Multiple Myeloma

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Article Written by Dr. Daniel A. Degner, Board-certified Veterinary Surgeon (DACVS)

Animal Surgical Center of Michigan

5045 Miller Road

Flint, MI 48507

www.animalsurgicalcenter.com

Phone: 810-671-0088

Key Points

Multiple myeloma is a plasma cell tumor that affects the bone marrow and may cause a multitude of clinical syndromes

Treat of choice is chemotherapy, however radiation is also used in some cases

The prognosis for patients treated for this condition is favorable


Introduction

  • The dogs, cats, humans and many other animals have cells that fight off infection called plasma cells. These cells produce antibodies. If one of the plasma cells in the body becomes cancerous, it produces many other plasma cells and forms a tumor called multiple myeloma (MM). Uniquely, this type of tumor usually produces it own specific type of antibody, which causes a variety of clinical syndromes. Multiple myeloma is a tumor that develops in multiple bone marrow sites (that is why it is called MM).
  • MM cells produce excessive immunoglobulin (antibodies) or a component there of called M-component. The M-component can be any class of immunoglobulin or a portion of the molecule called a light-chain (Bence Jones proteins) or heavy chain molecules (Heavy chain disease).
  • Multiple myeloma accounts for less than 1% of all malignant tumors in animals and represents 8% of all cancers of the blood cells.
  • The excessive secretion of immunoglobulin or infiltration of an organ (usually bones) cause the clinical signs of MM.
  • Conditions that are associated with MM
    • Bone lesions: bones that are very active in the production of blood cells are most commonly affected by MM; these include the ends of long bones of the limbs, back bones, ribs, pelvis and skull. About 25 to 66% of patients that have MM have visible bone lesions. This condition may cause a generalized thinning of the bones (diffuse osteopenia) or round punched out lesions. Due to weakening of the bone fractures of the bone(s) may occur.
    • bleeding tendencies are seen in about 33% of dogs affected by MM. M-components can prevent platelets from functioning properly and interfere with clotting factors; about 33% of the dogs will have this problem.
    • hyperviscosity syndrome is a condition in which the blood gets thicker than normal from excessive amounts of immunoglobulin in the blood stream. This can cause neurological signs such as depression seizures, coma and dementia; about 20% of the dogs will have this problem.
    • kidney failure can be caused by high calcium levels, Bence Jones proteins, hyerviscosity syndrome, tumor infiltration into the kidneys, and kidney infections due to poor immune system. About 33 to 50% of cases have this problem.
    • high calcium level in the blood may be caused by the production of a substance that acts like parathyroid hormone. Destruction of the bone may also cause increased calcium to enter into the blood stream (see fig above).
    • immune deficiency with resultant infections may be caused by displacement of normal cells from the bone marrow by the tumor cells (leaving no room for normal blood cell precursors).
  • There are no proven causes of MM, however exposure to the agricultural industry, petroleum products and irradiation are risk factors in humans.

Signs

  • The average age of dogs affected with MM is 8 to 9 years and German shepherds are more commonly affected. There is no predilection of males over females.
  • Clinical signs in decreasing frequency include lethargy/weakness, lameness, bleeding, eye problems (bleeding into eyes, retinal detachment, blindness), increased thirst and urination and neurological signs.
  • Many other nonspecific clinical signs may also be present such as vomiting, weight-loss and just not doing right

Diagnosis

  • The ultimate diagnosis of MM is based on finding cancer cells in the bone marrow, finding changes in the bones and finding abnormal proteins in the blood (serum) or urine. If there are no visible bony lesions, the diagnosis is based on finding the cancer cells in the bone marrow (see photo right) and the abnormal protein in the blood (serum).
  • Tests that are commonly run in patients that are suspected to have MM include:
    • Compete blood count, chemistry profile, urinalysis
    • Examination of the eyes by an ophthalmologist
    • Serum electrophoresis and immunoelectrophoresis (note that nonsecretory MM can exists and this test may be negative)
    • Testing of the urine for Bence Jones proteins
    • Bone marrow biopsy (normal to have less than 5% plasma cells)
    • X-rays of the bones (see radiograph to the right showing multiple holes in the bone due to the cancer eating the bone).

Treatment

  • Treatment for MM is used against the tumor itself and the secondary side effects of the tumor.
  • Chemotherapy never eradicates the entire tumor, but reduces the tumor burden significantly so that the patient feels well again.
  • Chemotherapy agents
    • Melphalan - alkylating agent is an oral medication that must be given daily to the patient
    • Prednisone - a steroid increases the efficacy of melphalan and is typically discontinued after 2 months of treatment
    • Cyclophosphamide - an alkylating agent can be used in place of melphalan or in combination with melphalan. Some oncologists will use this agent only in cases that have high calcium levels in the blood or if the tumor is widespread
    • Chlorambucil - an alkylating agent can be used to treat MM
  • A positive response to chemotherapy includes resolution of clinical signs (may take 3 to 4 weeks to see improvement), improvement of the bony lesions (based on radiographs) and reduction of the immunoglobulins in the blood and Bence Jones proteins in the urine (seen 3 to 6 weeks after induction of treatment).
  • Radiation can be used to treat isolated plasma cell tumors
  • Fractures of the bone can be repaired

Prognosis

  • In a study of 60 dogs treated for MM, 43% had a complete remission, 49% had partial remission, and 8% did not respond to treatment at all.
  • The presence of high calcium levels in the blood, Bence Jones proteins in the urine and extensive destruction of the bones are warning signs that chemotherapy may not be very effective.
  • The median survival in dogs with MM treated with chemotherapy is 540 days.
  • Cats tend to not respond as well as dogs.

References

  1. Matus RE, Leifer CE, MacEwen EG Hurvitz AI. Prognostic factors for multiple myeloma in the dog. J Am Vet Med Assoc 1986;188:1288-1291.
  2. Fox L, Alter S, Cronin K et al. Feline extramedullary plasmacytoma/multiple myeloma: Preliminary results of a VCOG retrospective study. Proc 19th Annu Vet Canc Soc, 1999, P 42.
  3. Vail D. Multiple myeloma. In Withrow SJ, MacEwen EG, Small Animal Clinical Oncology, 3rd ed, Philadelphia, WB Saunders, 2001, pp 626-638.
  4. Weber NA, Tebeau CS. An Unusual Presentation of Multiple Myeloma in two cats. J Am Anim Hosp Assoc 1998;34:477-483.
  5. Vail D, Thamm DH. Pearls of Veterinary Practice. J Am Anim Hosp Assoc 2005;41:209-214.
  6. Hendrix DVH, Gelatt KN, Smith PJ, et al. Ophthalmic disease as the presenting complaint in five dogs with multiple myeloma. J Am Anim Hosp Assoc 1998;34:121–128.

Frequently Asked Questions After Surgery

When should my dog have the first bowel movement after surgery?

  • Many dogs will not have a bowel movement for the first 4 to 5 days after surgery
  • Reasons that a dog will not have regular bowel movements after surgery include:
    • The dog has been fasted prior to surgery
    • Dogs do not eat well during the hospital stay
    • They frequently do not eat well when they go home
    • They are fed highly digestible food that produces little stool
    • Pain medication that contain narcotics (such as morphine, fentanyl patches, and tramadol) can be constipating
  • If a pet does not have a bowel movement on the 5th day of being home, a stool softener such as metamucil can be fed
    • Dose of metamucil is 1 tsp per 25 Kg mixed in with each meal (canned dog food); feed immediately after mixing, as the metamucil will gel the food and may make it less palatable

My pet had surgery and will not eat.  What can be done?

  • Dogs
    • Most pets will not eat their regular dog food after surgery, especially if it is kibble.
    • Offer a cooked diet having a 1:1 ratio of a protein source and carbohydrate source.  The protein source can be any meat (example: chicken breast, turkey breast, lean hamburger) that is low in fat and should be cooked (drain off all fat after the meat has been cooked).   The carbohydrate can be pasta, potato or white rice.
    • Try canned dog food; to enhance the flavor sprinkle a very small amount of garlic powder or chicken or beef broth (Chicken-in-a- MugTM or Beef-in-a-MugTM products)
    • Try Gerber strained meats for babies such as the chicken, beef, turkey, or veal
    • Try Hill's A/D diet available at most veterinary hospitals
    • Hand feeding: place a small amount of food in the mouth so that your dog gets the flavor
    • Warm the food slightly in a microwave, as the food will be more aromatic; stir the food before feeding and test the temperature on the bottom side of your wrist; it should only be luke warm.
    • Remember that most pets will not eat the first day or two after they get home from surgery
  • Cats
    • Offer smelly foods that contain fish such as tuna or smelly cat foods
    • Try Gerber strained meats for babies such as the chicken, beef, turkey or veal
    • Hand feeding:  with your finger place a small amount of food on the roof of your cat's mouth; use a syringe to get soft food into the mouth
    • Warm the food slightly in a microwave as the food will be more aromatic; remember to stir the food before feeding and test the temperature; it should be only luke-warm
    • Some cats will only eat dry food, try kibble if your cat normally has been fed that food
    • Petting and stroking your cat frequently will help to stimulate appetite
    • Remember that most pets will not eat the first day or two after they get home from surgery
    • Appetite stimulants such as cyproheptadine may be helpful
    • If your cat refuses to eat anything for 7 days a stomach tube or nasogastric tube should be placed to provide nutrition so that a serious liver problem (hepatic lipidosis) does not develop

My pet is vomiting.  What can be done?

  • The first thing for you to discern is whether your pet is vomiting or regurgitating.  Both will result in fluid or food being brought up.  Vomiting always will have heaving or retching of the abdomen prior to expulsion of the vomitus.  Regurgitation is not associated with heaving and the pet usually just opens the mouth and fluid or food will be expelled.  Usually the regurgited material will be clear or brown colored fluid. 
  • Next is to identify the cause of the vomiting or regurgitation.
  • Causes and treatment of vomiting after surgery
    • When some pets return home after a stay in the hospital they may drink excessive amounts of water at one time and then vomit; if this appears to be the case, the water should be limited to frequent smaller amounts.
    • Medications such as antibiotics, narcotics or nonsteroidal anti-inflammatory medication commonly cause vomiting after surgery.  In order to see which medication is causing the problem, the administration of each drug should be separated 2 hours apart.  Usually the pet will vomit or appear nauseated (drooling and sick look) within 1 hour of administration of the medication that they are sensitive to.  The antibiotic in some cases may be changed to a different one, or may be discontinued. 
    • Stomach upset from anesthesia is a potential cause of vomiting and will pass within a couple of days. 
    • An uncommon cause of vomiting after surgery is internal organ failure.  Blood testing will confirm this problem. For this reason vomiting should not be ignored if it persists for more than 24 hours.
    • If your pet had surgery of the bowels or stomach, vomiting is always a concern, as it may indicate that infection of the abdominal cavity, called peritonitis, is present.  Do not ignore this sign.
    • Symptomatic treatment of vomiting involves withholding food for 12 to 24 hours, then introducing small amounts of bland food such as rice and lean cooked hamburger, if your pet does not vomit after that then gradually wean him/her back onto the regular diet after 3 days.  In order to decrease the acidity of the stomach, Pepcid AC 0.5 mg/kg can be given by mouth twice daily for 5 days.  Metoclopramide and Cerenia are good anti-vomiting medications for dogs and cats.  You should always consult a veterinary healthcare professional before administering medication.
  • Causes and treatment of regurgitation after surgery
    • The most common cause of regurgitation is reflux of acid from the stomach into the esophagus while your pet is under anesthesia.  Acidic fluid from the stomach can cause a chemical burn of the esophagus and result in a bad case of heart burn, called esophagitis.  This results in poor motility of the esophagus, therefore water and food will accumulate in this structure.  In most cases, esphagitis is self-eliminating and will resolve within two or three days. 
    • If the esophagitis is severe the esophagus may develop one or more strictures.  A stricture is a narrowing or stenosis of the esophagus and does not allow passage of food down the esophagus, in regurgitation that lasts longer than one week.  This problem should be brought to the attention of your pet's doctor within the first two weeks so that it can be treated by ballooning the stricture (minimally invasive procedure, as it is done with the aide of an endoscope).  If an esophageal stricture is chronic surgery is needed.
    • Symptomatic treatment of regurgitation caused by esophagitis includes feeding bland food, and administering a coating agent (sucralfate) and an acid blocker (omeprazole or other).  Consult a veterinary health care professional if the regurgitation continues for more than a couple of days.

How do I know that my dog is in pain following surgery?

  • Signs of pain include
    • crying
    • biting if you get near the surgical site
    • grimacing (lips are pulled back and the the dog looks anxious)
    • tragic facial expression
    • panting
    • restlessness and unable to sleep; pacing
    • if abdominal surgery was done the pet will not lie down on the incision, or will continually sit up in spite of appearing very tired
    • the worst pain will be for the first 2 to 3 days after surgery

What can I do to control my dog's pain?

  • Narcotic medications that control pain: tramadol, butorphanol, Duragesic (fentanyl patch)
  • Anti-inflammatories used to control pain: Deramaxx, Rimadyl, Previcox, or Etogesic
  • If an orthopedic surgery has been done cold packing the surgical site may be helpful
    • A cold pack may be a pack of frozen peas, crushed ice in a Ziploc bag, or a cold gel pack; place a thin barrier between the skin and the cold pack.  An alternative to a cold pack is to freeze water in a styrofoam cup; after frozen cut the bottom of the styrofoam cup out. Cool the surgical site around the incision by rubbing the exposed ice directly on the skin in a circular pattern.  Cooling the surgical site helps to numb the area.

How do I know that my cat is in pain following surgery?

  • Pain is more difficult to assess in cats versus dogs, as signs can be more subtle and they usually do not vocalize when in pain
  • Signs of pain in a cat include the following:
    • biting if you get near the surgical site
    • growling or deep cry
    • not wanting to eat
    • hiding and not wanting to be near owner (remember that this could also be caused by the cat just being upset about leaving home and coming back)

What can be done for pain at home for my cat?

  • Pain medication such as buprenorphine or a Duragesic (fentanyl) patch
  • Tylenol will kill a cat as they lack abundant glutathione enzyme in the liver
  • Anti-inflammatories can be used, but the dose is much less than dogs

Is it okay for my pet to lick the incision?

  • If a dog licks the incision, the healing process may be delayed.
  • Licking can remove stitches and cause the incision to open
  • Licking can become a severe habit that is difficult to break
  • Licking can cause infection as the mouth has many bacteria
  • Dogs will frequently lick the incision when the owner is not watching such as at night time; if the skin looks red or excoriated the most common cause is from licking.
  • To stop your pet from licking the following can be tried:
    • Elizabethan collar can be placed on the neck; this will not help stop your pet from scratching at the region
    • Cervical collar (bite not collar) is a less awkward device and can be effective at stopping a pet from licking the surgical site
    • A tee shirt can be used to cover an incision on the chest or front part of the abdomen; gather the waist of the shirt up over the dog's back and wrap an elastic band around this part of the shirt.
    • A bandage or sock can be used to cover an incision on a limb; fasten the top of the sock to the dog's limb with tape.
    • Bitter apple can be applied around the incision; many dogs will continue to lick  after application of this topical
    • Bitter Apple and Liquid HeetTM (obtain this from a drugstore...it is used for sore muscles) mixed in a 2:1 ratio can be applied around the skin incision
    • Antipsychotic medication in some cases is needed

Board-certification by the American College of Veterinary Surgeons

What does it mean?

  • Four years of advanced training in surgery beyond the Doctor of Veterinary Medicine Degree

  • Experience in the development of new surgical treatments

  • Rigorous examination by the American College of Veterinary Surgeons to ensure competency in advanced surgical techniques

  • Assurance that a veterinarian is a surgical specialist

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