Unmanipulated haploidentical haematopoietic cell transplantation with radiation‐free conditioning in Fanconi anaemia: A retrospective analysis from the Chinese Blood and Marrow Transplantation Registry Group

Abstract

Summary Haematopoietic cell transplantation (HCT) is the only curative treatment for haematological complications in patients with Fanconi anaemia (FA). Haploidentical (haplo‐) HCT is a promising alternative for FA. We aimed to analyse the outcomes of unmanipulated haplo‐HCT in patients with FA with radiation‐free conditioning. A total of 56 patients from 11 centres between 2013 and 2021 in China were retrospectively analysed. The mean (SD) cumulative incidence was 96.4% (0.08%) for 30‐day neutrophil engraftment and 85.5% (0.24%) for 100‐day platelet engraftment. With a median (range) follow‐up of 2.4 (0.2–5.8) years, favourable mean (SD) overall survival of 80.9% (5.5%) and event‐free survival of 79.3% (5.6%) were achieved. The mean (SD) incidences of acute graft‐versus‐host disease (aGvHD) Grade II–IV and Grade III–IV were 55.4% (0.45%) and 42.9 (0.45%) respectively. The mean (SD) cumulative incidence of 3‐year chronic graft‐versus‐host disease (cGvHD) was 34.7% (0.86%) and that of moderate‐to‐severe cGvHD was 9.0% (0.19%). Our data demonstrate that in unmanipulated haplo‐HCT for patients with FA, radiation‐free regimens based on fludarabine and low‐dose cyclophosphamide ± busulfan achieved favourable engraftment and survival with relatively high incidences of aGvHD and cGvHD. These results prompt the use of low‐intensity conditioning without radiation and intensive GvHD prophylaxis when considering unmanipulated haplo‐HCT in patients with FA.

Irradiation‐free, T‐cell replete haploidentical transplant for Fanconi anaemia, weighing the benefits

“…Like Xu et al, other published outcomes to date with T‐cell replete haploidentical HCT demonstrate excellent engraftment but high rates of total and severe GVHD. In the two studies that did not incorporate PTCy, Wang et al reported grade II‐IV aGVHD in 40% of patients and the current paper reported a cumulative incidence of 55.4% 5,6 . Studies with low‐dose or alkylator‐free conditioning regimens that incorporate PTCy report lower rates of severe aGVHD, with the lowest incidence in patients receiving concurrent serotherapy 3,7 .…”

“…In the two studies that did not incorporate PTCy, Wang et al reported grade II-IV aGVHD in 40% of patients and the current paper reported a cumulative incidence of 55.4%. 5,6 Studies with low-dose or alkylator-free conditioning regimens that incorporate PTCy report lower rates of severe aGVHD, with the lowest incidence in patients receiving concurrent serotherapy. 3,7 There is no clear difference in cGVHD incidence across reports, in part due to differences in reporting this transplant outcome.…”

“…In a recent issue, Xu et al report the outcomes of 56 FA patients registered on the Chinese Blood and Marrow Transplantation Registry who underwent T-cell replete, haploidentical donor HCT for bone marrow failure or malignancy. 5 Only patients who received a conditioning regimen without irradiation were included in the retrospective study and the cohort was further subdivided into three categories based on conditioning agents. The study demonstrates that successful engraftment and favourable survival can be achieved without TBI across the three regimens.…”

Ovarian tissue cryopreservation in the pediatric with rare diseases- experience from China’s first and the largest ovarian tissue cryobank

“…FA is a challenging disease, and HSCT is the only curative therapy for the hematologic complications associated with this disease (28). The favorable mean overall survival was 80.9%, and event-free survival was 79.3% (29). MPS is a group of rare genetic diseases with abnormal glycosaminoglycan (GAG) catabolism (30).…”