HR-01. Our experience of haploidentical hematopoietic stem cell transplantation with previous TCRαβ/CD19 depletion in adult patients with hematological malignances
Maria V. Dovydenko, Larisa A. Kuzmina, Vera A. Vasilieva, Mikhail Yu. Drokov, Tatiana V. Gaponova, Irina V. Galtseva, Ekaterina D. Mikhaltsova, Olga M. Koroleva, Zoya V. Konova, Natalia N. Popova, Mobil I. Akhmedov, Daria S. Dubnyak, Anna A. Dmitrova, Olga S. Starikova, Natalia M. Nikiforova, Ulyana V. Maslikova, Feruza A. Omarova, Elmira I. Kolgaeva, Elena N. Parovichnikova, Valery G. Savchenko
National Research Center for Hematology, Moscow, Russia
Contact: Dr. Maria V. Dovydenko, e-mail: nareyko@yandex.ru
Summary
Introduction
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a method of treatment aimed at complete eradication of the tumor. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an attractive alternative, due to the donor’s availability and motivation. However, the high risk of developing graft-versus-host disease (GVHD) remains a serious problem. Ex vivo TCRαβ/CD19+ depletion has proved to be a reliable method of GVHD prevention in pediatric practice.
Patients and methods
Forty-one patients (18 males/23 females) underwent haplo-HSCT in National Research Center for Hematology between January 2018 and May 2020. Median age was 28 (17-58) years. The study included patients with acute leukemia (AL) (n=29, 18 – in 1st complete remission (CR), 9 – 2nd CR, 73.9% were MRD-negative), myelodysplastic syndrome (MDS, n=7), lymphoproliferative diseases (LPD, n=3) and primary myelofibrosis (PMF, n=2). Conditioning regimen and immunosuppressive therapy was based on the protocol of Dmitry Rogachev National Research Center. Conditioning: Treosulfan 42 g/m2 + Fludarabine 150 mg/m2 + Thiotepa 10 mg/kg or Melphalan 140 mg/m2. Immunosuppressive therapy: rituximab, abatacept, tocilizumab, bortezomib.
Results
The analysis included only those patients for whom haplo-HSCT with a previous TCRαβ/CD19 depletion was the first allo-HSCT. Cases of graft failure were censored by the date of the next allo-HSCT. With a median follow-up of 14.5 (2.3-28.5) months the overall survival (OS) in the whole group was 64.9%, relapse-free survival (RFS) – 72.4% (Fig. 1, 2); transplant related mortality (TRM) – 12.3%; graft engraftment was achieved in 94.1%. A statistical analysis was performed for patients with AL in CR and for a group of patients with other diagnoses (MDS, LPD, PMF) separately. With a median follow-up of 15.4 (2.3-28.5) months for patients with AL, OS and RFS were 82.2% and 85.0% (Fig. 3, 4). There were no TRM in this group. Engraftment was achieved in 95.7% of cases; the median time to leukocyte recovery was 13 days. The probability of acute and chronic GVHD in patients with AL was 26.1% and 14.8% (Fig. 5, 6) (only cases of grade 2 and more GVHD were taken into account). The results of haplo-HSCT were worse in the group of patients with other diagnoses. Thus, TRM was 55.6%. Engraftment was achieved in 90.9% of cases. At the same time, the median time to leukocyte recovery (14 days), the incidence of acute and chronic GVHD (27.3% and 12.5%) did not differ significantly.
Haplo-HSCT with previous TCRαβ/CD19 depletion proved to be a safe method of GVHD prevention: grade 2 (or more) acute GVHD frequency was 26-27%, no steroid-refractory forms were observed. A rapid leukocyte recovery was noted, which can be explained by the high cellularity of the graft. One should note high OS and the absence of TRM in AL patients, which may be associated with young age and MRD-negative status in the majority of patients.
Conclusion
Thus, on the basis of Federal Funding Program, haplo-HSCT with previous depletion of TCRαβ/CD19 + cells may be the method of choice for young patients with AL, provided there is no available HLA-identical donor.
Keywords
Hematopoietic stem cell transplantation, haploidentical, TCRαβ/CD19 depletion, graft-versus-host disease.
