癌症病患常見問題的處理 血液暨腫瘤科 R5 林煥超

Multidiscipline Treatment of Cancer Clinical oncologist Surgeon Radiation oncologist Pathologist Radiologist Cancer various tx: Fielld 內容, 各式的治療，團隊

The Description of Cancer Patients 1.The pattern of presenting symptoms and signs. 2.The evidence of diagnosis. 3.The disease extent. 4.The treatment plan. 5.The effects and side effects of treatments. 6.The ongoing problems.

Pathophysiology of Cancer Local effects: 1. Tumor necrosis, infection, bleeding. 2. Tumor invasion of adjacent structure.

Pathophysiology of Cancer Remote effects: 1. Tumor production: hormones, growth factors, cytokines, other peptides. 2. Tumor-evoked production: a. Immune cells: antibodies, immune complex. b. Non-immune cells: other peptides. Paroneoplastic syndrome, SIADH, cachexia Polymyositis, and dermatatomyositis, MG Parapenoplastic sensory neuropathy, encephalopathy Lambert-Eation myasthenic syndrome

如何給予化學治療藥物

Action sites of cytotoxic agents DNA synthesis Antimetabolites DNA Alkylating agents 5. Principles of Chemotherapy: Action Sites of Cytotoxic Agents/Cellular Level Most cytotoxic drugs target the DNA. Two exceptions are the poisons of the mitotic spindle—vinca alkaloids and taxoids—that target the tubulin. DNA transcription DNA duplication Mitosis Intercalating agents Cellular level Spindle poisons

Action sites of cytotoxic agents PURINE SYNTHESIS PYRIMIDINE SYNTHESIS 6-MERCAPTOPURINE 6-THIOGUANINE METHOTREXATE 5-FLUOROURACIL HYDROXYUREA CYTARABINE RIBONUCLEOTIDES DEOXYRIBONUCLEOTIDES ALKYLATING AGENTS ANTIBIOTICS DNA 6. Principles of Chemotherapy: Action Sites of Cytotoxic Agents Knowledge of the different sites of action for cytotoxic agents permits, for example, the better understanding of how drugs act in combination. ETOPOSIDE RNA L-ASPARAGINASE VINCA ALKALOIDS TAXOIDS PROTEINS ENZYMES MICROTUBULES

化學治療可以 延長轉移患者的存活期 @ Primary chemotherapy 減輕癌症引起的不適 @ Palliative chemotherapy 增加手術或放射治療的療效 @ Neoadjuvant & adjuvant @ Concommitent radiosensitizer 改善臨床的治療方式

化學藥物的給藥 靜脈注射: 大多數藥物 口服藥物: VP-16, UFT, Xeloda, Hydroxyurea, 6-MP, 6-TG 長期低劑量灌注 短期靜脈輸注 靜脈推注 口服藥物: VP-16, UFT, Xeloda, Hydroxyurea, 6-MP, 6-TG

化學藥物的給藥 局部化學治療 經皮給藥: 皮膚癌 動脈內注射: 肝臟腫瘤 腹腔內注射: 卵巢癌, 腸胃道癌 肋膜腔/心包膜腔內注射: 癌性積液 脊髓腔內注射: 腦膜侵犯 腦室內注射: 腦膜侵犯 經皮給藥: 皮膚癌 常見intrathecal, intraperitoneal injection

化學藥物的靜脈給藥 依藥物,腫瘤的種類而有不同 不同的注射方式有不同的治療結果 不同的注射方式有不同的毒性反應 Adriamycin, Epirubicin 不同的注射方式有不同的殺死癌細胞的機制 5-FU

化學藥物給藥前應注意 確定病人姓名, 診斷及化療醫囑 包括藥名清楚, 劑量, 給藥方式及時間 Mitoxantrone, Mitomycin-C Fluorouracil, Fluconazole Vincristine, Vinblastine

化學藥物給藥前 選定適當的注射位置 不可使用軟組織少又有重要構造的部位 手背, 腹股溝等部位 不可使用血液流通不佳的部位 不可使用關節部位 最佳位置為前臂手掌側 Port-A 為最佳輸注管道 給藥前要確定靜脈管道通暢 選定適當的注射位置 不可使用軟組織少又有重要構造的部位, 手背, 腹股溝等部位 不可使用血液流通不佳的部位 不可使用關節部位 最佳位置為前臂手掌側 Port-A 為最佳輸注管道

化學藥物的給藥 給藥前再確定患者姓名, 藥物名稱, 劑量,給藥方式及灌注時間長短. 依醫囑所述方式給藥, 包括給藥的順序, 若有困難應立即聯絡醫師. Ara-C: push, subcutaneous, slow infusion, long term infusion. etc. Cisplatin + Taxol. CDDP + MTX

化學藥物的給藥後 不同的藥物的給藥後注意事項根據其常見毒性反應可能不同 注意嚴重的立即性毒性反應 Cisplatin: hydration & urine output Adriamycin/ Epirubicin: heart failure High dose Methotrexate: renal failure Cyclophosphamide: hemorrhagic cystitis

Side effects of chemotherapy Alopecia Pulmonary fibrosis Cardiotoxicity Local reaction Renal failure Myelosuppression Phlebitis Mucositis Nausea/vomiting Diarrhea Cystitis Sterility Myalgia Neuropathy 10. Principles of Chemotherapy: Side Effects of Chemotherapy There are multiple side effects of chemotherapy. Some are common, such as alopecia, neutropenia. Some are rare such as cardiotoxicity. The side effects are generally the consequence of the cytotoxic effect of chemotherapy on normal cells, however they can also be related to the direct toxicity of the drug.

Aim of combination therapy INCREASED EFFICACY ACTIVITY SAFETY 9. Principles of Chemotherapy: Aim of Combination Therapy The aim of combination therapy is to increase efficacy while keeping an acceptable safety profile. For example, two drugs in a combination therapy may have different mechanisms of action, and/or limiting drug resistance. Different mechanisms of action Compatible side effects Different mechanisms of resistance

會引起組織壞死的藥物 Vinka alkaloids: Vincristine(Oncovin), Vinblastine, Vinorelbine(Navelbine) Anthracyclines: Epirubicin, Idarubicin Mitomycin-C, BCNU, DTIC Taxoids, Topotecan Mithramycin, Nitrogen Mustard VP-16, Cisplatin Fludarabine, Gemcitabine, Irinotecan

化學藥物外滲的處置 及早發現,立即停止輸注 局部冷敷 抬高患處,減少水腫 治療可能之局部感染 保持壞死皮膚所形成的水泡的完整及消毒 Cold Compression for 30 min. Q6H 抬高患處,減少水腫 治療可能之局部感染 保持壞死皮膚所形成的水泡的完整及消毒 開與止痛藥物,甚至morphine 若有皮膚表面壞死, 請教整形外科共同評估,甚至需要植皮. 局部冷敷 抬高患處,減少水腫 感染 保持壞死皮膚所形成的水泡的完整及消毒 開與止痛藥物,甚至morphine 整形外科共同評估,甚至需要植皮.

Chemotherapy-associated Emesis

Type of Treatment-related Emesis 1.Acute-phase symptoms: Correlated with serotonin (5-HT) release from enterochromaffin cells. Emetic signals are propagated at local 5-HT3 receptors.

Type of Treatment-related Emesis 2.Delayed-phase symptoms: Not to be related to serotonin. Severity and duration often correlate with drug dosage. Nausea severity reportedly is similar during both phases.

Type of Treatment-related Emesis 3.Anticipatory emetic symptoms: An aversive conditioned response Develops after repeated antineoplastic treatments that are characterized by poor emetic control. Complete control throughout antineoplastic treatment remains the best preventive strategy.

Antiemetic Options 1. Serotonin (5-HT3) receptor antagonists: Granisetron (Kytril) Ondansetron (Zofran) More effective and safer to use then other types of antiemetics.

Serotonin Antagonists Ondansetron, Granisetron. 健保給付規定 1.骨髓移植患者接受高劑量化學治療時。 2.惡性腫瘤患者使用cisplatin劑量超過50mg/m2可預防性使用一日劑量。Delay vomiting每療程使用以不得超過五日為原則

Serotonin Antagonists 3.惡性腫瘤患者使用中性致吐劑cisplatin劑量>30，< 50mg/m2可預防性使用一日劑量且發生嚴重延遲性嘔吐，使用dexamethasone及metoclopramide無效之病例，每療程使用以不得超過五日為原則。須檢附病歷摘要及使用 dexamethasone及 metoclopramide 無效之記錄。

Serotonin Antagonists 4.接受腹部放射照射之癌症病人，得依下列規範使用ondansetron及granisetron： (1)total body or half body irradiation (2)pelvis or upper abdominal region of single irradiation dose> 6 Gy (3)腹部放射治療中產生嘔吐，經使用dexamethasone、metoclopramide或prochlorperazine等傳統止吐劑無效，仍發生嚴重嘔吐之患者。

Antiemetic Options 2. Steroids: Acute-phase symptoms: effective against mildly to moderately symptoms. Delayed-phase symptoms: most active agents. Dexamethasone (2-20mg) & methylprednisolone + 5-HT3- and D2-receptor antagonists.

Antiemetic Options 3. Metoclopramide: A weak competitive 5-HT3-receptor antagonist at high dosages. 4. Benzodiazepines: Lorazepam (Ativan). 5. Dopaminergic (D2)-receptor antagonists: Phenothiazines—Prochlorperazine. Butyrophenones—Haloperidol.

Neutropenic Fever

Neutropenic Fever Fever: 1 oral temperature > 38.3oC. 2 oral temperatures > 38oC, an hour apart. Neutropenia: ANC (Band + Neutrophil) < 500/mm3. ANC 500/mm3 ~ 1,000/mm3, with a predicted decline to < 500/mm3 within 48 hours.

Neutropenic Fever In the absence of white cells: 1. Signs and symptoms of invasive infections may be absent. 2. Infections can invade and spread quickly. 3. Fever may be the only manifestation of a potentially life-threatening infection.

Neutropenic Fever Bacteremia: 10% to 20% Gram-positive bacteremia: 70% Coagulase-negative staphylococcus S. aureus. Gram-negative bacteremia: 30% Escherichia coli, Klebsiella sp., Enterobacter sp., and rarely, Pseudomonas aeruginosa.

Neutropenic Fever Common sites of local infection: The respiratory tract. Sinuses. Skin, soft tissue. Venous catheter entry/exit sites. Urinary tract. Gastrointestinal tract: oral cavity, anus.

Neutropenic Fever Laboratory evaluation: CBC/DC, Platelet. Chemistries (hepatic and renal function). Blood cultures. U/A and U/C. CXR.   Any accessible sites of possible infection.

IDSA 2002 Guidelines CID 2002; 730-51

Vancomycin In initial empirical therapy: 1. Clinically suspected serious catheter- related infections. 2. Known colonization with penicillin- and cephalosporin-resistant pneumococci or MRSA. 3. B/C gram-(+) bacteria before final identification and susceptibility testing. 4. Hypotension or other evidence of CV impairment.

G-CSF Filgrastim, Lenograstim. 健保給付規定 (1)造血幹細胞骨髓移植 (2)血液惡性疾病接受靜注化學治療後 (3)先天性或循環性中性白血球低下症者 (當白血球數量少於1000/mm3，或中性白血 球(ANC)少於500/mm3)。

G-CSF (5)重度再生不良性貧血病人嚴重感染時使用，惟不得作為此類病人之預防性使用。 (4)其他惡性疾病患者在接受化學治療後，曾經發生白血球少於1000/mm3，或中性白血球(ANC)少於500/mm3者，在下一療程即可使用。 (5)重度再生不良性貧血病人嚴重感染時使用，惟不得作為此類病人之預防性使用。 (6)化學治療，併中性白血球小於100 /mm3 癌症不受控制、肺炎、低血壓、多器官衰竭或侵犯性微菌感染等危機程度高之感染。 使用本品之患者應檢附治療記錄，其內容需包括診斷、白血球數量變化、所使用之化學治療藥物名稱、劑量及使用本品劑量，如白血球超過4000/mm3時或中性白血球超過2000/mm3時，應即停藥。

癌症疼痛 Cancer Pain

晚期癌症患者常見症狀 Pain 89% Fatigue 69% Weakness 66% Lack of energy 61% Dry mouth 57% Constipation 51% Dyspnea 50% Sleep Dis. 49% Depression 41% Cough 38% Nausea 36% Edema 28% Taste 28% Hoarseness 24% Anxiety 24% Vomiting 23%

癌症疼痛可由一些簡單的治療方式在90%的患者得到有效的處置 Cancer pain can be managed effectively through relatively simple means in up to 90% of Patients. Unfortunately, pain associated with cancer is frequently undertreated.

疼痛評估的基本原則 相信病人的疼痛抱怨 仔細詢問癌症及疼痛相關病史 評估心理狀態、可請精神科協助 進行理學、神經學檢查 開立診斷方式：如 CT，bone scan，MRI 開始治療疼痛以便利適當檢驗 重新評估治療的反應 再設計、討論進一步治療方式 Ask about pain regularly.經常關心有無疼痛 Assess pain systematically.系統性的評估 Believe the patient and family in their reports of pain and what relieves it.相信所言 Choose pain control options appropriate for the patient, family, and setting. 選擇可接受之治療 Deliver interventions in a timely, logical, and coordinated fashion.給予適當的治療 Empower patients and.their families.多加激勵 Enable them to control their course to the greatest extent possible 鼓勵參與 自我疼痛評估的主幹 可幫助患者描述: 疼痛 PAIN 部位 LOCATION 嚴重程度 INTENSITY OR SEVERITY 加強或減輕的因素 AGGRAVATING AND RELIEVING FACTORS 疼痛的認知及反應 COGNITIVE RESPONSE TO PAIN 疼痛控制的目標 GOALS FOR PAIN CONTROL

治療的基本原則 1.Dose "by mouth" whenever possible. 2. Around the clock (ATC): Basal analgesic administration should not be based on an "as needed" (prn) basis. 3.Dose by the WHO three-step ladder.

WHO Analgesic Ladder Co-analgesics Strong Opioids ± Non-Opioids Morphine, Oxycodone,Hydromorphone, TTS-Fentanyl, Methadon , Step 3 Co-analgesics Weak Opioids ± Non-Opioids Codein, Dihydrocodein, Tramadol, Tilidin/Naloxon Step 2 Non-Opioids Ibuprofen, Diclofenac, „Cox 2“ Paracetamol, Metamizol, Flupirtin Step 1

1 8 - 12 Morphine 2 Oxycodone 7.5 Hydromorphone 100 48 - 72 Strong Opioids Relation 1 2 7.5 100 Duration 8 - 12 48 - 72 Morphine Oxycodone Hydromorphone Fentanyl-TTS

Strong Opioids Morphine 10mg IV, IM = 20mg SC = 30mg PO

Morphine SR Fentanyl-TTS Dosage If pain continues: 2 x 30 mg A. 2 x 60 mg B. 3 x 30 mg never < 8 hrs 12 hrs 8 hrs Fentanyl-TTS Dosage If pain continues: 25 mg/h A. 50 mg/h B. 25 mg/h never < 2 days Every 3. day Every 2. day

Rapid Calculation of Duragesic for Cancer Pain Divide morphine equivalent dose (mg/day) PO by 2, round off to closest Duragesic patch in mcg/hr EXAMPLE: Pt is on morphine (PO) 180 mg/day -> 180 /2 = 90, round off to Duragesic 100 mcg/hr

癌病代謝性急症 (Metabolic Emergencies in Oncology)

高血鈣症:病程之變化 Early signs : fatique,lethargy, constipation, nausea and polyuria. Polyuria and nocturia secondary to renal tubular defect in water conservation. ==> Dehydration Stupor and coma are signs of severe hypercalcemia

高血鈣症的鑑別診斷 Endocrine/metabolic disorders Cancer Infectious disease Renal insufficiency Granulomatous diseases Dietary/drug related Milk_alkali syndrome 高血鈣症最常見原因為癌症及副甲狀腺功能亢進

高血鈣症的治療 Saline hydration and diuretics Steroids: inhibit bone resorption and decrease GI tract calcium absorption. most helpful in myeloma, leukemia and breast cancer Calcitonin: increase renal excretion and reduce bone resorption

高血鈣症的治療(II) Diphosphonates : reduce calcium flux from bone. osteoclast inhibitor. Gallium nitrate : inhibit bone resorption Mithramycin : kill osteoclasts. Biphosphonates mechanism check

腫瘤融解症候群 Tumor Lysis Syndrome

腫瘤細胞內含物及其代謝產物大量釋出於血液中所引發的全身性反應 Rapid release of intracellular contents into the blood stream

主要代謝異常及其引致之病變 Hyperuricemia: acute urate nephropahy --> obstruction and renal failure Hyperkalemia: cardiac arrhythmias Hyperphosphatemia : acute renal failure Hypocalcemia: muscle cramp, cardiac arrhythmias and tetany

Tumor Lysis常見於下列腫瘤 Large tumor burdens, rapid proliferative fraction and sensitive to chemotherapy. High grade lymphoma ,such as Burkit's lymphoma.Leukemia with high leucocyte counts, CML in blastic crisis Rarely seen in solid tumors: small cell lung ca, breast cancer Few hours to few days after initiation of treatment

Tumor Lysis臨床症狀 Oliguria-azotemia Hyperkalemia, hyperphosphatemia, hyperuricemia Tetany Cardiac arrhythmia Hypotension-shock Cardiac arrest

如何早期發現 Tumor Lysis 密切檢測 Chemistry screen : K+, Ca++, uric acid, PO4,LDH,BUN,creatinine

Tumor Lysis的治療方式 Prevention for high risk patients Hydration 2500-3000ml/sqm/day Sodium bicarbonate for alkalinization to urine PH >7 (50-100meq / L) Allopurinol 10 mg/kg/day ,, 300mg/day (12 hrs before C/T), reduces to 100mg/day if creatinine > 2mg%

Tumor Lysis的治療方式 Monitor elctrolytes, uric acid, phosphorus, calcium and creatinine daily for 1 week once tumor lysis developed, monitor the lytes every few hours. Hypocalcemia : calcium gluconate Hyperkalemia : Kayexalate (15 gm q6h), 20% dextrose with 10-20 U of insulin /liter. Hyperphosphatemia : aluminum gel 30cc q3-4 hrs

Tumor Lysis的治療方式 早期使用血液透析 potassium >6 mEq/l uric acid > 10mg/dl phospharus > 10 mg/dl, symptomatic hypocalcemia and fluid overload.

脊索壓迫症候群 Spinal Cord Compression

脊索Spinal cord壓迫症候群 硬腦膜外extradural的脊索壓迫症候是惡性腫瘤常見的神經學併發症. 不論是硬腦膜外的腫瘤或是較罕見的由脊髓內腫瘤所引起者,如未有立即的診斷及迅速的治療,皆可引起永久性的神經系統傷害.

部位分布 硬腦膜外轉移 頸椎 10% 胸椎 70% 腰椎及薦椎 20%

可能的腫瘤 任何可轉移的腫瘤皆可發生 肺癌約佔了15% 乳癌, 攝護腺癌, 淋巴瘤, 骨髓瘤及原發布為不明的轉移癌則各約佔 了10%.

臨床徵候 被壓迫脊髓相對神經分布部位的疼痛, 腸道及膀胱自主神經控制的異常(autonomic dysfunction), 肢體無力及被壓迫脊髓相對神經節以下部位的感覺喪失. 疼痛可以是局部的也可以是神經根壓迫式(radicular pain). 受侵犯部位的脊椎可有壓痛(point tenderness).

放射線及實驗室的診斷 要做可能侵犯部位的脊椎X光檢查,也常可見有脊椎骨的破壞. 傳統上是用脊髓腔攝影(myelography)來確定病灶的範圍,阻斷的部位及嚴重程度及是否有其他部位尚未有症狀的脊髓壓迫. 核磁共振攝影成為這類病患最佳的檢查方式

臨床症狀 90%以上的患者會有脊椎中線或脊柱旁區域 的疼痛. 通常再躺下時會加劇, 而在站著或坐著時會減輕 神經根的壓迫性疼痛(Radicular pain)是一常見的早期症狀, 疼痛與脊椎間盤疾病, 肋膜發炎, 膽囊炎及胰臟炎的疼痛類似. 下肢的無力及麻木感但無感覺異常 (paresthesias) 便秘或是大解失禁

理學檢查 脊椎部位的壓痛. 若加上脊髓病變的徵候則極有可能有硬腦膜上的轉移腫瘤. 被壓迫的脊椎部位以下可出現 DTR增加(hyperactive) Babinski 徵候陽性 運動無力 感覺異常(hypesthesia) 肛門括約肌張力減低

脊椎X光檢查 癌症患者有背痛者皆應做脊椎X光檢查 脊椎X光檢查在80%的患者可判斷有無硬腦膜外的轉移. 最常見的有 pedicles的喪失, 脊椎體的破壞及脊椎體的崩解(collapse)

臨床處置及治療 懷疑有這類併發症的患者需立即住院並會診神經外科醫師及放射腫瘤專科醫師. 需要立即且積極的使用類固醇(例如dexamethasone, 4-10 mg IV q6h) 緊急的放射治療或是神經外科手術減壓來治療.

Highlight of Leukemia Management Bleeding diasthesis Risks of life-threatening hemorrhage -- ICH, DIC, pulmonary hemorrhage Fever, neutropenic fever Hyperleucocytosis Severe anemia Organomegaly

Cytochemical staining Myeloperoxidase (MPO): AML M1,2,3,4,5 Chloroacetate esterase (CAE): M1,2,3,4 Alpha-naphthyl butyrate (ANBE): M4,M5 PAS: ALL, AML (15%) Tdt: ALL LAP score: leukocyte ALK P stain (80-100) LAP < 20 in CML, PNH

Approach of Acute Leukemia Blasts≧30% Peroxidase stain Positive Negative CAE PAS Positive Negative POS Neg ANBE ALL AML M6,7 CD41,61 Glycophyrin AML Mo CD13,33,65 ALL CD2,7,10,19 AML M1-M4 CD13,14,33,65 M4,M5

CHROMOSOME ANALYSIS For diagnosis For prognosis t(9,22) : CML t(2,5) : Ki-1 lymphoma ALCL t(4,11) : biphenotypic leukemia For prognosis Favorable : t(8,21), t(15,17), inv(16) Unfavorable : -5/del, -7/del, +8 For detection of minimal residual disease

AML-Treatment Remission induction: Ara-c 100mg/m2/d X7, Idarubicin 12mg / m2/d X3 Consolidation: Standard Ara-c 100mg/m2 X 5, Ida X2 High dose Ara-c 1-3gm/m2 Bid X 4days Maintenance: not helpful Stem cell transplant — Allo-BMT, Allo-PBSCT — ABMT, autologous PBSCT — MUD, no better than HiDAC — Allo-minitransplant (mixed chimerism) Acute GVHD, VOD, interstitial pneumonia, TRM 30%

COMMON CHEMOTHERAPY REGIMEN AML A) 7 + 3 Ara - C 100mg/m2 + N/S or D5W 500ml CIV qd or bid Idarubicin 10-12mg/m2×d + N/S 100ml IV infusion for 1hr (Mitoxantrone same as Idarubicin) B) HDAC Ara-C 1gm-3gm/m2×bid + N/S 500ml IV infusion for 3-4 hours

Acute Promyelocytic Leukemia ( M3 ) Remission induction : ATRA 45/m2/d WBC > 3000/cumm : ATRA + Idarubicin 12 mg/m2 WBC > 10000/cumm : ATRA + Ida × 3 + Ara – C Consolidation : 7+3 then HIDAC + DNR or IDA Maintenance : 1 yr ATRA or observation ( APL 93 trial ) 5 yr DFS = 70 % Retinoid acid syndrome : weight gain ,hyperleucocytosis ,interstitial pulmonary infiltrate , pleural or pericardial effusion , hypoxemia , hypotension Treatment : dexamethasone 10 mg bid × 3 day

Treatment of ALL Remission induction : - standard risk : vincristin , prednisolone - high risk : vincristin , PDN , doxorubicin Early intensification : L – asparaginase, MTX CNS prophylaxis : MTX , dexamethasone Consolidation : Ara – C , cyclophosphamide Maintenance : 6 MP/MTX , VCR/PDN , VP-16 ALLO-BMT, PBSCT ( auto, MUD )

Clinical Practice in Ward 1st WK: FAB subtype (confirm DX), Karyotype, set IV line, cyto-reduction , initiate C/T, blood component, control infection, risk factors 2nd WK: C/T, infection, hemorrhage 3rd WK: d15 BM exam, folic acid, G-CSF fungal infection, HSV, diarrhea 4th WK: recovery of CBC, fever should subside otherwise consider partial remission or fungal infection Always check skin, oral cavity, bowel, anus, venipuncture site, UA, CXR

MANAGEMENT OF ACUTE LEUKEMIAS SET IV line, CVP, PICC or port-A Blood component transfusion supportive care for bleeding and infection blood culture in febrile patients empirical antibiotics Reverse isolation, single room or HEPA Gut decontamination Bone marrow aspiration & biopsy Flow cytometry for leukemia markers lymphoid and myeloid Chromosome, cytogenetic study Cytochemical stain PCR, ISH

NOTICE OF PLATELET TRANSFUSION Hazards of low platelet count platelet　 70 - 80K guarantee safety for operation platelet　 ＜ 50K bleeding in minor trauma platelet　 ＜ 20K spontaneous bleeding Bleeding diathesis DIC, sepsis, aplastic anemia acute leukemias high dose chemotherapy stem cell transplantation thrombocytopenia of any cause

Fever in Acute Leukemia Before admission: pneumonia, leukemia 1st 7 days: infection, G(-) bacilli, Ara-c 2nd 7 days: infection, G(+) cocci, blood transfusion 3rd 7 days: G-CSF, blood transfusion, G(+)/G(-) fungi, herpes simplex HSV NEC: necrotizing neutropenic enterocolitis Common site of infection: mucositis, dental, perianal infection, IV catheter, skin, ENT, lung, G-I.

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