Acute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease
Copyright © 2021 Massachusetts Medical Society..
Gene therapy with LentiGlobin for sickle cell disease (bb1111, lovotibeglogene autotemcel) consists of autologous transplantation of a patient's hematopoietic stem cells transduced with the BB305 lentiviral vector that encodes the βA-T87Q-globin gene. Acute myeloid leukemia developed in a woman approximately 5.5 years after she had received LentiGlobin for sickle cell disease as part of the initial cohort (Group A) of the HGB-206 study. An analysis of peripheral-blood samples revealed that blast cells contained a BB305 lentiviral vector insertion site. The results of an investigation of causality indicated that the leukemia was unlikely to be related to vector insertion, given the location of the insertion site, the very low transgene expression in blast cells, and the lack of an effect on expression of surrounding genes. Several somatic mutations predisposing to acute myeloid leukemia were present after diagnosis, which suggests that patients with sickle cell disease are at increased risk for hematologic malignant conditions after transplantation, most likely because of a combination of risks associated with underlying sickle cell disease, transplantation procedure, and inadequate disease control after treatment. (Funded by Bluebird Bio.).
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:386 |
---|---|
Enthalten in: |
The New England journal of medicine - 386(2022), 2 vom: 13. Jan., Seite 138-147 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Goyal, Sunita [VerfasserIn] |
---|
Links: |
---|
Themen: |
Beta(A-T87Q) globin |
---|
Anmerkungen: |
Date Completed 25.01.2022 Date Revised 25.01.2022 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1056/NEJMoa2109167 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM334346169 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM334346169 | ||
003 | DE-627 | ||
005 | 20231225223520.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1056/NEJMoa2109167 |2 doi | |
028 | 5 | 2 | |a pubmed24n1114.xml |
035 | |a (DE-627)NLM334346169 | ||
035 | |a (NLM)34898140 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Goyal, Sunita |e verfasserin |4 aut | |
245 | 1 | 0 | |a Acute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 25.01.2022 | ||
500 | |a Date Revised 25.01.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2021 Massachusetts Medical Society. | ||
520 | |a Gene therapy with LentiGlobin for sickle cell disease (bb1111, lovotibeglogene autotemcel) consists of autologous transplantation of a patient's hematopoietic stem cells transduced with the BB305 lentiviral vector that encodes the βA-T87Q-globin gene. Acute myeloid leukemia developed in a woman approximately 5.5 years after she had received LentiGlobin for sickle cell disease as part of the initial cohort (Group A) of the HGB-206 study. An analysis of peripheral-blood samples revealed that blast cells contained a BB305 lentiviral vector insertion site. The results of an investigation of causality indicated that the leukemia was unlikely to be related to vector insertion, given the location of the insertion site, the very low transgene expression in blast cells, and the lack of an effect on expression of surrounding genes. Several somatic mutations predisposing to acute myeloid leukemia were present after diagnosis, which suggests that patients with sickle cell disease are at increased risk for hematologic malignant conditions after transplantation, most likely because of a combination of risks associated with underlying sickle cell disease, transplantation procedure, and inadequate disease control after treatment. (Funded by Bluebird Bio.) | ||
650 | 4 | |a Case Reports | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a beta(A-T87Q) globin |2 NLM | |
650 | 7 | |a beta-Globins |2 NLM | |
700 | 1 | |a Tisdale, John |e verfasserin |4 aut | |
700 | 1 | |a Schmidt, Manfred |e verfasserin |4 aut | |
700 | 1 | |a Kanter, Julie |e verfasserin |4 aut | |
700 | 1 | |a Jaroscak, Jennifer |e verfasserin |4 aut | |
700 | 1 | |a Whitney, Dustin |e verfasserin |4 aut | |
700 | 1 | |a Bitter, Hans |e verfasserin |4 aut | |
700 | 1 | |a Gregory, Philip D |e verfasserin |4 aut | |
700 | 1 | |a Parsons, Geoffrey |e verfasserin |4 aut | |
700 | 1 | |a Foos, Marianna |e verfasserin |4 aut | |
700 | 1 | |a Yeri, Ashish |e verfasserin |4 aut | |
700 | 1 | |a Gioia, Maple |e verfasserin |4 aut | |
700 | 1 | |a Voytek, Sarah B |e verfasserin |4 aut | |
700 | 1 | |a Miller, Alex |e verfasserin |4 aut | |
700 | 1 | |a Lynch, Jessie |e verfasserin |4 aut | |
700 | 1 | |a Colvin, Richard A |e verfasserin |4 aut | |
700 | 1 | |a Bonner, Melissa |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t The New England journal of medicine |d 1945 |g 386(2022), 2 vom: 13. Jan., Seite 138-147 |w (DE-627)NLM000008184 |x 1533-4406 |7 nnns |
773 | 1 | 8 | |g volume:386 |g year:2022 |g number:2 |g day:13 |g month:01 |g pages:138-147 |
856 | 4 | 0 | |u http://dx.doi.org/10.1056/NEJMoa2109167 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 386 |j 2022 |e 2 |b 13 |c 01 |h 138-147 |