Diffuse large B-cell lymphoma ICD-10-CM：C83.3 - 臺北榮民 ...

疾病名稱：Aggressive lymphoma - Diffuse large B-cell

lymphoma

ICD-10-CM：C83.3

壹、前言

一、適用範圍 Scope

Diffuse large B-cell lymphoma (DLBCL)is a neoplasm of medium or large B

lymphoid cells whose nuclei are the same size as, or larger than, those of normal

macrophages, or more than twice the size of those of normal lymphocytes, with a

diffuse growth pattern.

二、目的 Purpose

(一) To provide clinical physicians a practical approach of diffuse large B cell

lymphoma.

(二) To provide hema-oncologists a standard practice in a patient with a

diagnosis of diffuse large B-cell lymphoma.

三、指引使用者 The target users of the guideline

(一) General physicians

(二) Hema-oncologists

(三) Researchers

貳、重要臨床準則

一、評估 Assessment

(一) History taking including past history, family history, personal history,

occupation history, B symptoms,

(二) Through physical examination (exam lymphoid region, spleen, liver)

(三) Performance status, nutrition status, and mental status

二、診斷依據 Diagnosis criteria

(一) Diffuse large B-cell lymphoma

1. Lymph nodes demonstrate partial or more commonly total architectural

effacement by a diffuse proliferation of medium or large lymphoid

cells.

2. Immunophenotype: The neoplastic cells typically express pan B-cell

markers such as CD19, CD20, CD22 , CD79a, and PAX5, but may

lack one or more of these.

(二) Variants

Common morphologic variants

1. Centroblastic

2. Immunoblastic

3. Anaplastic

(三) Subtypes

1. Germinal center B-cell subtype

2. Activated B-cell subtype

三、鑑別診斷 Differential Diagnosis

(一) Hodgkin lymphoma

(二) Metastatic carcinoma

(三) Melanoma

(四) Anaplastic large cell lymphoma

(五) Burkitt lymphoma

(六) Disorders causing reactive hyperplasia of lymph nodes

四、疾病（病理）分期 Disease and Pathology stage

Ann harbor stage

(一) Stage I: Involvement of one node or a group of adjacent nodes or single

extranodal lesions without nodal involvement.

(二) Stage II: Involvement of two or more nodal groups on the same side of the

diaphragm ; or stage I or II by nodal extent with limited contiguous

extranodal involvement. Stage II bulky as above with “bulky” disease.

(三) Stage III: Involvement of lymph nodes on both sides of the diaphragm; or

involvement of nodes above the diaphragm with spleen involvement. .

(四) Stage IV: Additional noncontiguous extralymphatic involvement.

(五) Extent of disease is determined by positron emission tomograph/computed

tomography (PET/CT) for avid lymphomas and CT for nonavid histologies.

Tonsils, Waldeyer's ring, and spleen are considered nodal tissue.

五、臨床症狀 Signs and symptoms

(一) The key clinical and laboratory features

1. Lymphadenopathy, typically with rapidly enlarging tumor mass at

single or multiple nodal or extranodal sites.

2. Systemic B symptoms (i.e fever, weight loss, drenching night sweats)

(二) Other clinical features:

1. Hypercalcemia

2. SVC syndrome or airway compression

3. Hyperuricemia and tumor lysis syndrome

4. Intestinal obstruction

六、發生率與盛行率 Incidence and prevalence

(一) Diffuse large B-cell lymphoma comprises 25~35% of adult non-Hodgkin

lymphomas in western country.

(二) In the United States, the incidence of DLBCL is approximately 5.6 cases per

100,000 person years. Incidence varies by ethnicity with Caucasian

Americans having higher rates than Blacks, Asians, and American Indian or

Alaska Natives, in order of decreasing incidence.

(三) In Taiwan, 2474 cases were diagnosed of Non-Hodgkin lymphoma and

1326 cases diagnosed of DLBCL in 2016.

七、檢驗與其他檢查 Laboratory and other examination

(一) CBC with differential counts

(二) Comprehensive metabolic panel including serum creatinine, calcium, uric

acid, electrolytes, lactate dehydrogenase (LDH), alkaline phosphatase

(三) HBV testing

(四) Whole-body PET/CT scan or Chest/abdominal/pelvis CT with contrast

(五) Bone marrow aspirate and biopsy (1~2cm), bone marrow biopsy may not be

needed if PET/CT scan is negative for bone marrow involvement.

(六) MUGA scan/echocardiogram if anthracycline-based regimen is indicated

(七) Pregnancy testing

(八) Consider lumbar puncture in high risk patients: HIV associated lymphoma,

involvement of paranasal sinus, testicular involvement, epidural

involvement, double expresser lymphoma (MYC ≥40% and BCL2 ≥50%),

presence of 4-6 risk factors (including age > 60 years, stage III or IV

disease, serum LDH > normal limit, extranodal involvement > 1 site,

performance status > 1, kidney or adrenal gland involvement)

(九) If clinically indicated: head and neck MRI or CT, HIV testing, HCV testing,

β2-microglobulin

八、住院及出院條件 Admission and Discharge criteria

(一) Admission criteria

1. Confirm pathology and staging workup.

2. Surgical intervention.

3. Chemotherapy which is unable or unsafe to be completed at the

outpatient clinic.

4. Treat moderate to severe complications.

(二) Discharge criteria

1. No active problems needed to be managed

2. Scheduled chemotherapy is completed with an appointment for

outpatient clinic follow-up.

九、主要治療處置 Primary treatment and management

(一) First Line Chemotherapy:

1. Rituximab + CHOP( cyclophosphamide, doxorubicin, vincristine,

prednisolone)

2. Dose dense RCHOP 14

3. Dose adjusted R-EPOCH ( rituximab, etoposide, prednisolone,

vincristine, cyclophosphamide, doxorubicin)

(二) First line consolidation (optional):

1. High dose therapy with autologous stem cells rescue in age-adjusted IPI

high risk patients.

2. Lenalidomide maintenance for patients 60–80 y of age may be

considered.

(三) Second line Therapy (candidates for high dose therapy with autologous

stem cells rescue)

1. ESHAP (Etoposide, Methylpredisolone, high dose Cytarabine, Cisplatin)

+/- R

2. ICE (Ifosfamide, carboplatin, etoposide) +/- R|

3. DHAP (dexamethasone, cytarabine, cisplatin) +/- R

4. GDP (gemcitabine, dexamethasone, cisplatin) +/- R

5. MINE(Mitoxantrone,Ifosfamide, Mesna, Etoposide) +/- R

6. GemOx (gemcitabine, oxaliplatin) +/- R

(四) Second line therapy (Not candidates for high dose therapy)

1. Bendamustine +/- Rituximab

2. Bendamustine + Rituximab + Polatuzumab vedotin-pliq (after ≧ 2

prior therapies)

3. Brentuximab vedotin for CD30+ disease

4. CEOP (cyclophosphamide, etoposide, vincristine, prednisone)±

rituximab

5. DA-EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide,

doxorubicin) +/- R

6. GDP± rituximab

7. GemOx± rituximab

8. Ibrutinib (non-GCB DLBCL)

9. Lenalidomide ± rituximab (non-GCB DLBCL)

10. Rituximab

11. Clinical trial

(五) Radiotherapy

十、輔助或替代治療 Adjuvant /Substitute treatment

(一) Supportive care for tumor lysis syndrome (TLS)

1. Laboratory hallmarks of TLS: high potassium, high uric acid, high

phosphorous, low calcium

2. Treatment of TLS:

(1) Rigorous hydration.

(2) Management of hyperuricemia:

A. Allopurinol beginning 2-3 days prior to chemotherapy in

high-risk patients, and continued for 10-14 days.

B. Rasburicase indicated if any of the following risk factors:

spontaneous TLS, elevated WBC, bone marrow involvement,

pre-existing elevated uric acid, ineffectiveness of allopurinol,

renal disease or acute renal failure, bulky disease, adequate

hydration impossible or difficult.

(二) Prevention of HBV reactivation

1. Prophylactic antiviral therapy with entecavir is recommended for any

patient who is HBsAg-positive and receiving anti-lymphoma therapy.

2. If there is active disease (PCR+), it is considered treatment/management

and not prophylactic therapy.

3. In cases of HBcAb positivity, prophylactic antiviral therapy is preferred;

however, if there is a concurrent high-level hepatitis B surface antibody,

these patients may be monitored with serial hepatitis B viral load.

4. Entecavir is preferred prophylaxis agents, maintain prophylaxis up to 12

mo after oncologic treatment ends.

十一、預後 Outcome

In the R-CHOP era, the 5-year progression-free and overall survival rates are

approximately 60% and 65%.The International Prognostic Index (IPI) remains a

valuable prognostic tool.

(一) International prognostic index for aggressive lymphomas (N Engl J

Med1993; 329:987-994.)

1. Unfavorable variables

(1) Age > 60 years

(2) Serum LDH > normal

(3) Poor performance status 2-4

(4) Ann Arbor stage III or IV

(5) Extranodal involvement > 1 site

2. Risk group

(1) Low: 0 or l

(2) Low/Intermediate: 2

(3) High/Intermediate: 3

(4) High: 4 or 5

(二) NCCN-IPI in the rituximab era (Blood 2014;123:837-842.)

1. Unfavorable variables

(1) Age, years

A. >40 to ≤60: 1

B. >60 to <75: 2

C. ≥75: 3

(2) LDH, normalized

A. >1 to ≤3: 1

B. >3: 2

Ann Arbor stage III-IV: 1

Extranodal disease: 1

Performance Status ≥2: 1

2. Risk group

(1) Low: 0 or l

(2) Low/Intermediate: 2-3

(3) High/Intermediate: 4-5

(4) High: ≥6

十二、住院天數 Length of stay

(一) 3 days for standard first-line R-CHOP treatment.

(二) 14 days or more with major complications listed above.

十三、出院計畫 Discharge Plan

(一) Regular follow-up at out-patient clinic.

(二) Adequate symptomatic treatment.

(三) Inform major side effects of treatment (e.g. neutropenia, tumor lysis

syndrome side effects of chemotherapy, etc.)

(四) Inform symptoms and signs of major complications (as listed above)

十四、出院衛教 Discharge health education

(一) Nutrition education for cancer treatment patients.

(二) Oral hygiene instructions.

(三) Instructions for take-home drugs (eg. Corticosteroids, anti-HBV drugs,

granulocyte colony-stimulating factor, etc.)

(四) Warning signs that need urgent medical attention (eg. Fever, bleeding,

dyspnea, etc.)

十五、出院追蹤 Discharge Follow up

(一) CBC and differential counts, renal, liver function tests and electrolytes

(二) Interim and end of treatment imaging evaluations with CT scans or PET/CT

scans.

參、文獻

1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H. WHO

classification of tumours of haematopoietic and lymphoid tissues, revised

fourth edition. Lyon, France: IARC; 2017.

2. National Comprehensive Cancer Network. B-cell lymphomas. (Version

4.2019). Retrieved from

https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

3. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A

predictive model for aggressive non-hodgkin’s lymphoma. N Engl J

Med1993; 329:987-994.

4. Zhou Z, Sehn LH, Rademaker AW, et al. An enhanced International

Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell

lymphoma treated in the rituximab era. Blood 2014;123:837-842.

肆、編審人員

編審姓名職稱簡歷

撰寫者林庭安總醫師學歷國立陽明大學醫學系學士

經歷臺北榮總血液科總醫師

專長血液學、內科腫瘤學

審核者王浩元主治醫師學歷台北醫學大學醫學系醫學士

經歷臺北榮總血液科主治醫師

部定國立陽明大學內科學科講師

專長 (淋巴瘤、骨髓瘤、白血病、血球

過高或低、缺鐵性貧血) 固態性腫

瘤 (大腸直腸癌、肺癌)

疾病名稱：Immune Thrombocytopenic Purpura

ICD-10-CM: D69.3

壹、前言


Thrombocytopenia in which apparent exogenous etiologic factors are lacking

and in which diseases known to be associated with secondary thrombocytopenia have

been excluded.


(一) To provide clinical physicians a practical approach of thrombocytopenia.

(二) To provide oncologists a standard practice in a pt with a diagnosis of

immune thrombocytopenia.



(二) Hematologist

(三) Researchers


一、Assessment

(一) History taking, including past history, family history, personal history,

occupation history.

(二) Through physical examination

(三) Performance status, nutrition status, and mental status


(一) Mucocutaneous hemorrhage, purpura, ecchymosis, rnenometrorrhagia, visceral

hemorrhage.

(二) Thrombocytopenia below 120,000 (with otherwise normal blood routine)

(三) Prolonged bleeding time

(四) Positive anti-platelet antibodies in serum mostly


(一) Secondary thrombocytopenia such as drugs induced, septicemia etc.

(二) Aplastic anemia

(三) Acute leukemia

(四) Vascular purpura

(五) Disseminated intravascular coagulopathy (DIC)

(六) Hereditary disorders of coagulation

四、臨床症狀 Signs and symptoms

(一) Petechiae, purpura, and easy bruising are expected

(二) Epistaxis, gingival bleeding, and menorrhagia are common

(三) Overt gastrointestinal bleeding and gross hematuria are rare

(四) Intracranial hemorrhage, a potentially fatal bleeding complication, is so

uncommon that there is no reliable estimate of its frequency.

五、發生率與盛行率 Incident and prevalence

Annual incidence of ITP: 22 per million per year, using a platelet count cut-off of

50,000/microL

六、檢驗與其他檢查 Laboratory and other examination

(一) Peripheral blood smears to make sure platelet count and rule out platelet

clumping

(二) HIV and HCV testing

(三) Coagulation test such as P.T, & A.P.T.T. Special test-DIC test if differential

diagnosis necessary.

(四) Helicobacter pylori testing if clinical suspected.

(五) Thyroid function testing if clinical suspected.

(六) Coombs' test if combined with anemia

(七) Bone marrow aspiration-for ruling out other thrombocytopenic conditions.

七、住院及出院條件 Admission and Discharge criteria


1. severe thrombocytopenia

2. treatment for complications


1. stable blood cell count

2. no other active problems which need further management

八、主要治療處置 Primary treatment and management

(一) Transfusion therapy of PRBC if indicated

(二) Corticosteroid: dexamethasone 40mg for four days or prednisolone 1 mg/kg,

then tapering gradually.

(三) IVIG for urgent management of bleeding associated with thrombocytopenia or

before an urgent invasive procedure

九、輔助或替代治療 Adjuvant /Substitute and second-line treatment

(一) Thrombopoiesis-stimulating agents (romiplostim or eltrombopag)

(二) Rituxumab

(三) Splenectomy if steroid dose not response well.

十、預後 Outcome

(一) As with many aspects of ITP, there are better data for ITP in children than in

adults. Case series with long follow-up in children support a conservative

approach to treatment, since most children eventually achieve a spontaneous

remission from ITP if they are followed for 10 to 20 years. Appreciation of this

benign outcome has markedly diminished the frequency of splenectomy in

children

(二) The mortality of ITP in published case series ranges from 0.3- 5%,

consistent with the estimated frequency of intracranial hemorrhage

(三) Major complications:

1. Bleeding including cerebral hemorrhage, visceral hemorrhage

2. Hypovolemic shock

十一、住院天數 Length of stay

(一) Uncomplicated cases: 7 days

(二) Complicated cases: 21 days

十二、出院計畫 Discharge Plan

(一) Regular follow-up at out-patient clinic

(二) Inform major side effects of treatment

(三) Inform symptoms and signs of major complications

十三、出院衛教 Discharge health education

(一) lose observe if any symptoms/signs of bleeding

(二) Return to hospital if any significant bleeding

十四、出院追蹤 Discharge Follow up

(一) CBC and differential counts. Adjust medication accordingly.

(二) closely follow-up immunological status and identify and treat infection as

indicated

參、文獻

1. Cooper N. State of the art - how I manage immune thrombocytopenia.

British journal of haematology. 2017;177(1):39-54.

2. George, JN, Vesely, SK. Immune thrombocytopenic purpura--let the treatment

fit the patient. N Engl J Med 2003; 349:903.

3. Rodeghiero, F, Ruggeri, M. Is splenectomy still the gold standard for the

treatment of chronic ITP?. Am J Hematol 2008; 83:91.

4. Neunert CE. Management of newly diagnosed immune thrombocytopenia:

can we change outcomes? Hematology Am Soc Hematol Educ Program.

2017;2017(1):400-5.

5. Lambert MP, Gernsheimer TB. Clinical updates in adult immune

thrombocytopenia. Blood. 2017;129(21):2829-35.

6. Hill QA. How does dapsone work in immune thrombocytopenia?

Implications for dosing. Blood. 2015;125(23):3666-8.

7. Chaturvedi S, Arnold DM, McCrae KR. Splenectomy for immune

thrombocytopenia: down but not out. Blood. 2018;131(11):1172-82.

肆、編審人員


撰寫者蔡淳光住院總醫師學歷陽明大學醫學系學士

經歷內科部血液科總醫師

專長血液疾病

審核者王浩元主治醫師學歷台北醫學大學醫學系

經歷內科部血液科主治醫師

專長血液性疾病 (淋巴瘤、骨髓瘤、白血

病、血球過高或低、缺鐵性貧血)

疾病名稱：Multiple Myeloma

ICD-10-CM：C90.0

壹、前言


This clinical practice guideline encompasses all patients diagnosed with a

malignant proliferation of plasma cells derived from a single clone. The synonyms

include: plasma cell myeloma, myelomatosis, medullary plasmacytoma, Kahler’s

disease. Benign plasma cell dyscrasia, such as monoclonal gammopathy of

undetermined significance, heavy chain disease, and POEMS syndrome, are not

included in this guideline.


(一) To provide clinical physicians a practical approach of myeloma.

(二) To provide hema-oncologists a standard practice in patients with a diagnosis

of myeloma.



(二) Hema-oncologists

(三) Medical staff including nurses, technicians, and social workers

(四) Researchers

貳、重要臨床準則 1


(一) History taking, including past history, family history, personal history,

occupational history.

(二) Complete physical examination

(三) Performance status, nutritional status, and mental status

二、診斷依據 Diagnosis criteria2

(一) Symptomatic multiple myeloma

1. M-protein in serum or urine

(1) No level of serum or urine M-protein is included.

(2) M-protein in most cases is >30 g/dL of IgG, or >25 g/L of IgA, or

>1 g/24 hours of urine light chain. But some pts with symptomatic

myeloma have levels lower than these.

2. Bone marrow clonal plasma cells or plasmacytoma

Monoclonal plasma cells usually exceed 10% of nucleated cellsl in the

marrow but no minimal level is designated because about 5% of pts

with symptomatic myeloma have <10% marrow plasma cells.

3. Related organ or tissue impairment (CRAB: hypercalcemia, renal

insufficiency, anemia, bone lesions)

The most important criteria for symptomatic myeloma are

manifestations of end organ damage including anemia, hypercalcemia,

lytic bone lesions,renal insufficiency, hyperviscosity, amyloidosis or

recurrent infections.

(二) Asymptomatic (smoldering) myeloma

1. M-protein in serum at myeloma levels (>30 g/L)

and/or

2. 10% or more clonal plasma cells in bone marrow

3. No related organ or tissue impairment (so-called CRAB) or

myeloma-related symptoms

(三) Clinical variants

1. Non-secretory myeloma

2. Plasma cell leukemia

The number of clonal plasma cells in the peripheral blood (PB)

exceeds 2*109/L (2,000/cumm) or is 20% of the leukocyte differential

count.2


(一) Malignancy with osteolytic bone lesions

(二) Osteoporosis

(三) Amyloidosis not related to multiple myeloma

(四) Monoclonal gammopathy of undermined significant (MGUS)

(五) POEMS syndrome

Patients with POEMS syndrome have an osteosclerotic myeloma (versus

osteolytic in typical myeloma) with any one or more of the following:

1. P–demyelinating polyneuropathy

2. O–organomegaly: hepatosplenomegaly, lymphadenopathy

3. E–endocrinopathy: hypogonadism, hypothyroidism

4. M–M-protein in blood or urine

5. S–skin abnormalities: hyperpigmentation, hypertrichosis


(一) Durie and Salmon staging system

1. Stage I

(1) Low M-protein levels: IgG <50 g/L, IgA <30 g/L; urine BJ <4

g/24hr

(2) Absent or solitary bone lesions

(3) Normal hemoglobin, serum calcium, Ig levels (non-M protein)

2. Stage II

Overall values between I and III

3. Stage III: any one or more of the following

(1) High M-protein: IgG >70 g/L, IgA >50 g/L; urine light chain >12

g/24hr

(2) Advanced, multiple lytic bone lesions

(3) Hemoglobin <8.5 g/dL, serum calcium >12 mg/dL

4. Subclassification: based on renal function.

(1) Serum creatinine <2 mg/Dl

(2) Serum creatinine ≥2 mg/dL

(二) International staging system (ISS)3

1. Stage I: serum β2-microglobulin <3.5 mg/L and serum albumin >3.5

g/dL. Median survival is 62 months.

2. Stage II: not stage I or III. Median survival is 44 months.

3. Stage III: serum β2-microglobulin >5.5 mg/L. Median survival is 29

months.


(一) The key clinical and laboratory features4

1. Anemia <12 g/dL: 72%

2. Bone lesions (lytic lesions, pathologic fractures or severe osteopenia):

80%

3. Impaired renal function (serum creatinine ≥2 mg/dL): 19%

4. Hypercalcemia (≥11 mg/dL): 13%

5. M-protein on serum protein electrophoresis: 82%

6. M-protein on serum protein immunofixation: 93%

7. Increased ≥10% clonal bone marrow plasma cells: 96%

(二) Other clinical features:

1. Bleeding tendency: mostly caused by interference with coagulation by

M-protein or thrombocytopenia from marrow infiltration

2. Hyperviscosity syndrome: visual changes, headache, confusion,

bleeding, coma, “sausage veins” on funduscopy

3. Neurology: Cord compression from vertebral collapse and/or

plasmacytoma, mental changes (may be due to hyperviscosity,

hypercalcemia), peripheral neuropathy caused by M-protein or

amyloidosis

4. Recurrent infection

六、發生率與盛行率 Incident and prevalent

(一) Multiple myeloma comprises about 1% of malignant tumors, 10-15% of

hematopoietic neoplasm and causes 20% of deaths from hematologic

malignancies. It is more common in men than women (1.4:1).5

(二) In Taiwan, 194 males (1.49 per million) and 147 females were newly

diagnosed myeloma in 2005, which count for age-standardized rate of 1.49

and 1.10 per million persons, respectively.6


(一) Complete blood cell count with differential and reticulocyte counts

(二) Serum creatinine, calcium (total and free form), albumin, uric acid,

electrolytes, lactate dehydrogenase (LDH), alkaline phosphatase,

β2-microglobulin, C-reactive protein (CRP), immunoglobulins, plasma

viscosity

(三) Protein electrophoresis and immunoelectrophoresis of serum and urine

(四) 24-hour urine collection for total protein quantification and creatinine

clearance

(五) Coagulation tests, include factor assays if indicated

(六) Viral hepatitis markers, including HBsAg, anti-HBs, anti-HBc IgG (if

HBsAg -), HBeAg/anti-HBe (if HBsAg +), anti-HCV

(七) Bone marrow aspirate and biopsy with cytogenetics and molecular markers

if indicated

(八) Skeletal survey including skull routine and plain films for long bones and

spines, further MRI examination for bone lesions if indicated

(九) Consider biopsy for soft tissue mass with undetermined nature

(十) Ejection fraction and wall motion of heart



1. Confirm diagnosis and staging workup

2. Surgical intervention

3. Chemotherapy that is not suitable to be given in outpatient setting

4. Treat disease or therapy-related complications (e.g. infection,

hypercalcemia, skeletal related events, hyperviscosity, progressed renal

failure, etc.)


1. No more active problems needed to be managed in a hospitalized

setting

2. Complete scheduled chemotherapy with an appointment for outpatient

clinic follow-up

九、主要治療處置 Primary treatment and management7, 8

(一) Radiotherapy

(二) Chemtherapy (for non-transplant candidates):

1. Bortezomib/lenalidomide/dexamethasone (category 1)

2. Lenalidomide/low-dose dexamethasone (category 1)

3. Bortezomib/cyclophosphamide/dexamethasonef

4. Daratumumabk/bortezomib/melphalan/prednisone (category 1)

5. Carfilzomibh/lenalidomide/dexamethasone

6. Carfilzomibh/cyclophosphamide/dexamethasone

7. Ixazomib/lenalidomide/dexamethasone

8. Bortezomib/dexamethasonei

9. Cyclophosphamide/lenalidomide/dexamethasone

(三) Chemtherapy (for non-transplant candidates):

1. Bortezomib/lenalidomidee/dexamethasone (category 1)

2. Bortezomib/cyclophosphamide/dexamethasonef

3. Bortezomib/doxorubicin/dexamethasone (category 1)

4. Carfilzomibg,h/lenalidomidee/dexamethasone

5. Ixazomib/lenalidomidee/dexamethasone (category 2B)

6. Bortezomib/dexamethasone (category 1)i

7. Bortezomib/thalidomide/dexamethasone (category 1)

8. Cyclophosphamide/lenalidomidee/dexamethasone

9. Lenalidomidee/dexamethasone (category 1)i

10. Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/

etoposide/bortezomib (VTD-PACE)

(四) Maintenance therapy:

1. Lenalidomidel (category 1)

2. Other Recommended Regimens

3. Bortezomib

(五) Autologous stem cell transplant

(六) Allogeneic stem cell transplant

(七) Salvage chemotherapy


(一) Transfusion ± erythropoietin for anemia

(二) Therapy for bony disease:

1. Bisphosphonates

2. RANK ligand inhibitor

3. Vertebroplasty and/or kyphoplasty

4. Adequate pain control

(三) Plasmapheresis for hyperviscosity

(四) Prevention and therapy for recurrent infection

1. Immunization with pneumococcal and influenzal vaccines

2. Intravenous immunoglobulin (IVIg)

3. Antibiotic for active infection

十一、預後 Outcome

(一) Multiple myeloma is usually incurable, with a median survival of 3-4 years

(range <6 months to >10 years), and ISS for multiple myeloma applies good

prediction of survival:3

1. Stage I: Median survival is 62 months.

2. Stage II: Median survival is 44 months.

3. Stage III: Median survival is 29 months.

(二) Additional poor indicators include:

1. Elevated serum β2-microglobulin

2. Low serum albumin

3. Elevated LDH

4. High CRP

5. High degree of BM replacement

6. Plasmablastic morphology

7. Cytogenetics:

(1) del(13) or aneuploidy by metaphase analysis

(2) MAF translocations: t(4;14) or t(14;16) or t(14;20) by FISH

(3) Deletion 17q13 by FISH

(4) Hypodiploidy

(三) Major complications:

1. Pathological fracture 733.1

2. Hypercalcemia 275.4

3. Renal failure 584-586

4. Infection

5. Bone marrow failure 284.0-284.9

6. Hyperviscosity 273.3

7. Bleeding disorders

8. Amyloidosis 277.3


(一) 14 days

(二) 21 days or more with major complications listed above


(一) Regular follow-up at out-patient clinic

(二) Adequate pain control

(三) Inform major side effects of treatment (e.g. venothromboembolism,

hyperglycemia, osteonecrosis of the jaw, etc.)

(四) Inform symptoms and signs of major complications (as listed above)


(一) Adequate intake to prevent from dehydration and poor nutrition

(二) Avoid nephrotoxic agents, such as unknown Chinese herb

(三) Adequate physical support during exercise

(四) Search medical help in case of major complications (as listed above)


(一) CBC and differential counts, renal function tests and electrolytes

(二) Albumin, LDH, M-protein (immunoglobulin) and β2-microglobulin

(三) Quantitation of proteinuria

(四) Image study as indicated (e.g. bone pain, disability, etc.)

(五) Bone marrow study as indicated (e.g. elevated M-protein, progressed

cytopenia, etc.)

參、文獻

1. The NCCN Clinical Practice Guidelines in Oncology™ Multiple Myeloma

(Version 2.2019). © 2019 National Comprehensive Cancer Network, Inc.

Available at: www.nccn.org. Accessed [June 19, 2019]

2. Criteria for the classification of monoclonal gammopathies, multiple

myeloma and related disorders: a report of the International Myeloma

Working Group. Br J Haematol 2003;121:749-57.

3. Greipp PR, San Miguel J, Durie BG, et al. International staging system for

multiple myeloma. J Clin Oncol 2005;23:3412-20.

4. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly

diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33.

5. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics,

2007. CA Cancer J Clin 2007;57:43-66.

6. Taiwan Cancer Registry, 2006. (Accessed at

http://crs.cph.ntu.edu.tw/main.php?Page=A5.)

7. Harousseau JL, Shaughnessy J, Jr., Richardson P. Multiple myeloma.

Hematology Am Soc Hematol Educ Program 2004:237-56.

8. Kyle RA, Rajkumar SV. Multiple myeloma. Blood 2008;111:2962-72.

9. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin

2017;67:7-30. Available at:

https://www.ncbi.nlm.nih.gov/pubmed/28055103.

10. Mateos MV, Hernandez MT, Giraldo P, et al. Lenalidomide plus

dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med

2013;369:438-447. Available at:

http://www.ncbi.nlm.nih.gov/pubmed/23902483

11. Roussel M, Lauwers-Cances V, Robillard N, et al. Frontline transplantation

program with lenalidomide, bortezomib, and dexamethasone combination

as induction and consolidation followed by lenalidomide maintenance in

patients with multiple myeloma: a phase II study by the Intergroupe

Francophone du Myelome. J Clin Oncol 2014;32:2712-2717. Available at:

http://www.ncbi.nlm.nih.gov/pubmed/25024076.

12. Durie BG, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and

dexamethasone versus lenalidomide and dexamethasone alone in patients

with newly diagnosed myeloma without intent for immediate autologous

stem-cell transplant (SWOG S0777): a randomised, openlabel,phase 3 trial.

Lancet 2017;389:519-527. Available at:

https://www.ncbi.nlm.nih.gov/pubmed/28017406.

13. Zimmerman T, Raje NS, Vij R, et al. Final Results of a Phase 2 Trial of

Extended Treatment (tx) with Carfilzomib (CFZ), Lenalidomide (LEN), and

Dexamethasone (KRd) Plus Autologous Stem Cell Transplantation (ASCT)

https://www.ncbi.nlm.nih.gov/pubmed/28055103

http://www.ncbi.nlm.nih.gov/pubmed/23902483

https://www.ncbi.nlm.nih.gov/pubmed/28017406

in Newly Diagnosed Multiple Myeloma (NDMM). Presented at: the 58th

American Society of Hematology Annual Meeting and Exposition; 2016;

San Diego, CA. (suppl:abstract 1142).

肆、編審人員


撰寫者陳玟均總醫師學歷高雄醫學大學醫學系學士

經歷內科專科醫師

專長血液學、腫瘤學



專長血液性疾病 (淋巴瘤、骨髓瘤、

白血病、血球過高或低、缺鐵性貧血)

疾病名稱：Aplastic Anemia

ICD-10-CM: D61.9

壹、前言


Acquired aplastic anemia is a rare but important disease in bone marrow

failure syndrome. Most of the aplastic anemia in adult is acquired without

definitive etiology. Most congenital bone marrow failure syndromes attack early in

life but some might develop prominent disease after adolescence. The diagnosis and

treatment of congenital bone marrow syndrome is out of the scope of this guideline


Correct diagnosis and treatment of acquired aplastic anemia


Hematologist and Physician in internal medicine



Patient should be thoroughly evaluated with history, physical examination, and

appropriate laboratory examination.


(一) Peripheral blood: pancytopenia or at least decrease in one lineage

(二) Bone marrow examination: hypocellularity, decrease of hematopoietic

progenitors of all lineage, no evidence of dysplasia or increase of blast


(一) Congenital bone marrow failure syndrome with pancytopenia: Fanconi’s

anemia, Dyskeratosis congenital, Shwachman-Diamond syndrome

(二) Paroxysmal nocturnal hemoglobinuria, hypocellular myelodysplastic

syndrome and acute leukemia, hairy cell leukeomia and other

lymphoproliferative disease


(一) Severe form: two of three peripheral blood criteria

1. Absolute neutrophil count < 500 /uL

2. Platelet count < 20,000 /uL

3. Reticulocyte count < 20,000 /uL

(二) Very severe form:

Absolute neutrophil count < 200 /uL

(三) Moderate form

Patient with pancytopenia who do not fulfill the criteria of severe disease

五、臨床症狀 signs and symptoms

Bleeding with epistaxis, gingival bleeding, hematuria, petechiae or ecchymosis

because of thrombocytopenia; Anemia present with fatigue, malaise, cardiopulmonary

distress; Fever and chills due to bacterial or fungal infection


Aplastic anemia is a rare disease. The overall incidence was 5.67 per million

people per year in Taiwan. There was a biphasic age distribution of incidence rate.

The reported annual incidence in the Thailand and Western country is around 4.0

cases per 1 million people in the capital and slight higher incidence in the countryside.


(一) Complete blood count with differential count and review the blood smear

(二) Blood group and HLA typing

(三) Liver function and renal function test

(四) Viral serology including HBV, HCV, HIV and EBV

(五) Paroxysmal nocturnal hemoglobinuria, PNH markers

(六) Immunologic status including immunoglobulin level

(七) Bone marrow examination( both aspiration and biopsy ) is essential for the

diagnosis

(八) Cytogenetics and immunophenotype of bone marrow as possible


(一) Admission

1. Neutropenic fever

2. Active bleeding refractory to platelet transfusion

3. Hematopoietic stem cell transplantation

4. Immunosuppressant therapy

(二) Discharge

1. Infection and bleeding under control

2. Engraftment after hematopoietic stem cell transplantation with

recovery of blood count

3. Recovery of blood count after immunosuppressant therapy

九、主要治療處置 Primary treatment and management

For severe aplastic anemia, the management depends on the age of the patients,

which correlates with ability to tolerate hematopoietic stem cell transplantation; the

availability of an appropriate donor, and the severity of disease. Hematopoietic stem

cell transplantation from HLA matched sibling or unrelated donor is the best and

definitive treatment for suitable patient. The complication of hematopoietic stem cell

transplantation includes acute and chronic graft versus host disease, graft failure,

opportunistic infection like CMV or fungal infection, endothelial damage and leakage

syndrome. The treatment of complication of hematopoietic stem cell transplantation is

out of the scope of this guideline.

For patients of old age, multiple comorbidities, or without HLA-matched sibling

donors, immunosuppressant therapy including anti-thymocyte globulin combined

cyclosporine A is the first-line treatment. Eltrombopag can be added to increase

response rate.


Blood transfusion with packed red cell and platelet is important for supportive

treatment during transplantation, immunosuppressant therapy or no active treatment.

Broad spectrum antibiotics with or without antifungal agents are important treatment

for neutropenic fever.

十一、癒後 Outcome

(一) The outcome after hematopoietic stem cell transplantation is good.

(二) Response to immunosuppressant often is less durable.

(三) Patient who could not receive hematopoietic stem cell transplantation or

immunosuppressant often has grave outcome.


Depends on disease severity and timing of hematopoietic stem cell

transplantation


According to different kinds of treatment


(一) Close observe if any symptoms/signs of bleeding or infection

(二) Return to hospital if any significant bleeding or fever

(三) Avoid exposure to crowded environment and keep personal hygiene


Regular follow of blood routine and immunological status according to the

treatment and protocol

參、文獻

1. Calado RT and Young NS. Telomere maintenance and human bone marrow

failure. Blood 2008; 111: 4446-4455.

2. Teramura M, Kimura A, Iwase S, et al. Treatment of severe aplastic anemia

with antithymocyte globulin and cyclosporin A with or without G-CSF in

adults: a multicenter randomized study in Japan. Blood. 2007; 110:

1756-1761.

3. Schrezenmeier H, Passweg JR, Marsh JCW, et al. Worse outcome and more

chronic GVHD with peripheral blood progenitor cells than bone marrow in

HLA-matched sibling donor transplants for young patients with severe

acquired aplastic anemia. Blood. 2007; 110: 1397-1400.

4. Champlin RE, Perez WS, Passweg JR, et al. Bone marrow transplantation for

severe aplastic anemia: a randomized controlled study of conditioning

regimens. Blood. 2007; 109: 4582-4585.

5. Socie G, Mary J-Y, Schrezenmeier H, et al. Granulocyte-stimulating factor

and severe aplastic anemia: a survey by the European Group for Blood and

Marrow Transplantation (EBMT). Blood. 2007; 109: 2794-2796.

6. Young NS, Calado RT, and Scheinberg P. Current concepts in the

pathophysiology and treatment of aplastic anemia. Blood. 2006; 108:

2509-2519.

7. Li SS, Hsu YT, Chang C, Lee SC, Yen CC, Cheng CN, et al. Incidence and

treatment outcome of aplastic anemia in Taiwan-real-world data from

single-institute experience and a nationwide population-based database.

Annals of hematology. 2019;98(1):29-39.

8. Young NS. Aplastic Anemia. The New England journal of medicine.

2018;379(17):1643-56.

肆、編審人員




專長血液疾病



專長血液性疾病 (淋巴瘤、骨髓瘤、白

血病、血球過高或低、缺鐵性貧血)

疾病名稱：Acute lymphoblastic leukemia

ICD-10-CM: C91.0

壹、前言

一、適用範圍

Acute lymphoblastic leukemia (ALL) patients

二、目的

Guideline for diagnosis, treatment of ALL patients

三、指引使用者

physicians taking care of ALL patients, including visting staffs, chief residents,

and residents



(一) Complete medical history

(二) Physical examination

(三) Pertinent laboratory tests

二、Diagnostic criteria:

(一) Bone marrow cytology and pathology

(二) Cytology or pathology of tissue from involved site

(三) Immunophenotyping and cytogenetic evaluation

(四) Lymphoblastic precursor cells present in above-mentioned samples

三、鑑別診斷 Differential diagnosis

(一) Acute myeloid leukemia

(二) Lymphoma

(三) Chronic myelogenous leukemia in acute phase

(四) Aplastic anemia

四、疾病病理及分期 Disease pathology and stage


(一) Symptoms: fatigue, easy or spontaneous bruising/bleeding, fever, night

sweats, and unintentional weight loss

(二) Signs: petechiae, purpura, hepatomegaly, splenomegaly, lymphadenopathy

and other signs related to infections


(一) Precursor ALL/LBL accounts for approximately 16% of all leukemias

diagnosed in Taiwan. The annual incidence in Taiwan is around 1.6 persons

per 100,000. It occurs most frequently in childhood, but can also be seen in

adults.

(二) Precursor T-cell LBL/ALL occurs most frequently in late childhood,

adolescence, and young adulthood, with a 2:1 male predominance; it

comprises 15 and 25 percent of childhood and adult ALL, respectively, and

2 percent of adult non-Hodgkin's lymphoma.

七、檢驗與其他檢查 Laboratory and other examinations

(一) Laboratory tests: CBC, biochemistry data, tumor lysis syndrome panel,

peripheral smear, coagulation studies, fibrinogen level, ABO and Rh blood

group

(二) Hepatitis B/C, HIV

(三) Pregnancy testing, fertility counseling, and preservation

(四) Chest radiograph or computed tomography

(五) Lumbar puncture with intrathecal chemotherapy

(六) Bone marrow aspiration and biopsy for cytology, pathology, cytochemical

stains, immunophenotyping, , cytogenetic analysis and molecular analysis

of ALL-related genes, especially bcr-abl fusion gene


(一) 住院條件

1. Initial evaluation, bone marrow study, and image study

2. Treatment

3. Management of complications of treatment

4. Supportive treatment and hospice care.

(二) 出院條件

1. After complete evaluation

2. After treatment

3. Recovery from complications of treatment

4. Condition stabilized after supportive treatment

九、主要處置治療 Primary treatment

(一) Chemotherapy: remission induction, intensification therapy, maintenance

therapy

(二) Infection control

(三) Intrathecal chemotherapy for prophylaxis and treatment of central nervous

system disease

(四) Hematopoietic stem cell transplantation

(五) TKI for Ph-positive patients: imatinib, dasatinib

(六) Blinatumomab

(七) Inotuzumab ozogamicin

(八) Supportive treatment

十、預後 Outcome

great variation depending on various prognostic factors

十一、住院天數 Length of stay

(一) Initial evaluation: 7 days

(二) Chemotheray: 7-28days

(三) HSCT: 21-35 days

(四) Management of complications: 7-14 days

(五) Supportive treatment: 7-28 days

十二、出院計畫 Discharge plan

(一) 定期門診追蹤。

(二) 定期追蹤 CBC/DC、BM cytology、影像學檢查。

(三) 依病人狀況安排門診追蹤，或轉介其他科治療、安寧療護。

十三、出院衛教 Discharge health education

(一) 戒煙及停止服用不必要之藥物。

(二) 規則服用出院時所開立之藥物。

(三) 若病情惡化、異常出血、發燒，至急診或門診求診。

(四) 規則門診追蹤。

十四、出院追蹤 Discharge follow up

(一) 病房護理人員對初離院之患者電話追蹤

(二) 預先安排回門診追蹤。

(三) 未依預定時間回門診之治療中病患，應電話追蹤。

(四) 病患衛教長期追蹤觀念或安排或安寧療護。

參、文獻

1. UpToDate

2. Wintrobe’s clinical Hematology

3. NCCN guideline. Version 2.2019- May 15, 2019

4. Ravandi F. How I treat Philadelphia chromosome-positive acute

lymphoblastic leukemia. Blood. 2019;133(2):130-6.

5. Aldoss I, Stein AS. Advances in adult acute lymphoblastic leukemia therapy.

Leuk Lymphoma. 2018;59(5):1033-50.

6. Larson RA. Managing CNS disease in adults with acute lymphoblastic

leukemia. Leuk Lymphoma. 2018;59(1):3-13.

7. Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Topp MS, et

al. Complete Hematologic and Molecular Response in Adult Patients With

Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute

Lymphoblastic Leukemia Following Treatment With Blinatumomab:

Results From a Phase II, Single-Arm, Multicenter Study. Journal of clinical

oncology : official journal of the American Society of Clinical Oncology.

2017;35(16):1795-802.

8. Kantarjian HM, Vandendries E, Advani AS. Inotuzumab Ozogamicin for

Acute Lymphoblastic Leukemia. The New England journal of medicine.

2016;375(21):2100

肆、編審人員




專長血液疾病



專長血液性疾病 (淋巴瘤、骨髓瘤、白血

病、血球過高或低、缺鐵性貧血)

Diffuse large B-cell lymphoma ICD-10-CM：C83.3 - 臺北榮民 ...

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