ISSN 1866-8836
Клеточная терапия и трансплантация

PO-02. Results of hematopoietic stem cells transplantation from related donor with TCRαβCD19- depletion and additional injection of CD45RA-depleted memory T cells on day 0

Anna A. Bogoyavlenskaya, Larisa N. Shelikhova, Maria A. Ilyushina, Maria A. Dunaykina, Svetlana N. Kozlovskaya, Elena E. Kurnikova, Natalya V. Myakova, Dmitry V. Litvinov, Galina A. Novichkova, Alexey A. Maschan, Michael A. Maschan

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

Contact: Dr. Anna A. Bogoyavlenskaya, e-mail: anna.bogoiavlenskaia@fnkc.ru

doi 10.18620/ctt-1866-8836-2020-9-3-1-152

Summary

Introduction

Graft-versus-host disease (GVHD) and associated non-relapse mortality in the patients with malignant diseases are the main negative factors in pediatric HSCT practice. αβ T cell depletion of hematopoietic graft for allogeneic hematopoietic stem cell transplantation (allo-HSCT) was designed to prevent the development of clinically significant GVHD, and to achieve higher rates of engraftment and rapid immune reconstitution. We used a fixed dose of CD45RA-depleted mononuclear cells (1×106/kg) on day 0, in order to improve immune recovery post-transplant.

Patients and methods

A total of 30 children (19, acute leukemia; 11, non-malignant diseases; 10 females and 21 males, median age 10.5 y.o.) underwent allo-HSCT from matched related donors from 01.09.2014 to 01.04.2019. The patients with primary immune deficiency received fludarabine, ATG, and either busulfan (n=3), or treosulfan (n=3). The patients (pts) with severe aplastic anemia (n=4) received cyclophosphamide/fludarabine/ATG. A single patient with thalassemia was treated with treosulfan, thiotepa, fludarabine, ATG. rATG (n=10) or hATG (n=1) were administered as serotherapy. Rituximab was used in all the pts. For GVHD prophylaxis, an abbreviated calcineurin-based regimen was used. Conditioning regimen for the pts with acute leukemia included fludarabine (n=19), thiotepa (n=19), and either treosulfan (n-11), or TBI (12 Gy) (n=8). As GVHD prophylaxis, we used bortezomib (n=16), rituximab (n=19) and abatacept (n=19). αβ T cell depletion with CliniMACS was used in all cases. The median dose of CD34+ cells was 12.5×106/kg; αβ T cells were administered at a dose of 21.5×103/kg. Median follow-up period for survivors was 2.3 years (range, 0.3 to 4.5). All the patients on day 0 received CD45RO T cells at a dose of 1×106/kg.

Results

None of the patients died before engraftment. Primary engraftment was achieved in all evaluable pts (100%) with full donor chimerism, the median time to neutrophil and platelet recovery was 12 and 14 days. No signs of transplant rejection were recorded in any of the presented cases. In the patients with non-malignant disorders, the 2-year event-free survival (pEFS) was 80% (95% CI: 66-94); the 2-year overall survival (pOS) was 94% (95% CI:85-100). In the patients with malignant diseases, it was 90% (95% CI: 79-100); the 2-year transplant-related mortality (TRM) was 0% (95%CI:0-25), CI of relapse in pts with malignant disease was 30% (95%CI:15-65). Risk of aGVHD (stage 2 to 4) was 10% (95% CI: 3-28.5) for malignancies versus 0 % (95% CI) for non-malignant disorders. CI for chronic GVHD was 7% (95% CI: 2-26.5). In the group with available immune recovery data (n=20), recovery of αβ-Tcells on day 30 was associated with a tendency for reduction of recurrence rate, the recurrence risk was 20% (95% CI:5.8-69); in individuals with αβ-T cells < median it was 8 % (95% CI: 3-94) compared to individuals with αβ-cell > median (p=0.58).

Conclusion

We confirm that the depletion of αβ T cells from related graft in combination with intensive conditioning regimen and additional infusion 1×10^6/kg CD45Ra cells on day 0 provides a high chance of long-term survival, decreases a risk of GVHD, achieve a high level of engraftment, absent TRM.

Keywords

Acute leukemia, hematopoietic stem cell transplantation, allogeneic, αβ T cell depletion, related, GvHD prophylaxis, αβ T cell recovery.


Volume 9, Number 3
09/30/2020

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doi 10.18620/ctt-1866-8836-2020-9-3-1-152

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