Biology and Treatment of Leukemia and Bone Marrow Neoplasms

Introduction
Contents
1 Advances in Diagnosis and Risk Stratification of Acute Myeloid Leukemia and Myelodysplastic Syndromes
	1.1 Next Generation Sequencing (NGS)- Based Testing in Hematologic Malignancies
	1.2 CASE 1: 69 Year Old with Pancytopenia
	1.3 Discussion
	1.4 Genomic Alterations in MDS
	1.5 Clonal Hematopoiesis of Indeterminate Potential and Pathogenesis of MDS
	1.6 Interpretation of Results of Genomic Testing
	1.7 Role of Genomic Testing in Diagnosis and Prognosis of MDS
	1.8 Case 2: 52-Year-Old Male with Pancytopenia
	1.9 Discussion
		1.9.1 Genetic Alterations in AML
		1.9.2 ELN Classification Integrating Cytogenetics and Mutation Analysis
		1.9.3 Interpretation of NGS Mutation Panel Results
		1.9.4 Evaluation of Minimal/Measurable Residual Disease (MRD) in Management of AML
		1.9.5 Future Perspectives
	References
2 Genetics and Diagnostic Approach to Lymphoblastic Leukemia/Lymphoma
	2.1 Introduction
	2.2 B-lymphoblastic Leukemia/Lymphoma
		2.2.1 Epidemiology and Risk Factors
		2.2.2 Genomic Classification of B-Lymphoblastic Leukemia
	2.3 B-ALL with Recurrent Genetic Abnormalities
		2.3.1 B-ALL with BCR/ABL1
		2.3.2 B-ALL with KMT2A (MLL) Rearrangement
		2.3.3 ETV6/RUNX1 t(12;21)
		2.3.4 TCF3/PBX1 t(1;19)
		2.3.5 Hyperdiploidy
		2.3.6 Hypodiploidy
		2.3.7 IL3/IGH, t(5;14)
		2.3.8 Intrachromosomal Amplification of Chromosome 21 (iAMP21)
		2.3.9 Ph-Like ALL
	2.4 B-ALL Not-Otherwise Specified
		2.4.1 TCF3 (E2A)/HLF, t(17;19)
		2.4.2 IKZF1 Alterations
	2.5 T-lymphoblastic Leukemia/lymphoma
	2.6 Diagnostic Work up of ALL
	2.7 Our Approach to Genomic Testing of ALL
	2.8 Case 1: BCR-ABL1 (Ph) Positive B-ALL
		2.8.1 Clinical Presentation and Pathology
		2.8.2 Genomic Evaluation
	2.9 Case 2: Ph-Like B-ALL
		2.9.1 Clinical Presentation and Pathology
		2.9.2 Genomic Evaluation
		2.9.3 Interpretation of NGS Results
	2.10 Case 3. T-ALL
		2.10.1 Clinical Presentation and Pathology
		2.10.2 Molecular Genomic Evaluation
		2.10.3 Interpretation of NGS Mutation Panel Results
		2.10.4 Follow up and Treatment
	References
3 Acute Promyelocytic Leukemia: Update on Risk Stratification and Treatment Practices
	3.1 Background and Epidemiology
	3.2 Pathogenesis
	3.3 Coagulopathy
	3.4 Drug Development in APL
	3.5 Diagnosis and Initial Management
	3.6 Case 1
	3.7 Risk stratification
	3.8 Management of Low-Risk Disease
	3.9 Case 2
	3.10 High-Risk Disease
	3.11 Practical Aspects of ATRA and ATO Dosing
	3.12 Differentiation Syndrome
	3.13 Pseudotumor Cerebri (PTC)
	3.14 Response Assessment and Surveillance
	3.15 Role of Maintenance Therapy
	3.16 Case 3
	3.17 Management of Relapsed APL
	References
4 Current and Emerging Therapies for Acute Myeloid Leukemia
	4.1 Introduction
		4.1.1 Case 1
	4.2 Induction Therapy
		4.2.1 Induction Therapy for Unfit Patients
	4.3 Post-Remission Consolidation
		4.3.1 Case 1 (Continued)
	4.4 Relapsed/Refractory Disease
		4.4.1 Case 1 (Continued)
	4.5 FLT3-Mutated AML
		4.5.1 Case 2
		4.5.2 Case 2 (Continued)
	4.6 Other Novel Targeted Therapies
	4.7 Antibody-Based Therapies and Immunotherapies
		4.7.1 Antibody-Based Therapy
	4.8 Chimeric Antigen Receptor (CAR) Modified Cellular Therapy
	References
5 Current Management and New Developments in the Treatment of ALL
	5.1 Case 1
		5.1.1 Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL)
		5.1.2 Discussion
		5.1.3 Recent Clinical Observations in Pediatrics
	5.2 Case 2
		5.2.1 Philadelphia Chromosome-Negative (Ph-Negative) B-Cell Acute Lymphoblastic Leukemia (B-ALL)
		5.2.2 Which Treatment Regimen Should Be Used?
		5.2.3 Should Asparaginase Be Included?
		5.2.4 Should Rituximab Be Used?
		5.2.5 When Should Allogeneic Stem Cell Transplant Be Considered?
	5.3 Case 3
		5.3.1 Philadelphia Chromosome-Positive (Ph-Positive) B-Cell Acute Lymphoblastic Leukemia (B-ALL)
		5.3.2 Which Induction Regimen Should Be Used?
		5.3.3 Which TKI Should Be Used?
		5.3.4 Post-Remission Treatment
	5.4 Case 4
		5.4.1 Relapsed ALL
		5.4.2 Discussion
	References
6 CML Chapter
	6.1 Case 1
	6.2 Discussion
	6.3 Case 2
	6.4 Discussion
	6.5 Case 3
	6.6 Discussion
	6.7 Risks of TKIs
	6.8 Future Directions and Unmet Needs
	References
7 Current Management and New Developments in the Treatment of Myelodysplastic Syndrome
	7.1 Myelodysplastic Syndrome: Overview
	7.2 CASE 1—High-Risk MDS
	7.3 Discussion
		7.3.1 Azacytidine
		7.3.2 Decitabine
		7.3.3 Combination Therapy with HMA
	7.4 Allogeneic HCT
		7.4.1 Who Should Be Considered for Allogeneic HCT?
	7.5 CASE 2—Low-Risk MDS with Cytopenia
	7.6 Discussion
		7.6.1 Luspatercept
	7.7 CASE 3—Del(5q) Syndrome
	7.8 Discussion
	7.9 Clonal Cytopenia Versus MDS
	7.10 Novel Agents for MDS
	References
8 Chronic Lymphocytic Leukemia (CLL): Biology and Therapy
	8.1 Introduction and Epidemiology
	8.2 Workup and Diagnosis
		8.2.1 Immunophenotyping
		8.2.2 Additional Testing
	8.3 Prognostic Factors
		8.3.1 Cytogenetics/FISH
		8.3.2 IGHV Mutation Status
		8.3.3 Lymphocyte Doubling Time
		8.3.4 Other Prognostic Markers
		8.3.5 Disease Stage
	8.4 Case 1: Good Risk CLL, Previously Untreated
	8.5 Case 2: Poor Risk CLL, Previously Untreated
	8.6 Indications for Treatment of CLL/SLL
	8.7 Frontline Treatment Options for CLL/SLL
		8.7.1 BTK inhibitors
		8.7.2 BCL2 inhibitor
	8.8 Case 3: Relapsed/refractory CLL
	8.9 Treatment of Relapsed/Refractory Disease
	8.10 Complications
		8.10.1 Autoimmune Complications [31]
		8.10.2 Infections
		8.10.3 Richter’s Transformation
	References
9 Biology and Current Treatment of Myeloproliferative Neoplasms
	9.1 Introduction
	9.2 Diagnosis
	9.3 Biology and Genetics of MPN
		9.3.1 Driver Mutations
	9.4 CASE 1: Primary Myelofibrosis
	9.5 Discussion
	9.6 CASE 2. Polycythemia Vera
	9.7 CASE 3: Essential Thrombocythemia
	References
10 Systemic Mastocytosis: Advances in Diagnosis and Current Management
	10.1 Introduction
	10.2 Biology and Genetics of SM
	10.3 Diagnosis and Classification of SM
		10.3.1 Case 1. SM-AHN
		10.3.2 Case 2. ISM
	10.4 Clinical Features of SM
	10.5 Treatment of SM
	References
11 Chimeric Antigen Receptor (CAR) T Cell Therapy for B-Acute Lymphoblastic Leukemia (B-ALL)
	11.1 CASE 1: CAR-T Cell Therapy for Refractory/Relapsed B-ALL with Extramedullary Disease
	11.2 Discussion
	11.3 CASE 2: Identification and Management of CAR-T Cell Toxicities
	11.4 Discussion
	11.5 CASE 3: Sequencing CAR-T Cell Therapy with Other Treatments for Refractory/Relapsed B- ALL
	11.6 Discussion
	11.7 Summary and Future Directions
	References