastic lymphoid cells are present

      • Prognosis after treatment with corticosteroids is excellent in retroviral negative cats (beware of latent infection)


    Diagnosis4

    Diagnosis

    Normal lymph node


    Diagnosis5

    Diagnosis

    Reactive lymph node


    Diagnosis6

    Diagnosis

    Feline large cell lymphoma


    Diagnosis7

    Diagnosis

    large cell lymphoma


    Diagnosis8

    Diagnosis

    SI biopsy touch prep

    Small cell lymphoma on histopath


    Diagnosis9

    Diagnosis

    SI biopsy touch prep

    Large cell granular lymphoma (feline)

    Azurophilic granules


    Diagnosis10

    Diagnosis

    FNA enlarged kidney diffusely hyperechoic

    Large cell lymphoma (feline)


    Diagnosis11

    Diagnosis

    Chylothorax – mediastinal mass

    Thymoma


    Diagnosis12

    Diagnosis

    Chylothorax – mediastinal mass

    Mediastinal Lymphoma – large cell


    Diagnosis13

    Diagnosis

    Liver aspirate

    Hepatic Lymphoma


    Diagnosis14

    Diagnosis

    Liver aspirate

    Hepatic Lymphoma & fatty liver


    Diagnosis15

    Diagnosis

    Is histopathology necessary?

    • Lymph nodes cytology by boarded oncologist or pathologist is often sufficient

    • Some circumstances might require biopsy

      • Low grade lymphoma resembling mature lymphocytes

        • Feline lymphomas

        • Small cell lymphomas in dogs

      • Severe inflammation and necrosis

      • GI lymphoma (full thickness biopsies)

      • Hepatic lymphoma (Reno)


    Diagnosis16

    Diagnosis

    Cell Size – Degree of anaplasia

    • Most dogs have large cell lymphomas

    • Most cats have large or intermediate cell lymphomas

    • Small cell lymphomas are more common in the cat than in the dog

    • Small cell more common in old cats

    • Large cell more common in young cats


    Diagnosis17

    Diagnosis

    Special tests for atypical sites

    • Nasal rads in cats

      • Open mouth, DV, frontal sinus skyline

      • Soft tissue opacities

      • Turbinate lysis

    • Nasal biopsy in cats

      • Anterograde and retroflexed behind soft palate

      • blind biopsy yields diagnosis more often than rhinoscopy guided

      • Use radiographs as a guide

    • Rhinoscopy – low yield


    Diagnosis18

    Diagnosis

    Right nasal lymphoma in a cat


    Diagnosis19

    Diagnosis

    posterior nares – small mass on the left


    Diagnosis20

    Diagnosis

    posterior nares – large mass on the left


    Managing lymphoma in small animal practice

    x

    x


    Diagnosis21

    Diagnosis

    Nasal biopsy

    • Platelet count and BMBT

    • Anesthetize and intubate the dog

    • Count 4x4 gauze use to pack off the pharyngeal area

    • Elevate the shoulders above the nares

    • Absorbent pad on the floor


    Diagnosis22

    Diagnosis

    Nasal biopsy

    • Platelet count and BMBT

    • Anesthetize and intubate the dog

    • Count 4x4 gauze use to pack off the pharyngeal area

    • Elevate the shoulders above the nares

    • Absorbent pad on the floor

    • Wait 10 minutes after biopsies complete to begin anesthetic recovery

    • Hospitalize overnight – they sneeze blood


    Lsa stage

    LSA - Stage

    • Stage I – Single node or site involved

      • No evidence of distant metastasis

    • Stage II - Two or more lymph node regions both on the same side of the diaphragm

    • Stage III - Two or more lymph node regions on different sides of the diaphragm

    • Stage IV - Any lymph nodes PLUS liver or spleen involvement

    • Stage V - Involvement of extranodal tissue


    Lsa stage1

    LSA - Stage

    Substage – added to any stage

    • Substage A – no clinical signs

    • Substage B – illness caused by tumor

      Histopathologic grade – MI

      • Little effect on prognosis

        Staging of limited prognostic value EXCEPT

    • Stage V worse prognosis than others

    • Substage B negatively impacts prognosis


    Classification

    Classification

    Location

    • 80% of dogs with LSA have multicentric

    • Cat lymphomas not as likely to be multicentric as in dogs

      • GI most common in cats

      • mediastinal 2nd most common

    • Cats with multicentric LSA are less likely to have peripheral lymphadenopathy than dogs

    • Skin Lymphoma – different behavior than the typical multicentric lymphoma in dogs

      • T cell in dogs – resistant to treatment

      • Both T and B cell in cats – variable response to treatment


    Classification1

    Classification

    Immunophenotyping – immunohistochemistry, flow cytometry, PCR

    • B (CD79) or T (CD3) cell?

    • Also null cell lymphomas

    • Dog LSA – >70% B cell, <30% T cell

    • Cat LSA – B cell more common than T cell

    • More of a prognostic indicator in dogs as compared to cats

      • High grade B lymphomas have better response and longer survival than high grade T cell lymphomas


    Classification2

    Classification

    Colorado State University Testing

    • Guide to Lymphoid Neoplasia Testing

    • Flow Cytometry

    • Immunocytochemistry

    • Immunofixation

    • PARR (PCR for Antigen Receptor Rearrangement)

    • $100-125 each test, plus shipping

      Use these tests:

    • To tell lymphoma from lymphoid hyperplasia

    • To tell B from T cell – prognosis

    • To tell if in remission – planning chemo


    Treatment chemotherapy

    Treatment - Chemotherapy

    Many protocols, and most have similar prognosis and outcome

    • CHOP – cyclophosphamide, doxorubicin, Oncovin (vincristine), prednisone

    • COPA – cyclophosphamide, Oncovin, prednisone, Adriamycin (doxorubicin)

    • VELCAP – vincristine, Elspar, cyclophosphamide, Adriamycin, prednisone

      Other induction protocols are out there, but those including these 4 drugs are thought to be most effective

      Elspar is added for high tumor burden


    Treatment chemotherapy1

    Treatment - Chemotherapy

    Examples of CHOP Protocols

    • Wisconsin 19 Week Protocol (4)

    • Wisconsin 25 Week Protocol (4)

      • Same as above with 6 weeks off

    • TAMU Canine Large Cell Protocol (2)

    • TAMU Feline Large Cell Protocol (7)

    • Tufts VELCAP-L (6)

      • Final “L” distinguishes from another shorter intermittent Tufts protocol

    • Ohio State 3 Week Cycle (max)


    Treatment chemotherapy2

    Treatment - Chemotherapy

    Ohio State 3 Week Cycle

    • Week 1 - doxorubicin 30 mg/m2 IV

      • 1 mg/kg in dogs under 15 kg

      • Dispense prednisone 20 mg/m2 PO EOD

    • Week 2, day 1 - vincristine 0.7 mg/m2 IV

    • Week 2, day 3 - Cyclophosphamide 200 mg/m2 PO

    • Week 3 – vincristine 0.7 mg/m2 IV

      Repeat for 20-25 weeks (7-9 cycles), or until out of remission

      Doxorubicin reaches maximum lifetime dose


    Treatment chemotherapy3

    Treatment - Chemotherapy

    Other protocols – with prednisone

    See Rescue Handout for details

    • Doxorubicin q3 weeks

    • Doxorubicin + cyclophosphamide

    • Lomustine q3-4 weeks

      Oral Chemotherapy

    • Chlorambucil 6-8 mg/m2 QOD

    • Prednisone 40 mg/m2 PO SID, then QOD

    • CBC every 2-3 weeks

    • Likely productive only for small cell LSAs


    Treatment chemotherapy4

    Treatment - Chemotherapy

    • Most protocols last about 5-6 months (20-25 weeks)

    • Older protocols continued chemo until the patient came out of remission

      • “Maintenance Therapy”

    • Current thinking is that chemo beyond 25 weeks is not beneficial when in remission

      • Maintenance chemo may increase drug resistance at relapse

      • If relapse occurs more than 2-3 months after chemo stopped, 60-70% will respond again to CHOP

      • Maintenance chemo increases cost of chemo and increases side effects


    Treatment chemotherapy5

    Treatment - Chemotherapy

    • Maintenance therapy beyond 25 weeks indicated only for indolent low grade tumors

      Typical response to chemo for large cell lymphoma in dogs:

      • In remission within 4-8 weeks

      • 5-6 months chemo

      • 2-3 months remission after chemo

      • Variable response to rescue therapy

      • Minimal illness

      • Each successive remission lasts as about half as long as the last

      • More than 3 remissions is unusual


    Treatment chemotherapy6

    Treatment - Chemotherapy

    Common misconceptions

    • My pet will lose his hair

    • My pet will likely be ill as a trade off for attempting a longer life

    • It would be better for my pet to die of cancer than to die of chemo treatment


    Treatment chemotherapy7

    Treatment - Chemotherapy

    Things important to say

    • You will likely think your dog is cured

      • The probability of this is just about zero

    • I can give you the averages, but whatever happens to you is 100% for you

    • If at any time you want to stop chemo, all you have to do is say the word

    • You know your pet best, and what is best for your pet. Our job is to give you information and help you manage your pet’s cancer as you think best. You are in the driver’s seat and we are here to help.


    Treatment chemotherapy8

    Treatment - Chemotherapy

    Rescue Therapy

    • Drugs used at the time of relapse are no longer effective and should not be used

    • Repeat CHOP if not being used at relapse

    • Then maximize doxorubicin dose

    • Then try either CCNU and MOPP, in either order

    • Then try various other rescue protocols


    Treatment chemotherapy9

    Treatment - Chemotherapy

    Low Grade, small cell tumors

    • GI lymphomas in cats

    • CLL in dogs

    • Chlorambucil 15 mg/m2 PO SID x 4d

      • Repeat every 3 weeks

    • Prednisone 40 mg/m2 PO SID, taper

    • 70-75% remission

    • Median remission 19 months

    • Survival 1-2 years is usual


    Treatment chemotherapy10

    Treatment - Chemotherapy

    ALL

    • Can try large cell protocol, but expect more myelosuppression

    • Or Cytosine arabinoside 400 mg/m2 over 6-8 hours

      • Administer weekly

    • Monitor for sepsis and treat accordingly

    • Blood transfusions as needed for RBC

    • Platelet rich plasma for platelets

    • Whole fresh blood for depleted factors


    Managing lymphoma in small animal practice

    x

    x

    x

    x


    Other treatments

    Other Treatments

    • Pulse chemo protocols

    • Intestinal resection and anastomosis for obstructive GI LSA

    • Whole body radiation (1/2 at a time)

    • Nasal cavity radiation

    • Monoclonal antibodies

    • Cerebral lesions

      • Mannitol, furosemide, diazepam acutely

      • Chemo long term

      • Anticonvulsants (zonisamide or phenobarbital)

    • Natural alternatives


    Other treatments1

    Other Treatments

    Treatment of Hypercalcemia Handout

    • Treat if >15-16 or symptoms

    • IV 0.9% NaCl

      • Increased GFR and calciuresis

      • Decreases renal calcium reabsorption

    • Furosemide 1-4 mg PO BID

      • inhibits Ca++ reabsorption in ascending loop of Henle

    • Prednisone 1-2 mg/kg PO BID

      • Inhibits VitD and GI calcium absorption

      • Cytotoxic effect on LSA and myeloma


    Other treatments2

    Other Treatments

    Treatment of Hypercalcemia Handout

    • >18 is a medical emergency

      • Salmon calcitonin 4-8 U/kg BID-TID

      • Pamidronate 1-2 mg/kg IV in 0.9% NaCl over 2–4 hrs; repeat in 2-4 weeks)

      • Zoledronate 0.25 mg/kg IV over 15 minutes q 4-5 weeks


    Prognosis

    Prognosis

    Response to chemotherapy – canine large cell multicentric lymphomas

    • 70-80% achieve full remission

    • 20-25% are partial or non-responders

    • Average length of remission is 6-11 months

    • Median survival 12 months

    • 20-25% survive 2 years or longer

    • Each remission is shorter lived and more difficult to achieve

    • Every tumor is expected to eventually become responsive to all treatment


    Prognosis1

    Prognosis

    Response to chemotherapy – canine large cell multicentric lymphomas

    • Short term prognosis usually good, long term prognosis is invariably dismal

    • Staging doesn’t matter, except V is worse

    • Grade doesn’t matter

    • Things that worsen prognosis

      • systemically ill (substage B)

      • Hypercalcemia

      • dyspnea on presentation

      • Bone marrow involvement, especially if cytopenias

      • (T cell is worse than B cell)


    Prognosis2

    Prognosis

    GI lymphoma is more often T cell in dogs

    • Median survival 13 days for SI LSA

    • Colorectal LSA can have prolonged survival

    • There can be a histopathologic gray area between IBD and LSA

      • Some Dx LSA behave as IBD

      • Some Dx IBD behave as lymphoma

      • Perhaps misdiagnosed?

        Lymphoid granulomatosis in dogs is highly variable

    • 6 days to 4 years


    Prognosis3

    Prognosis

    ALL has grave prognosis

    • Days to weeks common

    • Occasionally a few months

    • Chemo may not prolong life

    • ALL distinguished from Stage V LSA (bone marrow) by immunohistochemistry

    • The latter does not carry grave prognosis, though not as good as lower stages

    • Death usually by hemorrhage


    Prognosis4

    Prognosis

    Prognostic indicators in cats

    • Retroviral status

    • Anatomic location

    • Initial response to therapy

    • Stage & grade do not matter

    • immunophenotyping matters less in cats as compared to dogs

      Some of the indolent low grade tumors can have long survivals (2 years+)

    • GI small Lymphoma in cats

    • chronic lymphocytic leukemias in dogs


    Prognosis5

    Prognosis

    Nasal lymphoma in cats

    • increased risk for kidney lymphoma

    • Presence of anorexia worsens prognosis if not treated with chemo or radiation

      • Median survival 5 months if anorectic

      • Median survival 11 months if eating

    • Same prognosis for chemo alone, radiation alone, or both together

      • Median survival 1.5 years

      • Much shorter MST if cribriform breach (76 days)


    Prognosis6

    Prognosis

    Mediastinal lymphoma in cats

    • Associated more with FeLV+ than GI

    • Younger cats than GI LSA

      Feline Hodgins-like lymphoma

    • Not common

    • Affect lymph nodes in head and neck

    • Cells are of mixed phenotype

    • Long term prognosis is good


    Prognosis7

    Prognosis

    Hepatic lymphoma in cats

    • Associated more with FeLV+ than GI

    • Younger cats than GI LSA

      Cutaneous Lymphoma

    • Better prognosis in cats - B cell

    • 50% remission in dogs – T cell

    • Average remission 4-6 months in dogs

    • CCNU + Elspar in dogs

    • Treated as multicentric in cats

      • CHOP for large cell

      • Chlorambucil + pred for small cell


    Client handouts

    Client Handouts

    • Lymphoma in Dogs

    • Lymphoma in Cats

    • Skin Lymphoma

    • Acute Lymphoid Leukemia

    • Drug and Chemotherapy Client Handouts discussed under chemotherapy (Sunday)


    Acknowledgements

    Acknowledgements

    • Philip J. Bergman, DVM, MS, PhD, DACVIM (Oncology)VIN, BrightHeart Veterinary Centers

    • Louis-Philippe de Lorimier, DVM, ACVIM (Oncology)VIN, U Illinois Urbana-Champaign

    • Karri A. Meleo, DVM, ACVIM (Oncology), ACVRVIN, Veterinary Oncology Services, Edmonds, WA


    Acknowledgements1

    Acknowledgements

    • Mark Rishniw, BVSc, MS, ACVIM (SAIM), ACVIM (Cardiology)VIN, Clinical Research CoordinatorIthaca, NY

    • Kurt R. Verkest, BVSc, BVBiol, MACVSc (Small Animal)VIN, Univ Queensland, Australia

    • Kari Rothrock, DVM, Tennessee


    Acknowledgements2

    Acknowledgements

    Linda Shell, DVM, DACVIM (Neurology)

    • VIN Consultant

      Nancy Johnstone McLean, DVM, DACVO

    • U of Tennessee CVM

      Amanda Podles, DVM

    • Massachussets


    Acknowledgements3

    Acknowledgements

    • Robert J. Vasilopulos DVM, DACVIM (Internal Medicine)

      VIN Consultant, Vet Spec Ctr of Tucson

    • Dennis J. Chew, DVM, ACVIM (Internal Medicine)The OSU CVM, Columbus, OH

    • Patricia A. Schenck, DVM, PhD

      Mich State U, East Lansing, MI, USA

    • Zachary Wright, DVM, ACVIM (Oncology)Animal Diagnostic Clinic, Dallas TX


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