appendix 1 - springer978-1-59259-203-6/1.pdf · appendix 1 glossary of cytostatic drugs a number of...

APPENDIX 1 Glossary of Cytostatic Drugs

A number of antimetabolites or cytostatic agents are employed in treating leukemias and lymphomas. These drugs act through different mechanisms and their correct use requires special knowledge and expertise. We have listed them as follows in alphabetical order. Brief descriptions of the various modes of application, the mechanisms of action, and the common side effects are provided. Details about the dosage of the cytostatic drugs are given in the treatment protocols and product information.

Amsacrine (m-AMSA)

MODE OF APPLICATION: intravenous

TYPE OF DRUG: alkylating agent

MECHANISM OF ACTION: alkylates and intercalates DNA, inhibitor oftopoisomerase II

INDICATIONS: acute myelogenous leukemia, acute lymphoblastic leukemia

SIDE EFFECTS: severe myelosuppresson, cardiac toxicity (arrhythmias, heart failure), nausea, vomiting, mucositis, in some cases neurotoxicity, severe local toxicity if paravasate

Asparaginase


TYPE OF DRUG: enzyme

MECHANISM OF ACTION: depletes cells of L-asparagine

INDICATIONS: acute lymphoblastic leukemia

SIDE EFFECTS: hypersensitivity and anaphylactic reactions, fever, bronchospasm, reduced synthesis of coagulation factors, increase in liver enzymes, hyperglycemia, rarely pancreatitis, central nervous system toxicity (25-50%)

COMMENT: During treatment, a substitution of fresh frozen plasma or fibrinogen and antithrombin III may become necessary. Because of anaphylactic reactions, a test dose should be given first. In case of intolerance, an alternative preparation of asparaginase should be used (e.g., erwinia asparaginase).

333

334 Cytostatic Drugs

Bleomycin

MODE OF APPLICATION: intravenous, in some cases also intracavitary, topical, intraarterial

TYPE OF DRUG: antibiotic

MECHANISM OF ACTION: intercalates DNA, induces DNA breaks

INDICATIONS: lymphomas, other malignant tumors

SIDE EFFECTS: fever, myalgias, anorexia, skin pigmentation, rash, mucositis, alopecia, pneumonitis (may progress to lung fibrosis), occasionally hypersensitivity reactions, minor myelosuppression

COMMENT: Pulmonary toxicity may be severe in older patients, in patients with chronic lung disorders, or after thoracic irradiation. If higher dose therapy is planned, lung function should be controlled regularly.

Carmustin (BCNU)


TYPE OF DRUG: nitrosourea

MECHANISM OF ACTION: bifunctional alkylating agent, induces DNA breaks

INDICATIONS: lymphomas, solid tumors

SIDE EFFECTS: prolonged myelosuppression, cumulative lung toxicity, nausea, vomiting, in some cases hepatic and renal toxicity, in some cases neurotoxicity

Chlorambucil

MODE OF APPLICATION: oral


MECHANISM OF ACTION: alkylates DNA, RNA, induces DNA breaks

INDICATIONS: chronic lymphocytic leukemia (CLL), other low-grade lymphomas

SIDE EFFECTS: leukopenia, minor gastrointestinal discomfort, rarely neurotoxicity, sterility at high doses, pulmonary toxicity

Cladribine (2-CDA)



MECHANISM OF ACTION: alkylates DNA, RNA, induces DNA breaks

INDICATIONS: CLL, other low-grade lymphomas

SIDE EFFECTS: leukopenia, minor gastrointestinal discomfort, rarely neurotoxicity, sterility at high doses, pulmonary toxicity

Cytostatic Drugs

Cyclophosphamide

MODE OF APPLICATION: intravenous, oral

TYPE OF DRUG: oxazaphosphorin (bifunctional alkylating agent)

MECHANISM OF ACTION: alkylates DNA and RNA, imduces DNA breaks

335

INDICATIONS: lymphomas, leukemias, solid tumors, immunosuppression, conditioning for bone marrow transplantation

SIDE EFFECTS: myelosuppression, thrombocytopenia, nausea, vomiting, mucositis, fever, hemorrhagic cystitis, tubular nephropathy

COMMENT: Hemorrhagic cystitis can be prevented if adequate hydration (>200 mLlh) and mesna are given. Mesna should always be given when cyclophosphamide is administered at >400 mg/m2/d. If renal function is compromised, the dosage of cyclophosphamide has to be adapted accordingly.

Cytosine-Arabinoside (ARA-C)

MODE OF APPLICATION: intravenous, subcutaneous, intrathecal

TYPE OF DRUG: antimetabolite, analogue of deoxycytidine

MECHANISM OF ACTION: incorporates into DNA, inhibits DNA polymerases, S-phasespecific

INDICATIONS: acute and chronic leukemias, malignant lymphomas

SIDE EFFECTS: myelodepression, gastrointestinal toxicity (nausea, vomiting, rarely pancreatitis), pulmonary toxicity at high doses, alopecia, keratoconjunctivitis, rash, neurotoxicity (at higher doses and in older patients severe cerebellar syndrome, other neurologic disturbances)

Dacarbacine (OTIC)



MECHANISM OF ACTION: methylates DNA

INDICATIONS: lymphomas, other malignancies

SIDE EFFECTS: severe nausea and vomiting, myelosuppression, alopecia, less frequent: hepatotoxicity, diarrhea, thrombophlebitis

Daunorubicin

Mainly used in the treatment of acute leukemias; daunorubicin belongs to the class of anthracyclin-antibiotics; for details see Doxorubicin.

336

Doxorubicin


TYPE OF DRUG: anthracycline antibiotic

Cytostatic Drugs

MECHANISM OF ACTION: intercalates DNA, forms free oxygen radicals, inhibits topoisomerase II

INDICATIONS: lymphomas, solid tumors

SIDE EFFECTS: myelosuppression, acute and chronic cardiotoxicity, mucositis, nausea, alopecia, severe tissue necrosis in case of paravasates

COMMENT: The cumulative cardiotoxicity (dilative cardiomyopathy) limits the total dose to 450-550 mg/m2• Risk factors are mediastinal irradiation, previous cardiac disease.

Epirubicin

Used for the treatment of lymphomas, belongs to the class of anthracyclin-antibiotics, for details see Doxorubicin.

Etoposide (VP-16)


TYPE OF DRUG: derivative of epipodophyllotoxin (alkaloid)

MECHANISM OF ACTION: complexes with topoisomerase II, induces DNA breaks

INDICATIONS: leukemias, lymphomas, solid tumors

SIDE EFFECTS: bone marrow depression, especially neutropenia, alopecia, some nausea, some patients experience allergic or anaphylactic reactions, rarely neuropathy

Fludarabine


TYPE OF DRUG: antimetabolite (purine analogue)

MECHANISM OF ACTION: inhibits enzymes of DNA synthesis

INDICATIONS: low-grade lymphomas

SIDE EFFECTS: myelosuppression, some nausea, hepatotoxicity, neurotoxicity (encephalopathy at high doses), protracted immunosuppression

Cytostatic Drugs

Hydroxyurea


TYPE OF DRUG: antimetabolite

MECHANISM OF ACTION: inhibits ribonucleotide reductase

337

INDICATIONS: chronic myelogenous leukemia, other myeloproliferative syndromes

SIDE EFFECTS: short-acting myelosuppression; some gastrointestinal toxicity; rarely pigmentation; renal, hepatic, and neurologic side effects (dose adjustment in renal failure necessary)

Idarubicin

Used for the treatment of acute leukemias and lymphomas, belongs to the class of anthracyclin-antibiotics, for details see doxorubicin.

Ifosfamide


TYPE OF DRUG: alkylating agent (derivative of cyclophosphamide with a particular toxicity profile)

MECHANISM OF ACTION: alkylates DNA and RNA, induces DNA breaks

INDICATIONS: lymphomas, other malignancies

SIDE EFFECTS: myelosuppression, nausea, vomiting, mucositis, diarrhea, hemorrhagic cysitis (see Cyclophosphamide), alopecia, acute CNS toxicity (encephalopathy, cerebellar syndrome, ataxia, seizures; especially in older patients and higher dosage)

COMMENT: Hemorrhagic cystitis can be prevented if adequate hydration (>200 mL/h) and mesna are given. If renal function is compromised, the dosage of cyclophosphamide has to be adapted accordingly. The infusion of Na bicarbonate is recommended for the prophylaxis of CNS toxicity.

Lomustin (CCNU)


TYPE OF DRUG: alkylating agent (nitrosourea derivative)

MECHANISM OF ACTION: alkylates DNA and RNA

INDICATIONS: Hodgkin's disease, solid tumors

SIDE EFFECTS: nausea, stomatitis, alopecia, delayed myelotoxicity, less frequent renal and hepatic toxicity

338

Melphalan



MECHANISM OF ACTION: cross-links DNA

INDICATIONS: multiple myeloma, solid tumors

Cytostatic Drugs

SIDE EFFECTS: nausea, protracted myelosuppression, rarely skin rash, pulmonary toxicity, alopecia

6-Mercaptopurine



MECHANISM OF ACTION: inhibits purine synthesis

INDICATIONS: acute leukemias

SIDE EFFECTS: nausea, bone marrow toxicity, liver toxicity (cholestasis), fever, skin rash

COMMENT: If concomitant allopurinol is given, the dose of mercapturin has to be reduced to 25-40%.

Methotrexate

MODE OF APPLICATION: intravenous, oral, intrathecal


MECHANISM OF ACTION: inhibits dihydrofolate reductase

INDICATIONS: leukemias, lymphomas, other malignancies

SIDE EFFECTS: myelosuppression, severe mucositis (dose dependent), nausea, diarrhea, hepatic, renal and pulmonary toxicity, skin rash, acute encephalopathy

COMMENT: At high doses of methotrexate, measurement of plasma levels and "rescue" with folinic acid are important.

Pentostatin (Desoxycoformine)



MECHANISM OF ACTION: purine analogue, inhibits adenosine deaminase

INDICATIONS: hairy cell leukemia, other low-grade non-Hodgkin's lymphomas

SIDE EFFECTS: myelosuppression, nausea, less frequent hepatic and renal toxicity

Cytostatic Drugs

Procarbacin



MECHANISM OF ACTION: alkylates DNA, methylates nucleic acids

INDICATIONS: lymphomas

339

SIDE EFFECTS: myelosuppression, nausea, vomiting, skin toxicity, in some cases renal, hepatic, central nervous toxicity

6-Thioguanine



MECHANISM OF ACTION: inhibits purine synthesis, incorporated into DNA

INDICATIONS: leukemias

SIDE EFFECTS: myelodepression, some nausea, diarrhea, cholestasis

Vincristine, Vindesine


TYPE OF DRUG: vinca alcaloids

MECHANISM OF ACTION: inhibit function of microtubuli, inhibit DNA-dependent RNA polymerases

INDICATIONS: lymphomas, leukemias, other malignancies

SIDE EFFECTS: nausea, vomiting, pulmonary toxicity, myelosuppression (minor with vincristine, major with vindesine), diarrhea, constipation, stomatitis, mouth ulcers

major neurotoxicity (especially with vincristine, cumulative, dose limiting: peripheral neuropathy, paresthesias, autonomous neuropathy, rarely ataxia, seizures)

Designation

CDI

CD2

CD3

CD4 CD5 CD6 CD7 CD8 CD9

CDlO

CDlla CDIIb

CDIlc

CDl2 CD 13 CDl4 CD15 CD16

CD 17

CD18

APPENDIX 2

CD Nomenclature for Human Leukocyte Antigens

Cellular distribution Function, comments

Cortical thymocytes, dendritic Role in antigen presentation cells

Pan T cell, NK cells Receptor for sheep red blood cells, interaction with CD48 and CD58

Pan T cell Signal transduction from T-cell receptor

T -helper subset Binds to class II MHC antigen Pan T, B-cell subset Marker for B-CLL T -cell subset Early T-cell marker Expressed on T-ALL T suppressor cells Coreceptor in antigen recognition Broad (platelets, lymphoid

progenitors, activated active lymphocytes)

Immature, some mature B cells CALLA-antigen, expressed in pre-B-ALL, some lymphomas, kidney, intestine, brain

Leukocytes Adhesion Granulocytes, monocytes, NK Adhesion

cells Granulocytes, monocytes, Adhesion

macrophages, NK cells Monocytes, granulocytes Monocytes, granulocytes Membrane metalloprotease Monocytes Receptor for lipopolysaccharide Granulocytes, monocytes Lewis x antigen NK cells, granulocytes, mast Fc receptor III

cells Granulocytes, monocytes, Lactosy lceramide

platelets Leukocytes Integrin ~2 subunit (adhesion)

(continued)

341

342

Designation

CD19 CD20 CD21

CD22 CD23

CD24 CD25

CD26

CD27

CD28 CD29 CD30

CD31

CD32

CD33

CD34

CD35

CD36 CD37 CD38

CD39

CD40

CD41

HLA Nomenclature

CD Nomenclature for HLA (continued)

Cellular distribution

B cells B cells Mature B cells

B cells Activated B cells, macrophages,

follicular dendritic cells B cells, granulocytes Activated T cells, B cells

macrophages Thymocytes, activated T cells,

other cells T cells, other cells

T cells, plasma cells Most cells Activated T and B cells

Monocytes, platelets, granulocyte, lymphocyte subset, endothelial cells

Monocytes, platelets, other cells

Monocytes, immature myeloid cells

Hematopoietic progenitors, endothelial cells

Red cells, B cells, subset of T cells, granulocytes, other cells

Platelets, monocytes, other cells Mature B cells, some other cells Immature Band T cells, plasma

cells, some other cells Activated B cells, some other

cells Mature B cells

Platelets, megakaryocytes

Function, comments

Receptor for EBV, complement type 2, C3d

Regulates IgE synthesis

Receptor for interleukin-2 (a-chain)

Membrane-bound protease

Member of TNF receptor superfamily

T-cell, B-cell interactions Adhesion (integrin ~1 subunit) Member of TNF receptor

superfamily (present on ReedSternberg cells)

PECAM-l, mediates adhesion

Fc yRII (Fc receptor for aggregated IgG)

Member of sialoadhesin family

Complement receptor type1 (binds C3b, C4b)

Multifunctional glycoprotein

Member of TNF receptor superfamily, interacts with CD154

Integrin allb subunit, interacts with glyco-protein IlIa, defect in Glanzmann thrombasthenia

HLA Nomenclature 343

CD42a,b Platelets, megakaryocytes Platelet adhesion, binds to VWF, defect in Bernard-Soulier syndrome

CD43 Leukocytes Leukosialin CD44 Widely expressed on Several isoforms, adhesion of

hematopoietic and leukocytes to endothelial cells, nonhematopoietic cells stroma, and extracellular matrix

CD45 Leukocytes Leukocyte common antigen, several epitopes with differential expression

CD46 Leukocytes, endothelial, Regulates complement activation epithelial cells

CD47 Broad tissue expression Integrin-associated protein, absent on Rhnull erythrocytes

CD48 Hematopoietic cells CD49a Monocytes, activated T cells Subunit of alphal-integrin

(VLA-lalpha) CD49b Monocytes, platelets, T and B Subunit of integrin-a2

cells CD49c Cultured adherent cell lines Subunit of integrin-a3 CD49d Most leukocytes Subunit of integrin-a4 CD4ge T cells, monocytes, platelets, Subunit of integrin-a5

activated B cells CD49f T cells, monocytes, Subunit of integrin-a6

nonlymphoid tissues CD50 Leukocytes ICAM-3, mediates adhesion CD51 Platelets and endothelial and Alpha subunit of vitronectin

other cells receptor CD52 Leukocytes CD53 Leukocytes and other cells CD54 Hematopoietic and ICAM-l, mediates adhesion, T-cell

nonhematopoietic cells activation CD55 Broad expression Decay-accelerating factor CD56 NK cells, T-cell subpopulation, isoform of NCAM, cell-cell

neural tissue interactions CD57 Subset of NK cells and T -cells CD58 Most hematopoietic cells, other LFA-3 adhesion ligand for CD2

cells CD59 Many cells Complement protectin (via GPI

anchor) CD60 T -cell subset, platelets CD6l Platelets, monocytes, Integrin ~3 subunit (combines with

megakaryocytes, endothelial CD4l and with CD5l) cells

(continued)

344 HLA Nomenclature


Designation Cellular distribution Function, comments

CD62E Endothelial cells E-selectin (adhesion of leukocytes) CD62L Most hematopoietic cells L-selectin (homing of

lymphocytes) CD62P Megakaryocytes, activated P-selectin (adhesion)

endothelial cells and platelets CD63 Widely distributed CD64 Monocytes, macrophages High-affinity Fc y-receptor CD65 Granulocytes CD66 Granulocytes Cell adhesion (belong to CEA

family) CD68 Monocytes, macrophages, Belong to family of lysosomal-

other cells associated membrane proteins CD69 Activated T cells, B cells, NK Signal transduction

cells CD70 Activated B cells, some Member of TNF Receptor

activated T cells superfamily, costimulation of T -cell proliferation

CD71 Proliferating cells Transferrin receptor CD72 B cells CD73 Subsets of mature lymphocytes Ecto-5'-nucleotidase CD74 B cells, monocytes MHC class II-associated invariant

chain Cdw75 Mature B cells CD76 Mature peripheral B cells,

mantle zone B cells, activated cells

CD77 Subset of germinal center B Marker for Burkitt's lymphomas cells

CD79 B lymphocytes B-cell antigen receptor complex CD80 Activated T cells, B cells, Costimulatory signal for T cells

monocytes (B7-l) CD81 Broad expression CD82 Broad expression Suppresses metastasis in tumor

cells (KAI -1) CD83 Dendritic cells Cdw84 Macrophages and platelets CD85 Plasma cells, monocytes, other

cells CD86 Monocytes, dendritic cells, Costimulatory signal for T cells

activated cells (B7-2)

HLA Nomenclature

CD87 Monocytes, granulocytes, large granular lymphocytes

CD88 Myeloid and other cells

CD89 Most phagocytic cells, other cells

CD90 Prothymocytes, brain CD91 Phagocytes of liver, lung,

lymphoid tissues Cdw92 Myeloid cells CD93 Granulocytes, monocytes,

endothelial cells CD94 NK cells, subset of T cells CD95 Activated lymphocytes,

monocytes, fibroblasts, cell lines

CD96 Activated T cells, NK cells, T -cell lines

CD97 Granulocytes, monocytes, activated T and B cells

CD98 Monocytes, some other cells CD99 Pan leukocyte CD 100 B cells, T cells, NK cells, most

myeloid cells CDlOl Monocytes, granulocytes,

mucosal T cells CD 102 Most leukocytes, vascular

endothelium CDI03 Intraepitheliallymphocytes CD 104 Desmosomes of epithelia CD 105 Endothelial cells CD 106 Vascular endothelium, dendritic

cells, some other cells CD 107 Granulocytes, T cells, other

cells Cdw108 Some lymphoid and other cells CDI09 Platelets, activated T cells,

umbilical vein endothelial cells

CD1l7 Hematopoietic progenitors, mast cells, some AMLs

CD120a,b Low-level expression on many cells

Receptor for urokinase plasminogen activator

Receptor for C5a (G proteincoupled receptor)

Receptor for IgA

Thy-l

345

Binds protease-inhibitor complexes

Member of TNF receptor superfamily (induces apoptosis)

ICAM-2, major LFA-lligand on endothelial cells

Integrin nE subunit Integrin ~4 subunit Endoglin (receptor for TGF~) VCAM-l

Lysosome-associated membrane protein

Govalb alloantigen

c-kit

TNF receptors (type I and II)

(continued)

346 HLA Nomenclature


Designation Cellular distribution Function, comments

CD134 Activated T cells Member of TNF receptor family, co stimulates T-cell proliferation

CD135 Hematopoietic stem cells FLT-3, receptor for FLT-3/flk-2 ligand

Cdw137 Activated T, B cells, monocytes Costimulation of T-cell growth CD138 Immature B cells, plasma cells Syndecan-l CDl47 Activated cells Extracellular matrix

metalloproteinase inducer CDl48 Broad expression Cdw150 Immature thymocytes, some B

cells CD151 Platelets, megakaryocytes,

monocytes CD152 Activated T lymphocytes Binds CD80, CD86 CD153 Activated T cells CD30 ligand CD154 Activated T cells CD40 ligand CD161 Natural killer cells, some T cells CD162 Granulocytes, monocytes, most Ligand for selectins

lymphocytes CD163 Monocytes, macrophages CD166 Broad expression

The list is not complete, and additional surface markers do not yet have a CD designation.

BIBLIOGRAPHY

Barclay A.N., Brown MH, Alex Law SK, et aI., The Leucocyte Antigen Facts Book, 2nd ed. San Diego: Academic, 1997.

Parameter

Hemoglobin

Red cell number

Hematocrit

MCV MCHC Reticulocytes Leukocytes (white cells) Neutrophils Lymphocytes Monocytes Eosinophils Basophils Platelets LDH (lactate dehydrogenase) Haptoglobin Serum bilirubin (total) Serum transferrin receptors Serum iron

Serum ferritin

Serum vitamin B 12 Serum folate C-reactive protein Serum ~_rmicroglobulin Total protein IgG IgA IgM IgD

APPENDIX 3

Laboratory Values

Normal range

Males: 13.5-17.5 g/dL Females: 11.5-15.5 g/dL Males: 4.5-6.5 x 10 9/L Females: 3.9-5.6 x 10 91L Males: 40-52% Females: 36-48%

80-95 fL 30-35 g/dL

0.5-2.5% or 50-100 000 x 10 91L 4000-10,500/111 2500-7500/111 1500-4000/111 200-800/111

40-500/111 0-100/111

150,000-440,000/111 250-450 lUlL 0.3-2 gIL

<10 mg/L or 17 IlmollL 4-9Ilg/L

Males: 80-150 Ilg/dL or 14-27 IlmollL Females: 60-140 Ilg/dL or 11-251lmollL Males: 40-350 Ilg/L Females: 20-250llglL

347

160-900 ng/L 3.0-15 IlglL <5 mg/L

1.2-2.4 mglL 60-80 gIL

6-16.5 gIL 0.8-4.0 gIL 0.5-2.0 giL <100 U/mL

(continued)

348

Parameter

IgE Fibrinogen Activated PTT Prothrombin time Thrombin time D-dimer

Laboratory Values

Laboratory Values (continued)

Normal range

25-150 U/mL 2-4 gIL

26-35 s 12-14 s

± 3 s of control <0.5 mg/L

All laboratory values depend on the methods used and may vary in different age and ethnic groups. The values in the table can only be considered as an approximate range.

APPENDIX 4

Specific Program Requirements for Residency Education in Hematology

(Accreditation Council for Graduate Medical Education, Version 7/99)

CLINICAL EXPERIENCE

Clinical experience must include opportunities to observe and manage patients with a wide variety of blood diseases on both an inpatient and an outpatient basis. The resident must be given opportunities to assume continuing responsibility for acutely and chronically ill patients in order to observe the evolution of blood diseases as well as the benefits and adverse effects of therapy. Inpatient assignments should be of sufficient duration to permit continuing care of a majority of the patients throughout their hospitalization.

AMBULATORY MEDICINE EXPERIENCE

The program must provide residents with experiences in an ambulatory care setting at least one day each week over the 24 months of training. In addition, the program must provide residents with continuity experiences, each at least 6 months in duration, throughout the residency program.

TECHNICAL AND OTHER SKILLS

1. The program must provide residents with the opportunity to develop competence to work effectively as part of a multidisciplinary team.

2. The program must provide the opportunity for residents to gain competence or expertise in the performance and (where applicable) interpretation of the following:

349

350 Residency Education Requirements

a. Bone marrow aspiration and biopsy, including preparation, staining, examination, and interpretation of blood smears, bone marrow smears, bone marrow aspirates, and touch preparations and interpretation of bone marrow biopsies

b. Use of chemotherapeutic agents and biologic products through all therapeutic routes

c. Correlation of clinical information with the findings of cytology, histology, immunodiagnostic and imaging techniques

3. The program should provide experience or observation of the following: a. Apheresis procedures b. Performance and interpretation of partial thromboplastin time, pro

thrombin time, platelet aggregation, and bleeding time and other standard coagulation assays

c. Bone marrow or peripheral stem cell harvest for transplantation d. Fine needle aspiration and biopsy

SPECIFIC PROGRAM CONTENT

The residents must have formal instruction, clinical experience, or opportunities to acquire knowledge in the following:

1. Morphology, physiology, and biochemistry of blood, marrow, lymphatic tissue, and the spleen

2. Related basic fields, including immunology, basic and clinical pharmacology and pharmacokinetics, cell and molecular biology, tumor immunology, molecular genetics, and prenatal diagnosis

3. Basic molecular and pathophysiologic mechanisms, diagnosis and therapy of diseases of the blood, including anemias, diseases of white blood cells and stem cells, and disorders of hemostasis and thrombosis

4. Etiology, epidemiology, natural history, diagnosis, pathology, staging, and management of neoplastic diseases of the blood, blood-forming organs, and lymphatic tissues

5. Measurement of the complete blood count, including platelets and white cell differential, using automated or manual techniques with appropriate quality control

6. Immunophenotyping, cytochemical studies, and cytogenetic and DNA analysis of neoplastic disorders of blood, blood-forming organs, and lymphatic tissues

7. Molecular mechanisms of hematopoietic and lymphopoietic malignancies, including the nature of oncogenes and their products.

8. Relevant chemotherapeutic drugs, biologic products, and growth factors and their mechanism of action, pharmakokinetics, clinical indications, and limitations

Residency Education Requirements 351

9. Multiagent chemotherapy protocols and combined modality therapy for hematopoietic and lymphopoietic malignancies

10. Management and care of indwelling venous access catheters 11. Principles and application of radiation medicine to hematopoietic and lym

phopoietic malignancies 12. Management of the neutropenic and the immunocompromised patient 13. Effects of systemic disorders and drugs on the blood, blood-forming

organs, and lymphatic tissues 14. Allogeneic and autologous bone marrow or peripheral blood stem cell trans

plantation and the nature and management of posttransplant complications 15. Tests of hemostasis and thrombosis for both congenital and acquired dis

orders and regulation of anti thrombotic therapy 16. Treatment of patients with disorders of hemostasis and the biochemistry

and pharmacology of coagulation factor replacement therapy 17. Transfusion medicine, including the evaluation of antibodies, blood com

patibility, and the use of blood-component therapy and apheresis 18. Indications and applications of imaging techniques in patients with blood

disorders 19. Personal development, attitudes, and coping skills of physicians and other

health-care professionals who care for critically ill patients 20. Pain management in patients with blood disorders 21. Rehabilitation and psychosocial aspects of clinical management of patients

with hematologic disorders 22. Hospice and home care 23. Recognition and management of paraneoplastic disorders 24. Clinical epidemiology and medical statistics, including clinical study and

experimental protocol design, data collection, and analysis 25. Participation in a tumor board 26. Human immunodeficiency virus-related malignancies 27. Care and management of geriatric patients with hematologic disorders

Abciximab, arterial thrombosis treatment, 308

ABO blood group system, hemolytic disease of the newborn, 90, 91 overview, 317, 318

Acanthocytosis, definition and associated conditions, 63

Acenocoumarol, bioavailability, 311 complications, 312 drug interactions, 312, 313 mechanism of anticoagulation activity,

311 monitoring of therapy, 311, 312

Acquired immunodeficiency syndrome (AIDS), see also Human immunodeficiency virus,

Kaposi's sarcoma, 244 non-Hodgkin's lymphoma association,

206,235 opportunistic infections, 242, 243 prognosis, 236 treatment, 235, 236

Activated partial thromboplastin time (aPTT), hemorrhagic disorder evaluation, 261, 262

Acute lymphoblastic leukemia (ALL), chromosomal abnormalities, 131-133 classification, 132, 136-139 clinical manifestations, 134 complications, 139, 141 diagnosis, 134, 136, 140 incidence, 131 laboratory features, 137, 139

Index

Acute lymphoblastic leukemia (ALL) (cant,).

minimal residual disease, 132-134 prognostic factors, 139 treatment,

B-lineage disease, 144 consolidation treatment, 141, 142 cure rates, 143 induction treatment, 141, 142 maintenance therapy, 141, 142 meningeal leukemia prophylaxis, 141,

143 novel therapies, 144, 145 relapsed disease, 144 supportive treatment, 143, 144

Acute myelogenous leukemia (AML), chromosomal abnormalities, 117-119 classification, 120, 122, 123 clinical manifestations, 119, 120 diagnosis, 120 differential diagnosis, 122 etiology and pathophysiology, 117-119 incidence, 117 laboratory findings, 122, 123 prognostic factors, 124 treatment,

acute promyelocytic leukemia, 128 bone marrow transplantation,

allogeneic, 126, 127 autologous, 127

complications, 125, 126 consolidation treatment, 126 induction treatment, 124, 125 novel therapies, 128

From: Modern Hematology: Biology and Clinical Management Edited by: R. Munker, E. Hiller, R. Paquette © Humana Press Inc., Totowa, NJ

353

354

Acute myelogenous leukemia (AML) (cont.). treatment (cont.).

relapsed disease, 127, 128 secondary treatment, 128

Adenosine deaminase deficiency, gene therapy, 25

Agnogenic myeloid metaplasia (AMM), clinical manifestations, 114, 115 diagnosis, 115 etiology, 115 treatment, 115, 116

Agranulocytosis, drug induction, 99,101,102 AIDS, see Acquired immunodeficiency

syndrome AIHA, see Autoimmune hemolytic anemia Albumin, types, 15 ALCL, see Anaplastic large-cell lymphoma ALL, see Acute lymphoblastic leukemia Alpha-granule deficiency, features, 280,

281 Amifostine, myelodysplastic syndrome

treatment, 154 AML, see Acute myelogenous leukemia AMM, see Agnogenic myeloid metaplasia Amsacrine (m-AMSA), chemotherapy

features, 333 Amyloidosis, ligh-chain, 225 Anaplastic large-cell lymphoma (ALCL),

see also Non-Hodgkin's lymphoma, chromosomal abnormalities, 205, 206 incidence. 205 treatment and prognosis, 206

Anemia, aplastic anemia, see Aplastic anemia bleeding as cause,

acute bleeding, 61, 62 chronic bleeding and causes, 62. 64, 65

chronic disease anemias, endocrine disorders, 69 lead poisoning, 70 liver disease, 68 malnutrition, 68 overview, 67, 68 pregnancy, 68 renal failure, 69 sideroblastic anemia, 69 thalassemia minor, 69

Anemia (cont.). definition, 61 hemolytic anemias,

Index

autoimmune hemolytic anemia, 86-89 disseminated intravascular coagulation.

94 glucose-6-phosphate dehydrogenase

deficiency, 79, 80 hemolysis causes, 94, 95 hemolytic disease of the newborn, 90-92 hereditary elliptocytosis, 79 hereditary spherocytosis, 77-79 microangiopathic anemias, 94 overview, 77, 78, 81 parasitic infection and hemolysis, 92-94 paroxysmal nocturnal hemoglobinuria,

89,90 pyruvate kinase deficiency, 80, 81 sickle cell anemia, 81-84 thalassemias, 84-86

iron deficiency anemia, diagnosis, 66, 67 epidemiology, 65 pathogenesis, 64 pathophysiology, 65, 66 treatment, 67

megaloblastic anemias, folate deficiency, 75 overview, 70 pernicious anemia,

autoimmune dysfunction, 72 diagnosis, 73, 74 onset, 73 pathogenesis, 72, 73 treatment, 74

vitamin physiology, 70-72 Angioimmunoblastic T -cell lymphoma, see

Non-Hodgkin's lymphoma Anisocytosis, definition and associated

conditions, 63 Anticoagulants, see specific agents Antiemesis, regimens with chemotherapy,

41 Antithrombin (AT),

assay, 264 coagulation inhibition, 254 deficiency, 301

Index

Antithymocyte globulin/antilymphocyte globulin therapy, aplastic anemia, 163, 164

Aplastic anemia, acquired versus hereditary, 157, 158 classification, 162 clinical manifestations, 159, 160 diagnosis, 160, 161 differential diagnosis, 160 etiology,

benzene, 158 drug induction, 157, 158 hepatitis, 158 radiation and chemotherapy, 158, 159

Fanconi's anemia, 159, 163 incidence, 157 late complications, 164, 165 pathophysiology, 159 treatment,

anti thymocyte globulin/antilymphocyte globulin, 163, 164

bone marrow transplantation, 161, 163 growth factors, 163, 164 immunosuppression, 163

aPTT, see Activated partial thromboplastin time ARA-C, see Cytosine-arabinoside Arterial thrombosis,

pathogenesis, 307 treatment,

abciximab, 308 aspirin, 307 clopidogrel, 308 heparin, 308 ticlopidine, 308 tissue plasminogen activator, 308, 309

Asparaginase, chemotherapy features, 333 Aspirin, arterial thrombosis treatment, 307 AT, see Antithrombin Ataxia telangiectasia, features, 230 Autoimmune hemolytic anemia (AIHA),

cold type, clinical presentation, 88 laboratory features, 88, 89 treatment, 89

warm type, clinical presentation, 87 laboratory features, 87 treatment, 87, 88

355

B B cell,

antigen specificity, 13 differentiation and growth, 13 immunoglobulin gene rearrangement, 22 life span, 13 memory cells, 13

Babesiosis, hemolytic anemia, 94 parasi tes, 93 treatment, 94

Basophil, differentiation, see Myelopoiesis features, 10 normal blood values, 347

Basophilia, differential diagnosis, 103 BCNU, see Carmustin Bernard-Soulier syndrome (BSS), features,

279 Bilirubin, normal serum values, 347 Bleeding disorders, see Hemorrhagic disor

ders Bleeding time, hemorrhagic disorder evalu

ation,260 Bleomycin, chemotherapy features, 334 Blood product transfusion,

ABO system, 317, 318 bone marrow translantation patients, 49-

51 autologous transfusion, 331, 332 coagulation disturbances with massive

transfusions, 296, 297 disease transmission,

bacteria, 327, 328 prevention, 327 viruses, 328-330

fresh frozen plasma, 325 graft-versus-host disease, 331 granulocyte concentrates, 324, 325 immunoglobulins, 325 intrauterine transfusion, 91, 92 iron overload, 330, 331 Kell blood group system, 320 lung injury reaction, 331 myelodysplastic syndrome treatment, 153 packed red cells, 324 platelet concentrates, 324

356

Blood product transfusion (cont.), posttransfusion purpura, 275 reactions,

acute hemolytic reactions, 326 allergic reactions, 326, 327 delayed hemolytic reactions, 326 febrile nonhemolytic reactions, 326

Rhesus system, 318, 319 sickle cell anemia, 83 stem cell transplant recipients, 49-51 typing and cross-matching,

agglutination assay, 320 Coombs test, 320, 321 overview, 320

whole blood, 323 Bone marrow,

aspiration, disease diagnosis, 15, 16 sample handling, 16 sites, 16

biopsy, 17 erythropoiesis, 5, 6 hematopoiesis, 1, 2 transplantation,

acute lymphoblastic leukemia, 144 acute myelogenous leukemia,

allogeneic bone marrow transplantation, 126, 127

autologous bone marrow transplanta-tion, 127

allogeneic transplants, 44, 45, 47 aplastic anemia treatment, 161, 163 autologous transplants, 45-47 blood product transfusion in patients,

49-51 chronic myelogenous leukemia, 108,

109 collection of stem cells, 47, 48 conditioning therapy, 48, 49 failure of graft and treatment, 53 graft-versus-host disease,

acute phase staging, 54 blood transfusion guidelines for pre-

vention, 49, 50 chronic phase, 54, 55 diagnosis, 55 overview, 44, 45

Bone marrow (cont.), transplantation (cont.),

graft-versus-host disease (cont.), prevention, 55 risk factors, 53 treatment, 55, 56

HLA-matching, 45-47 indications, 43, 44

Index

infection in posttransplant period, empiric treatment, 51 Pneumocystis pneumonia, 51, 57 pneumonia management, 51, 56-58 prophylaxis, 50, 51 viral infection, 52, 53

multiple myeloma, chemotherapy with stem cell rescue, 219-222

myelodysplastic syndrome treatment, 155

principles, 43, 44 screening for infection, 47 thrombotic microangiopathy manage-

ment,59 veno-occlusive disease,

diagnosis, 58 prophylaxis, 58, 59 risk factors, 58

BSS, see Bernard-Soulier syndrome Burkitt's lymphoma, see also Non-

Hodgkin's lymphoma, epidemiology, 200 Epstein-Barr virus role, 181, 182 histopathology, 200 treatment, 200, 201

Burr cell, definition and associated conditions,63

C Carmustin (BCNU), chemotherapy fea-

tures, 334 Cavernous hemangioma, features, 277, 278 CCNU, see Lomustin CD, human leukocyte antigen nomencla

ture, 320, 341-346 2-CDA, see Cladribine Cerebral lymphoma, see Non-Hodgkin's

disease Chediak-Higashi syndrome, features, 229

Index

Chemotherapy, see specific diseases and drugs

Chlorambucil, chemotherapy features, 334 Chromosomal abnormalities,

blood diseases, see specific diseases tumors, 20-22

Chronic lymphocytic leukemia (CLL), see also Non-Hodgkin's lymphoma,

chromosomal abnormalities, 194 classification, 195 clinical features, 194, 195 histopathology, 194 incidence, 194 laboratory findings, 195, 196 prognosis, 196 prolymphocytic leukemia, 198 smoldering disease, 198 T-cell disease, 198-199 treatment,

chlorambucil, 196 combination chemotherapy, 197 cyclophosphamide, 197 fludarabine. 197 immunotherapy, 197 indications, 196 stem cell transplantation, 197

Chronic myelogenous leukemia (CML). age of onset, 105 chromosomal abnormalities, 105, 106 clinical manifestations, 106, 107 diagnosis, 107 juvenile disease, 116 treatment, 107-109

Chronic renal failure, anemia, 69 Cladribine (2-CDA), chemotherapy fea

tures, 334 CLL, see Chronic lymphocytic leukemia Clonality, tumors,

cytogenetics, 20, 21 light chain restriction, 22 loss of heterozygosity, 23 molecular cytogenetics, 21, 22 overview, 20 rearrangement of lymphocyte genes, 22 X-inactivation assay, 23

Clopidogrel, arterial thrombosis treatment, 308

Clotting factors, assays, 262-264 cascade diagram, 261

357

deficiencies, see also Hemophilia; von Willebrand disease,

acquired inhibitors, 296 contact phase coagulation factors, 291 factor XI, 290 factor XIII, 290, 291 liver disease effects, 292, 293 therapeutic recommendations, 291 vitamin K-dependent factors, 290

factor V Leiden mutation and APC resis-tance, 299, 300, 302

fibrin formation, 253, 254 half-lives, 291 hypercoagulability, see Hypercoagulabil

ity inhibitors,

antithrombin, 254 protein C, 254, 255, 257 protein S, 255

intrinsic versus extrinsic clotting pathways, 252. 253

types. 252 vitamin K dependence, 291, 292

CML, see Chronic myelogenous leukemia CMV, see Cytomegalovirus Cold agglutinin disease, features. 226 Coombs test, blood typing, 320, 321 Coumadin, see Warfarin Creutzfeld-lakob disease, transmission by

blood transfusion, 330 Cryoglobulinemia, features, 226 Cutaneous T-ce\llymphoma, see Mycosis

fungoides Cyclophosphamide, chemotherapy fea

tures, 335 Cytomegalovirus (CMV),

clinical manifestations, 239, 240 diagnosis, 240 prophylaxis, 240 transmission by blood transfusion, 328,

329 treatment, 240

Cytosine-arabinoside (ARA-C), chemotherapy features, 335

358

o Dacarbacine (DTIC), chemotherapy fea

tures, 335 Daunorubicin, chemotherapy features, 335 Deep-vein thrombosis, see Venous throm

bosis Delta-granule deficiency, features, 281 Dendritic cell,

differentiation, see Myelopoiesis features, II, 12

Dense granule deficiency, see Delta-granule deficiency

Desidurin, thrombin inhibitor therapy, 315, 316

Di George syndrome, features, 232 DIC, see Disseminated intravascular co

agulation Dicoumarol,

bioavailability, 311 complications, 312 drug interactions, 312, 313 mechanism of anticoagulation activity, 311 monitoring of therapy, 311, 312

Diffuse large B-ceillymphoma, see also Non-Hodgkin's lymphoma,

histopathology, 186 prognostic factors, 186, 187 treatment, 187, 189

Disseminated intravascular coagulation (DIC), associated disorders, 293, 294 clinical features, 294 laboratory findings, 295 treatment, 295, 296

Doxorubicin, chemotherapy features, 336 DTIC, see Dacarbacine

E Ehlers-Danlos syndrome, features, 268 Elliptocytosis,

definition and associated conditions, 63 hereditary disease, 79

Embolism, see Pulmonary embolism Endothelium, hemostasis role, 247, 248 Eosinophil,

differentiation, see Myelopoiesis features, 10 normal blood values, 347

Index

Eosinophilia, differential diagnosis, 103 Epirubicin, chemotherapy features, 336 EPO, see Erythropoietin Epstein-Barr virus,

epidemiology, 237 Hodgkin's disease role, 173 infectious mononucleosis,

clinical manifestations, 237, 238 course, 237-239 diagnosis, 238, 239 differential diagnosis, 239

non-Hodgkin's lymphoma role, 181, 182 transmission by blood transfusion, 329

Erythropoiesis, bone marrow, 5, 6 compensation for anemia, 7 differentiation stages, 5 gene regulation, 5

Erythropoietin (EPO), clinical applications, 29, 30 myelodysplastic syndrome treatment, 153 receptors and signal transduction, 5 structure, 29

Essential thrombocythemia, clinical definition and manifestations,

113, 114,278,279 diagnosis, 114 etiology, 113 prognosis, 114 treatment, 114

Etoposide (VP-16), chemotherapy features, 336

F Factors, see Clotting factors Fanconi's anemia, see Aplastic anemia Fas ligand, functions, 31 Fibrin,

D dimer assays, 265 degradation, 257, 258 fibrinogen,

assays, 262, 263 deficiency, 290

formation from fibrinogen, 253, 254 Fibrinolytic therapy, see also specific agents,

agents, 313, 314 contraindications, 313, 314

Index

Flow cytometry, immunophenotyping, 16 FL T3-ligand, functions, 30 Fludarabine, chemotherapy features, 336 Folic acid,

deficiency, causes and anemia, 75 dietary sources, 71, 72 normal serum values, 347 pregnancy supplementation, 75 structure, 71

Follicular lymphoma, see also Non-Hodgkin's lymphoma,

chromosomal abnormalities, 190 clinical symptoms, 190 incidence, 188 pathology, 188 prognosis, 190, 191 treatment,

G

chemotherapy, 191, 192 immunotherapy, 192, 193 observation, 191 radiotherapy, 191

Gasser's syndrome, see Hemolytic-uremic syndrome

Gastric lymphoma, see also Non-Hodgkin's lymphoma,

incidence, 203 pathogenesis, 204 stages, 204, 205 treatment, 205

G-CSF, see Granulocyte colony-stimulating factor

Gene mutation, assays, 22 Gene therapy,

applications, 23, 27 clinical protocols,

antitumor immunity stimulation, 26 cell behavior modification, 26, 27 gene marking, 26 missing gene replacement, 25

liposome transfection, 25 viral vectors,

adeno-associated virus, 24 adenovirus, 24 effeciency, 25 retrovirus, 24

359

Glanzmann's disease, see Thrombasthema

Glucose-6-phosphate dehydrogenase (G6PD) deficiency,

diagnosis, 80 factors causing hemolysis, 79, 80 heredity, 80 incidence, 79 treatment, 80

GM-CSF, see Granulocyte-macrophage colony-stimulating factor

G6PD deficiency, see Glucose-6-phosphate dehydrogenase deficiency

Graft-versus-host disease (GVHD), acute phase staging, 54 blood transfusion,

association, 331 guidelines for prevention, 49, 50

chronic phase, 54, 55 diagnosis, 55 overview, 44, 45 prevention, 55 risk factors, 53 treatment, 55, 56

Granulocyte, transfusion of concentrates, 324, 325

Granulocyte colony-stimulating factor (G-CSF),

aplastic anemia treatment, 163, 164 functions, 27, 28 myelodysplastic syndrome treatment,

153,154 stem cell mobilization for transplanta

tion,48 therapy in hematologic disorders, 28,

29 Granulocyte-macrophage colony-stimu

lating factor (GM-CSF), functions, 27, 28 myelodysplastic syndrome treatment,

154 stem cell mobilization for transplanta

tion,48 therapy in hematologic disorders, 28, 29

Gray platelet syndrome, see Alpha-granule deficiency

GVHD, see Graft-versus-host disease

360

H Hairy cell leukemia, see also Non-

Hodgkin's lymphoma, diagnosis, 202, 203 histopathology, 202 incidence, 202 treatment, 203

Haptoglobin, normal blood values, 347 HDN, see Hemolytic disease of the new-

born HE, see Hereditary elliptocytosis Heavy-chain disease, features, 225 Heinz body, definition and associated

conditions, 63 Hematocrit, normal blood values, 347

Hematopoiesis, sites, I, 2 stem cells, 2, 4 stromal cell regulation, 2

Hemoglobin, deficiency, see Anemia genetic diseases, see Sickle cell anemia;

Thalassemia iron, 7 metabolism, 8 normal adult red cell values, 61, 62 normal blood values, 347 oxygen dissociation curve, 6, 7 structure, 6 types, 6

Hemolytic disease of the newborn (HDN),

ABO incompatibility as cause, 90, 91 Rhesus antibodies as cause, 91, 92

Hemolytic-uremic syndrome (HUS), clinical manifestations, 276 management following stem cell trans

plantation, 59 treatment, 277

Hemophilia, clinical presentation, 284, 286 complications of treatment, 288, 296 factor IX deficiency in type B, 284 factor VIII deficiency in type A, 283,

284 laboratory findings, 286 treatment, 286, 287

Index

Hemorrhagic disorders, see also specific disorders,

clinical evaluation, bleeding history, 258 physical examination, 258, 259

laboratory evaluation, activated partial thromboplastin time,

261,262 bleeding time, 260 interpretation, 262 overview, 259, 260 platelet count, 260 prothrombin time, 261, 262 thrombin time, 262

vascular causes, overview, 267, 268

Hemostasis, blood coagulation overview, 252-254 inhibitors, 254, 255, 257 disorders, see Hemorrhagic disorders endothelium role, 247, 248 fibrinolysis role, 257, 258 mechanisms, 247 platelet role, 248, 249, 251 primary hemostasis, 247

Henoch-Schonlein purpura, features, 269 Heparin,

arterial thrombosis treatment, 308 complications of therapy, 310, 311 low molecular weight heparin therapy,

310 unfractionated heparin therapy, 309, 310

Hepatitis, transmission by blood transfusion, 328-330

Hereditary elliptocytosis (HE), etiology and management, 79

Hereditary hemorrhagic telangiectasia, features, 267, 268

Hereditary spherocytosis, clinical presentation, 78 diagnosis, 78 genes, 77 treatment, 78, 79

HHV-6, see Human herpesvirus-6 HHV-8, see Human herpesvirus-8 Hirudin, thrombin inhibitor therapy, 315,

316 HIV, see Human immunodeficiency virus

Index

HLA, see Human leukocyte antigen Hodgkin's disease,

clinical features, 174 diagnosis, 174, 175 epidemiology, 173 Epstein-Barr virus role, 173 histopathologic classification, 176, 177 pathogenesis, 173, 174 prognosis, 173, 178 staging, 175, 176 treatment,

chemotherapy, 178, 180 combination therapy, 178 late complications, 179 radiation, 178 relapse management, 179

Howell-Jolly body, appearance following splenectomy, 172

HTL V, transmission by blood transfusion, 328

Human herpesvirus-6 (HHV -6), infections, 243,244

Human herpesvirus-8 (HHV -8), associated disorders,

Kaposi's sarcoma, 244, 245 overview, 245 primary effusion lymphoma, 244, 245

diagnosis, 245 epidemiology, 245 Epstein-Barr virus homology, 244 treatment, 245, 246

Human immunodeficiency virus (HIV), see also Acquired immunodeficiency syndrome,

cell specificity for infection, 233, 234 clinical manifestations of infection, 234,

235 diagnosis of infection, 234, 235 hematology of infection, 235, 236 hemophiliac transmission from blood

products, 288 stages of infection, 233, 234 transmission by blood transfusion, 328 types, 233

Human leukocyte antigen (HLA), CD nomenclature, 320, 341-346 classes, 320-322

361

Human leukocyte antigen (HLA) (cont.). disease susceptibility role, 323 functions, 320, 322 genes, 321 heredity, 322 matching for stem cell

transplantationmatching, 45--47 minor antigens, 323 typing, 322, 323

HUS, see Hemolytic-uremic syndrome Hydroxyurea,

chronic myelogenous leukemia treatment, 108

essential thrombocythemia treatment, 114

polycythemia vera treatment, 113 Hydroxyurea, chemotherapy features, 337 Hyper-IgE syndrome, features, 229 Hyper-IgM syndrome, features, 230 Hypercoagulability,

acquired states, 302, 303 antithrombin deficiency, 301 classification of states, 299, 300 factor V Leiden mutation and APC resis-

tance, 299, 300, 302 hyperhomocysteinemia,302 management, 303 protein C deficiency, 301 protein S deficiency, 301, 302 prothrombin gene mutation, 301 testing, 264, 265, 299, 302

Hyperhomocysteinemia, hypercoagulability state, 302

Hypochromasia, definition and associated conditions, 63

I Idarubicin, chemotherapy features, 337 Idiopathic hypereosinophilic syndrome

(IRES), features, 103 Idiopathic purpura, see Purpura simplex Idiopathic thrombocytopenic purpura

(ITP), autoimmune pathogenesis, 273 diagnosis, 272, 273 incidence, 272 treatment, 273, 274

362

IFN-a, see Interferon-a IFN-p, see Interferon-p IFN-y, see Interferon-y Ifosfamide, chemotherapy features, 337 IHES, see Idiopathic hypereosinophilic

syndrome IL, see specific interleukins Immunocytochemistry, overview, 16 Immunocytoma, see Lymphoplasmacytoid

lymphoma Immunodeficiency,

acquired immunodeficiencies, AIDS, see Acquired immunodeficiency

syndrome diseases, 228, 233 drug induction, 233

congenital deficiencies, humoral immunity defects, 231 lymphocyte defects, 230 overview, 228 phagocytic system defects, 229 T-cell system defects, 232

laboratory testing, 227, 228 Immunoglobulin A deficiency, features, 231 Immunoglobulins, normal blood values, 347 Infection, neutropenic patients,

diagnosis, 35, 36 prophylaxis, 39, 40 stem cell recipients, posttransplant infec-

tion, empiric treatment, 51 Pneumocystis pneumonia, 51, 57 pneumonia management, 51, 56-58 prophylaxis, 50, 51 viral infection, 52, 53

treatment, empiric treatment, 36, 37 established infection, 37-39

Infectious mononucleosis, see Epstein-Barr virus

Interferon-a (IFN -a), chronic myelogenous leukemia treatment,

108 essential thrombocythemia treatment, 114 functions, 31, 34 polycythemia vera treatment, 113

Interferon-p (lFN-P), functions, 34

Interferon-y (IFN-y), functions, 34 Interleukin-I (lL-I), functions, 32 Interleukin-2 (IL-2), functions, 32 Interleukin-3 (IL-3),

functions, 27, 28

Index

therapy in hematologic disorders, 28 Interleukin-4 (lL-4), functions, 32 Interleukin-5 (IL-5), functions, 32 Interleukin-6 (IL-6), functions, 32 Interleukin-7 (lL-7), functions, 32 Interleukin-8 (IL-8), functions, 33 Interleukin-9 (lL-9), functions, 33 Interleukin-IO (IL-IO), functions, 33 Interleukin-II (IL-II), functions, 33 Interleukin-12 (IL-12), functions, 33 Interleukin-13 (lL-13), functions, 33 Interleukin-15 (IL-15), functions, 33 Interleukin-16 (IL-16), functions, 33 Interleukin-17 (IL-17), functions, 33 Interleukin-18 (IL-18), functions, 33 Iron,

absorption and transport, 7, 8, 65, 66 deficiency, see Anemia normal serum values, 347 overload in blood transfusion, 330, 331

ITP, see Idiopathic thrombocytopenic purpura

J lC virus (lCY), see Progressive multifocal

leukoencephalopathy, lCY, see lC virus

K Kaposi's sarcoma (KS), human herpesvi

rus-8 role, 244, 245 Kasabach-Meritt syndrome, see Cavernous

hemangioma Kell blood group system, 320 Kostmann syndrome, colony-stimulating

factor therapy, 28, 29 KS, see Kaposi's sarcoma

L Lactate dehydrogenase (LDH), normal

blood values, 347 LDH, see Lactate dehydrogenase

Index

Lead poisoning, anemia, 70, 94 Lepirudin, thrombin inhibitor therapy, 316 Leukocytosis,

clinical definition, 97 differential diagnosis, 97-99

Leukopenia, clinical definition, 97 differential diagnosis, 99-101

Light-chain ayloidosis, features, 225 LOH, see Loss of heterozygosity Lomustin (CCNU), chemotherapy features,

337 Loss of heterozygosity (LOH), tumors, 23 Lupus anticoagulant, features, 296 Lymph node swelling, see Lymphadenopathy Lymphadenopathy,

differential diagnosis, 168-170 imaging, 167 physical examination, 169

Lymphocyte, see B cell; T cell Lymphocytopenia,

clinical definition, 167 differential diagnosis, 168

Lymphocytosis, clinical definition, 167 differential diagnosis, 167, 168

Lymphoid organs, types, 12, 13 Lymphoplasmacytoid lymphoma, 199,200,

see also Non-Hodgkin's lymphoma, Waldenstroms' disease, 199, 200, 211,

225

M Macrocytosis, definition and associated

conditions, 63 Macrophage colony-stimulating factor (M

CSF), functions, 27, 28 therapy in hematologic disorders, 28

Macrophage, differentiation, see Myelopoiesis features, 11

Malaria, hemolytic anemia, 92 parasites, 92 transmission by blood transfusion, 330 treatment and prophylaxis, 93

363

MALT, see Mucosa-associated lymphoid tissue

m-AMSA, see Amsacrine Mantle cell lymphoma, see also Non-

Hodgkin's lymphoma, clinical manifestations, 193 histopathology, 193 incidence, 193 prognosis, 193 treatment, 194

Marcumar, see Phenprocoumon M-CSF, see Macrophage colony-stimulating

factor MDS, see Myelodysplastic syndromes Megakaryopoiesis, platelet production, 12 Megaloblastic anemia, see Anemia Melphalan, chemotherapy features, 338 6-Mercaptopurine, chemotherapy features,

338 Methotrexate, chemotherapy features, 338 Metoclopramide, antiemesis, 41 MGUS, see Monoclonal gammopathy of

undetennined significance Microcytosis, definition and associated

conditions, 63 Monoclonal gammopathy of undetennined

significance (MGUS), clinical manifestations, 210 diagnosis, 209, 210 differential diagnosis, 210 paraproteinemia, 209 prevalence, 209

Monocyte, differentiation, see Myelopoiesis features, 10, II nonnal blood values, 347

Monocytosis, differential diagnosis, 104 Moschcowitz's disease, see Thrombotic

thrombocytopenic purpura Mucosa-associated lymphoid tissue (MALT)

lymphoma, see also Non-Hodgkin's lymphoma,

classification, 203 pathogenesis, 204

Multiple myeloma, asymptomatic disease, 224 clinical manifestations, 212, 213

364

Multiple myeloma (cant.), course and prognosis, 223, 224 definition, 211 diagnosis,

bone marrow examination, 214 criteria, 217 laboratory findings, 213, 214 radiology, 214, 216

etiology, 212 frequency, 211 pathogenesis, 212 plasma cell leukemia, 224 smoldering disease, 224 solitary plasmacytoma, 224 staging, 217, 218 treatment,

chemotherapy with stem cell rescue, allogeneic stem cell transplantation,

221,222 chemotherapy regimens, 219-221 dexamethasome, 221

interferon-a, 222 radiation therapy, 222 refractory disease, 223 selection of therapy, 218 supportive care, 223

Mycosis fungoides, see also NonHodgkin's lymphoma,

staging, 20 I treatment, 201, 202

Myelodysplastic syndromes (MDS), chromosomal abnormalities, 147-149 classification, 150, 152 clinical manifestations, 149 differential diagnosis, 150, 152 etiology, 147 incidence, 147 laboratory findings, 149, 150 pathophysiology, 147-149 prognosis, 152 treatment,

amifostine, 154 blood transfusion, 153 bone marrow transplantation, 155 chemotherapy, 154, 155 growth factors, 153, 154 supportive care, 152, 153

Myelopoiesis, kinetics, 9 precursors, 9

Index

Myeloproliferative syndromes, see also Agnogenic myeloid metaplasia; Chronic myelogenous leukemia; Essential thrombocythemia; Polycythemia vera,

overview, 105 rare syndromes, 116

N Natural killer (NK) cell,

functions, 14, 15 inhibitors of activation, 15 Iymphokine-activated killer cells, 15

Neutropenia, see also Kostmann syndrome,

clinical definition, 97 cyclic neutropenia,

diagnosis, 102 treatment, 102, 103

differential diagnosis, 99-101 drug induction, 99,101,102 infection in neutropenic patients,

diagnosis, 35, 36 prophylaxis, 39, 40 stem cell posttransplant period,

empiric treatment, 51 Pneumocystis pneumonia, 51, 57 pneumonia management, 51, 56-58 prophylaxis, 50, 51 viral infection, 52, 53

treatment, empiric treatment, 36, 37 established infection, 37-39

Neutrophil, bacteria uptake and killing activity, 9,

10 differentiation, see Myelopoiesis features, 9 leukocytosis, see Leukocytosis normal blood values, 347

NHL, see Non-Hodgkin's lymphoma NK cell, see Natural killer cell

Index

Non-Hodgkin's lymphoma (NHL), see also Anaplastic large-cell lymphoma; Burkitt's lymphoma; Chronic lymphocytic leukemia; Diffuse large B-cell lymphoma; Follicular lymphoma; Gastric lymphoma; Hairy cell leukemia; Lymphoplasmacytoid lymphoma; Mantle cell lymphoma; Mucosaassociated lymphoid tissue lymphoma; Mycosis fungoides,

angioimmunoblastic T-cell lymphoma, 205 cerebral lymphoma, 206, 207 chemotherapy protocols, 189 children, 206 chromosomal abnormalities, 182 classification systems, 181, 183, 185 clinical features, 183 diagnostic strategies, 183, 185 etiology, 181, 182 human immunodeficiency virus infection

association, 206 low versus high grade disease, 186 lymphoblastic lymphomas, 201 prognostic factors, 186, 187 splenic marginal zone lymphoma, 207 staging, 183 virus infection roles, 181, 182

o Odansetron, antiemesis, 41 Osler-Weber-Rendu disease, see Heredi-

tary hemorrhagic telangiectasia Osteogenesis imperfecta, features, 268

P p53, tumor suppression, 148 Pancytopenia, differential diagnosis, 160 Paroxysmal nocturnal hemoglobinuria (PNH),

diagnosis, 89, 90 gene mutations, 89 treatment, 90

Parvovirus B 19, diagnosis, 241 hematologic relevance, 240, 241 immunity, 240 transmission by blood transfusion, 329 treatment, 241

365

PCV, see Polycythemia vera PE, see Pulmonary embolism Pentostatin, chemotherapy features, 338 Peripheral blood film, diagnostic utility, 18 Pernicious anemia,

autoimmune dysfunction, 72 diagnosis, 73, 74 onset, 73 pathogenesis, 72, 73 treatment, 74

Phenprocoumon, bioavailability, 311 complications, 312 drug interactions, 312, 313 mechanism of anticoagulation activity,

311 monitoring of therapy, 311, 312

PK deficiency, see Pyruvate kinase deficiency Plasma,

fresh frozen plasma transfusion, 325 protein electrophoretic fractions, 15

Plasma cell leukemia, features, 224 Plasmin, fibrin degradation, 257, 258 Platelet,

acquired disorders drug-induced abnormalities, 283 dysproteinemias, 282 liver disease, 282, 283 myeloproliferative disorders, 282 uremia, 282

aggregation, 249, 251, 263 count in hemorrhagic disorder evaluation,

260 disorders,

qualitative, 279-283 quantitative, 270-279

endothelial inhibitors, 247 functional tests, 263, 264 granule types and secretion disorders,

280,281 hemostasis role, 248, 249, 251 life span, 248, 270 megakaryopoiesis, 12 normal values in peripheral blood, 248,

270,347 transfusion, 49-51, 324 ultrastructure, 248, 249

366

PLL, see Prolymphocytic leukemia PML, see Progressive multifocalleukoen

cephalopathy Pneumocystis pneumonia,

clinical manifestations, 243 risk factors, 242, 243 stem cell transplant recipients, 51, 57 treatment, 243

PNH, see Paroxysmal nocturnal hemoglobinuria

Poikilocytosis, definition and associated conditions, 63

Polycythemia vera (PCV), clinical manifestations, 110, III diagnosis, III, 112 differential diagnosis, 112 etiology, 109, 110 treatment, 112, 113

Pregnancy, anemia, 68 folic acid supplementation, 75

Procarbacin, chemotherapy features, 339 Progressive multifocalleukoencephalopa-

thy (PML), clinical manifestations, 241, 242 JC virus infection, 241 treatment, 242

Prolymphocytic leukemia (PLL), see Chronic lymphocytic leukemia

Protein C, assay, 264, 265 coagulation inhibition, 254, 255, 257 deficiency, 30 I

Protein S, assay, 264, 265 coagulation inhibition, 255 deficiency, 301, 302

Prothrombin, gene mutation and hypercoagulability, 301

Prothrombin time (PT), anticoagulation therapy monitoring, 311,

312 assay, 260, 261 international normalized ratio, 261, 312

Pseudo xanthoma elasticum, features, 268 PT, see Prothrombin time

Pulmonary embolism (PE), clinical features and diagnosis, 306 treatment, 306, 307

Index

Purine nucleoside phosphorylase defi-ciency, features, 232

Purpura due to infection, features, 269 Purpura simplex, features, 268, 269 Pyruvate kinase (PK) deficiency,

diagnosis and treatment, 81 heredity, 80

R RAS, mutation in myelodysplastic syn

dromes, 149 Recombinant DNA technology, overview,

19,20 Red blood cell, 8

differentiation, see Erythropoiesis morphological abnormalities, 63 normal adult red cell values, 61, 62, 347 packed red cell transfusion, 324

Residency program, hematology, ambulatory medicine experience, 349 clinical experience, 349 content of program, 350 skill requirements, 349, 350

Reticular dysgenesis, features, 229 Retinoids, acute promyelocytic leukemia

treatment, 128 Rhesus blood group system,

hemolytic disease of the newborn, 91, 92 overview, 318, 319

Rituximab, follicular lymphoma treatment, 192,193

S SCA, see Sickle cell anemia SCF, see Stem cell factor Schistocyte, definition and associated

conditions, 63 Senile purpura, features, 269 Severe combined immunodeficiency, 230 Sickle cell anemia (SCA),

clinical presentation, 82 diagnosis, 82 gene mutation and heredity, 81 treatment and prophylaxis, 82-84

Index

Sideroblastic anemia, overview, 69 Sintrom, see Acenocoumarol Solitary plasmacytoma, features, 224 Splenic marginal zone lymphoma, see

Non-Hodgkin's disease Splenomegaly,

clinical definition, 167 differential diagnosis, l7{}-172 hypersplenism, 171 splenectomy, 171, 172

Stem cell, assay, 2, 4 cytokine regulation, 4 differentiation, 2-4, 97 function, 43 gene regulation, 4 identification, 43 markers, 2 telomere length, 4 transplantation,

acute lymphoblastic leukemia, 144 acute myelogenous leukemia,

allogeneic bone marrow transplantation, 126, 127

autologous bone marrow transplanta-tion, 127

allogeneic transplants, 44, 45, 47 aplastic anemia, 161, 163 autologous transplants, 45-47 blood product transfusion in patients,

49-51 CD34 identification, 43, 48 chronic myelogenous leukemia treat-

ment, 108, 109 collection of stem cells, 47, 48 conditioning therapy, 48, 49 failure of graft and treatment, 53 graft-versus-host disease,

acute phase staging, 54 blood transfusion guidelines for pre-

vention, 49, 50 chronic phase, 54, 55 diagnosis, 55 prevention, 55 risk factors, 53 treatment, 55, 56

Stem cell (con t.) , transplantation (cont.),

HLA-matching, 45-47 indications, 43, 44 infection in posttransplant period,

empiric treatment, 51

367

Pneumocystis pneumonia, 51, 57 pneumonia management, 51, 56-58 prophylaxis, 50, 51 viral infection, 52, 53

multiple myeloma, chemotherapy with stem cell rescue, 219-222

myelodysplastic syndrome, 155 principles, 43, 44 screening for infection, 47 thrombotic microangiopathy manage-

ment,59 umbilical cord blood, 45 veno-occlusive disease,


Stem cell factor (SCF), functions, 30 Streptokinase, fibrinolytic therapy, 314 Stromal cell, hematopoiesis regulation, 2 Syphilis, transmission by blood transfu-

sion, 327, 328

T T cell,

CD4-positive helper cells, 14 CD8-positive cytotoxic T lymphocytes,

14 differentiation, 14 receptor gene rearrangement, 22

Target cell, definition and associated conditions,63

TGF-~, see Transforming growth factor-~ Thalassemia,

a-thalassemia, 85 ~-thalassemia,

diagnosis, 85 treatment, 85 types, 84, 85

thalassemia intermedia, 85, 86 Thalassemia minor, anemia, 69

368

6-Thioguanine, chemotherapy features, 339

Thrombasthenia, clinical features, 279, 280 diagnosis, 280 treatment, 280

Thrombin inhibitor therapy, 315, 316 Thrombin time (TT), hemorrhagic disor

der evaluation, 262 Thrombocythemia, see Essential thromb

ocythemia Thrombocytopenia, see also specific

forms, autoimmune states, 272-274 cardiopulmonary bypass association,

278 classification,

decreased platelet production disorders, 270, 271

increased platelet destruction disor-ders, 272-279

clinical definition, 270 drug induction, 274, 275 hypersplenism association, 278 investigations, 270 neonatal purpura, 275 posttransfusion purpura, 275

Thrombocytosis, clinical definition, 278 Thrombophilia, see Hypercoagulability Thrombopoietin (TPO),

clinical applications, 29 megakaryopoiesis role, 12,29 receptor, 29 structure, 29 tissue distribution, 29

Thrombosis, see Arterial thrombosis; Venous thrombosis

Thrombotic microangiopathy (TM), see Hemolytic-uremic syndrome

Thrombotic thrombocytopenic purpura (TTP),

clinical manifestations, 276 treatment, 277 von Willebrand factor abnormalities,

276,277 Thymidine kinase, suicide gene therapy,

26,27

Index

Ticlopidine, arterial thrombosis treatment,308

Tissue plasminogen activator (t-PA), arterial thrombosis treatment, 308, 309 fibrin degradation role, 257, 258 fibrinolytic therapy, 314 inhibitors, 258

TM, see Thrombotic microangiopathy TNF-a, see Tumor necrosis factor-a Toxoplasmosis, features, 242 t-PA, see Tissue plasminogen activator TPO, see Thrombopoietin Transforming growth factor-~ (TGF-~),

functions, 31 Transfusion, see Blood product transfusion TT, see Thrombin time TTP, see Thrombotic thrombocytopenic

purpura Tumor clonality, see Clonality, tumors Tumor necrosis factor-a (TNF-a), func

tions,30

U Urokinase, fibrinolytic therapy, 314

V Veno-occlusive disease (VOD),


Venous access, catheters, 40 cytostatic drug delivery, 40, 41 infection, 40 thrombus clearance, 40

Venous thrombosis, clinical manifestations, 304 diagnosis, 305 pathogenesis, 304 prophylaxis, 305 treatment, 305, 306

Vincristine, chemotherapy features, 339 Vitamin B12

deficiency, causes, 74 diagnosis, 72, 73 pernicious anemia, 72-74

Index

Vitamin B12 (cont.) enzymes, 71 malabsorption in pernicious anemia, 72, 73 normal serum values, 347 structure, 70 transport, 70, 71

Vitamin K, adults, 292 clinical manifestations in newborns. 292 clotting protein dependence, 291, 292 inhibitors, see specific compounds

VOD, see Veno-occlusive disease von Willebrand disease (VWD),

acquired disease, 296 clinical presentation, 289 genetics, 288, 289 laboratory diagnosis, 289 platelet adhesion abnormality, 249, 288 prevalence, 289 treatment, 289, 290

von Willebrand factor (VWF),

assay, 263 thrombotic thrombocytopenic purpura

abnormalities, 276,277

VP-16, see Etoposide VWD, see von Willebrand disease VWF, see von Willebrand factor

w

369

Waldenstroms' disease, see Lymphoplasmacytoid lymphoma

Warfarin. bioavailability, 311 complications. 312 drug interactions, 312, 313 mechanism of anticoagulation activity,

311 monitoring of therapy, 311. 312

White cells, normal blood values, 347 Whole blood, transfusion, 323 Wiscott-Aldrich syndrome, features. 232

X X-inactivation assay, overview, 23 X-linked agammaglobulinemia, features,

231

appendix 1 - springer978-1-59259-203-6/1.pdf · appendix 1 glossary of cytostatic drugs a number of...

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