Dr Patrick Tunney ( left ) Haematology clinical trials fellow , Concord Hospital , Sydney , NSW .

Professor John Gibson ( right ) Emeritus consultant haematologist , Royal Prince Alfred Hospital , Sydney , NSW .

First published online on 19 January 2024

BACKGROUND

CELLULAR therapies are treatments

where human cells are infused into a patient following conditioning therapy . These therapies may replenish the bone marrow with healthy cells , activate the immune system to fight disease or infection , or act as a vehicle for the replacement of a deficient or dysfunctional gene .

The cellular therapies currently in routine clinical use in patients with haematological disorders in Australia are haematopoietic stem cell transplant and chimeric antigen receptor ( CAR ) T-cell therapy . Autologous stem cell transplantation refers to the reinfusion of a patient ’ s own cells following conditioning chemotherapy , while an allogeneic stem cell transplant involves the infusion of a related or unrelated donor ’ s stem cells . A CAR T-cell is a genetically modified lymphocyte with specificity to a tumour antigen . In addition , in a clinical trial setting , limited numbers of Australian

patients with haemoglobinopathies have received genetically modified haematopoietic stems cell to replace defective haemoglobin production .

Administering cellular therapies requires highly specialised care by a multidisciplinary team composed of experienced haematologists , specialised nursing staff , laboratory scientists and pharmacy and allied health professionals . A haematopoietic stem cell or CAR T-cell centre requires a dedicated apheresis unit , a transplant laboratory , an ICU and access to specialised testing and therapeutics .

While cellular therapies are potentially life-saving and curative , they are complicated and expensive , and have the potential to be associated with significant toxicity and mortality . It is important for GPs to be aware of the potential complications of these treatments and the long-term implications . These include effects on cardiovascular , hormonal , bone and psychological

health as well as secondary malignancies and recurrence of the patient ’ s primary pathology .

This How to Treat describes the key types of cellular therapies in routine practice , when they are used and their toxicities , and aims to ensure GPs can detect the shortterm and long-term side effects of cellular therapies .

AUTOLOGOUS STEM CELL TRANSPLANT

AN autologous stem cell transplant

involves the collection of a patient ’ s stem cells , most commonly from their peripheral blood , with subsequent reinfusion , usually following high-dose conditioning . This process essentially allows the administration of a much higher dose of chemotherapy than would otherwise be possible , to the point that , without reinfusion of cells ( salvage ), the patient may not recover their bone marrow function .

Process

After identification of a suitable recipient , the first step in autologous transplant is to mobilise and collect stem cells ( see figure 1 ) from the peripheral blood . While such cells are normally present in low numbers in the peripheral blood , the mobilisation process uses granulocyte colony stimulating factor ( G-CSF , filgrastim ), often following chemotherapy , to dramatically increase numbers of circulating haematopoietic stem cells . Stem cells are then collected using apheresis ( see figure 2 ) over 1-3 daily collections , and flow cytometry is used to identify and count the CD34 antigen expressed on haematopoietic stem cells . The stem cell laboratory then cryopreserves the cells at -70 ° C .

In the next phase and immediately before reinfusion of stem cells , patients undergo conditioning with high-dose chemotherapy with the aim of removing pathological cells . Following stem cell reinfusion ,