Leukemias

A 68 year old lady who has been experiencing fatigue for a couple of months comes to see you in the office. She has felt slightly depressed and mildly short of breath. She denies any diarrhea, vomiting, fever chills or rigors.

HENT exam reveals mild pallor, dental examination is normal, Chest is clear, cardiac exam reveals an ejection systolic murmur. Quality of pulse is normal.  Abdomen reveals fullness in the upper part and there is dullness in the peri-umbilical region and left upper quadrant.

Serum chemistry is normal, CBC shows Hb. 10.2, WBC 84,000/cumm, Predominantly neutrophils with altered nuclear morphology, Platelet count 104K/cumm.

Which of the following is NOT compatible with the patient's condition?

1. Chest X ray with indentation of the gastric bubble.

2. Philadelphia chromosome

3. Busulfan is the drug of choice

4. Gleevac (Imatinib) is commonly used to treat it.

5. Interferon is a helpful drug in such cases.

Answer is 3. This patient has CML and Hydroxyurea is the drug of choice not Busulfan. Although Busulfan is used to help, because of its cost advantage over hydroxyurea, Busulfan is not the DOC. Gleevac is contending to be the DOC on account of its effectivity and good side effect profile..

Management of CML ( Chronic myelocytic/granulocytic leukemia)

Explanation

CML/CGL is a leukemia with a relatively good prognosis and patients usually survive a long time without intervention. One should only intervene if patient has symptoms or a high white count (>50,000 and stop once count falls below 20,000).

Latest drug Nilotinib (Tasigna) does even better than Gleevac thus becoming the drug of choice for CML.

The drug of choice was Hydroxyurea. Busulfan is an inexpensive alternative.

Bone marrow transplant in patients <50 is a chance for cure.

Interferon reduces the number of cells with the Philadelphia chromosome.

Beware of hyperviscosity which is due to sludging of cells. Treat it with leukapheresis/exchange transfusion.

Philadelphia chromosome is sometimes talked about and is a sign of good prognosis when present in CML.

On the other hand, if it is present in AML, it is a warning of bad outcome.

Many doctors had made me write about Gleevec (Imatinib) - a tyrosine kinase inhibitor that stops the formation of an abnormal tyrosine kinase that the Philadelphia chromosome produces. Thus these abnormal cells die. CML gets well controlled. I have not yet read about this being the drug of choice in CML. Now Nilotinib outperforms Gleevac by about 25%.

Latest drug Nilotinib (Tasigna) does even better than Gleevac thus becoming the drug of choice for CML.

62 year old man comes to your office with complaints of fatigue, and bleeding from the gums whenever he brushes. The fatigue has been going on for the past 8 months. He denies any unusual sexual exposure or drug usage.

Examination reveals a relatively well looking man with normal nutritional status. Vitals reveal a Blood pressure of 168/90 and a pulse of 88. Lungs reveal bibasilar crackles that do not disappear on coughing.

labs reveal Hb 9.7g/dL, WBC 32,000/cumm 95% lymphocytes, Platelets of 402,000/cumm . Smudge cells are present on the manual film interpretation. Chest Xray is normal. Peak flow is 430LPM

Which of the following is NOT a reasonable advice for this patient?

1. Start Atenolol

2. Reassure him that most patients with his condition have a good, long life

3. Do a bone marrow analysis

4. Chlorambucil is the drug of choice

5. CT of the chest is needed to diagnose his pathology

Answer is 5. This patient most likely has CLL.

Manage a case of CLL.

Explanation

This is the commonest leukemia in the US. It is typically found on routine blood screening.

Prognosis is good, especially if  Platelet count is >100 and Hb >10gm & <3 areas (of lymphatic tissue) involved.

Treatment is with Chlorambucil (Leukeran) and Prednisone (Prednisone is especially helpful in those with auto-immune cytopenias which are a common feature associated with CLL). We know that Steroids reduce Lymphocytes and Eosinophils.

In this particular case, the patient will need evaluation of different lymphatic sites to prognosticate him but diagnosis does not require CT of the chest. It will be confirmed with bone marrow biopsy/aspiration. Smudge cells in peripheral smear is highly indicative of CLL.

ALL is yet another story:

Prognosis is poor. Almost all cases occur in children under the age of 10.

Symptoms are of pancytopenia - anemia (fatigue, SOB), thrombocytopenia (bleeding, poor healing) and Leucopoenia (many infections). fatigue, bleeding.

Diagnosis is by marrow analysis.

Treatment includes Chemotherapy ASAP and Stem cell/Bone marrow transplant.

Marrow transplant is today facilitated by the enormous database of the marrow registry. http://www.marrow.org/NMDP/registry.html