hematologic malignancies- lymphomas

where do hematologic malignancies originate

bone marrow or cells in the immune system

2 major lineages of blood cells

myeloid and lymphoid

formation of blood cells

hematopoiesis

what cell develops into myeloid and lymphoid stem cells

pluripotent stem cell

which hematologic cancer leads to an accumulation of cells into a solid like mass

lymphoma

immature cells that develop from stem cells and give rise to all types of blood cells

blast cell

features of blast cells that indicate malignancy

abnormal looking blast cells or extremely high level of blasts

2 major types of lymphomas

Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL)

cell type specific to HL and where do they originate from

Reed-sternberg cells, originate from B-lymphocytes

pathophysiology of HL

B cell transcription disrupted, lack of apoptosis pathways, proliferation of malignant cells

virus exposures that increases HL risk

Epstein Barr virus (EBV), HIV

genetic factor that increases HL risk

ataxia telangiectasia

presentation of HL

painless, rubbery, enlarged, lymph node and sometimes B symptoms

what are the B symptoms

fever, drenching night sweats, weight loss

what is the preferred way to diagnose HL

excisional biopsy

staging for HL and how it is done

ann arbor staging: I through IV, based on XRT

A vs B staging

A= asymptomatic

B= B symptoms

stage I-II HL without unfavorable factors

early-stage favorable

stage I-II HL with unfavorable factors

early stage unfavorable

stage III-IV HL

advanced stage

unfavorable factors for HL

multiple involve nodal regions

B symptoms

extranodal involvement

goal and modalities of HL treatment

cure while minimizing toxicities and long term complications

- combination chemotherapy

- radiation

- autologous stem cell transplant

preferred treatment for IA and IIA favorable HL

ABVD+ RT

treatments for stage I-II unfavorable HL

ABVD + RT

nivolumab - AVD

preferred treatment for stage III/IV HL

nivolumab- AVD

what chemos are apart of ABVD

doxorubicin

bleomycin

vinblastine

dacarbazine

main toxicities of ABVD

cardiotoxicity and pulmonary toxicity

what mAb is substituted for bleomycin in the alternative chemo regimen

nivolumab

difference in treatment with ABVD in stages I/II vs stages III/IV

more cycles (6) in III/IV vs 4 cycles in stage I/II

benefits of nivolumab-AVD vs ABVD

better outcomes + less toxicity

treatment options for relapsed HL

salvage therapy

autologous stem cell transplant

multi agent chemo for relapsed HL

brentixumab-nivolumab

ICE

how does an autologous stem cell transplant work

high dose chemo followed by stem cell rescue to save the patient from dose limiting toxicity

malignant cells proliferate and replace normal cells in the lymph nodes and/or bone marrow

non-hodgkins lymphoma (NHL)

which immune cells primarily become malignant in NHL

B lymphocytes

two types of risk factors for NHL

infections and immunodeficiency states

presentation of NHL in B vs T cells

B cell: lymph nodes, spleen, bone marrow

T cell: extra nodal (skin/lung)

can lead to organ dysfunction

lymphadenopathy

where can extra-nodal involvement of NHL occur

GI tract, skin, testes, bone

diagnosis method for NHL

excisional biopsy

diagnosis procedure for NHL in patients with symptoms or high risk disease

lumbar puncture to get CSF fluid

classifications of B cell lymphomas

indolent, aggressive, highly aggressive

aggressive B cell lymphoma with rapid growth but is usually curable

diffuse large B cell lymphoma(DLBCL)

highly aggressive B cell lymphomas with very fast doubling times

Burkitt's or lymphoblastic

staging used for NHL

HL Ann Arbor staging

genetic abnormalities of DLBCL

double/triple hit (MYC, BCL2, BCL6 translocations)

presentation of DLBCL

extra-nodal disease

multi agent chemotherapy regimens for DLBCL

R-CHOP

DA-EPOCH + rituximab

Pola + R + CHP

R-CHOP regimen

Rituximab

Cyclophosphamide

Doxorubicin

Vincristine

Prednisone

DA-EPOCH + rituximab regimen

etoposide

prednisone

vincristine

doxorubicin

cyclophosphamide

what does DA stand for in DA-EPOCH

dose adjustment- based on nadir ANC count

pola + R + CHP regimen

polatuzumab

rituximab

cyclophosphamide

doxorubicin

prednisone

R- CHOP vs CHOP regimen

RCHOP has better event free survival and overall survival

drug class of polatuzumab

CD19 ADC

specific recommendations for use of pola + R + CHP and why its use is limited

IPI 2-5

grade II bulky to grade III

higher risk of toxicity so only used for more severe disease

viral reactivation that can occur from rituximab use and consequence

hepatitis B, liver failure and death

what drug class is rituximab

anti-CD20 mAb

what should be tested for prior to rituximab therapy to avoid hep B reactivation

hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb)

how to treat if Hep B tests are positive prior to rituximab therapy

entecavir

unique toxicity of rituximab

late neutropenia, weeks to months after last exposure to drug

treatment for late neutropenia by rituximab

gram colony stimulating factors (G-CSF)

curative intent treatments for relapsed DLBCL

CART cell therapy or salvage chemotherapy followed by stem cell rescue

other treatment options for relapsed DLBCL

subsequent chemotherapy or bispecific T cell engagers

CAR T-cells in NHL

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