blabla Flashcards
Classification of bone marrow malignancies
French-American-British
Main feature is the histology (morphology)
• Acute lymphoblastic leukemia (ALL, L1-L3)
• Acute myeloid leukemia (AML, M0-M7)
who classification
Classification of bone marrow malignancies World Health Organisation (WHO) • Main features are the cellular origin and the molecular alterations
Frequency order of hematological malignancies (7-9%): o non-Hodgkin lymphomas o Leukemias o Myeloma multiplex o Hodgkin disease
Frequency order of hematological malignancies (7-9%): o non-Hodgkin lymphomas o Leukemias o Myeloma multiplex o Hodgkin disease
howto diagnose
Identification of disease specific marker(s) as
initial diagnostics :
o flow cytometry: unique marker patterns (coexpression),
o cytogenetics: karyotyping, FISH,
o molecular diagnostics: PCR, QPCR, next
generation sequencing (NGS), micro-array,
• Follow-up: evaluation of remission or relapse
prediction using high sensitivity test systems:
o molecular diagnostics: QPCR, NGS.
Main groups of myeloid diseases
• Myeloproliferative neoplasms (MPN); • Myeloid and lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB or FGFR1 abnormality; • Myelodysplastic syndromes (MDS); • Akut myeloid leukemias (AML).
myeloporliferative disease
Clonal alterations of stem cells affecting multiple cell lineages
with elevated peripheral cell counts, splenomegaly, increased
bone marrow cellularity BUT without differentiation block and
dysplasia.
• BCR-ABL1 positive chronic myeloid leukemia (CML)
• Polycythaemia vera (PV)
• Essential thrombocythaemia (ET)
• Primary myelofibrosis (PMF)
• Novel therapeutic targets: targeted JAK2-inhibitor – ruxolitinib.
• Novel therapeutic targets: targeted JAK2-inhibitor – ruxolitinib.
Myelodysplastic syndrome (MDS)
WHO-entities:
• Refractory cytopenia with unilineage dysptasia
• Refractory anaemia with ring siderobtasts
• Refractory cytopenia with multilineage dysplasia
• Refractory anaemia with excess blasts
• Myelodysplastic syndrome with isolated del(5q)
• Myelodysplastic syndrome, unclassifiable (NOS)
• Childhood myelodysplastic syndrome
acute myeloid leukemia
Acute myeloid leukemia (AML)
• A result of a series of somatic mutations affecting the
multipotent (myeloid committed) hematopoetic stem cell.
• Malignant clone: (i) Increased proliferation, (ii) decreased
apoptosis and (iii) decreased differentiation capabilities.
• In general >20% immature, monomorphic (blast) cells
(myelo-peroxidáz pozitív) in the periphery or bone marrow.
• In adults, AML is the most frequent acute leukemia type,
while in children AML only represents 10-15% of the acute
cases.
• Its frequency is increased by the age,
median age at diagnosis: 65 years.
• Agressive disease without treatment.
• Symptoms at diagnosis: bone marrow insuff.
aml groups (who)
Main groups of AML (WHO)
1 AML with recurrent genetic abnormalities 40-60 2 AML with myelodysplasia-related changes 24-35 3 Therapy related AML 10-15 4 AML not otherwise specified (NOS) 5
lymphoid malignancies
Lymphoid disease with bone marrow dominance • Acute lymphoblastic leukemia (ALL) – precursor cell • Monoclonal gammopathies – myeloma multiplex (MM) • Chronic lymphocytic leukemia (CLL) • Hairy cell leukemia (HCL) • Lymphoplasmocytic lymphoma (Waldenström macroglobulinaemia)
all character
Acute lymphoblastic leukemia (ALL) – precursor
• Enrichment of lymphoblasts (>20%) in the bone marrow or the
periphery: 85% B cell, 15% T cell origin.
• The most frequent pediatric malignancy: maximum frequency
between ages of 3-7 years, 75% of the cases presents below 6
years of age, second frequency peak: 40 years of age.
myeloma multiplex char
Tumor cell: post-germinal center, mature, B lymphocyte with
immunglobulin class switch and somatic hypermutation.
• Increased production of antibodies leads to
hyperproteinaemia that increases the viscosity of the blood and
may cause neurology symptoms.
• The decrase of the A/G ratio (as a result of globulin fraction
increase) accelerates RBC sedimentation rate (Westergreen). • Hypercalcaemia and pathological fractures due to osteolysis. • Renal insufficiency caused by light chains, amyloidosis,
nephrocalcinosis.
• In 50% of cases: Bence-Jones proteinuria (light chain).
• CRAB: hypercalcaemia + renal insufficiency + anaemia + bone
involvement.
C
stages of mm
MGUS: monoclonal gammopathy of undetermined significance – precancerous condition, frequent in elderly (10% above 75 years
of age), rarely recognised, treatment is not needed.
SMM: smoldering myeloma multiplex.
MM: myeloma multiplex
drugs
Main drug classes: (i) alkylating agents (cyclophosphamide, melphalan); (ii) anti-metabolites (methotrexate, fludarabine); (iii) cytotoxic antibiotics (daunorubicin, adryamycin); (iv) plant derivatives (vincristine, ethoposide).
