Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab.

Abstract

We report on posttransplant relapsed pediatric patients with B-precursor acute lymphoblastic leukemia with no further standard of care therapy who were treated with the T-cell engaging CD19/CD3-bispecific single-chain antibody construct blinatumomab on a compassionate use basis. Blast load was assessed prior to, during and after blinatumomab cycle using flow cytometry to detect minimal residual disease, quantitative polymerase chain reaction for rearrangements of the immunoglobulin or T-cell receptor genes, and bcr/abl mutation detection in one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dosage of 5 or 15 μg/m(2)/day. Nine patients received a total of 18 cycles. Four patients achieved complete remission after the first cycle of treatment; 2 patients showed a complete remission from the second cycle after previous reduction of blast load by chemotherapy. Three patients did not respond, of whom one patient proceeded to a second cycle without additional chemotherapy and again did not respond. Four patients were successfully retransplanted in molecular remission from haploidentical donors. After a median follow up of 398 days, the probability of hematologic event-free survival is 30%. Major toxicities were grade 3 seizures in one patient and grade 3 cytokine release syndrome in 2 patients. Blinatumomab can induce molecular remission in pediatric patients with posttransplant relapsed B-precursor acute lymphoblastic leukemia and facilitate subsequent allogeneic hematopoietic stem cell transplantation from haploidentical donor with subsequent long-term leukemia-free survival.

• Authors: Patrick Schlegel, Peter Lang, Gerhard Zugmaier, Martin Ebinger, Hermann Kreyenberg, Kai-Erik Witte, Judith Feucht, Matthias Pfeiffer, Heiko-Manuel Teltschik, Christina Kyzirakos, Tobias Feuchtinger, Rupert Handgretinger
• Journal: Haematologica (Haematologica) Vol. 99 Issue 7 Pg. 1212-9 (Jul 2014) ISSN: 1592-8721 [Electronic] Italy
• PMID: 24727818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Antibodies, Bispecific
• Antineoplastic Agents
• blinatumomab

Topics

• Adolescent
• Antibodies, Bispecific (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Bone Marrow (pathology)
• Child
• Child, Preschool
• Combined Modality Therapy
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, mortality, pathology, therapy)
• Recurrence
• Remission Induction
• Transplantation, Homologous
• Treatment Outcome