Australian Doctor 10th May issue 2024 | Page 20

20 HOW TO TREAT : CELLULAR THERAPIES IN HAEMATOLOGY

20 HOW TO TREAT : CELLULAR THERAPIES IN HAEMATOLOGY

10 MAY 2024 ausdoc . com . au
the patient is monitored closely
until their blood cell counts start to
recover ( engraftment ), which takes
10-14 days on average . This may
occur as an inpatient or outpatient ,
or a combination , depending on the
specifics of the chemotherapy and
the patient ’ s clinical condition .
Indications
Autologous stem cell transplants are most frequently performed in patients with multiple myeloma or relapsed / refractory lymphoma . However , there are several other emerging indications ( see box 1 ).
Complications
Conditioning chemotherapy is associated with a range of complications including mucositis , pancytopenia , organ dysfunction and gastrointestinal toxicity . An inflammatory ‘ engraftment syndrome ’ ( fever , skin rash , capillary leak and pulmonary infiltrates ) may uncommonly occur because of a massive
release of cytokines as the patient ’ s peripheral blood cell counts recover . Failure to engraft is a possible , though rare , complication . Engraft-
Figure 1 . A patient having stem cells collected .
ment describes the process of the
blood-forming cells received via
transplant starting to home to the
bone marrow and generate new
blood cells .
Because of the immunosuppression
associated with conditioning
chemotherapy , patients are at
increased risk of bacterial , viral and
fungal infection . Febrile neutropenia
most commonly occurs in these
patients because of translocation of
gut bacteria into the blood ; bacteraemia
may also result from venous
catheter-related , gut or respiratory
infections . Resistant organisms are
often cultured from patients who
have had a transplant , as a result of
previous antimicrobial therapy .
Febrile neutropenia is rapidly
treated using protocol-based
broad-spectrum antibiotics that are
quickly rationalised based on culture
results . All patients receive
prophylaxis against pneumocystis
and herpesviruses .
In the context of the COVID-19
pandemic , patients are encouraged
to be fully vaccinated for COVID-
19 , receive tixagevimab / cilgavimab
prophylactically , and receive
COVID-19 antivirals for symptomatic
infection .
Supportive care is an important aspect of post-transplant care . Reg-
Figure 2 . An apheresis machine .
ular mouth washes are used to help
to prevent mucositis , and patients may be transfused with irradiated blood products if they become significantly anaemic or thrombocytopenic . Nutritional support is provided by experienced dietitians
complications , energy levels and patient preference .
ALLOGENEIC STEM CELL TRANSPLANT
ALLOGENEIC transplantation
malignant cells , resulting in ongoing disease control . This creates a delicate balance between this beneficial graft versus disease ( GVD ) effect — for example , graft versus leukaemia — and the potentially severe complication of
matched unrelated donor transplant in 1979 . 5-7 In 1988 , CD34 + cells were identified in small numbers in peripheral blood , and the administration of G-CSF allowed for collection of stem cells from peripheral
compatibility is the testing of HLA . An ideal donor would be a 10 / 10 match , involving both alleles of HLA- A , HLA-B , HLA-C , HLA-DRB1 and HLA-DQB1 .
because of the high risk of mal-
involves the transplantation of
graft versus host disease ( GVHD ).
blood rather than bone marrow . 8
TYPE OF DONOR
nutrition . Dedicated psychological support is available for patients undergoing transplantation .
Following transplant , a bone
haematopoietic stem cells from a related or unrelated donor after high-dose chemotherapy and subsequent immunosuppression . Stem
History of allogeneic stem cell transplant
The first allogeneic bone marrow
By the late 2000s , new conditioning regimens allowed the use of haploidentical ( half-matched ) family member donors in patients
The preferred donor for allogeneic stem cell transplant is an HLAmatched sibling , with a 25 % chance of any given sibling being a com-
marrow biopsy or repeat imaging will assess the patient ’ s disease status , as appropriate . Patients are
cells may come from the donor ’ s bone marrow , mobilised peripheral blood or cord blood . Despite greater
transplant was performed in 1957 by Dr E Donnall Thomas ( physician , researcher and Nobel laureate )
without a matched sibling or unrelated donor . 9 The subsequent development of reduced intensity
plete match . An identical twin essentially shares all the same antigens ; this is therefore functionally
then monitored for relapse and for
risks , when compared with autolo-
in six patients with acute leukae-
conditioning treatment ( that is , a
similar to an autologous transplant
late complications . Patients typically remain on viral and pneumocystis prophylaxis for
gous stem cell transplants , there is the opportunity for greater reward , including the potential to cure an
mia . Two patients engrafted , and all died within 100 days . 4 Following drastic improvements in con-
conditioning regimen that uses less chemotherapy and radiation than the standard regimen ) and its more
and is often not the first choice . In adult practice , if a fully matched sibling is not available , the
3-6 months post-transplant and
otherwise incurable disease . 3
ditioning , histocompatibility ( for
widespread use has allowed for
second choice is usually a search of
undergo selective revaccination ,
This type of transplant goes
HLA ) testing , GVD prevention and
treatment of older patients .
the international stem cell donor
starting at six months post-transplant . A return to ‘ normal life ’ such as returning to work depends on several patient factors including
beyond simply replacing a patient ’ s bone marrow after high-dose chemotherapy : allogeneic stem cells can exert an anti-tumour effect on residual
peritransplant care , the first successful transplants from matched sibling donors were performed in the late 1960s , followed by the first
Sources of stem cells
COMPATIBILITY TESTING A major part of transplant
registry for a fully matched unrelated donor , who has either 8 / 8 or 10 / 10 matched HLAs . As a result of improvements in the technology of