title: 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.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen peter.lang@med.uni-tuebingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.affiliation: Amgen Research Munich GmbH.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zugmaier
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Frankfurt, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Kreyenberg
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Kai-Erik
authors.initials: KE
authors.lastname: Witte
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Judith
authors.initials: J
authors.lastname: Feucht
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfeiffer
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Heiko-Manuel
authors.initials: HM
authors.lastname: Teltschik
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Christina
authors.initials: C
authors.lastname: Kyzirakos
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
mesh_terms: D000293:Adolescent; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012008:Recurrence; D012074:Remission Induction; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; C510808:blinatumomab
references.citation: Blood. 2011 Apr 28;117(17):4403-4
references.pmid: 21527536
references.citation: Hematology Am Soc Hematol Educ Program. 2011;2011:243-9
references.pmid: 22160041
references.citation: Leukemia. 2011 Jan;25(1):181-4
references.pmid: 20944674
references.citation: Blood. 2000 Mar 15;95(6):2098-103
references.pmid: 10706880
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7021-5
references.pmid: 7624362
references.citation: Blood. 2011 Dec 1;118(23):6043-9
references.pmid: 21967976
references.citation: Blood Rev. 2004 Sep;18(3):181-92
references.pmid: 15183902
references.citation: Blood. 2013 Jun 27;121(26):5154-7
references.pmid: 23678006
references.citation: Hematology Am Soc Hematol Educ Program. 2010;2010:7-12
references.pmid: 21239764
references.citation: Blood. 2004 May 15;103(10):3982-5
references.pmid: 14764538
references.citation: Front Oncol. 2012 Jan 30;2:3
references.pmid: 22645714
references.citation: Blood. 2012 Dec 20;120(26):5185-7
references.pmid: 23024237
references.citation: Blood. 2007 Feb 1;109(3):896-904
references.pmid: 17003366
references.citation: Leukemia. 2002 Nov;16(11):2228-37
references.pmid: 12399966
references.citation: Bone Marrow Transplant. 2012 Oct;47(10):1307-11
references.pmid: 22367344
references.citation: Blood. 2008 May 1;111(9):4477-89
references.pmid: 18285545
references.citation: Nat Med. 2012 Aug;18(8):1254-61
references.pmid: 22842478
references.citation: Leukemia. 2010 Aug;24(8):1462-9
references.pmid: 20535148
references.citation: Pediatr Blood Cancer. 2007 Jan;48(1):93-100
references.pmid: 16521130
references.citation: Bone Marrow Transplant. 2007 Nov;40(10):951-5
references.pmid: 17873916
references.citation: Ann Hematol. 2012 Feb;91(2):183-92
references.pmid: 21710165
references.citation: Leukemia. 2009 Dec;23(12):2259-64
references.pmid: 19741725
references.citation: Br J Haematol. 2005 Mar;128(6):774-82
references.pmid: 15755280
references.citation: J Clin Oncol. 2009 Sep 10;27(26):4392-7
references.pmid: 19652076
references.citation: Blood. 2003 May 15;101(10):3835-9
references.pmid: 12732501
references.citation: Science. 2008 Aug 15;321(5891):974-7
references.pmid: 18703743
references.citation: Leukemia. 2002 Sep;16(9):1668-72
references.pmid: 12200679
references.citation: J Clin Oncol. 2010 Feb 10;28(5):884-92
references.pmid: 20048186
references.citation: J Clin Oncol. 2008 Jun 20;26(18):3046-50
references.pmid: 18565891
references.citation: Nat Rev Immunol. 2002 Dec;2(12):945-56
references.pmid: 12461567
references.citation: Blood. 1984 Jun;63(6):1424-33
references.pmid: 6609729
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2493-8
references.pmid: 21576633
references.citation: Nat Rev Rheumatol. 2009 Oct;5(10):572-7
references.pmid: 19798033
references.citation: J Clin Oncol. 2009 Jan 20;27(3):377-84
references.pmid: 19064980
references.citation: Nat Rev Drug Discov. 2007 Feb;6(2):149-65
references.pmid: 17268486
references.citation: Nat Rev Immunol. 2009 Mar;9(3):195-205
references.pmid: 19240758