ISSN 1866-8836
Клеточная терапия и трансплантация

NM-08. Transplantation from matched unrelated donors in pediatric severe aplastic anemia: TCR alpha/beta and CD19 depletion of the graft is associated with high survival and low GvHD rates

Daria A. Shasheleva, Larisa N. Shelikhova, Dmitriy N. Balashov, Olga O. Molostova, Svetlana N. Kozlovskaya, Maria A. Ilyushina, Elena E. Kurnikova, Yakov O. Muzalevsky, Alexei S. Kazachenok, Varvara V. Briliantova, Elena V. Raikina, Dina D. Baidildina, Rimma D. Khismatullina, Sergey L. Blagov, Elena V. Suntsova, Michael A. Maschan, Alexei A. Maschan, Galina A. Novichkova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia


Contact: Dr. Daria A. Shasheleva, e-mail: shasheleva@mail.ru

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

Hematopoietic stem cell transplantation (HSCT) from matched unrelated donor is a curative option for severe aplastic anemia (SAA) patients, refractory to ATG+CsA immunosuppression. Although the results of MUD HSCT in SAA have improved significantly, graft-versus-host disease (GvHD) remains a serious problem, associated with significant morbidity and mortality. We investigated the role of TCR alpha/beta depletion of the graft as a way to improve the results of MUD in SAA.

Patients and methods

Forty-two patients with SAA were treated since November 2012 till February 2021. Median age at HSCT was 11.7(2.7-22.6) years, 24 males/18 females. All patients were either refractory or relapsed (32:10) after at least two courses of ATG+CsA, 6 pts had concurrent severe hemolytic PNH. The median time from diagnosis to transplant was 16 (6-142) months. Preparative regimen included cyclophosphamide (100 mg/kg), fludarabine (150 mg/kg), ATGAM at 50 mg/kg (26pts) or thymoglobulin 5-7.5 mg/kg (16 pts), and thoraco-abdominal irradiation (2 to 6 Gy). Two patients received alemtuzumab instead of ATG because of anaphylaxis. Patients with PNH (n=6) received eculizumab 600 mg once every 7 days from -7 to +14 days. Post-transplant GvHD prophylaxis included tacrolimus and MMF. PBSC grafts were depleted of TCR alpha/beta cells and CD19 cells with CliniMACS device, as recommended by the manufacturer. Patients received a median of 9.9 (6.0-16.5)×106 CD34+ cells per kg, 17(1-39)×104 αβ T cells per kg.

Results

Forty of forty-two patients (95%) engrafted with a median of 14 (11-24) days for WBC and 13 (7-22) days for platelet numbers. In 6 patients after MUD transplantation, secondary graft failure (rejection) developed at the cumulative incidence of 15% (95% CI: 7-30%), one of them was successfully retransplanted. Cumulative incidence of aGvHD grade II was 12% (95% CI: 5-27%). No cases of grade III-IV aGvHD were registered. Cumulative incidence of cGvHD was 5% (95% CI: 1-18%). Two patients had mild cGvHD, one had persistent aGvHD. All patients were off-IST at last follow-up. A median follow-up is 4.8 years. Nine patients died. The causes of death were CMV disease (n=2), infectious complications after rejection (n=1), Gram-negative sepsis before engraftment (n=1), 5 pts died after second transplantation. Event-free survival was 74% (95 CI: 60-87). Overall survival was 79% (95% CI: 66-91%) for MUD transplants.

Conclusion

TCR alpha/beta depletion is a robust platform for allogeneic HSCT from MUD in severe aplastic anemia. The results should be further improved by additional measures to control viral infections and prevent rejection in MUD transplants.

Keywords

Aplastic anemia, TCR alpha/beta lymphocytes, depletion, hematopoietic stem cell transplantation, matched unrelated donors.


Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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