The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index; 10 of the 27 sources its claims cite were checked for support.
Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia
Open accessAbstract
Background Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (β A-T87Q ) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia. Methods In two phase 1-2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent β-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbA T87Q ). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbA T87Q , transfusion requirements, and average vector copy number. Results At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non-β 0 /β 0 genotype had stopped receiving red-cell transfusions; the levels of HbA T87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic…
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Claims the paper makes
10 of 27 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The risks of serious complications from transfusion-related iron toxicity and viral infections persist despite improvements in care.10,11”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > RESULTS
What the sources say
- Supportedcites [10] 10. Tubman VN, Fung EB, Vogiatzi M, et al. Guidelines for the standard monitoring of patients with thalassemia: report of the Thalassemia Longitudinal Cohort. J Pedi- atr Hematol Oncol 2015; 37(3): e162-e169. source
The Transfusion-Associated Iron Deposition section says iron overload remains a major cause of mortality despite improvements in monitoring and treatment. The Transfusion-associated infections section recommends continued viral surveillance, reports hepatitis C seropositivity, and notes that fewer young patients now seroconvert. Page numbers are unavailable in our copy. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [11] 11. Bonifazi F, Conte R, Baiardi P, et al. Pattern of complications and burden of disease in patients affected by beta thal- assemia major. Curr Med Res Opin 2017; 33: 1525-33. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Thus, the current standard of care for patients with β-thalassemia consists of lifelong, regular red-cell transfusions and iron chelation.9”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > RESULTS
What the sources say
- Could not verifycites [9] 9. Engert A, Balduini C, Brand A, et al. The European Hematology Association Roadmap for European Hematology Re- search: a consensus document. Haemato- logica 2016; 101: 115-208. sourceExperimental — accuracy not yet measured
The Introduction mentions thalassemia as an inherited blood disease but does not describe its standard care. Searches for regular transfusions, iron chelation, and thalassemia treatment found relevant titles in the References, not a passage in the cited paper stating the claimed regimen. (LLM, conf=0.74)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Limited changes in the LentiGlobin vector (HPV569 vs. BB305) did not significantly alter the expression of β A-T87Q -globin per integrated vector copy, but they contributed (along with changes in vector manufacturing) to an increase in vector titers by a factor of approximately 4. 14,24,37”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
What the sources say
- Partly supportedcites [14] 14. Negre O, Eggimann AV, Beuzard Y, et al. Gene therapy of the β-hemoglobin- opathies by lentiviral transfer of the β(A(T87Q))-globin gene. Hum Gene Ther 2016; 27: 148-65. sourceExperimental — accuracy not yet measured
The BB305 lentiviral vector section says BB305 is identical to HPV569 after integration except for removal of the cHS4 insulator, whose effect on transgene expression was limited. It does not report a direct comparison of βA-T87Q-globin expression per integrated vector copy or establish that the difference was statistically nonsignificant. No page number is available in our copy. (LLM, conf=0.78)
- Supportedcites [24] 24. Negre O, Bartholomae C, Beuzard Y, et al. Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease. Curr Gene Ther 2015; 15: 64-81. source
The Results section on primary-transplant β-thalassemia mice states that expression per vector copy was similar for BB305 and HPV569, citing in vitro studies in human CD34+ cells. The vector-design Results section also says the integrated βA-T87Q-globin expression cassette was identical in the two vectors. Page numbers are not available in our copy. (LLM, conf=0.92)
- Not matchedcites [37] 37. Walters MC, Thompson A, Hongeng S, et al. A phase 3 study to evaluate safety and efficacy of LentiGlobin gene therapy for transfusion-dependent beta-thalassemia in patients with non-beta0/beta0 geno- types: the Northstar-2 (HGB-207) trial. Haematologica 2017; 102: 335. abstract.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The BB305 vector is similar to the initial HPV569 vector.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Limited changes in the LentiGlobin vector (HPV569 vs. BB305) did not significantly alter the expression of β A-T87Q -globin per integrated vector copy, but they contributed (along with changes in vector manufacturing) to an increase in vector titers by a factor of approximately 4. 14,24,37”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
What the sources say
- Partly supportedcites [14] 14. Negre O, Eggimann AV, Beuzard Y, et al. Gene therapy of the β-hemoglobin- opathies by lentiviral transfer of the β(A(T87Q))-globin gene. Hum Gene Ther 2016; 27: 148-65. sourceExperimental — accuracy not yet measured
The BB305 lentiviral vector section (page unavailable) reports that changes from HPV569 to BB305 increased vector titers 3–4-fold, supporting the approximate fourfold figure. The Production of lentiviral vectors section describes manufacturing, but does not say manufacturing changes contributed to that increase. (LLM, conf=0.86)
- Supportedcites [24] 24. Negre O, Bartholomae C, Beuzard Y, et al. Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease. Curr Gene Ther 2015; 15: 64-81. source
The Results section reports that BB305 harvest titers were approximately 3–4 times higher than HPV569 titers. The Introduction says the vector redesign also reduced the number of plasmids required for production and improved vector yield. Page numbers were not provided in our copy. (LLM, conf=0.91)
- Not matchedcites [37] 37. Walters MC, Thompson A, Hongeng S, et al. A phase 3 study to evaluate safety and efficacy of LentiGlobin gene therapy for transfusion-dependent beta-thalassemia in patients with non-beta0/beta0 geno- types: the Northstar-2 (HGB-207) trial. Haematologica 2017; 102: 335. abstract.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The BB305 vector is similar to the initial HPV569 vector.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The feasibility of the addition of a gene to autologous hematopoietic cells using a lentiviral vector was shown previously in a single patient with β-thalassemia who safely discontinued transfusions for more than 6 years with ongoing, sustained β A-T87Q -globin expression.14,20”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
What the sources say
- Supportedcites [14] 14. Negre O, Eggimann AV, Beuzard Y, et al. Gene therapy of the β-hemoglobin- opathies by lentiviral transfer of the β(A(T87Q))-globin gene. Hum Gene Ther 2016; 27: 148-65. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [20] 20. Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 2010; 467: 318-22. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A patient with a severe β E /β 0 genotype safely discontinued transfusions for more than 6 years with sustained β A-T87Q -globin expression.13,20”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > RESULTS
What the sources say
- Partly supportedcites [13] 13. Mansilla-Soto J, Riviere I, Boulad F, Sadelain M. Cell and gene therapy for the beta-thalassemias: advances and pros- pects. Hum Gene Ther 2016; 27: 295-304. sourceExperimental — accuracy not yet measured
The Phase I Clinical Trials section reports a patient whose vector-derived globin contributed to transfusion independence and whose clinically beneficial clone persisted for seven years. It does not identify that patient as having a βE/β0 genotype; it describes a β+ form of the disease. Calling the outcome unqualifiedly safe also omits the reported adverse clonal expansion, although the clone did not progress to leukemia. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [20] 20. Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 2010; 467: 318-22. source
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The remaining 3 patients with a β 0 /β 0 genotype or two copies of the IVS1-110 mutation had not received transfusions for 14 to 20 months”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Blood HbA T87Q Levels and Changes in Transfusion Requirements
Strength:plain· not yet calibratedn = 3Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With follow-up extending to 3 years (median, 26 months) after infusion, no serious adverse events related to the drug product have been detected, and there were no significant unexpected safety issues.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With follow-up extending to 3 years (median, 26 months) after infusion, no serious adverse events related to the drug product have been detected, and there were no significant unexpected safety issues.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and red-cell transfusions were discontinued in 3 patients.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 5
- It may state two separate claims as one. 30
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“whereas an earlier study at Memorial Sloan Kettering Cancer Center was suspended to allow for testing of a revised lentiviral vector.13”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
What the sources say
- Partly supportedcites [13] 13. Mansilla-Soto J, Riviere I, Boulad F, Sadelain M. Cell and gene therapy for the beta-thalassemias: advances and pros- pects. Hum Gene Ther 2016; 27: 295-304. sourceExperimental — accuracy not yet measured
The Phase I Clinical Trials section describes the New York trial and says the authors planned to resume it with a modified lentiviral vector containing an added safety element. That supports a pause and a planned vector revision, but the paper does not say the trial was suspended to allow testing of the revised vector. (LLM, conf=0.84)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Another phase 1/2 study of lentiviral vectormediated gene therapy in patients with β-thalassemia is ongoing in Italy and has shown reductions in transfusion requirements, 14”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
What the sources say
- Partly supportedcites [14] 14. Negre O, Eggimann AV, Beuzard Y, et al. Gene therapy of the β-hemoglobin- opathies by lentiviral transfer of the β(A(T87Q))-globin gene. Hum Gene Ther 2016; 27: 148-65. sourceExperimental — accuracy not yet measured
The Introduction’s Table 2 identifies an ongoing phase I/II lentiviral gene-therapy study for β-thalassemia in Italy. It reports only that the first patient was recently treated, not a reduction in transfusion requirements; the decrease it reports belongs to a separate US trial. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The preenrollment transfusion requirement, spleen status, and age were not observed to have an effect on the study outcome.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the last study visit (12 to 36 months after infusion), the median HbA T87Q level was 6.0 g per deciliter (range, 3.4 to 10.0), and the median total hemoglobin level was 11.2 g per deciliter (range, 8.2 to 13.7)”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Blood HbA T87Q Levels and Changes in Transfusion Requirements
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“neutrophil engraftment occurred within a median of 18.5 days (range, 14.0 to 30.0) in HGB-204 and 16.5 days (range, 14.0 to 29.0) in HGB-205.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Hematopoietic Recovery and Gene Marking of Blood Cells
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the most recent follow-up (12 to 30 months), the patients' HbA T87Q level ranged from 6.6 to 8.2 g per deciliter, and the total hemoglobin level ranged from 8.3 to 10.2 g per deciliter.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Blood HbA T87Q Levels and Changes in Transfusion Requirements
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 1121, who had a vector copy number of 0.3 in the drug product, had a blood vector copy number of 0.10 at the last follow-up and continued to receive red-cell transfusions.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Blood HbA T87Q Levels and Changes in Transfusion Requirements
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“After receiving the drug product, Patient 1003 had received no red-cell transfusions during year 2 through year 8 while maintaining a total hemoglobin level of approximately 8 g per deciliter.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Safety
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During year 9 through year 12, the patient resumed sporadic transfusions, although the HbA T87Q levels had remained stable above 2 g per deciliter since month 18 20”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Safety
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the time of this report (year 12), the HMGA2 locus was no longer dominant in Patient 1003 and had not been associated with serious adverse events.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Safety
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In HGB-205, in an exploratory analysis that was performed among patients who had stopped receiving red-cell transfusions after gene therapy, the degree of hemolysis at first stabilized relative to pretransplantation levels and was fully corrected in Patients 1201 and 1202 by 36 months after treatment”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Effect on Hemolysis and Dyserythropoiesis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“BB305 and other lentiviral vectors have been used in more than 50 patients thus far without vector-related adverse events.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Strength:plain· not yet calibratedn = 50Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The median vector copy number at 15 months was 0.3 copies per diploid genome (range, 0.1 to 0.9) in HGB-204 and 2.0 copies per diploid genome (range, 0.3 to 4.2) in HGB-205.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Hematopoietic Recovery and Gene Marking of Blood Cells
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 12 months after infusion, the median number of unique integration sites was 1646 per patient (range, 202 to 5501) in HGB-204 and 5322 (range, 756 to 8685) in HGB-205.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Safety
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with steady-state hemoglobin levels of at least 9 g per deciliter (>8 g per deciliter in Patient 1118)”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Strength:plain· not yet calibratedn = 12Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 22 treated patients, 7 expressed at least 8 g per deciliter of HbA T87Q , including 3 patients with a β 0 /β 0 genotype or the severe IVS1-110 mutation; all have been free from transfusion for more than 1 year.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, Patient 1118 received a single transfusion 13 months after drug product infusion during an acute viral illness.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Blood HbA T87Q Levels and Changes in Transfusion Requirements
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nine serious adverse events were reported, including two episodes of veno-occlusive liver disease attributed to busulfan conditioning.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Safety
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 22 patients who were treated, 13 had a non-β 0 /β 0 genotype.Of these 13 patients, all but 1 stopped receiving red-cell transfusions after gene therapy.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Blood HbA T87Q Levels and Changes in Transfusion Requirements
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the 2 years before study enrollment, the median annual red-cell transfusion volume was 164 ml per kilogram per year (range, 124 to 261), which included 183 ml per kilogram per year in the 8 patients with a β 0 /β 0 genotype and 147 ml per kilogram per year in the 10 patients with other genotypes.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Characteristics of the Patients
Strength:plain· not yet calibratedn = 8Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Platelet engraftment occurred within a median of 39.5 days (range, 19.0 to 191.0) in HGB-204 and 23.0 days (range, 20.0 to 26.0) in HGB-205, during which time there were no bleeding complications resulting in serious adverse events.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Hematopoietic Recovery and Gene Marking of Blood Cells
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such discontinuation of treatment was reported in Patient 1202, who is no longer receiving iron chelation therapy and who completed phlebotomy 36 months after gene therapy.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Effect on Hemolysis and Dyserythropoiesis
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the current studies, genomewide mapping of chromosomal sites of vector integration showed a highly polyclonal pattern with no dominance observed.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In several treated patients, hemoglobin levels reached or approached normal ranges, thereby correcting dyserythropoiesis.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One patient also had normalization of iron overload and was able to discontinue both iron chelation and therapeutic phlebotomy.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia.”
- Also stated in: § RESULTS · plain
“The only potentially curative option for β-thalassemia is allogeneic hematopoietic-cell transplantation, but owing to risks of graft rejection, graft-versus-host disease, and other treatment-related toxic effects, transplantation is primarily reserved for young children with an HLA-identical sibling donor.[6][7][8]”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Abstract
What the sources say
- Not matchedcites [6][7][8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § RESULTS · plain
In the paper
“Vector-encoded β A-T87Q -globin was engineered with a single amino acid substitution (T87Q) that strongly inhibits the polymerization of sickle hemoglobin in patients with sickle cell disease and also permits precise quantification of vector-derived therapeutic globin expression in vivo.23”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [23] 23. Takekoshi KJ, Oh YH, Westerman KW, London IM, Leboulch P. Retroviral trans- fer of a human beta-globin/delta-globin hybrid gene linked to beta locus control region hypersensitive site 2 aimed at the gene therapy of sickle cell disease. Proc Natl Acad Sci U S A 1995; 92: 3014-8. source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The treatment population, which included all the patients who had received the LentiGlobin BB305 drug product, was the primary population for this interim analysis, and data were analyzed separately for each study.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Independent data and safety monitoring committees regularly reviewed safety data.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Study Oversight
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“even the partial reduction in transfusion requirements that we observed in these patients may result in a reduction in iron loading (and thereby long-term damage to target organs) and in increased life expectancy.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In addition, two other protocol-related features may have had an effect on efficacy: an enhanced series of red-cell transfusions before harvesting of CD34+ cells to mitigate the dilution of hematopoietic-cell targets in the expanded erythroid CD34+ cell compartment in patients with β-thalassemia and monitoring of plasma busulfan con-centrations with dose adjustments to optimize myeloablation.30”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
What the sources say
- Not matchedcites [30] 30. Bourget P, Falaschi L, Suarez F, et al. A medical-pharmaceutical partnership model as a contributor to the success in conditioning regimen for allogenic hema- topoietic stem cell transplantation in adults: a cross-reflection on our organizations. Bull Cancer 2012; 99: 643-53. (In French.)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Below 8.5 g per deciliter, ineffective erythropoiesis was maintained and hepcidin repressed”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At values of more than 9.5 g per deciliter of hemoglobin, the erythroid mass was reduced and peripheral iron control was restored by hepcidin.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of patients who were treated remains relatively small, so extended follow-up is required to establish the durability of transduction hematopoietic stem cells and progenitor cells after a single infusion.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
The paper relies on this without support.
A limited number of vector integration sites may suggest clonal outgrowth, a potential precursor to oncogenesis.
“The observation of a limited number of integration sites may suggest clonal outgrowth, a potential precursor to oncogenesis.”
The paper relies on this without support.
A histocompatible donor is lacking for allogeneic hematopoietic-cell transplantation.
“which is a lack of a histocompatible donor.”
The paper relies on this without support.
The theoretical possibility of genotoxicity by semirandom vector integration in the genome remains.
“Although the theoretical possibility of genotoxicity by semirandom vector integration in the genome remains”
The paper relies on this without support.
The clinical severity of the homozygous IVS1-110 mutation mirrors that of patients with a β0/β0 genotype.
“the patient with two copies of the IVS1-110 mutation, in whom the clinical severity mirrored that of patients with a β 0 /β 0 genotype”
The paper relies on this without support.
The threshold HbA T87Q level necessary for discontinuation of red-cell transfusion is higher in the absence of endogenous production of β-like globin chains.
“for whom the threshold HbA T87Q level that was necessary for discontinuation of red-cell transfusion was higher in the absence of endogenous production of β-like globin chains”
The paper relies on this without support.
The BB305 vector is similar to the initial HPV569 vector.
“a lentiviral vector (BB305) that is similar to our initial HPV569 vector.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In a phase 1/2 study, a similar HbA T87Q -lentiviral construct was introduced into autologous CD34 1 stem and progenitor cells that were infused into myeloablated patients with severe forms b thalassemia.The requirement for chronic transfusion was reduced or eliminated in all patients.116”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [116]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Betibeglogene autotemcel, a lentiviral vector-based gene-addition product, is approved in the European Union for the treatment of patients with TDT who have non-β 0 mutations and who do not have a matched sibling donor 14 and is being studied in patients with β 0 /β 0 TDT genotypes and in those with SCD.15,16”
From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
A patient counted as transfusion-free was still receiving transfusions
MajorThe discussion says all seven patients with HbA T87Q of at least 8 g/dl had been free from transfusion for more than a year. Table 2 lists Patient 1103 at 8.7 g/dl but says the patient was still receiving transfusions.
“Of the 22 treated patients, 7 expressed at least 8 g per deciliter of HbA T87Q , including 3 patients with a β 0 /β 0 genotype or the severe IVS1-110 mutation; all have been free from transfusion for more than 1 year.”
“1103 β 0 /β 0 24 8.7 9.8 Yes NA”
Table 2 footnote gives a range incompatible with listed visit times
MinorThe footnote says the listed values were obtained 15 to 42 months after infusion, but Table 2 includes a last study visit at 12 months.
“* Listed are the values a median of 26 months (range, 15 to 42) after drug product infusion.”
“1123 β 0 /β 0 12 6.8 10.2No 13.5”
Citations
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Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Walters MC, Thompson A, Hongeng S, et al. A phase 3 study to evaluate safety and efficacy of LentiGlobin gene therapy for transfusion-dependent beta-thalassemia in patients with non-beta0/beta0 genotypes: the Northstar-2 (HGB-207) trial. Haematologica 2017;102:335-335. abstract.
Cited by
Sorted by citations
Items 101–200 of 681
Pseudotyping Lentiviral Vectors: When the Clothes Make the Virus
Duvergé, A., & Negroni, M. (2020) · Viruses · doi:10.3390/v12111311 · Cited by 65
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Innate Immune Response to Viral Vectors in Gene Therapy
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Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives
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Gene Therapy For Beta-Thalassemia: Updated Perspectives
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Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
Rao, V. K., Kapp, D., & Schroth, M. K. (2018) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2018.24.12-a.s3 · Cited by 62
Coquerelle, S., Ghardallou, M. E., Ali, S. R., Taupin, P., Touzot, F., Boquet, L., Blanche, S., Benaouadi, S., Brice, T., Tuchmann‐Durand, C., et al. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.178 · Cited by 54
“4,5 10–12 In addition to safety and effectiveness, the cost of gene therapy versus other options needs to be considered.”
Self-citationAdenovirus vectors in hematopoietic stem cell genome editing
Li, C., & Lieber, A. (2019) · FEBS Letters · doi:10.1002/1873-3468.13668 · Cited by 53
The variable manifestations of disease in pyruvate kinase deficiency and their management
Al-Samkari, H. T., van Beers, E. J., Kuo, K. H. M., et al. (2020) · Haematologica · doi:10.3324/haematol.2019.240846 · Cited by 53
Hematopoietic Stem Cell Gene-Addition/Editing Therapy in Sickle Cell Disease
Germino-Watnick, P., Hinds, M., Le, A., Chu, R., Liu, X., & Uchida, N. (2022) · Cells · doi:10.3390/cells11111843 · Cited by 63
“The first gene therapy patient with transfusion-dependent β-thalassemia (TDT) was part of the LG001 trial in France in 2006.”
BackgroundInfluentialDiscussing investigational AAV gene therapy with hemophilia patients: A guide
Sidonio, R. F., Pipe, S. W., Callaghan, M. U., Valentino, L. A., Monahan, P. E., & Croteau, S. E. (2020) · Blood Reviews · doi:10.1016/j.blre.2020.100759 · Cited by 52
Thalassemias: from gene to therapy
Simone, G. D., Quattrocchi, A., Mancini, B., di Masi, A., Nervi, C., & Ascenzi, P. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101028 · Cited by 59
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs
Longo, F., Piolatto, A., Ferrero, G. B., & Piga, A. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137229 · Cited by 53
Transdermal delivery for gene therapy
Singh, P., Muhammad, I., Nelson, N. E., Tran, K. T. M., Vinikoor, T., Chorsi, M. T., D’Orio, E., & Nguyen, T. D. (2022) · Drug Delivery and Translational Research · doi:10.1007/s13346-022-01138-1 · Cited by 52
“In addition, ex vivo lentiviral and retroviral-based gene therapies are able to help modify hematopoietic cells and treat diseases such as beta-thalassemia and sickle-cell disease [10].”
BackgroundHardouin, G., Antoniou, P., Martinucci, P., Félix, T., Manceau, S., Joseph, L., Masson, C., Scaramuzza, S., Ferrari, G., Cavazzana, M., et al. (2022) · Blood · doi:10.1182/blood.2022016629 · Cited by 51
Self-citationLong-term lineage commitment in haematopoietic stem cell gene therapy
Calabria, A., Spinozzi, G., Cesana, D., Buscaroli, E., Benedicenti, F., Pais, G., Gazzo, F., Scala, S., Lidonnici, M. R., Scaramuzza, S., et al. (2024) · Nature · doi:10.1038/s41586-024-08250-x · Cited by 55
Kwiatkowski, J. L., Walters, M. C., Hongeng, S., Yannaki, E., Kulozik, A. E., Kunz, J. B., Sauer, M. G., Thrasher, A. J., Thuret, I., Lal, A., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01884-1 · Cited by 55
Self-citationCardiovascular manifestations of sickle cell disease
Hammoudi, N., Lionnet, F., Redheuil, A. B., & Montalescot, G. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz217 · Cited by 54
Khandros, E., & Kwiatkowski, J. L. (2019) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2019.01.003 · Cited by 52
“The results of 22 treated patients ranging from 12 to 35 years old, with median follow-up of 26 months recently were published.(47) Of 13 patients with a non-b0/b0 genotype, 12 achieved transfusion independence with hemoglobin levels ranging from 8.”
BackgroundSelf-citationSchott, J. W., León‐Rico, D., Ferreira, C. B., Buckland, K. F., Santilli, G., Armant, M. A., Schambach, A., Cavazza, A., & Thrasher, A. J. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.05.015 · Cited by 54
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Masiuk, K. E., Zhang, R., Osborne, K. S., Hollis, R. P., Campo-Fernández, B., & Kohn, D. B. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.03.005 · Cited by 53
“Transfusion lead-in and plerixafor mobilization protocols have been explored to improve the quality and quantity of CD34 HSPCs collected(12,27) and monitoring of plasma busulfan concentrations with dose adjustments has been explored to optimize myeloablation.(25)”
Cruz, L. J., van Dijk, T., Vepris, O., Li, T. M. W. Y., Schomann, T., Baldazzi, F., Kurita, R., Nakamura, Y., Grosveld, F. G., Philipsen, S., et al. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120580 · Cited by 51
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“Gene therapy represents a promising therapy, but its long-term efficacy remains to be determined.(5) Therefore, effective and affordable remedies are urgently needed to save patients with TDT, especially for those who are 14 years of age and older.”
BackgroundGenome editing in large animal models
Maynard, L. H., Humbert, O., Peterson, C. W., & Kiem, H. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.026 · Cited by 50
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Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation
Ferrari, S., Vavassori, V., Canarutto, D., Jacob, A., Castiello, M. C., Omer, A., & Genovese, P. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618378 · Cited by 52
“Although no guidelines currently exist, previously validated unintended onand off-target events should be strictly monitored after infusion in patients, similarly to longitudinal integration site analyses that are considered a standard in current gene addition clinical protocols (Aiuti et al., 2013; Thompson et al., 2…”
BackgroundInfluentialGene Therapy for Hemoglobinopathies
Leonard, A. K., Tisdale, J. F., & Bonner, M. A. (2022) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.03.008 · Cited by 49
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Long-Term Follow-Up of Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy
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“Metachromatic leukodystrophy, 11,12 severe combined immunodeficiencies, 13 Wiskott–Aldrich syndrome (WAS), 14–16 b -thalassemia, 17,18 and sickle cell disease 19 were also successfully treated with LV vectors.”
Self-citationTherapy Development by Genome Editing of Hematopoietic Stem Cells
Koniali, L., Lederer, C. W., & Kleanthous, M. (2021) · Cells · doi:10.3390/cells10061492 · Cited by 50
Thalassemia: A Review of the Challenges to the Families and Caregivers
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“Gene therapy with autologous CD34+ cells (transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans) transduced with the BB305 vector (an exploratory gene therapeutic agent for the management of sickle cell disease and β-thalassemia) diminishes or puts an end to the necessity for longstanding red-ce…”
BackgroundGene therapy: principles, challenges and use in clinical practice
Ay, C., & Reinisch, A. (2024) · Wiener klinische Wochenschrift · doi:10.1007/s00508-024-02368-8 · Cited by 50
Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque
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Gene therapy for Fabry disease: Progress, challenges, and outlooks on gene-editing
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Advances in Gene Therapy for Fanconi Anemia
Rı́o, P., Navarro, S., & Bueren, J. A. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.124 · Cited by 41
“6,49,50 On the basis of the efficacy of hematopoietic gene therapyachievedforvariousmonogenicdiseases, 51–55 and taking into account advances in preclinical and clinical gene therapy studies for FA, 56,57 this therapeutic approach is now considered to be an important alternative to HSCT for the…”
Lu, A., Liu, H., Shi, R., Cai, Y., Ma, J., Shao, L., Rong, V., Gkitsas-Long, N., Lei, H., Highfill, S. L., et al. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02358-0 · Cited by 43
Gene therapy for primary mitochondrial diseases: experimental advances and clinical challenges
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Gene Therapy and Gene Editing for β-Thalassemia
Christakopoulos, G. E., Telange, R., Yen, J. S., & Weiss, M. J. (2023) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.12.012 · Cited by 43
Enhancing pediatric access to cell and gene therapies
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Taher, A. T., Bou‐Fakhredin, R., Kattamis, A., Viprakasit, V., & Cappellini, M. D. (2021) · Expert Review of Hematology · doi:10.1080/17474086.2021.1977116 · Cited by 41
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“Failure of early attempts of achieving stable factor IX in lentivirally transduced mouse liver, led Brown and coworkers to develop lentiviral vectors carrying target sites for hematopoietic-specific microRNAs [111].”
BackgroundMethodInfluentialSickle Cell Disease: From Genetics to Curative Approaches
Hardouin, G., Magrin, E., Corsia, A., Cavazzana, M., Miccio, A., & Semeraro, M. (2023) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120122-081037 · Cited by 40
Self-citationPorter, J. B. (2018) · Hematology · doi:10.1182/asheducation-2018.1.361 · Cited by 40
“The procedure has been generally well tolerated with adverse events and frequencies typical of an autologous transplant.(15) A less intensive myeloablative regime would presumably lead to lower VOD risk, which although less frequent than in allogeneic transplantation, is not 0.”
BackgroundMethodInfluentialGene therapy for blood diseases
Kohn, D. B. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2018.11.016 · Cited by 39
Farrell, A. T., Panepinto, J. A., Desai, A. A., Kassim, A. A., Lebensburger, J. D., Walters, M. C., Bauer, D. E., Blaylark, R. M., DiMichele, D., Gladwin, M. T., et al. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019000883 · Cited by 41
Self-citationAn overview of development in gene therapeutics in China
Wang, D., Wang, K., & Cai, Y. (2020) · Gene Therapy · doi:10.1038/s41434-020-0163-7 · Cited by 45
“Gene therapy of β-thalassemia has achieved tremendous success from clinical trials in both USA and Europe regarding safety and efficacy [31, 32].”
BackgroundGene Therapy Potential for Genetic Disorders of Surfactant Dysfunction
Cooney, A. L., Wambach, J., Sinn, P. L., & McCray, P. B. (2022) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.785829 · Cited by 42
“, 2021), β-Thalassemia (Thompson et al., 2018), and Wiskott-Aldrich syndrome (Sereni et al.”
BackgroundTherapeutic gene editing in haematological disorders with CRISPR /Cas9
Jensen, T. I., Axelgaard, E., & Bak, R. O. (2019) · British Journal of Haematology · doi:10.1111/bjh.15851 · Cited by 40
“In a recent similar study from 2018, 15 out of 22 patients receiving lentiviral gene therapy became transfusion- independent with a median follow-up of 26 months (Thompson et al, 2018).”
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Hematopoietic Stem Cell-Targeted Gene-Addition and Gene-Editing Strategies for β-hemoglobinopathies
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Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing
Anurogo, D., Budi, N. Y. P., Ngo, M.-H. T., Huang, Y., & Pawitan, J. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126275 · Cited by 43
Novel Therapeutic Advances in β-Thalassemia
Makis, A. C., Voskaridou, E., Papassotiriou, I., & Hatzimichael, E. C. (2021) · Biology · doi:10.3390/biology10060546 · Cited by 39
“The outcomes of two phase 1/2 clinical trials (HGB-204/NCT01745120 and HGB205/NCT02151526) using the LentiGlobin BB305 vector in 22 TDT patients (12–35 years of age) were published in 2018 [25].”
BackgroundArtuso, I., Lidonnici, M. R., Altamura, S., Mandelli, G., Pettinato, M., Muckenthaler, M. U., Silvestri, L., Ferrari, G., Camaschella, C., & Nai, A. (2018) · Blood · doi:10.1182/blood-2018-05-852277 · Cited by 38
Engineered stem cells by emerging biomedical stratagems
Wang, J., Zhang, X., Chen, H., Ren, H., Zhou, M., & Zhao, Y. (2024) · Science Bulletin · doi:10.1016/j.scib.2023.12.006 · Cited by 37
Genetic therapies for sickle cell disease
Esrick, E. B., & Bauer, D. E. (2018) · Seminars in Hematology · doi:10.1053/j.seminhematol.2018.04.014 · Cited by 39
Soni, S. (2020) · American Journal of Hematology · doi:10.1002/ajh.25909 · Cited by 37
“Though conceptually straightforward, the field has technologically advanced only recently, where the vectors (packaged with the large HBB gene and its regulatory elements; promoter, enhancer and parts of LCR) can now be produced on a large scale, with high level of purification and potency to transfect large number of…”
BackgroundSelf-citationTreatment of Fabry Disease: Established and Emerging Therapies
Umer, M., & Kalra, D. K. (2023) · Pharmaceuticals · doi:10.3390/ph16020320 · Cited by 38
“thalassemia, have shown long-term safety [76].”
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Revolutionising healing: Gene Editing's breakthrough against sickle cell disease
Dimitrievska, M., Bansal, D., Vitale, M., Strouboulis, J., Miccio, A., Nicolaides, K. H., Hoss, S. E., Shangaris, P., & Jackow, J. (2024) · Blood Reviews · doi:10.1016/j.blre.2024.101185 · Cited by 41
Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice
Sii-Felice, K., Giorgi, M., Leboulch, P., & Payen, E. (2018) · Experimental Hematology · doi:10.1016/j.exphem.2018.05.004 · Cited by 39
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Regenerative medicine: the red planet for clinicians
Ciccocioppo, R., Cantore, A., Chaimov, D., & Orlando, G. (2019) · Internal and Emergency Medicine · doi:10.1007/s11739-019-02126-z · Cited by 37
Brendel, C., Río, P., & Verhoeyen, E. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.113711 · Cited by 39
Genetically modified cell sheets in regenerative medicine and tissue engineering
Jiang, Z., Li, N., Zhu, D., Ren, L., Shao, Q., Ke, Y., & Yang, G. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120908 · Cited by 37
Gene Therapy of the Hemoglobinopathies
Kunz, J. B., & Kulozik, A. E. (2020) · HemaSphere · doi:10.1097/hs9.0000000000000479 · Cited by 40
β-Thalassemia: evolving treatment options beyond transfusion and iron chelation
Langer, A. L., & Esrick, E. B. (2021) · Hematology · doi:10.1182/hematology.2021000313 · Cited by 39
Lüftinger, R., Zubarovskaya, N., Galimard, J., Cseh, A., Salzer, E., Locatelli, F., Algeri, M., Yeşilipek, A., de la Fuente, J., Isgrò, A., et al. (2022) · Annals of Hematology · doi:10.1007/s00277-021-04732-4 · Cited by 35
Gene therapy for genetic diseases: challenges and future directions
Beibei, Q. I. E., Tuo, J., Chen, F., Ding, H., & Lyu, L. (2025) · MedComm · doi:10.1002/mco2.70091 · Cited by 38
Optimizing lentiviral vector transduction of hematopoietic stem cells for gene therapy
Jang, Y., Kim, Y., Wielgosz, M. M., Ferrara, F., Ma, Z., Condori, J., Palmer, L. E., Zhao, X., Kang, G., Rawlings, D. J., et al. (2020) · Gene Therapy · doi:10.1038/s41434-020-0150-z · Cited by 35
Metabolic regulation of erythrocyte development and disorders
Lyu, J., Ni, M., Weiss, M. J., & Xu, J. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104153 · Cited by 36
An Optimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype
Weber, L., Poletti, V., Magrin, E., Antoniani, C., Martin, S., Bayard, C., Sadek, H., Félix, T., Meneghini, V., Antoniou, M. N., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.07.012 · Cited by 33
Self-citationRecent trends in treatment of thalassemia
El-Beshlawy, A. M., & El-Ghamrawy, M. (2019) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2019.01.006 · Cited by 33
Metabolomics in genetic testing
Troisi, J., Cavallo, P., Colucci, A., Pierri, L., Scala, G., Symes, S. J. K., Jones, C., & Richards, S. M. (2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.009 · Cited by 37
Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering
Piras, F., & Kajaste‐Rudnitski, A. (2020) · Gene Therapy · doi:10.1038/s41434-020-0175-3 · Cited by 32
“Donor variability remains a significant issue for the field as underscored also by the high variability in gene marking recently observed for β-Thalassemia gene therapy patients [5, 6].”
BackgroundStrategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges
Yoder, K. E., Rabe, A. J., Fishel, R. A., & Larue, R. C. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.662331 · Cited by 37
“However, a subsequent study of 22 patients do not observe any clonal expansion (Thompson et al., 2018).”
BackgroundModeling blood diseases with human induced pluripotent stem cells
Georgomanoli, M., & Papapetrou, E. P. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.039321 · Cited by 35
“The first human iPSC gene and cell therapy study used a lentiviral vector similar to those that have since shown therapeutic benefit in clinical trials of autologous HSC gene therapy for β-thalassemia and SCD (Boulad et al., 2014; Thompson et al., 2018; Papapetrou et al., 2011).”
MethodOzog, S., Timberlake, N. D., Hermann, K. J., Garijo, O., Haworth, K. G., Shi, G., Glinkerman, C. M., Schefter, L. E., D'Souza, S. S., Simpson, E., et al. (2019) · Blood · doi:10.1182/blood.2019000040 · Cited by 33
Molecular Medicine: Found in Translation
Orkin, S. H. (2021) · Med · doi:10.1016/j.medj.2020.12.011 · Cited by 36
Genome Editing for β-Hemoglobinopathies: Advances and Challenges
Frati, G., & Miccio, A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10030482 · Cited by 31
Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology
Gurkan, U. A. (2021) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000639 · Cited by 31
“Globin gene addition using lentiviral gene therapy has potential to cure both SCD and bthalassemia [53,54].”
BackgroundCRISPR/Cas-based gene editing in therapeutic strategies for beta-thalassemia
Zeng, S., Lei, S.-Y., Qu, C., Wang, Y., Teng, S., & Huang, P. C. (2023) · Human Genetics · doi:10.1007/s00439-023-02610-9 · Cited by 31
“%) with β + TDT gained transfusion independence (TI), i.e., weighted average Hb ≥9 g/dL without RBC transfusions for ≥12 months (Thompson et al. 2018).”
BackgroundA Review of Gene Therapy Delivery Systems for Intervertebral Disc Degeneration
Chen, S., Luo, M., Kou, H., Shang, G., Ji, Y., & Liu, H. (2019) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201020666191024171618 · Cited by 32
Yang, H., Qing, K., Keeler, G. D., Yin, L., Mietzsch, M., Ling, C., Hoffman, B. E., Agbandje‐McKenna, M., Tan, M., Wang, W., et al. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.03.009 · Cited by 31
Hebert, N., Rakotoson, M. G., Bodivit, G., Audureau, É., Bencheikh, L., Kiger, L., Oubaya, N., Pakdaman, S., Sakka, M., Liberto, G. D., et al. (2020) · American Journal of Hematology · doi:10.1002/ajh.25937 · Cited by 31
Yasara, N., Wickramarathne, N., Mettananda, C. D., Silva, I., Hameed, N., Attanayaka, K., Rodrigo, R., Wickramasinghe, N., Perera, L., Manamperi, A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-06774-8 · Cited by 35
Perspectives of current understanding and therapeutics of Diamond-Blackfan anemia
Liu, Y., & Karlsson, S. (2023) · Leukemia · doi:10.1038/s41375-023-02082-w · Cited by 39
“The use of self-inactivating lentiviral vectors for ex vivo gene correction of HSPCs has been successfully applied to treat primary immunode fi ciencies [108, 109], haemoglobinopathies [110, 111] and metabolic disorders [112, 113] with superior engraftment and safer pro fi le in patients [106, 107].”
MethodGene Therapy for Beta-Hemoglobinopathies: Milestones, New Therapies and Challenges
Ghiaccio, V., Chappell, M., Rivella, S., & Breda, L. (2019) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-019-00383-4 · Cited by 29
“TDT patients enrolled in the bluebird bio trial (NCT02151526) had their dosage of busulfan modified based on pharmacokinetic analysis of their plasma levels [21].”
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Genetic therapies for the first molecular disease
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“Most autologous HSCT protocols use high-dose myeloablative conditioning to promote full replacement of bone marrow with corrected HSCs (32, 33, 53, 147, 148).”
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Gene therapy for sickle cell disease
Leonard, A. K., & Tisdale, J. F. (2023) · Hematology · doi:10.1182/hematology.2023000487 · Cited by 30
Gene therapy in pediatrics – Clinical studies and approved drugs (as of 2023)
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Gene Therapy for β-Hemoglobinopathies: From Discovery to Clinical Trials
Segura, E., Ayoub, P. G., Hart, K. L., & Kohn, D. B. (2023) · Viruses · doi:10.3390/v15030713 · Cited by 30
“In trials performed in the United States and France, 22 thalassemia patients were treated [74].”
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Current and Future Therapeutics for Treating Patients with Sickle Cell Disease
Barak, M., Hu, C., Matthews, A. K., & Fortenberry, Y. M. (2024) · Cells · doi:10.3390/cells13100848 · Cited by 32
“Gene-addition mechanisms using gene transfer vectors (lentiviral vectors or LV) have been optimized over the past few decades to increase the expression of normal or antisickling globins as strategies to treat SCD [65,66].”
BackgroundPromise of gene therapy to treat sickle cell disease
Romero, Z. G., DeWitt, M. A., & Walters, M. C. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1536119 · Cited by 27
“Since this initial report 10 years ago, an additional 22 patients with transfusion-dependent β-thalassemia, enrolled in separate French and US trials, were treated with a next generation LV vector expressing the HbA gene [56].”
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Metadata
- Authors
- Thompson, A. A., Walters, M. C., Kwiatkowski, J., Rasko, J. E. J., Ribeil, J.-A., Hongeng, S., Magrin, E., Schiller, G. J., Payen, E., Semeraro, M., Moshous, D., Lefrere, F., Puy, H., Bourget, P., Magnani, A., Caccavelli, L., Diana, J.-S., Suarez, F., Monpoux, F., Brousse, V., Poirot, C., Brouzes, C., Meritet, J.-F., Pondarré, C., Beuzard, Y., Chrétien, S., Lefebvre, T., Teachey, D. T., Anurathapan, U., Ho, P. J., von Kalle, C., Kletzel, M., Vichinsky, E., Soni, S., Veres, G., Negre, O., Ross, R. W., Davidson, D., Petrusich, A., Sandler, L., Asmal, M., Hermine, O., De Montalembert, M., Hacein-Bey-Abina, S., Blanche, S., Leboulch, P., & Cavazzana, M.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago (A.A.T., M.K.); University of California, San Francisco, Benioff Children’s Hospital, Oakland (M.C.W., E.V.), Lucile Salter Packard Children’s Hospital at Stanford, Palo Alto (S.S.), and David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (G.J.S.) — all in California; Children’s Hospital of Philadelphia and University of Pennsylvania Perelman...
- ORCID
- Thompson, Alexis A.
- Walters, Mark C.
- Kwiatkowski, Janet
- Rasko, John E.J.
- Ribeil, Jean-Antoine
- Hongeng, Suradej
- Magrin, Elisa
- Schiller, Gary J.
- Payen, Emmanuel
- Moshous, Despina
- Puy, Hervé
- Magnani, Alessandra
- Caccavelli, Laure
- Diana, Jean-Sébastien
- Brousse, Valentine
- Poirot, Catherine
- Brouzes, Chantal
- Pondarré, Corinne
- Chrétien, Stany
- Teachey, David T.
- Anurathapan, Usanarat
- Ho, P. Joy
- Kletzel, Morris
- Vichinsky, Elliott
- Soni, Sandeep
- Asmal, Mohammed
- Hermine, Olivier
- Blanche, Stéphane
- Leboulch, Philippe
- Cavazzana, Marina
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-04-19
- Volume
- 378
- Issue
- 16
- Pages
- 1479-1493
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2802087233
- Cited by
- 684
- References
- 41
- Citations by year
- 2026: 44 · 2025: 52 · 2024: 65 · 2023: 78 · 2022: 79 · 2021: 123 · 2020: 88 · 2019: 101 · 2018: 53
- FWCI
- 55.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- bluebird bio
- National Center for Advancing Translational Sciences (UL1TR000003 and UL1TR001878)
- Assistance Publique - Hôpitaux de Paris
- Institut National de la Santé et de la Recherche Médicale
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives
- Agence Nationale de la Recherche
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- beta-thalassemia, gene therapy, autologous stem cell transplantation, CD34+ cells, transfusion dependence, vector copy number, clonal dominance, beta-globin gene
- MeSH terms
- Adolescent, Adult, Child, Female, Genetic Vectors, Hemoglobins, Humans, Male, Mutation, Transplantation, Autologous, Genetic Therapy, Lentivirus, beta-Thalassemia, Erythrocyte Transfusion, Gene Transfer Techniques, Antigens, CD34, beta-Globins, Young Adult
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