Malignant Hemopathies Flashcards
Define malignant hemopathies.
Neoplasms of the hemoatopoietic and immune system
What is the difference between leukemia and lymphoma
same disease, different tumour mass distribution
- leukemia: mainly in bone marrow + blood
>20% blasts in bone marrow and > 5%blast in peripheral blood - lymphoma: extranodal or in lymph nodes
< 20% blasts in bone marrow and < 5% blast in peripheral blood
What are the types of lymphoproliferative diseases?
- Acute Lymphoproliferative diseases
e.g. ALL - Chronic Lymphoproliferative diseases
e.g. lymphomas: HL and NHL - Immunoproliferative disease: Plasma Cell Dyscrasia
e.g. Multiple myeloma
What are the histological variants of HL?
Classic (95%) CD20+
- nodular sclerosis
- mixed cellularity
- classical HL T-Cell Rich
- lymphocytic depletion
Non-classical (5%) CD20 -
- nodular lymphocytic predominant (NLP HL)
What common cell is seen in histology of HL?
Reed Sternberg Cells (Owl Eyes)
- 1-5 % of cell population
Of B-cell origin in undetermined differentiation state - the rest are pleomorphic cells plasmocytes, eosinophils basophils, granulocytes, macrophages and fibroblasts
-variants: hodgkin cell, popcorn, lacunar variant
What is NHL?
- group of extremely heterogenous chronic lymphoproliferative disease differing biologically, clinically and prognostically
- 99% malignant
- cell of origin of B, T, NK type
What is the clinical classification of NHL?
Indolent
- slow and indolent growth
- incurable but long survival
- with periods of remission and relapse
e.g. SLL, CLL, Follicular Lymphoma
Aggressive
- aggressive, tx necessary or lethal in 1 year
- 60% curability
e.g. diffuse large B-cell lymphoma, Mantle cell lymphoma, angioimmunoblastic T cell
Very aggressive
- highly aggressive, death in a month
e.g. burkitt lymphoma/leukemia, B-cell, T/NK-cell lymphoblastic lymphoma/leukemia
How do you diagnose lymphoma or leukemia?
- Biopsy of complete lymph nodes
- If extra nodal, perform needle biopsy
- Flowcytometry of peripheral blood or bone marrow to provide info on cell origin etc.
- Definitive diagnosis: immunohistochemistry
PCR for genetic rearrangements
What is the Ann Arbor Lymphoma Staging? Include A, B, E & V+
- Stage I: one area of lymph node involvement
- Stage 2: one side of diaphragm and more than 2 lymph node groups
- Stage 3: Both sides of diaphragm and more than 2 lymph node groups
- Stage 4: Disseminated spread into one or more extra-lymphatic organs independent of lymph node group involvement
A- no symptoms
B- B symptoms: malaise, fatigue, night sweats, loss of weight (10kg in 6 months)
E- extranodal disease
V+- bulky disease = tumour mass longest diameter > 7cm
What are the lab findings for lymphoma?
- CBC: leukocytopenia, anaemia and eosinophilia
- Assess virological studies e.g. HIV, EBV, HCV
- Immunological status: plasma Ig, electrophoresis and immunoelectrophoresis of plasma proteins
- Serum study: hypercalcemia and increase LDH
According to EORTC and GHSG group, when is HL advanced stage?
EORTC - Stage IIIA
GHSG - Stage IIB
What are the treatment plans for limited HL?
2 cycles ABVD
20 Gy irradiation of local LN
or
2 cycles of ABVD (can also be PET-CT guided)
*if positive 2 cycles of escalated BEACOPP then 30Gy irradiation
*if negative 1 cycle of ABVD and 20Gy irradiation
What is ABVD?
1st treatment for HL
ABVD (adriamycin aka doxorubicin, bleomycin, vinblastine, dacarbazine)
What is escalated BEACOPP?
bleomycin, etoposide, doxorubicin, cyclophosphamide, and vincristine, prednisone and procarbazine
How do you treat intermediate HL?
same as limited but 4 cycles of ABVD and 30 Gy irradiation
*can also be PET-CT guided with 2 cycles of ABVD and increases in irradiation dose
How do you treat advanced HL?
First line when extra-nodal involvement: 2 cycles of BEACOPPesc
Follow up by PET-CT and tailor BEACOPPesc cycles accordingly e.g. PET + then 4 cycles PET - then 2 cycles
FU with PET-CT again
+ again = localised RT
- = observation
How do you treat refractory/remission HL?
salvage ChT
e.g. autologues Stem Cell Tx,
BV (Brentiuximab Vedotin)
If further relapse: allogenic Stem Cell Tx or Pembrolizumab immune
What is the basic treatment recommendation in NHL?
Indolent: wait and watch strategy
-If B symptoms + fast progression then Rituximab plus chemo or Target Tx with maintenance Tx with Ritux
Aggressive: immediate tx R-CHOP
Very Aggressive: immediate treatment (R) HyperCVAD
*allogenic SC Tx in high risk lymphoma/leukemia
What is Hyper-CVAD?
Indicated in very aggressive NHL:
- cyclophosphamide
- vincristine
- doxorubicin
- methotrexate
- cytarabine
- dexamethasone
What is the method of follow ups for NHL and HL?
- FDG PET/CT
- PCR/FISH (fluorescein in-situ histology)
- FU recommended every 3 months in first 2 years
- FU every 6 months until 5 years and then annually
What is plasma cell dyscaria?
- monoclonal proliferation of plasma cells with secretion of monoclonal protein in blood and urine
What is the CRAB criteria?
Used for Multiple Myeloma
OLD - old age ( approx. 70)
C - calcium elevated (hypercalcemia)
R - renal failure
A - anemia
B - bone lytic lesions
What is diagnostics for MM?
- biopsy of bone marrow aspiration
- confirmation of monoclonal plasma cell infiltration > 10%
- presence of Bence Jones protein in blood or urine
What is the IMWG 2014 criteria?
- > 10 % plasma cells in bone marrow
- Presence of > 1 of CRAB elements
- Presence of > 1 plasma cell neoplasia biomarkers (> 60% PLC infiltration, FLC > 100n and > 1 focal bone lesion on MRI (> 5mm)
Smoldering Myeloma - 10-59% PLC and absence of CRAB elements
What is the treatment plan according to eligibility for autologous stem cell transplantation?
Yes (fit and less than 70)
Induction VRd
Melphalan followed by ASCT
Lenalidomide maintenance
No (more than 70)
VRd
Whats VRd and what is VTD?
VRD: Bortezomib, lenalidomide and dexamethasone
VTD: Brotizomib, thalidomide and dexamethasone
What is the relaps/refractory treatment for MM?
Re-induction of agents not previously used
e.g.
Daratumumab (anti-CD38)
Carfilzomib (Protease inhibitor)
Secondary Auto SCT if possible
What are the main reason for deaths in MM?
- Immunosuppression
- TE
- Infection
What is autologous stem cell transplantation?
- transplant own hematopoietic stem cells after high dose chemo tx
- conducted in chemosensitive tumours
- conducted as a transfusion after HD chemo
What are the indications for autologous SCT?
- MM after 4-6 cycles of induction tx in case of CR1 or PR, age 70 with good PS
- HL in second complete remission after salvage tx
- NHL of B cell origin in second complete remission after salvage tx
- NHL of NK/T cell origin in first complete remission
- Ewings Sarcoma: resistance to induction Tx
- Carcinoma Embryonal Testis/Yolk sac endodermal sinus tumour: resistance to second line treatment
What is allogenic SCT?
- hematopoietic stem cells from a donor
- after myeloablative regimen
total body irradiation, HD cyclophosphamide/Bulsafan
*Cyclosporin, an immunosuppression drug,with MTX and anti-thymocytic glubiline, must also be given for allogenic graft control during engraftment period
graft vs leukemia effect is good
graft vs host disease is not good
-both are mediated by CD8+ T cells of donor against recipients antigens
What are the indications for allogenic SCT?
- ALL, AML: High Risk in CR1
- HL: CR3
- NHL of B/T/NK cell origin: CR3
- CML: very rare
- Myelodysplastic syndrome: high risk CR1
What are the types of plasma cell dyscrasia?
-MGUS-monoclonal gammopathy of undetermined significance
-Solitary plasmocytoma (osseal, extramedullary)
-Myeloma multiplex
-Plasma cell leukemia
What is MGUS?
- this is a pretty benign condition
- pre cancerous
- potential to become MM after 30 ish years
What are the chronic lympoproliferative diseases?
Lymphomas (Hodgkin and non-Hodgkin B, T/NK-cell origin)
What are acute lymphoproliferative diseases?
Acute lymphoblastic leukemia/ lymphoblastic lymphoma of B, T/NK-cell origin
What are acute myeloproliferative diseases?
-Acute myeloid leukemia (AML)
-Myeloid sarcoma (CHLOROMA)
-extramedullary solitar myeloid neoplasm (extramedullar AML)
What are chronic myeloproliferative disease?
-Chronic myeloid leukemia (CML) Ph+ and very rarely Ph-
-Osteomyelofibrosis Ph-
-Policitemia rubra vera Ph-
-Essential trombocitemia Ph-
-Myelodisplastic proliferations
C-POEM
What is the philadelphia chromosome?
Ph-Phyladelphia chromosome, translocation 9;22. Neoplasms that carries Ph chromosome are delineated as Ph positive (Ph+) other are Ph negative (Ph-)
