1. Hematologic Malignancies
An Introduction to
Hematologic Malignancies
Francesco Lo-Coco
Università Tor Vergata, Roma
Summer Medical School
Tor Vergata University, July 2011

2. Oncohematology Dealing with malignant tumors of the
hematopoietic system
Tumors affecting blood and/or bone marrow and/or lymphoid organs
Synonim: hematologic malignancies

3. Hematologic Malignancies
Systemic diseases (with few exceptions)
Laboratory assessment of paramount
relevance for diagnosis and management

4. Hematologic Malignancies
Leukemias
Lymphomas
Myeloproliferative syndromes
Multiple myeloma

5. Leukemia Metastatic disease (by definition)
Early diagnosis (almost) irrelevant
Etiology mostly unknown

7. Demographics of Leukemia Types
CLL=Chronic Lymphocytic
ALL=Acute Lymphoblastic
CML=Chronic Mylogenous
AML=Acute Mylogenous
Sources from Leukemia, Lyphoma, Myeloma Facts 2001
Total Reported Cases = 31,500

8. Leukemia Metastatic disease (by definition)
Early diagnosis (almost) irrelevant
Etiology mostly unknown

9. Leukemia: a paradigm for research
Tumor cells easily and promptly available
Can be cultured, manipulated, stored and thawed as viable cells
Biomarker detection of paramount relevance to guide therapy

10. Laboratory characterization of blood tumors
Morphologic exam (blood/marrow smear)
Immunophenotype
Cytogenetics
Molecular biology

11. Biomarkers in Leukemia
Diagnostic hallmarks or refinement
Prognostic markers
Minimal residual disease (MRD)
Targeted therapy

12. Therapeutic targets in APL
Retinoic Acid
Arsenic trioxide
Anthracyclines
Gemtuzumab- Ozogamicin (GO)
HuM195
ROS
Apaf
Caspase 9
CD33
Caspase 3
FLT3
FLT3 inhibitors
Sin3A
RARa
RARa
N-CoR/
SMRT
HDAC
PML
PML
Histone deacetylase
inhibitors Ac Ac Ac

13. Targeted therapy with retinoic acid for APL
+ All-trans Retinoic Acid

14. The landmark discoveries that revolutionized APL therapy
1. Differentiating effect of ATRA
2. Cloning of PML/RARA
Huang ME, Blood 1988; Castaigne S, Blood 1990; Borrow J, Science 1990;
Longo L, J Exp Med 1990; de Thé H, Nature 1990

15. Outcome results in APL prior and after ATRA
Pre-ATRA era
Sanz, M. A. et al. Blood 2004;103:
Sanz et al. Blood, 2009
Copyright ©2004 American Society of Hematology. Copyright restrictions may apply.

16. From Confucius to differentiation therapy
“If you use laws to direct the people, and punishments to control them, they will merely try to evade the laws, and will have no sense of shame.
But if by virtue you guide them, and by the rites you control them, there will be a sense of shame and of right.”
Confucius
ATRA
G. Lo Coco, Westminster School Hook Magazine. May 2011

17. Targeted therapy with imatinib in CML

18. Outcome of AML in older adults (60+ yrs)18

19. Outcome of AML in younger adults (15-59 yrs)19

20. Lymphomas
Hodgkin’s
Non Hodgkins (B-cell or T-cell)

21. Lymphomas Malignant disease of the lymphoid system
highly heterogeneous, both histologically
and clinically
Highly curable malignancies in oncological
practice:
90%of Hodgkin ’s disease
40-50%of high-grade NHL

22. Epidemiology of lymphomas
5th most frequently diagnosed cancer in both sexes
males > females
incidence
NHL increasing
Hodgkin lymphoma stable

23. Frequencies of different lymphomas
Non-Hodgkin Lymphomas
Diffuse large B-cell
Hodgkin
Lymphoma
11%
NHL
Follicular
Other NHL
~85% of NHL are B-lineage

24. Age distribution of Hodgkin lymphoma

25. Frequency of NHL Subtypes in Adults
Mantle cell (6%)
Peripheral T-cell (6%)
Indolent (35%)
Other subtypes with a frequency 2% (9%)
Key Point: The REAL/WHO classification system makes it possible to define clinically distinct types of NHL.1,2
This is a clinical evaluation of the REAL classifications in 1403 cases of NHL at 9 study sites worldwide.2
For most subtypes, diagnostic accuracy and reproducibility were ≥85%.2
The most common NHL subtypes2
Indolent lymphomas 35%
Follicular lymphoma 22%
Small lymphocytic lymphoma 6%
Marginal zone B-cell MALT 5%
Marginal zone B-cell nodal 1%
Lymphoplasmacytic 1%
Mantle cell lymphoma 6%
Peripheral T-cell lymphoma 6%
Diffuse large B-cell lymphoma 31%
Composite lymphomas 13%
The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997;89:3909–3918.
Armitage JO, Weisenburger DD, for the Non-Hodgkin’s Lymphoma Classification Project. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. J Clin Oncol. 1998;16:2780–2795.
Composite lymphomas (13%)
Diffuse large B-cell (31%)

26. Lymphomagenesis

27. Chromosomal translocations in NHL

28. Chromosomal translocations in NHL

29. Multiple myeloma
Plasma cell malignancy: clonal proliferation of plasma cells by monoclonal protein
1% of all malignancies
10% of hematologic malignancies

32. Epidemiology

33. Multiple myeloma: hallmarks
Presence of monoclonal protein
Anemia
Renal failure
Bone destruction (lytic lesions)
Compressive neuropathy
Hypercalcemia
Increased risk of infection