Managing Lymphoma. Professor Clare Knottenbelt BVSc MSc DSAM MRCVS

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1 Managing Lymphoma Professor Clare Knottenbelt BVSc MSc DSAM MRCVS

2 Lymphoma Common cancer (18% of dog cancers) DOGS: Multicentric CATS: Alimentary Presentation varies with site of LSA and paraneoplastic effects. Multicentric patients often very bright

3 Lymphoma Protocol affects survival Prednisolone only COP CHOP or M-W 3 months 6-9 months 13 months All based on time from diagnosis Is this accurate? Make decisions based on a variety of factors incl client preconceptions

4 Lymphoma Consider: What are the symptoms? What is the stage? What cell type is the LSA? What are the clients expectations? What is the patient s temperament? What other treatments can I offer? 3

5 Lymphoma What are the symptoms? Multicentric LSA often bright & well Paraneoplastic disease = v unwell Hypercalcaemia: PU/PD Anorexia, vomiting, constipation Muscle weakness, tremors, lethargy CNS depression, coma Bradycardia, dysrhythmias 4

6 Hypercalcaemia Can cause soft tissue calcification and irreversible renal damage Symptoms rapidly controlled with Ca 2+ Ca 2+ Normalises with steroid Tx/chemo BUT Prognosis is worse 5

7 Lymphoma What is the stage of LSA? Physical examination: Stage 3 Chest radiographs: useful for stage 1-2 Abdominal ultrasound: Stage 4 (liver/spleen) Haem &Biochem: Stage 5 & substage Bone marrow: Stage 5 confirmed Detection of concurrent disease that may affect chemo

8 Lymphoma How does Stage alter Tx? Influences treatment Stage 1 - may be cured with surgery Stage 2 - pred/chloram may be enough Stage 3 - chemo req Stage 4 - Hepatic chemo req, hepatic = poor prognosis Stage 5 - poorer prognosis & chemo is challenging

9 Lymphoma What cell type is the LSA? Determined by: Immunohistochemistry Flow cytometry on FNA T cell carries worse prognosis Can adapt protocol for T cell 8

10 Lymphoma What are the clients expectations? Chemo will not cure LSA Will prolong life with good quality for most Are they any Health and Safety concerns?

11 Which protocol shall I use? What is the patients temperament? Will it tolerate regular visits? Can chemo be given safely? Would oral Tx be preferable What other treatments could be used?

12 Oral only treatments Prednisolone (2mg/kg SID) Controls paraneoplastic effects Significant side effects No monitoring required Survival times relatively short

13 Oral only treatments Lomustine (q3wk) + Prednisolone Low incidence of side effects Monitor haem and liver parameters Cat dose requires reconstitution Can be relatively cheap due to reduced visits

14 Oral only treatments Prednisolone + Chlorambucil Low grade maintenance protocol Useful for low grade LSA Low incidence of side effects Monitor haematology Size of tablets difficult for large dogs

15 Less Regular Visits CHOP protocol Side effects may be higher due to Doxorubicin Longer survival than COP Is this protocol more or less intense than COP?

16 Less Regular Visits CHOP protocol At week 10 COP = 9 visits CHOP = 8 visits (2 oral) At 6 months COP = 17 visits CHOP = 16 visits (4 oral) CHOP then stops until recurrence COP continues with visits q4wk

17 Less Regular visits Doxorubicin only Given q 3wk for up to 6 doses GIT S-E common Requires premed (injections can be painful) Need to assess cardiac function after 4 doses Survivals up to 6 mth

18 Less Regular visits Lomustine, L-asparaginase + Pred L-asp is very painful to inject IM Improves remission rates but not survival Monitor haem and liver parameters

19 Lymphoma What monitoring is required? Haematology prior to every chemo dose Assess WBC, neutrophils, HCT & PLT 18

20 Lymphoma Chemo related Neutropenia Seen 7-10 days after chemo Rare complication Low risk of infection if >1.0 But GIT effects of chemo increase risk of sepsis 19

21 Managing Neutropenia Managing neutropenia Asymptomatic, Count >1.0 and <2.0 Delay chemo by 4-7 days Asymptomatic, Count <1.0 Send HOME, Antibiotic cover (TMS) Monitor Temp. 20

22 Managing Neutropenia Symptomatic, Count <1.0 HOSPITALISE Reverse isolation Broad spec antibiotics IV Monitor Temp & Avoid use of NSAIDs 21

23 Managing Neutropenia Consider dose reductions in future Patients that experience neutropenia may do better Dose reduction can increase drug resistance 22

24 10 y.o. MN Collie cross Thyroid carcinoma resected 3y ago Inappetant for 4 days Increased respiratory noise Difficult to exam as nervous rescue dog Multicentric LN enlargement

25 10 y.o. MN Collie X FNA LN = LSA (B cell) Routine bloods NAD Abdomen U/S Mesenteric LN enlargement Changes in liver and spleen FNA of spleen and liver showed lymphoblasts Chest rads NAD What stage is this dog?

26 What is the stage of LSA? Stage IVa What are the clients expectations? Sensible would like to try No Health and Safety concerns What is the patients temperament? Gets stressed by its visits Very nervous and difficult to restrain Oral Tx would be preferable

27 ALP protocol L-asparaginase given during staging sedation Lomustine 80mg q 3wk Prednisolone 75mg SID for 2 wk, 37.5mg SID for 2wk Gut protectants (famotidine, sucralfate) Owner able to give tablets Staff able to restrain for jugular bloods Hospital stay minimised (blood collection only)

28 ALP protocol Continued for 24 weeks (8 doses) In remission so stop chemo PTS at 21 months

29 10 y.o. MN Labrador Weight loss and GIT signs Multicentric LN enlargement Biopsy at referring vet = LSA

30 10 y.o. MN Labrador Routine bloods Thrombocytopenia Neutropenia (1.4) Lymphocytosis Hypercalcaemia Abdomen U/S (done prior to referral) Mesenteric LN enlargement Changes in liver and spleen Chest rads NAD What stage is this dog?

31 What is the stage of LSA? Stage Vb (confirmed on BMB) What are the clients expectations? Sensible keen to get the best they can No Health and Safety concerns What is the patients temperament? Slightly nervous, but can be restrained Less regular visits would be preferable

32 CHOP protocol L-asparaginase & preds given first as not myelosuppressive Gut protectants (famotidine, sucralfate) Start vincristine in 5 days Owner able to give tablets Staff able to restrain for chemotherapy CHOP has better survival and fewer visits than COP and more oral visits

33 CHOP protocol continued for 16 weeks (8 doses) Out of remission so change to ALP Developed marked elevation in ALT (2171) at 24 weeks Stop Lomustine Try Mitoxantrone q 3wk Survival of 12 months despite Stage Vb and hyperca

34 13 y.o. MN DSH Weight loss Intermittent GIT signs NAD on clin Ex

35 13 y.o. MN DSH Routine bloods Hypoalbuminaemia (22) Urinalysis SG =1.020 Abdomen U/S Intestinal mass (2 cm) (ICC junction) Loss of wall layering Renal enlargement Changes in liver and spleen FNA = Round cell tumour (LSA or MCT) Chest rads NAD

36 13 y.o. MN DSH Exp Lap GIT Biopsies Pancreatic mass removed Dx = LSA + Pancreatic adenoma

37 What is the prognosis for GIT LSA? Care with aggressive treatment What are the clients expectations? Human Dr keen to get the best they can No Health and Safety concerns What is the patients temperament? Easy to restrain

38 CHOP protocol Better than COP for GIT as chemo drugs are staggered Mitox instead of Doxo Owner able to give tablets CHOP has better survival

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