3. Discussion
GVHD is a clinicopathological syndrome caused by the mismatch of HLA
recognized by donor-derived T cells through T cell receptor α β, thus
attacking the organs and tissues of patients[6].
CAR-T therapy involves using genetic engineering technology to make
allogeneic T cells specific to tumour antigens, such as CD19, rather
than to all cells. Moreover, CAR-T cell therapy involves a small number
of cells, which in theory induces a low rate of GVHD. However, in
clinical application, we found that both haploid and non-haploid
donor-derived CAR-T cell therapy can induce GVHD, and the reasons need
to be further explored.
Here we describe two cases, one involving a matched-sibling donor
(patient 1) and the other a haploid donor (patient 2).The incidence of
GVHD after haploid transplantation is higher than with matched-sibling
donor and unrelated donor transplantation[6].
Whether CAR-T from a haploid donor is more likely to induce GVHD and
cause safety concerns is an important question. The incidence of GVHD
after CAR-T infusion is lower than with donor leukocyte infusion and
seems to be related to the tumour load. If the tumour load is low, the
incidence of GVHD also is low[7-10,12,13].At
present, there is no relevant research on cGVHD after CAR-T cell
therapy, only limited clinical data from some samples.
We report here that two patients had different degrees of cGVHD after
donor-derived CAR-T treatment. The most serious was lung involvement.
The clinical diagnosis was BOS, which mainly manifested as shortness of
breath after active, intractable cough, imaging findings of gas
retention, and pulmonary function suggesting obstructive pulmonary
disease with restricted ventilation. Studies have shown that the
mortality rate with BOS after transplantation can be as high as 80%,
and the main causes of death are respiratory failure and severe
infection [11]. In theory, secondary BOS after
CAR-T would be similar to that after transplantation. We actively
intervened in these two cases at an early stage, including strengthening
immunosuppressant, FAM regimen, TKI, and auxiliary cell therapy.
Fortunately, the dyspnoea and lung function of the two children were
significantly improved and recovered. They were in a state of continuous
remission without a second transplant.
Donor-derived CAR-T cell therapy adds to the toolkit clinicians can use
to prevent recurrence after transplantation and provides an effective
treatment option for patients. However, there is a real risk of GVHD
caused by donor-derived CAR-T. How to increase and extend the effect of
CAR-T treatment while reducing the incidence and mortality of GVHD are
being explored. In the near future, more effective and lasting
off-the-shelf CAR-T products are anticipated.