Sunday 17 June 2007

ACUTE LYMPHOBLASTIC LEUKEMIA

QUESTION 1
Select a patient in your clinical setting and provide a brief descriptive profile outlining their age, diagnosis, disease stage and general treatment plan.
WT is a seventeen years old boy who was referred to Emergency Department by a GP with two weeks of legs petechia rash, hematuria, bilateral lower leg pain and general lethargic. It was also noted that he had a bruising and bleeding easily over last few days, tachycardic, and haematomesis. There were no epistaxis or melena presents.
From blood test showed that his blood counts were abnormal.
Haemoglobin: 110 l
White Cell Count: 268.5 c
Neotrhophills: 21.6 h
Platelets: 17 c
Circulating Blast Cells: 198.5 c
Lymp: 35.6 h
Mono: 8.9 h
RBC: 3.77 l
HCT: 0.33 l
Microscopy MSU:
WBC: >100 x 10,000,000
RBC: >100 x 6
Epi: <10
Chemistry: Positive of ketones, protein,
From blood test’s result, Tom was suspected with Acute Leukemia. Tom was then referred to haematology ward for further investigations after stayed overnight at children’s ward. These investigations include Bone Marrow Aspirate, CT Abdoment, Chest Xray, HIV V2V HSU serology and routine blood test such as FBC, EUC, CRP, LFT, Co agulation, & C3 nephritic factor.
After investigations were performed, Tom was finally diagnosed with Acute Lymphacytic Leukemia (ALL). The treatment plan for him includes:
To commence induction chemotherapy by using BFM 95 protocol.
Tissue typing of the family if allogenic stem cells transplant required in the future.
Sperm Banking.
Further Bone Marrow Biopsy and other test to view the response to induction therapy.
To understand leukemia, it is important to understand the process of blood formation. The formation of blood cells started in bone marrow which called haematopoiesis. Leukemia is a type of blood cancer affecting the bone marrow. Bone marrow is the spongy center of the bone that produces blood cells. All mature blood cells are originated from a pluripotent stem cell which is produced in bone marrow. Stem cell can be divided into two lineages, myeloid lineage and lymphoid lineage. These are a type of mature myeloid and lymphoid cells, including white cells or leukocytes (help the body fight against infection and other disease), red blood cells or erythrocytes (carry oxygen from the lungs to the body’s tissues and take carbon dioxide from the tissue back to the lungs), and Platelets (help form blood clots that control bleeding). These cells are normally produced in an orderly controlled way when the body needs them, but with leukemia that process gets out of control.

Leukemia means white blood. In leukemia the marrow produces too many immature white blood cells, which is called blasts. These immature white blood cells are abnormal shaped and cannot carry out their normal duties. These blasts are multiplying and crowding the bone marrow, as they interfere the production of other type of blood cells. Red cells, platelets and mature white cells will be affected. When they circulate in the body, they can be stayed in different places causing swelling or pain. Leukemia has a sudden onset and rapid progression of symptoms and disease.
Acute leukemia can be classified into acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML develops when maturation and proliferation of myeloid stem cell are abnormal, and ALL is established when abnormalities in maturation and proliferation of the lymphoid stem cells are occurred. In other word lymphocytic leukemia that affects the white blood cells called lymphocytes, which is the overproduction of the immature lymphocytes. Lymphocytes control the body’s immune response by finding and destroying foreign substances.

ALL is common occurred in children by two third (Cremer et al. 2002, 6). As the abnormal white blood cells cannot help the body fights against infection, frequent infections and flu-like symptoms such as fever and chills will occur. As the abnormal cells keep multiplying and move out into the body, they are tend to be collected in the lymph nodes organs such as liver or spleen or joints.

QUESTION 2
Outline the role of diagnosis and staging in the evaluation of your patient’s disease and its relevance to the general treatment plan.
Untreated ALL shows the presence of abnormal white blood count, haematocrit, haemoglobin, platelets counts, bone marrow (more than 5% blast) as well as the presents of signs and symptoms of the disease. The diagnosis can be made by performing full physical examination, blood test, bone marrow aspirate/biopsy and other additional tests. The physical examination is to find out the swelling in the liver, the spleen, and the lymph nodes under the arms, groin and the neck. From Tom’s physical examination were found that he had swelling under the arms, groin and the neck. He also had an enlarged spleen.

Blood test is performed to see what the cells look like under the microscope and compare the number of abnormal cell with the normal cells. Tom’s blood test showed that he had excessive white blood cells count (268.5) and circulating blast cells (198.5). There is no blasts should be circulating in the blood.

Bone marrow aspirate is a procedure by taking a sample of bone marrow using needle inserted into large bone, usually hip. Sometimes a small cykindrical piece of bone and marrow are also needed, this procedure is called bone marrow biopsy. This procedure will confirm weather or not the leukemia is present. The ALL can be established when 25% more of nucleated cells in the marrow contain lymphoblast.
There is no clear cut staging system for ALL according to Pui and Evans (1998, 2). They also noted that the diagnosis of ALL is depending on immunophenotyping. Unlikely AML which can be identified by the presence of auer rods, myelophoblastic leukemia, or monocyte associated esterases, ALL is lack of specific morphologic or cytochemical features (Pui & Evans, 1998, 2).
World Health Organisation (WHO) classified the types of leukemia in respect to where the cell formation is disruptive and with prognosis of outcomes. Cytogenetics can confirm the diagnosis and favourable or unfavourable outcomes.
Leukemic cell characteristic such as morphological features cytocemistry, immunologic cell surface and biochemical markers and cytogenic characteristics are important when diagnosing leukemia. However cellular classification using French, American and British (FAB) classification is limited for ALL, it is still used. The FAB classification classified ALL into three morphology types including L1 T-cell and B-cell in children, L2 T-cell and B-cell in adult, and L3 B-cell (Burkitt cell types). L1 morphology occurred in 84% of children with ALL, and 80% of Adult ALL have L2 morphology.
Immunophenotyping is more relevant to ALL when makes diagnose or prognosis. Immunophenotyping can be studied by flow cytometry. Flow cytometry and the use of monoclonal antibodies allow detecting cell surface antigents. Antigens are identified by cluster differentiation (CD) number.
The treatment plan for Tom is to commence induction chemotherapy with Vincristine, Daunorubicin, and Asparaginase without methotraxate.

QUESTION 3
Considering your answer to question 2, review the current literature and rationalize the treatment regime your patient is currently receiving.
The course of therapy for ALL can be divided into three stages:
1. Induction therapy.
2. CNS propylaxis.
3. Post remission therapy.

The aim of induction chemotherapy therapy is to achieve complete remission. Complete remission is defined by restoration of normal haematopoesis including less than 5% of blast cells present on bone marrow and no circulating blast cells.
Front-line therapy for children with ALL is mostly similar in all developed countries including Australia.

Induction chemotherapy used for Tom included:
Prednison 60 grams/m2/day per oral from day 1 to day 29.
Vincristine 1.5 grams/m2 per intravenous on day 8, 15, 22, 29. Daunorubicin 30 milligrams /m2 per intravenous on day 8 & 15. Asparaginase 5000 units/m2 per intravenous on day 12, 15, 18, 21, 24, 27, 30, 33.
It is called BFM 95 protocol with modification. For his treatment, metotraxate was not used.
The side effect of Asparaginase is quite significant. For some patients, coagulopathies, pancreatitis and allergic reaction could occur. Therefore, a test dose of 100 units of asparaginase subcute is required 45 minutes prior to the therapy. APPT, PT, Fibronogen level and Pancreatic Lipase test should be taken prior to asparaginase. If fibrinogen level <1.0 g/l or Lipase level are rising, a specialist has to be contacted. When pancreatitis is present, no further dose is to be given (RNSH Hematology Department, 2001).
Gated heart pool scan cardiac echo needs to be considered to rule out ventricular dysfunction if further dose of daunorubicin required, as this chemotherapy is toxic to the heart at cumulative dose of 400 mg/m2. For high risk ALL, additional dose might be added on day 22 and 29 (RNSH Hematology Department, 2001).
After normal hematopoesis was restored post induction therapy which is called in remissio, patient will be a candidate for intensification (consolidation) therapy. The treatment will commence shortly after the induction of remission. According to RNS Haematology Protocol for Chemotherapy (2001), the treatment protocol for Tom is called BFM 95 Protocol MCA which includes Methotrexate given in high dose, 6-mercaptopurine per oral plus Cytarabine. For High risk ALL, Etoposide and Asparaginase are added without 6-Mercaptopurine. This protocol is called BFM 95 Element HR-3.
Pui et al (p. 7) also suggested that intensive multi drug therapy commenced post induction of remission will make remission lasting-longer, especially in young adults. Cyclosphomide and Cytarabine might be benefit for patient’s with T-cell ALL. It was also suggested that Cytarabine with dose will improve the outcome of patient with standard, risk, or high risk ALL (Pui et al. p. 7).
Some suggestion made by Gaynon (2002, 1) that the progress of the treatment also can be achieved by improving the post induction therapy. Pui et al (p. 7) concluded that the successful cure of ALL depends on the development of more effective multi drugs regime on well designed clinical trial. Tom has not started with intensification therapy yet as he just commenced with induction therapy.
Most of the patient with ALL can be expected to attain complete remission status following appropriate induction therapy. According to Pui et al. (p.6) the rate of complete remission for ALL in children now ranges from 97 to 99 percent and lower in adult from 75 to 90 percent. All patients with ALL are at risk of developing central nervous system involvement during the course of their disease.

QUESTION 4
Identify two actual or potential complications that may confront your patient in light of their treatment regime or disease progression.

Nausea and vomiting was perceived by patients to be the most distressing side effect of chemotherapy (Coulbourne, 1995, p. 442; Potter & Schafer, 1999, p.2). Chemotherapy drugs have been cited to often cause nausea and vomiting within 1-2 hours. However, some drugs induce these symptoms several hours after treatment. Symptoms observed ranged between a mild to severe level of severity, depending on the types of the drugs and the doses used. Usually this condition was cited to resolve within 24 hours or over several days (Held-Warmkessel, 1998, p. 43).
Chemotherapy drugs were seen to have a potential inducing nausea and vomiting in a variety of ways. Drugs associated with pronounced nausea and vomiting were noted to be that of Camustine, Cisplatin, Cyclophosphomide, Cytarabine, Dacarbazine, Dactinomycin, Doxorubicin HCl, Lomustine, Mechlorethamine HCL, and Procarbazine HCl (Glick, Griffith & Mortimer, 1998, p. 50). According to RNSH Chemotherapy Patient Information Leaflet (2001), Asparaginase and Daunorubicin have a potential nausea and vomiting side effects. It is not only on early side effects, but also on late side effects. However, mild nausea might be expected in Vincristine.
Dodd, Onishi, Dibble & Larson (1996, p. 160) determined the differences in the side effects of nausea, vomiting and retching between younger and older patients receiving chemotherapy. This research reported that younger patients’ consistently had higher nausea, vomiting, and retching than older patients. Therefore, this finding suggested that older patients could be given more aggressive chemotherapy regimes, as they were seen to be able to tolerate them better than younger patients (Dodd et al., 1996, p. 160).

Fatigue was reported as the most common and debilitating response to chemotherapy treatment (Carrol-Johnson et al, p. 116; Held-Warmkessel, 1998, p. 42; Mast, 1998; Richardson, et al. 1998). Patients receiving chemotherapy for the treatment of cancer, frequently experience severe fatigue, which was seen to be highly distruptive and distressing (Richardson & Ream, 1997, p. 35). Fatigue will be expected for patients who are receiving Asparaginase, Vincristine, and Daunorubicin (RNSH Chemotherapy Patient Information Leaflet, 2001).
Fatigue was also cited to increase over the time that the patient receives chemotherapy treatment (Berger, 1998, p. 51-62; Carrol-Johnson, et al. 1998, p 116; Richardson, et al. 1998) and after treatment (Carrol-Johnson, et al. 1998, p 116). The level of fatigue was reported to occur frequently in the afternoon and early evening, and perpetuate throughout the day (Richardson, et al. 1998). It was cited that fatigue reverted to baseline levels before the next chemotherapy cycle, and persisted for years after treatment has been completed (Carrol-Johnson, et al. 1998, p 116).
Fatigue was cited to affect the general well-being of patients, by weakness, and negative effects such as their general well-being, their specific body parts, change in self image and their daily activities. There were reported to be varying degrees and dimensions of ‘being tired’. Tiredness was not only seen as physical in nature, but also mentally exhausting (Messias, Yeager, Dibble & Dood, 1997, p. 45). Medication, nutritional status, work, and other physical conditions were seen to implicate the cause of fatigue. Patients, who were viewed to have more energy, were reported to be less tired with a lower dose of chemotherapy or on the termination of treatment (Messias et al. 1997, p.46).
When it came to patients’ awareness and expectations, some persons were reported to not have prepared for the degree or the extent of fatigue that they may experience, while others recognized the invetability and the expectations of the fatigue on the bases of their prior knowledge (Messias et al. 1997, p.46). It was also reported that "patient express frustration, worry, concern, displeasure, fear, depression, and disappointment regarding their fatigue" (Messias et al. 1997, p.46). Some patients experience frustration by the extent and the dimension of their tiredness. Others reported being annoyed or bothered by the fatigue. Fatigue was also viewed to be associated with mood and energy levels. It was seen to diminish patients’ levels of functioning and slow their pace of operation, decrease their threshold for activity, and make the person totally disabled. Patients who were tired have been seen to have difficulty with sleeping, a need for increased sleep, and also observed to lack a desire to be active. As a result of the adverse reactions from chemotherapy, patients who had fatigue were cited to be working fewer hours, taking increased time off, experiencing diminished interest and productivity, and frequently expressing their concern about the possible negative effects of not working or not going to school (Messias et al. 1997, p.46).

Dimensions of fatigue were described as the extent of fatigue, distress caused by fatigue, the influence of fatigue on the ability to engage in social activities and impact of fatigue on work related activities. By knowing these dimensions of fatigue, the nurse will be able to provide more effective help for individual who experienced fatigue (Richardson et al. 1998).