PO-07. Outcomes of second hematopoietic stem cell transplantation in children with malignant and non-malignant blood disorders: a single center study

Summary

The main reasons for allogeneic hemopoietic stem cell transplantation (allo-HSCT) failure are relapses for malignant and graft failure/rejection for non-malignant conditions. However, the second allogeneic transplant may be a clinical option in these situations.

Materials and methods

The Sverdlovsk Regional Children Hospital Bone Marrow Transplant Unit was opened in 2006. By August 2022, a total 330 of allo-HSCTs were performed in 290 patients with different malignant and non-malignant conditions. Our study includes 18 pediatric patients aged 1 to 17 years who received second allo-HSCT due to underlying acute leukemia (n=12), CMML (n=1), acquired aplastic anemia (n=3), constitutional aplasia (n=1), and primary immune disorder (Nijmegen syndrome). In 7 cases, the second allo-HSCT was performed due to disease relapse, and in 11, because of graft failure/rejection. In half of the cases, the second transplant took place more than 6 months after the first HSCT.

Results

The underlying disorder in 7 relapsing patients with malignancies were ALL (4 cases); AML (1 patient), and CMML (1 case). The relapses were registered from 2 months to 2 years after the first transplant. All patients belonged to a high-risk group characterized by unfavorable disease biology and refractory clinical course. The presence of minimal residual disease (MRD) at the moment of allo-HSCT was the main risk factor for relapse. In all cases, the second transplant was performed from other donors and with another conditioning regimen (however, using myeloablative schedule). The following donors were recruited: haploidentical (n=5), HLA-matched unrelated donor (n=1), and HLA-matched related donor (n=1). The time from 1^st to 2^nd transplant exceeded 6 months in all cases (6.5 months to 2.5 years). One patient developed a refractory relapse and died due to disease progression, 6 patients are currently alive. Moreover, 6 patients with previously diagnosed leukemia received a second transplant due to graft failure/rejection. Three patients with complete donor chimerism received selected CD34+ boosts from the same donor without any conditioning regimen 40-60 days after the 1^st allo-HSCT leading to WBC engraftment in 2 cases. However, all 3 patients remained transfusion-dependent and died from complications (infections in 2, or TMA in 1 case). In 3 cases, a second allo-HSCT was performed from another donor after myeloablative conditioning. All patients were engrafted and achieved complete donor chimerism by the D+28. Two of these patients are currently alive (with 1.5 and 2 years of follow-up), one patient died with therapy-refractory relapse 5 months after the 2^nd transplant. Among 5 patients with non-malignant conditions, all second transplants were performed due to graft failure/rejection. The median interval between 1^st and 2^nd transplant was 2 months. In 4 cases, the same donors were used, with different conditioning regimen applied. In one patient with Nijmegen syndrome, a new donor was recruited. Four of 5 patients are currently alive and disease-free 6 months to 10 years after the second transplant. One patient with acquired aplastic anemia died of infection.

Conclusions

A gradual improvement in second allo-HSCT technique and supportive therapy makes it a feasible option for many patients. Its outcomes are mostly influenced by the disease status, patient’s performance score, and presence of infections/toxicity. The second transplant from haploidentical donor and subsequent immune- or chemotherapy may be an option for a number of high- or very high-risk patients.

Keywords

Children, leukemia, non-malignant conditions, hematopoietic stem cell transplantation, allogeneic, repeated.