Email this article Immunotherapy of high-risk infant acute lymphoblastic leukemia using blinatumomab and infusion of donor lymphocytes
- Authors: Paina O.V.1, Tsvetkova L.A.1, Rakhmanova Z.Z.1, Kozhokhar P.V.1, Frolova A.S.1, Osipova A.A.1, Ekushov K.A.1, Dobrovolskaya E.D.1, Gindina T.L.1, Barkhatov I.M.1, Semenova E.V.1, Kulagin A.D.1, Zubarovskaya L.S.1
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Affiliations:
- R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
- Issue: Vol 21, No 4 (2022)
- Pages: 53-59
- Section: ORIGINAL ARTICLES
- Submitted: 17.01.2023
- Accepted: 17.01.2023
- Published: 26.12.2022
- URL: https://hemoncim.com/jour/article/view/678
- DOI: https://doi.org/10.24287/1726-1708-2022-21-4-53-59
- ID: 678
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Abstract
Pleuropulmonary blastoma (PPB) is a very rare tumor of childhood that arises from the mesenchyme of the lung and is associated Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. Despite intensified therapy protocols, infant ALL remains a difficult-to-treat disease, with a high relapse rate. Allogeneic bone marrow transplantation is the only curative method aimed to curing the disease. Over the last decades, donor lymphocyte infusion (DLI) has been used as a salvage therapy after post-transplant relapses in B-ALL patients with a proven antileukemic effect. The combination of blinatumomab and DLI is a promising immunoadoptive therapy for resistant ALL based on the induction of “graft versus leukemia” effect by activating donor T-lymphocytes. We analyzed the results of combined immunoadoptive therapy with a bispecific T-cell activator blinatumomab and DLI in 3 infants with ALL, as well as the outcome of monotherapy with a bispecific T-cell activator in one infant. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. All infants initially had the KMT2A gene rearrangement and were classified as high-risk. The indication for immunoadoptive therapy was an early combined relapse of the disease after haploidentical hematopoietic stem cell transplantation in one patient and minimal residual disease (MRD) in three patients. All patients achieved long term hematological remission of the disease, 3 (75%) patients – MRD negative remission. The median duration of bone marrow response was 24 (8–63) months. One patient developed a bone marrow relapse in 8 months after therapy, two patients developed isolated extramedullary relapse. We did not see toxic complications and induction of graft-versus-host disease during immunoadoptive therapy. At the time of the follow up, all patients are alive, three remains in lasting hematological remission.
About the authors
O. V. Paina
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
Author for correspondence.
Email: paina@mail.ru
ORCID iD: 0000-0001-7263-4326
Olesya V. Paina, Cand. Med. Sci., Hematologist, Head of the 1st Pediatric Transplant Department
197022, Saint Petersburg, Lva Tolstogo St., 6–8
Russian Federation
L. A. Tsvetkova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0003-4952-0704
Saint-Petersburg
Russian FederationZ. Z. Rakhmanova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0002-3386-0942
Saint-Petersburg
Russian FederationP. V. Kozhokhar
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0002-5721-0207
Saint-Petersburg
Russian FederationA. S. Frolova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0003-1143-4851
Saint-Petersburg
Russian FederationA. A. Osipova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0001-7629-4293
Saint-Petersburg
Russian FederationK. A. Ekushov
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0002-1104-6499
Saint-Petersburg
Russian FederationE. D. Dobrovolskaya
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
Saint-Petersburg
Russian FederationT. L. Gindina
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0002-1302-3311
Saint-Petersburg
Russian FederationI. M. Barkhatov
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0002-8000-3652
Saint-Petersburg
Russian FederationE. V. Semenova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0001-5077-9225
Saint-Petersburg
Russian FederationA. D. Kulagin
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0002-9589-4136
Saint-Petersburg
Russian FederationL. S. Zubarovskaya
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0000-0003-2594-7703
Saint-Petersburg
Russian FederationReferences
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