Australian Doctor 10th May issue 2024 | Page 25

HOW TO TREAT 25 severity varies from mild fevers to a severe syndrome involving fevers , hypoxia , hypotension and multiorgan failure . The onset is variable , typically starting 2-7 days after CAR T-cell infusion ; however , the interval may be up to 21 days . CRS is managed using tocilizumab , a monoclonal antibody directed against interleukin-6 , one of the principal mediators of the syndrome . Corticosteroids are used infrequently , and only in severe cases .
ausdoc . com . au 10 MAY 2024

HOW TO TREAT 25 severity varies from mild fevers to a severe syndrome involving fevers , hypoxia , hypotension and multiorgan failure . The onset is variable , typically starting 2-7 days after CAR T-cell infusion ; however , the interval may be up to 21 days . CRS is managed using tocilizumab , a monoclonal antibody directed against interleukin-6 , one of the principal mediators of the syndrome . Corticosteroids are used infrequently , and only in severe cases .

Immune effector cell-associated neurotoxicity syndrome ( ICANS ) occurs in 12-30 % of cases . 21 , 29 This is secondary to the release of cytokines from immune cells that disrupt the blood-brain barrier and results in CNS pathology . ICANS may manifest with tremor , confusion , aphasia , motor weakness , cerebral oedema , seizures or coma . The median time similar to allogeneic transplant , however there is insufficient evidence to fully understand the longterm complications . 30
Follow-up
In addition to standard follow-up protocols , patients are advised to remain within a two-hour drive of the treating centre for 4-8 weeks . The patient ’ s observations — particularly temperature , oxygen saturation and blood pressure — are monitored for immune-related complications . Immune effector cell encephalopathy scores are performed regularly to screen for neurotoxicity / ICANS .
Anti-infective prophylaxis directed toward herpesviruses and pneumocystis as well as vaccinations ( including close family members ) are strongly recommended . 3
Multifactorial immunosuppression predisposes patients to a wide variety of infections .
Figure 5 . Diffuse large B-cell lymphoma .
to onset is four days after infusion of CAR T-cells . Management includes steroids and supportive care . The
CASE STUDIES
Case study one
STELLA , a 60-year-old female pre-
condition is typically reversible with
sents with lower back pain . An X-ray
a good prognosis .
demonstrates multiple lytic lesions ,
Haemophagocytic lymphohistio-
in L4 and L5 vertebrae and ribs .
cytosis is an uncommon and severe
Serum electrophoresis and immu-
complication . In this condition ,
nofixation demonstrate an immu-
activation of autologous histiocytes
noglobulin G kappa paraprotein
and T-cells leads to an inflamma-
measuring 21g / L . A bone marrow
tory syndrome involving the skin ,
biopsy demonstrates 40 % plasma
spleen , liver and bone marrow . If
cells including atypical binucleated
present , this may be treated with
forms . Stella is diagnosed with multi-
corticosteroids and potentially
ple myeloma ( see figure 8 ).
chemotherapy .
She is treated with bortezomib ,
lenalidomide and dexamethasone
OTHER COMPLICATIONS
for four cycles , with an excellent
Cytopenias including anaemia ,
response . Following her third cycle ,
thrombocytopenia and neutrope-
she receives a course of G-CSF to
nia may occur following CAR T-cell therapy ; these complications are likely multifactorial in the setting of conditioning chemotherapy and immune destruction of cells .
Multifactorial immunosuppression predisposes patients to a wide variety of infections . Hypogammaglobulinaemia may develop because of B-cell aplasia , requiring ongoing IV immunoglobulin ther-
mobilise her stem cells resulting in a successful collection of 8.5x10 9 / kg of CD34 + positive cells . Some weeks later she is admitted to hospital , receives high-dose melphalan and the next day her stem cells are reinfused ( day zero ). Her white cell count drops to 0.0x10 9 / L by day four ( normal is 4.0-10.0x10 9 / L ), and she develops severe thrombocytopenia requiring platelet transfusions . Dur-
Figure 6 . PET of a patient with widespread diffuse large B-cell lymphoma .
apy . Infective symptoms may cloud the assessment of immune-related complications , and vice versa .
ing her stay Stella develops febrile neutropenia that is treated with piperacillin and tazobactam . Her
haematology clinic ; she starts maintenance therapy with oral lenalido-
Case study two
Mark , a 21-year-old male presents
blasts seen on a blood film . He is transferred to ED and admitted
The long-term effects of CAR
white cell count starts to recover by
mide and a revaccination program
to his GP with bleeding gums .
under haematology . A bone mar-
T-cells are largely unknown . There is the potential for secondary malignancies , bone metabolism disorders and endocrinopathies
day 10 and she no longer requires platelet transfusions by day 12 , at which time she is discharged home . Stella is closely monitored in the
six months post-transplant . Three years later , her paraprotein slowly starts to increase and further treatment is started .
Bloods reveal a platelet count of 21x10 9 / L ( normal is 150-400x10 9 / L ) and a white cell count of 54x10 9 / L ( normal is 4.0-10.0x10 9 / L ) with
row biopsy demonstrates 65 % myeloblasts ( positive for CD33 , CD34 , CD117 and myeloperoxidase ) confirming a diagnosis of acute
US National Cancer Institute / bit . ly / 42XEE9T
Figure 7 . Technician prepares for a viral wholegenome sequencing experiment at the US Cancer Genomics Research Laboratory .
Figure 8 . Histological image of multiple myeloma .