ALL Topic review- Case presentation

Transcription

1 ALL Topic review- Case presentation 26 June 2014 By: Boudor AL-Ghabban Pharma D student, KSU- college of pharmacy

2 Outlines: Topic Review Introduction Epidemiology Etiology Pathophysiology Signe and symptom Work up Diagnosis 5 years survival rate Treatment Case Components

3 Topic review Acute lymphoblastic leukemia (ALL) Introduction Acute leukemia, the most common form of cancer in children, comprises approximately 30 percent of all childhood malignancies, with acute lymphoblastic leukemia (ALL) being five times more common than acute myeloid leukemia (AML) -ALL is most common in childhood with a peak incidence at 2 5 years of age, and another peak in old age. National Vice President, Intramural Research, American Cancer Society, Atlanta, GA.

4 Topic review cont. Introduction cont. -It is the leukemia most responsive to therapy. -Poor prognostic indicators are as follows: age <2 or >9; WBC >l05/mm3 and/or CNS involvement. -Presence of any of the following is associated with an increased risk for CNS involvement: B-cell phenotype, increased LDH, rapid leukemic cell proliferation. National Vice President, Intramural Research, American Cancer Society, Atlanta, GA.

5 Topic review cont. Epidemiology Annual Report Prepared by the Staff of the Tumor Registry Research Unit, Oncology Centre King Faisal Specialist Hospital and Research Centre,2011

6 Topic review cont. Etiology Risk Factors/Causes: Prenatal exposure to x-rays. Postnatal exposure to high doses of radiation. ** Genetic conditions that include the following: Down syndrome. Neurofibromatosis. Bloom syndrome. Inherited genetic polymorphisms. Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and Iceland.

7 Topic review cont. Pathophysiology

8 Topic review cont. Pathophysiology cont. Morphology : According to the FAB system: L1 lymphoblasts are small cells with scant cytoplasm, condensed nuclear chromatin, and indistinct nucleoli. Most children with ALL cases (85 to 89 %) are classified as having FAB L1. L2 lymphoblasts are larger cells with a moderate amount of cytoplasm, dispersed chromatin, and multiple nucleoli. In some studies, L2 has been associated with worse prognosis than has L1. However, when patients are stratified according to age, sex, and initial WBC, differences in prognosis between L1 and L2 are no longer observed 11 to 14 % of cases of ALL in children are classified as FAB L2. Prognostic importance of morphology (FAB classification) in childhood acute lymphoblastic leukaemia (ALL).

9 Topic review cont. Pathophysiology cont. Morphology : L3 lymphoblasts have deep cytoplasmic basophilia with prominent cytoplasmic vacuolation. L3 morphology correlates with a more guarded prognosis. The L3 cell usually has mature B cell characteristics and often is treated using drugs effective for highly aggressive B cell lymphoma variants. Less than 1 % of cases of ALL in children are classified as FAB L3. Prognostic importance of morphology (FAB classification) in childhood acute lymphoblastic leukaemia (ALL).

10 Topic review cont. Pathophysiology Immunophenotype Leukemia cells in ALL are classified according to immunophenotype using an extensive panel of monoclonal antibodies to cell surface "cluster of differentiation" (CD) markers The genetic basis of early T-cell,B-cell precursor acute lymphoblastic leukaemia.

11 Topic review cont. Signs and symptoms: They result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature leukocytes (white blood cells). Therefore, people with ALL experience symptoms from malfunctioning of their erythrocytes (red blood cells), leukocytes, and platelets. -Anemia -Generalized weakness and fatigu -Dizziness -Breathlessness -Pallor -Headache due to low RBC level -Increased risk of bacterial infection such as pneumonia, urinary tract infection (due to neutropenia) Cranial nerve involvement in children with leukemia and lymphoma.

12 Topic review cont. Signs and symptoms cont. -Excessive and unexplained bruising -Epistaxis -petechiae due to low platelets -Bone pain, joint pain (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity) -Enlarged lymph nodes, liver and/or spleen -Fever, Weight loss and/or loss of appetite -CNS involvement-diffuse or focal neurological dysfunction(e.g, menengitis, seizures) Cranial nerve involvement in children with leukemia and lymphoma.

13 Topic review cont. Diagnosis: Because the symptoms are so general, many other diseases with similar symptoms must be excluded. -Medical history and physical examination -Complete blood count(anemia, thrombocytopenia, granulocytopenia, WBC count is variable from 1000/mm 3 to 100,000/mm 3 ) -Blood smears(blast cells are seen on blood smear in majority of cases). Brunning RD, Flandrin G, Borowitz M, et al. Precursor B lymphoblastic leukaemia/lymphoblastic lymphoma (Precursor B-cell acute lymphoblastic leukaemia).

14 Topic review cont. Diagnosis cont. -Bone marrow biopsy is conclusive proof of ALL(replacement of marrow by blast). -Lumbar puncture will tell if the spinal column and brain have been invaded. -Medical imaging (such as ultrasound or CT scanning) can find invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys, and reproductive organs. Brunning RD, Flandrin G, Borowitz M, et al. Precursor B lymphoblastic leukaemia/lymphoblastic lymphoma (Precursor B-cell acute lymphoblastic leukaemia).

15 Topic review cont. Classification: WHO recognizes two immunophenotypic subtypes of ALL: Precursor B-cell. Precursor T-cell. Brunning RD, Flandrin G, Borowitz M, et al. Precursor B lymphoblastic leukaemia/lymphoblastic lymphoma (Precursor B-cell acute lymphoblastic leukaemia). In: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds), IARC Press, Lyon p.111.

16 Topic review cont. Treatment: * Goal: Cure (absence of detectable cancer cells in the body (usually less than 5% blast cells in the bone marrow). * Modalities: Chemotherapy. Radiation Therapy. Hematopoietic stem cell transplantation. Terry L. Schwinghammer _Pharmacotherapy handbook 7th edition_ The McGraw-Hill Companies,US: 2009 chapter 14 p 163

17 Topic review cont. Treatment cont: Duration: Approx years of continuation therapy, boys might take longer time -The earlier acute lymphocytic leukemia is detected, the more effective the treatment. Terry L. Schwinghammer _Pharmacotherapy handbook 7th edition_ The McGraw-Hill Companies,US: 2009 chapter 14 p 163

18 Topic review cont. Treatment cont: Chemotherapy is the initial treatment of choice. Most ALL patients will receive a combination of different treatments. There are no surgical options, due to the bodywide distribution of the malignant cells. Chemotherapy for ALL consists of four phases: Induction: The goal is to induce remission, it lasts 4 weeks. includes a Glucocorticoid, Vincristine, Asparaginase, and possibly an Anthracycline. Intensification: To reduce the leukemic cell burden before the emergence of drug resistance and relapse. High dose Methotrexate with continuous Mercaptopurine. Combinations of Vincristine, Peg-aspargaseor,Cyclophosphamide,Mercaptopurine and Cytarabine. Terry L. Schwinghammer _Pharmacotherapy handbook 7th edition_ The McGraw-Hill Companies,US: 2009 chapter 14 p 163

19 Topic review cont. Treatment cont: Maintenance: Non myelosuppressive chemotherapy for 4-8 weeks to maintain remission and allow the BM to recover, followed by delayed intensification. Weekly Methotrexate and daily 6- Mercaptopurine, In addition pulses of GC and Vincristine. Reintensification: High risk patients before Hematopoietic stem cell transplantation (HSCT). Dexamethasone, Etoposide, Cytarabine, Asparginaseand IT (Methotrexate, Cytarabine, Hydrocortisone) Terry L. Schwinghammer _Pharmacotherapy handbook 7th edition_ The McGraw-Hill Companies,US: 2009 chapter 14 p 163

20 Topic review cont. Treatment cont. Radiation therapy is used on painful bony areas, in high disease burdens, or as part of the preparations for a bone marrow transplant (total body irradiation). Survival rate in adult with ALL = %

21 Case contents

22 General information : AS is a 9 years old girl known case of pre B low risk ALL diagnosed on 29/4/2014 on chemotherapy drug consolidation phase 2 week(6) {not started yet }. There is a history of moderate oral thrush {chemo was held once only}.

23 Chief Complaint : She was presented to the ER on complaining of back pain and fever for 1 day.

24 History of Present illness: Patient came to the ER with fever and mild back pain, on paracetamole(400mg PO). She was diagnosed with Fever without neutropenia T=38.5 o c WBC=9.6 10e9 /L ( e9 /L). ANC= e9 /L ( e9/L). Negative blood culture.

25 Past Medical History : Conditions Pre B low risk ALL Oral thrush Date of Diagnosis 29/4/ /5/ 2014 Treated with fluconazole

26 surgical history: Unremarkable. Family History : Unremarkable. Social History : Unremarkable. Allergies : Not known to have allergy.

27 Medication History : Medication Route Dosing Regimen Indication Lasix IV 25 mg OD Constipation Paracetamol PO 400 mg q 4-6 hours Pain and fever Ceftriaxone IV 2000 mg OD FN Amikacin IV 650mg OD FN Fluconazole PO 135mg OD Oral thrush Specific mouth wash PO 5ml Q6h Oral thrush Gentamicen IV 190mg OD FN Tazocin IV 2250mg Q6h FN

28 Medication History cont. : Medication Route Dosing Regimen Indication vincristine IV 1.5 mg /m2 (1.23 mg )for 5 weeks starting on day 2 and continuing in day 9,16,23,30 ALL Pegylated l- asparaginase IM 1000 iu / m2 (2500 iu) on Day 4 and 18 ALL

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30 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. PICO P: Newly diagnosed ALL patients N= 174. I: PEG asparaginase. C: placebo. O: Relapse-Free Survival {RFS} (The median follow-up was 36 months ).

31 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Outcome measures The primary efficacy end point: Relapse-Free Survival (RFS). Secondary efficacy end points: - Overall survival (OS). - Duration of objective response.

32 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Study designs Randomized, double-blind, placebo-controlled, phase III trial.

33 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Statistical analysis Secondary end point Primary end point

34 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Statistical analysis ** Secodary end point- Duration of objective response-. Samples were obtained from 62 patients after a single IV dose (2000/IU/m2) of pegaspargase. Serum asparagine concentration of less than 3 M is considered optimal deamination.

35 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Statistical analysis ** Secodary end point- Duration of objective response-. Samples were obtained from 62 patients after a single IV dose (2000/IU/m2) of pegaspargase. Serum asparagine concentration of less than 3 M is considered optimal deamination.

36 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Statistical analysis ** Secodary end point- Duration of objective response-.

37 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Statistical analysis ** Safety of IV pegasparaginase.

38 First-line treatment of acute lymphoblastic leukemia with pegasparaginase cont. Conclusion of the study In conclusion, pegasparaginase chemotherapy show better RFS in comparison to placebo with low incidence of serious AEs.

39 On Physical Examination : Day of admission ( 15/6/2014) Gen Looks lethargic, febrile, not dehydrated ENT VS CV Chest Abdomen NEURO Oral thrush BP 110/ 62 mm Hg, HR 128 bpm, RR 25 bpm, T 38.5 C. S1+S2+0 Clear bilaterally Soft, lax No neurological insult

40 Labs and Diagnostic tests (15/6/2014) : Laboratory data WBC NEUT (Absolute neutrophils) RBC HGB Hct Plt Na K Urea Patients labs e9 /L (N) e9 /L (N) e12/L (L) 7.1 g/dl (L) (L) 95 10e9/L (L) 132 mmol/l (L) 4 mmol/l (N) 8.9 mmol/l (H) Normal Range e9 /L e9/L e12/L g/dl L e9/L mmol/l mmol/l mmol/l

41 Labs and Diagnostic tests cont.(15/6/2014) : Laboratory data Creatinine Patients labs 26 umol/l (N) Normal Ranges umol/l Calcium Corrected calcium Phosphorus Mg Albumin Bilirubin (total) ALT 2.03mmol/L(L) 2.33mmol/L(N) 1.42 mmol/l(n) 1.03 mmol/l(n) 28 g/l (N) 17 umol/l (N) 40 U/L (N) mmol/l mmol/l mmol/l mmol/l g/l 2-22 umol/l 2-40 U/L Alkaline Phosphatase 145 U/L (N) U/L

42 Problem List: 1-FN. 2-ALL. 3- Oral thrush. 4- Back pain.

43 Management on day 1 (15 /6/2014) Assessment: -Child looks lethargic, febrile T =38.5 C, not dehydrated not in distress. -BP 110/ 62 mm Hg, HR 128 bpm, RR 25 bpm -Lab tests: ANC= e9 /L ( e9/L). Plt=95 10e9/L ( e9/L). CRP=4 mg/l Normal: < 0.8 mg/l, Low risk: <1.00 mg/l. Average risk: mg/l. High risk: >3.00 mg/l.

44 Management on day 2,3 (16-17/6/2014) Assessment: -She looks well, pale, not in distress, febrile T=38.7 C -BP 92/ 50 mm Hg, HR 130 bpm, RR 25 bpm -Lab test: ANC=2.6 10e9/L ( e9/L) Plt=93 10e9/L ( e9/L) CRP= 4 mg/l Normal: < 0.8 mg/l, Low risk: <1.00 mg/l. Average risk: mg/l. High risk: >3.00 mg/l.

45 Labs and Diagnostic tests (16-17/6/2014) Laboratory data Patients labs Normal Ranges WBC NEUT (Absolute neutrophils) RBC HGB Hct Plt Na K Urea 4 10e9 /L (N) e9 /L (N) e12/L (L) 7.4 g/dl (L) (L) 93 10e9/L (L) 136 mmol/l (N) 3.3 mmol/l (N) 6.8 mmol/l (H) e9 /L e9/L e12/L g/dl L e9/L mmol/l mmol/l mmol/l

46 Labs and Diagnostic tests cont. (16-17/6/2014) Laboratory data Patients labs Normal Ranges Creatinine Calcium Corrected calcium Phosphorus Mg Albumin 24 umol/l (N) 2.09mmol/L(L) 2.27mmol/L(N) 1.17 mmol/l(n) 0.79 mmol/l(n) 29 g/l (N) umol/l mmol/l mmol/l mmol/l mmol/l g/l

47 18-20/6/2014 Assessment: -She looks well, pale, not in distress, febrile T=38.3 C -BP 92/ 50 mm Hg, HR 130 bpm, RR 25 bpm -Lab test: ANC=2.6 10e9/L ( e9/L). Plt=93 10e9/L ( e9/L). Negative blood culture. Patient developed diarrhea.

48 18-20/6/2014 cont. Assessment cont. : - The diarrhea is watery 4 time /day. - Patient started on metronidazol 200 mg IV. Q 8 hours for 7-10 days. - IVF D5% NS. - Stool for culture.

49 21/6/2014 Assessment: -She looks well, pale, not in distress, febrile T=38.3 C -BP 91/ 50 mm Hg, HR 130 bpm, RR 25 bpm -Lab test: ANC= 3 10e9/L ( e9/L). Plt=95 10e9/L( e9/L).

50 21/6/2014 cont. Assessment cont. : - Stool is negative Clostridium difficile. - The frequency of diarrhea become1 time/day. - Patient started on liposumal Amphotericin B 135 mg IV OD.

51 22-23/6/2014 Assessment: -She looks well, pale, not dehydrated not in distress, low grade fever T=37.5 C, diarrhea one time / day. -BP 91/ 50 mm Hg, HR 130 bpm, RR 25 bpm. -Lab test: ANC= 3 10e9/L ( e9/L). Plt=95 10e9/L( e9/L). - Chest and Sinuses CT ordered to role out any viral infection. - Repeat stool culture. - Negative blood culture.

52 24-25/6/2014 Assessment: -She looks well, pale, not dehydrated not in distress, low grade fever T=37.5 C, diarrhea one time / day. Plane: - Follow up the ordered test. - Continue the same treatment.

53 Medication : Medication Route Dosing Regimen Indication Paracetamol PO 400 mg q 4-6 hours Pain and fever - Day 11. Liposumal Amphotericin B IV 135 mg OD To cover any fungal infection - Day 5. Metronidazol IV 200 mg Q 8 hours Diarrhea - Day 8. Specific mouth wash PO 5ml Q6h Oral thrush - Day 11. Gentamicen IV 190mg OD FN - Day 10. Tazocin IV 2250mg Q6h FN - Day 10.

54 Thank you