haematological malignancies: lymphoid

week 7 bloodsci

lymphoid malignancies classification

neoplasmas that originated from lymphocytes

2 main groups:

• precursor lymphoid neoplasma

• mature B, T and NK cell lymphoid neoplasms

acute lymphoblastic leukaemia (ALL)

• characterised by the presence of a series of genetic alterations in the undifferentiated haematopoitetic cells of the bone marrow

• provides them with an indefinite capacity for self renewal and prevents differentiation and therefore disrupts normal developement

• can be either B or T cell

• can occur in both children and adults (peak age of incidence is 3-7 years of age)

ALL symptoms

• bone marrow infiltration

  • anaemia, neutropenia, thrombocytopenia

• organ infiltration

  • tender bones, lymphadenopathy, moderate splenomegaly, hepatomegaly

diagnosis of ALL

• FBC

  • normocytic normochromic anaemia with thrombocytopenia

  • presents with leukocytosis

• blood film

  • lymphoblasts present

• bone marrow biopsy

  • hypercellular with >20 % blasts

• immunophenotyping

• cytogenetics

chronic lymphocytic leukaemia (CLL)

• a group of disorders characterised by accumulation in blood of mature lymphocytes

• can be:

  • B cell (CLL, B cell prolymphocytic leukaemia)

  • T cell

    • large granular lymphocytic leukaemia (T-LGL), T cell prolymphocytic leukaemia (t-PLL), adult T cell leukaemia, Sezary syndrome

CLL symptoms

• CLL pts are often asymptomatic

• condition normally being found in routine testing

• leukocytosis present but not all the white cells are functioning correctly

• pt may suffer from frequent/lingering infections

CLL diagnosis

• FBC

  • leukocytosis, possible mild normocytic anaemia

• blood film

  • leukocytosis, smear cells

• bone marrow biopsy

  • hypercellular with lymphocytic replacement of normal bone marrow

• immunophenotyping

• molecular

4 most common mutations causing CLL

1. 13q14

2. trisomy 12

3. deletion at 11q3

4. 17p deletion

CLL treatment

• conservative and more supportive treatment

• cytotoxic reagents would only be started with symptoms like enlarged lymph nodes/spleen, weight loss, cytopenia

• alternative treatment: monoclonal ABs

lymphoma

• group of neoplastic diseases caused by malignant lymphocytes that accumulate in the lymph odes and other lymphoid tissue

• cause characteristic feature of lymphadenopathy

• lymphomas can have a leukaemic phase

2 main classifications of lymphoma

1. Hodgkin lymphoma

   • represents 30% of all lymphomas

   • disease of B lymphoid lineage

   • present with Reed-Sternberg cells

2. Non-Hodgkin lymphoma

   • includes: diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma, hairy cell leukaemia

lymphoma symptoms

• most pts present with painless asymmetrical enlargement of superficial lymph nodes (most common: cervical nodes)

• persistent fatigue

• night sweats

• unexplained weight loss

• shortness of breath

lymphoma diagnosis

• FBC

  • normocytic normochromic anaemia

  • may present with neutrophilia and eosinophilia

• ESR

  • often raised

• lymph node biopsy

  • check for presence of RS cells where abnormal growth is occuring

• imaging studies

  • check for enlargement of lymphoid tissue

lymphoma treatment

• main strategy: combination of radiotherapy and chemotherapy

• chemo started first due to it being able to act on all locations

• in advanced cases an autologous haematopoietic stem cell transplantation may be only option of treatment

multiple myeloma/plasma cell myeloma

• neoplastic disease

• characterised by clonal proliferation of plasma cells in the bone marrow

• accumulations of plasma cells causes myelosuppression and activates osteoclasts

• myeloma neoplastic cell is a post germinal centre plasma cell that has undergone immunoglobulin class switching and somatic hypermutation

symptoms of multiple myeloma

• anaemia: lethargy, weakness, pallor, tachycardia

• impaired renal function: polyuria

• hypercalcaemia

• recurrent or persistent infection

• hyperviscosity

• abnormal bleeding tendency

• bone disease: common complaint of backache caused by vertical collapse

multiple myeloma diagnosis

• FBC

  • shows normocytic anaemia, occasional macrocytic, neutropenia, thrombocytopenia

• blood film

  • rouleax present, plasma cells present

• bone marrow biopsy

• ESR high

• elevated serum calcium and creatinine

• serum free light chains/protein electrophoresis

• bence jones proteins: free light chains found in urine

• immunophenotyping: CD38, CD138 high, CD45 low

• imagine reveals bone lesions

multiple myeloma treatment

2 types of therapy: supportive and specific

• supportive: transfusion top ups, prophylactic immunoglobulin concentrates, bisphosphates, surgical decomperssion

• specific: intensive chemo for autologous SCT, alkylating agens, monoclonal ABs