Chronic Myelogenous Leukemia

History, Lab Data

The 39 year old white male came into the University Hospital on February 25, 1971.  He stated that he was fine up until three months ago until he had a dull achy pain across his chest.  Four weeks later, he had a sharp pain on his left side, despite it previously improving with rest.  After an in depth look, the pain was in the upper left quadrant of his chest.  A pattern occurred when this happened once a week due to much physical activity.  The patient also noticed an increase in dyspnea the past two weeks.  He then decided to go to see another doctor to seek additional help.

He saw his family doctor.  This physician found an enlarged spleen as well as anemia and leukocytosis.  The next option was to go back to the University Hospital, so he went.  According to his family history; consequently, both of his parents died of malignant tumors.  Other than that, everything was fine in the patient’s history.

During the physical examination, he was alert and oriented, nourished, and cooperative adult.  His mucous membranes appeared pale.  In the left auxilla, a freely movable axillary node with the size of 2×2 was present.  The spleen was 13 cm below the left costal margin, and the liver was 6 cm below the left costal margin.  Everything else was found normal.

Here are the lab results.  The Hemoglobin was at 9.0% gm, and Hematocrit was 29.0% gm.  However, the Leukocyites were 36,300/cu mm.  Erthrocyte was 100mm/60 minutes.  The Urine Analysis came baack normal.  Uric acid was at 9 mgm %.  The L.D.H. was 560 I.U.; SGOT was 68 I.U.; Alkaline Phosphatase was 110 I.U.; Bilrubin is 1 mgm%; B.U.N. is 15% mgm, and the Blood Glucose was 102 mgm%.  The last area that was checked is the Neutrophillic alkaline phosphatase score indicated a 3.

The patient was put on a drug therapy program immediately.  He was put on busulfan 4 mgm daily, and then after two weeks it was decreased to 2 mgm daily, which was continued for another four weeks. The leukocyte count decreased to 13,900, and the platelet count was at 120,000.  However, the liver and spleen did not change.  After eight weeks, the liver and spleen remained unchanged, so the patient was started on dibromommannitol with 350 mgm in the morning.  After eight days, his hemoglobin was at 9.0 gm, and shown that there was no change while on busulfan, so dibromommannitol was discontinued, but the amnesia continued.  Once two weeks passed, the leukocyte count was 4,700/ cu mm with 3% metamyelocytes.  The platelet count was 121,000.  A repeat bone marrow aspiration occurred, and again the marrow was hypercellular.  The differential consisted of 3.0% of myeloblasts, promyelocytes at 1.3%, myelocytes at 5.3%, metamyelocytes at 15.6%, bands and segments at 78.3%, eosinophils at 2.3%, , and normoblasts at 36.3%.  He was transfused with four units of packed cells with no more chemotherapy scheduled.

Study Questions

• What is the patient’s diagnosis?
• What is his prognosis?
• Is there a cure for his disease?

Answers to the study questions.

• The patient has Chronic Myelogenous Leukemia.
• A patient can improve, and go into remission for many years.
• The only known cure at this time is a bone marrow transplant.

Discussion Section

Definition

This disease resides in the colon area in regards to the stem cells.  Later on it changes into the “acute blastic phase,” unless it is eradicated by a stem cell transplantation.[1]

Symptoms

Some patients are asymptomatic, while other patients experience “fatigue, malaise, and weight loss.” Other symtoms include a spleen enlargement, platelet dysfunction, heart attack, bleeding, infections, veous thrombosis, priapism, visual problems, vasoocclusive disease, and cerebrovascular accidents.[2]

Physical Findings

In regards to what is found physically, “Minimal to moderate splenomegaly is the most common physical finding; mild hepatomegaly is found occasionally. Persistent splenomegaly despite continued therapy is a sign of disease acceleration. Lymphadenopathy and myeloid sarcomas are unusual except late in the course of the disease; when they are present, the prognosis is poor.”[3]

Tests

In the medical field, before a person can receive treatments, tests are a requirement both for the patient and the physician.  Some include, “Complete Blood Count (CBC), Bone Marrow Biopsy (BMB), Bone Marrow Aspiration (BMA), Cytogenetics Testing, Fluorescence In Situ Hybridization (FISH) testing, Polymerase Chain Reaction (PCR) testing, Kinase Domain Mutation testing, Gleevec Blood Level testing, and miscellaneous other tests.”[4]

Results

Cell suspension immunophenotypic studies were performed on bone marrow aspirate and two regions were analyzed.
Region 1 (R1) represents the small, non-complex cells (7% of the events).

Region 2 (R2) represents the large, non-complex cells (48% of the events).

Treatment

One form of treatment is chemotherapy.  This is used for reducing symptoms, and to reverse symptomatic splenomegaly.[10] “Hydroxyurea, a ribonucleotide reductase inhibitor, induces rapid disease control. The initial dose is 1–4 g/d; the dose should be halved with each 50% reduction of the leukocyte count. Unfortunately, cytogenetic remissions with hydroxyurea are uncommon. Busulphan, an alkylating agent that acts on early progenitor cells, has a more prolonged effect.”[11]

Another form of treatment is Intensive leukapheresis, which could control the count in the blood in chronic-phase of Chronic Myleogenous Leukemia.  This can also become quite expensive, but is useful in certain emergencies The unique thing is that it helps preganant women too.[12]

The last resort is a Splenectomy.  This is used mainly for relieving symptoms of the Spleen, and for not responding to chemotherapy, or for anemic conditions.  Radiation for the spleen is rarely used to make it smaller.[13]

Current Case Study

Case 11

Physical examination

A sixty six year old man was admitted to the regional hospital due to progressive weakness and resting  dyspnea. The patient did not call his family physician for several years and he did not performed any lab tests. He started to feel unwell two months ago having occasionally minor nasal  bleedings. Four months earlier he found enlarged lymph nodes.  He did not loose any weight nor had any fever. He did not report any concomitant diseases.

• Generalized haemorrhagic diathesis on the skin
• Generalized lymph nodes enlargement (up to 3 cm of diameter)
• Mild hepatomegaly (2 cm below costal margin at deep breath)

Laboratory findings:

• Chest x-ray: Generalized emphysema, some peribronchial infiltrations in lower lungs segments, lung hila widened and polycyclic
• Abdominal ultrasonography:Minor liver enlargement. Generalized  enlargement of all retroperitoneal lymph nodes together with lymph nodes in liver and splenic hilum

Results obtained from 5-diff. counter:

• Hemoglobin “ 4.4 g/dl;
• Erythrocytes “ 1.08  T/l;
• Leucocytes “ 98.7 G/l;
• Neutrophils – 2.1 G/l;
• Lymphocytes – 53.8 G/l;
• Monocytes – 39.9 G/l;
• Platelets “ 7 G/l;

Blood film

• Anisocytosis of red cells.
• Neutrophils contains thick or toxic granulation.
• There are very numerous lymphocytes and a population of lymphoid cells with blastic appearance. These cells have very large, clearly visible nucleoli. Most of cells have smal vaculoles, their cytoplasm contain no granules…
• Platelets have normal morphology, but theit number is very depressed.

The differential count: neutrophilic segments “ 3%, monocytes – 1%, lymphocytes – 58%, lymphoid cells “ 38%,

Pictures of peripheral blood smears

• Dry aspiration.
• Trephine biopsy was not done.

Final diagnosis

Mononuclear cells of peripheral blood divided into two populations on Forward/Side scatter cytogram: population R1 consisted of lymphocytes, gate R2 contained large, hypogranular cells. Cytograms presenting the expression of antigens on the cells of R1 and R2 gate are included below:

Diffuse large B-cell lymphoma as a transformation of Chronic Lymphocytic Leukemia (Richter’s syndrome) (diagnosed on the basis of lymph node biopsy).

Refernces

1. Anthony S. Fauci, Eugene Braunwald, Dennis L. Kasper, Stephen L. Hauser, Dan L.
2. Longo, J. Larry Jameson, and Joseph Loscalzo, Eds. Harrison’s Principles of Internal Medicine, 17e.  Part Six:  Oncology and Hemotology- Chronic Myelogemous Leukemia. http://www.accessmedicine.com/content.aspx?aID=2891657&searchStr=leukemia%2c+myelocytic%2c+chronic.
3. A P Rapoport, B L Levine, A Badros, B Meisenberg, K Ruehle, A Nandi, S Rollins,
4. S Natt, B Ratterree, S Westphal, D Mann and C H June.  Molecular Remission of CML After Autotransplantation Followed by Adoptive Transfer of Costimulated Autologous T Cells.  Greenebaum Cancer Center, University of Maryland, Baltimore, MD.  33, 53–60. doi:10.1038/sj.bmt.1704317 Published online 27 October 2003. http://www.accessmedicine.com/content.aspx?aID=2891657&searchStr=leukemia%2c+myelocytic%2c+chronic
5. Atlas of Hematology:  Medyczne Wdawntwo Multimedialine.  Retrieved on February 19, 2009.  http://www.hematologica.pl/Atlas3/Angielska/Przypadek11.htm.
6. Flow Cytometry- Sore Throat and Leukocytosis.  Unniversity of Pittsburg School of Medicine:  Department of Pathology.  Retrived on February 19, 2009.  http://path.upmc.edu/cases/case56/flow.html.
7. Trey. The Leukemia and Lymphomia Society Discussion Board.  Regrieved on February 19, 2009.
8. http://ubb-lls.leukemia lymphoma.org/ubb/Forum17/HTML/001649.html