MYELODYSPLASTIC SYNDROME IS REPORTABLE

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MYELODYSPLASTIC SYNDROME IS REPORTABLE
Zora R. Rogers, MD Associate Professor of
Pediatrics University of Texas Southwestern
Medical Center Dallas, Texas
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National Program For Cancer Registries

• Public Law 102-515. October 1992
• Cancer Registries Amendment Act
• National system of cancer registries to better
  understand and target cancer control efforts
• Initially pre-malignant conditions such as
  myelodysplastic syndromes not addressed
• January 1, 2001 MDS IS reportable

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New Sequence Numbers

• World Health Organization - International
  Classification of Diseases for Oncology (ICD-O-3)
• 9951/1-3 Langerhans Cell Histiocytoses
• 9920/3 Therapy related AML
• 9950-64/3 Myeloproliferative Disorders
• 9980-9989/3 Myelodysplastic Syndromes

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Overview
Definitions Classification Systems
Myelodysplastic Syndromes Langerhans Cell
Histiocytoses Hints and Helps
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Megaloblastic Erythropoiesis
blebs
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Psuedo - Pelger Huet Anomaly
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Spectrum of Disease
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STEM CELL
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Spectrum of Disease
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Bone Marrow Failure Syndromes
Idiopathic Aplastic Anemia - pancytopenia
- The not-enough disease - Heterogeneous
clinical manifestations - 10 cases are
really MDS or pre-leukemia Constitutional or
familial aplastic anemia - Not usually
present at birth - Genetic, usually
autosomal recessive Specific predisposition
syndromes - Fanconis Anemia DNA repair
defect - Dyskeratosis Congenita ectodermal
dysplasia - Shwachman Diamond pancreatic
insufficiency - Kostmanns Syndrome white
blood cells - Diamond-Blackfan Anemia - red
blood cells
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Aplastic Anemia Bone Marrow Biopsy
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Bone Marrow Failure Syndromes
Idiopathic Aplastic Anemia - pancytopenia
- The not-enough disease - Heterogeneous
clinical manifestations - 10 cases are
really MDS or pre-leukemia Constitutional or
familial aplastic anemia - Not usually
present at birth - Genetic, usually
autosomal recessive Specific predisposition
syndromes - Fanconis Anemia DNA repair
defect - Dyskeratosis Congenita ectodermal
dysplasia - Shwachman Diamond pancreatic
insufficiency - Kostmanns Syndrome white
blood cells - Diamond-Blackfan Anemia - red
blood cells
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Aplastic Anemia ? MDS/AML
Idiopathic Aplastic Anemia - Chromosomes
are normal at diagnosis - Therapy or time
may promote clonal hematopoiesis -
Immunosuppression 10-50 risk most PNH -
Transplant 7x relative risk solid tumors
Paroxysmal Nocturnal Hemoglobinuria - PNH -
Acquired clonal stem cell disorder - Loss of
PIG-A protein product, CD55/59 on cells -
Abnormal sensitivity of red cells to complement
Constitutional Syndromes - DNA repair
defects predispose to MDS, AML and
squamo-epidermal carcinomas - Growth factors
may stimulate progression
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Spectrum of Disease
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MDS MPS Definitions
Abnormal maturation or excessive proliferation
of myeloid cells with a variable tendency to
evolve to acute non-lymphocytic leukemia
(ANLLAML) Older adults 7th decade, is
reported in children Myeloproliferative
Syndrome - MPS - Proliferation of one or
more cell type in blood - Trisomy 21
transient MPS syndrome in newborn
Myelodysplastic Syndrome - MDS - Too few or
odd forms of one or more cell type - Bone
marrow abnormalities that arent leukemia, yet
- 30 to 75 progress to AML
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Spectrum of Disease
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Myeloproliferative Disorders
Polycythemia Vera - PV - Too many red
cells and/or platelets - Rx phlebotomy,
hydroxyurea, interferon, P32 Essential
thrombocytemia - ET - Too many platelets
- Rx observation, aspirin, anagrelide,
interferon Myelosclerosis with myeloid
metaphasia - Big spleen, immature
leukocytes - Rx splenic irradiation,
splenectomy, HU Chronic myelproliferative
disease, neutrophillic leukemia,
hypereosinophilic syndrome
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Spectrum of Disease
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JMML AKA JCML
Juvenile Myelomonocytic Leukemia -
Neither chronic nor strickly myeloid - Ph
negative, lt20 blasts, increased monos -
Hepatomegaly, adenopathy, pallor, fever, rash
MPS of childhood, usually lt 5 years of age -
Associated with neurofibromatosis, monosomy 7
- Ras activation and GM-CSF hypersensitivity
seen Therapy - AML style chemotherapy vs
low dose Ara-C - 13 cis retinoic acid,
farnesyltransferase inhibitors -
Transplantation best chance of cure
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5q- Syndrome
Deletion of long arm of chromosome 5 -
isolated del 5q, 5q- - genes for cytokines
and cytokine receptors Separate syndrome with
different risks - More common in women -
RBC transfusion dependence - Low rate of
progression to AML
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Spectrum of Disease
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Lymphoma Classification Schemes
Lymphoma - Rappaport morphology - Kiel
maturational arrest - Lukes and Collins -
NCI working formulation mix - Revised
European-American Lymphoma (REAL)
morphology, immunophenotype, cytogenetics,
clinical presentation/location MDS -
French-American-British (FAB) Morphology -
World Health Organization (WHO) combined
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Myelodysplastic Syndromes
French American British or FAB Classification -
Refractory Anemia - Refractory Anemia with
Ringed Sideroblasts - Refractory Anemia with
Excess Blasts - Refractory Anemia with Excess
Blast - RAEBT in Transformation to acute
leukemia
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Ringed Sideroblast
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Myelodysplastic Syndromes
French American British or FAB Classification -
Refractory Anemia - Refractory Anemia with
Ringed Sideroblasts - Refractory Anemia with
Excess Blasts - Refractory Anemia with Excess
Blast - RAEBT in Transformation to acute
leukemia
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Bone Marrow MDS
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WHO Classification
Blood Bone Marrow RA Anemia lt5
blasts No blasts lt15 ringed
sideroblasts RARS Anemia lt5 blasts No
Blasts ³15 ringed sideroblasts RAEB Cytopenias
Dysplasia I lt5 blasts I 5-9 blasts, no
Auer rods II 5-19 blasts II 10-19
blasts RAEBT NOT part of WHO classification -
AML gt20 blasts
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WHO Classification
Blood Bone Marrow Refractory Bi- or
pancytopenia lt5 blasts, no Auer rods
cytopenia no blasts, no Auer rods MDS
5q- Anemia, 5 blasts Isolated 5q
deletion nl or plt count lt5 blasts, no Auer
rods MDS NOS Cytopenias, rare blasts Unilineage
dysplasia No Auer rods lt5 blasts, no Auer
rods
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Secondary MDS
Alkylating agent-related 85 cases cytoxan,
myleran, leukeran, MOPP, nitrosourea interval
usually 5-7 years Epipodophyllotoxin-related
15 cases VP-16, etoposide, teniposide
interval shorter 2 years Both rapidly
progressive to AML - poor prognosis
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Myelodysplastic Syndrome Therapy
Depends on disease, age of patient, anecdote
Supportive care transfusion - red cells,
platelets Growth factors - erythropoietin, G-
or GM- CSF Immunomodulatory therapy -
amifostine, cytokines as differentiating agents
- antithymocyte globulin (Atgam)
Chemotherapy - cytarabine, azacytidine -
topotecan, melphalan Allogeneic Stem Cell
Transplantation
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International Prognostic Scoring System
An estimate of survival rate and risk of
progression to AML Score 0 0.5
1.0 1.5 2.0 Marrow Blast
lt5 5-10 --- 11-20 21-30 Karyotype G
ood Int Poor ---
--- Cytopenias 0-1 2-3 Good normal
-Y, del(5q), del(20q) Poor complex (gt3
abnormalities), Ch 7 Hgblt10, plts lt100,000,
ANClt1500
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International Prognostic Scoring System
An estimate of survival rate and risk of
progression to AML Score 0 0.5
1.0 1.5 2.0 Marrow Blast
lt5 5-10 --- 11-20 21-30 Karyotype Goo
d Int Poor --- --- Cytopenias
(lines) 0-1 2-3 --- ---
--- Total Score Risk Group Low
0 Intermediate 1 0.5-1.0 Intermediate 2
1.5-2.0 High gt 2.5
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Survival with MDS by IPSS
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Survival Post-BMT by IPSS
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Langerhans Cell Histiocytoses
Names Organ Systems Lesions
Reportable LCH NOS any any
no Histiocytosis X LCH mono-ostotic
single single no Eosinophilic
granuloma LCH multifocal-poly-ostotic
single multiple no Hand-Schuller-Christian
Disease Multifocal Eosinophilic Granuloma LCH
disseminated, progressive multiple
multiple yes Letterer-Siwe Disease -
bone, skin Infantile Reticuloendotheliosis
- liver, spleen - lymph nodes
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LCH Treatment
Isolated bone lesion - Surgical curettage
or radiation Corticosteroids - usually
prednisone - Skin, lesion, and systemic
disease Chemotherapy - Vinca alkaloids
vinblastine, vincristine - Etoposide or
VP16 - Cladribine or 2-CDA - 6MP,
methotrexate, cytoxan, cytarabine
Immunotherapy - cyclosporine, interferon
alpha, PUVA
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Hints and Helps
Report only new diagnoses - Diagnosed
prior to 2001 do not report - New treatment
does not affect reportability Transition to
new diagnosis is reportable - MDS after
Hodgkins Disease - Serial bone marrows
(finally) with a new diagnosis even if
part of same process Ask your doctors and
pathologists to help
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One only sees what ones knows Goethe
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Spectrum of Disease
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MDS Unanswered Questions

• How many people in the United States have these
  diseases?
• Who are they? How old are they? Where do they
  live? How are they treated?
• Which people with MDS develop cancer? When does
  their MDS progress?
• Answers to questions like these can help cancer
  researchers to understand WHY

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