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…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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
Cites
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903
Position-independent, high-level expression of the human β-globin gene in transgenic mice
Grosveld, F. G., van Assendelft, G. B., Greaves, D. R., & Kollias, G. A. (1987) · Cell · doi:10.1016/0092-8674(87)90584-8 · Cited by 1,908
Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
Cavazzana-Calvo, M., Payen, E., Negre, O., Wang, G., Hehir, K., Fusil, F., Down, J., Denaro, M., Brady, T., Westerman, K., et al. (2010) · Nature · doi:10.1038/nature09328 · Cited by 1,276
Self-citationCRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells
Dever, D. P., Bak, R. O., Reinisch, A., Camarena, J., Washington, G., Nicolas, C. E., Pavel-Dinu, M., Saxena, N., Wilkens, A. B., Mantri, S., et al. (2016) · Nature · doi:10.1038/nature20134 · Cited by 864
Cao, A., & Galanello, R. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181cd68ed · Cited by 722
Gene therapy in a patient with sickle cell disease
Ribeil, J.-A., Hacein-Bey-Abina, S., Payen, E., Magnani, A., Semeraro, M., Magrin, E., Caccavelli, L., Neven, B., Bourget, P., El Nemer, W., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609677 · Cited by 696
Self-citationThe "beta-like-globin" gene domain in human erythroid cells.
Tuan, D., Solomon, W., Li, Q., & London, I. M. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.19.6384 · Cited by 601
Correction of sickle cell disease in transgenic mouse models by gene therapy
Pawliuk, R., Westerman, K. A., Fabry, M. E., Payen, E., Tighe, R., Bouhassira, E. E., Acharya, S. A., Ellis, J., London, I. M., Eaves, C. J., et al. (2001) · Science · doi:10.1126/science.1065806 · Cited by 579
Self-citationMay, C., Rivella, S., Callegari, J., Heller, G., Gaensler, K. M. L., Luzzatto, L., & Sadelain, M. (2000) · Nature · doi:10.1038/35017565 · Cited by 567
A Modified γ-Retrovirus Vector for X-Linked Severe Combined Immunodeficiency
Hacein-Bey-Abina, S., Pai, S.-Y., Gaspar, H. B., Armant, M., Berry, C. C., Blanche, S., Bleesing, J., Blondeau, J., de Boer, H., Buckland, K. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1404588 · Cited by 412
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 501–600 of 681
Ayçiçek, A., Kalkan, Ş., Uysalol, E. P., Tekgündüz, S. A., Salcioglu, O. Z., Özdemir, G. N., Arslantaş, E., & Bayram, C. (2022) · Turkish Archives of Pediatrics · doi:10.5152/turkarchpediatr.2022.22042 · Cited by 2
“Follow-up time, months, median 108 (9-196) 126 (38-285)”
Progrès de la thérapie génique dans les maladies génétiques du système hématopoïétique
Cavazzana, M. (2022) · médecine/sciences · doi:10.1051/medsci/2022120 · Cited by 2
Self-citationCore, L. D., Pellin, D., Wit, E. C., & Grzegorczyk, M. A. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad605 · Cited by 2
“…longitudinally from the peripheral blood of four patients affected by Wiskott–Aldrich syndrome (WAS) (Hacein-Bey Abina et al. 2015), two patients with b haemoglobinopathy, one with b S/ b S sickle cell disease (Ribeil et al. 2017), and one with b 0/ b E b thalassaemia (Thompson et al. 2018).”
BackgroundEfficacy and safety of thalidomide in patients with β-thalassemia intermedia and major
Ju, W., Din, G., Huang, J., et al. (2024) · Medicine · doi:10.1097/md.0000000000040328 · Cited by 2
“[7] Therefore, there is an urgent need to develop effective and affordable treatments for TM or TDT patients.”
BackgroundGammon, R. R., Rahimi‐Levene, N., Bandeira, F. M. G. D. C., & Al‐Riyami, A. Z. (2024) · Springer eBooks · doi:10.1007/978-3-031-67332-0_9 · Cited by 2
Pediatric Advances in Gene Therapies for Hemoglobinopathies
Thompson, C., Ferdjallah, A., & Gupta, A. O. (2024) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2024.5366 · Cited by 2
Udeze, C., Li, N., Kunzweiler, C. P., et al. (2025) · PharmacoEconomics - Open · doi:10.1007/s41669-024-00550-2 · Cited by 2
Successful treatment of transfusion-dependent β-thalassemia: multiple paths to reach potential cure
Morgan, M. A., & Schambach, A. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02135-9 · Cited by 3
Application Advances of Lentiviral Vectors: From Gene Therapy to Vaccine Development
Fang, E., He, G., Chang, Y., He, Q., Chen, P., & Hu, K. (2025) · Molecular Biotechnology · doi:10.1007/s12033-025-01472-y · Cited by 2
Gene Therapies for Hemoglobinopathies: Efficacy, Cell Collection & Transfusion Support
Inam, Z. S., Han, H., Webb, J. L., & Delaney, M. (2025) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2025.150930 · Cited by 3
Advances in transplantation and gene therapy in transfusion-dependent β-thalassemia
Angelucci, E., & Abutalib, S. A. (2018) · Advances in Cell and Gene Therapy · doi:10.1002/acg2.25 · Cited by 2
A new medical therapy for anemia in thalassemia
Angelucci, E. (2019) · Blood · doi:10.1182/blood-2019-01-897587 · Cited by 3
Advances in Gene Therapy Offer Hope for Rare Disorders
Bates, M. (2019) · IEEE Pulse · doi:10.1109/mpuls.2019.2958020 · Cited by 2
The role of Peroxin 7 during Drosophila embryonic development
Pridie, C., & Simmonds, A. J. (2020) · Genome · doi:10.1139/gen-2019-0207 · Cited by 2
Mulas, O., Pili, I., Sanna, M., & Nasa, G. L. (2021) · Clinical Practice and Epidemiology in Mental Health · doi:10.2174/17450179-v17-e211208-2021-ht2-1910-4 · Cited by 3
Current status of producing autologous hematopoietic stem cells
Li, Z., & Yang, L. (2023) · Current Research in Translational Medicine · doi:10.1016/j.retram.2023.103377 · Cited by 2
Juggling between the Cost and Value of New Therapies: Does Science Still Serve Patient Needs?
Eleftheriou, A., Farmakis, D. T., Englezos, P., et al. (2023) · Thalassemia Reports · doi:10.3390/thalassrep13010004 · Cited by 2
“When gene therapy marked a historical milestone in the history of the disease [1], we expected a more humane approach by governments, healthcare funders and the industry, and not a series of financial studies that have shattered the dreams of hundreds of thousands of patients globally [2].”
BackgroundStem Cell-Based Therapeutic Approaches in Genetic Diseases
Aslan, A., & Yuka, S. A. (2023) · Advances in experimental medicine and biology · doi:10.1007/5584_2023_761 · Cited by 2
Suwito, B. E., Adji, A. S., Widjaja, J. S., Angel, S. C. S., Hajiri, A. Z. Z. A., Salamy, N. F. W., & Choirotussanijjah, C. (2023) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2023.11435 · Cited by 3
New horizons for reduction of blood use: Patient blood management
Shamsasenjan, K., Gharehdaghi, S., Khalaf-Adeli, E., & Pourfathollah, A. (2022) · Asian Journal of Transfusion Science · doi:10.4103/ajts.ajts_14_21 · Cited by 2
Noguer, M., Berthon, P. M., Makowski, C., & Messonnier, L. A. (2024) · British Journal of Haematology · doi:10.1111/bjh.19847 · Cited by 2
Transfusing children with hemoglobinopathies
Allali, S., Taylor, M., Albinni, S., Amiranoff, D., & de Montalembert, M. (2019) · Transfusion Clinique et Biologique · doi:10.1016/j.tracli.2019.06.323 · Cited by 3
“utcomes of gene therapy vary according to genotypes and excelent results have been observed in non- 0/ 0 patients [6].”
BackgroundGene Therapy: A Revolutionary Step in Treating ThalassemiaPreprint
Attia, R. A., Qureshi, G. S. A., Safdar, M., et al. (2024) · Preprints.org · doi:10.20944/preprints202406.0024.v1 · Cited by 2
Does the world need germline editing for β-thalassemia?
Kulozik, A. E. (2021) · Haematologica · doi:10.3324/haematol.2021.279998 · Cited by 1
RS12574989 and haplotype associated with α/β-chain imbalance and population HbA2 reduction
Lin, Q.-Y., Xie, Y., Zhong, X., Sun, X., & Wang, D. (2022) · BMC Medical Genomics · doi:10.1186/s12920-022-01333-6 · Cited by 1
“Furthermore, the clinical symptoms of β-thalassemia were effectively alleviated by transplantation of autologous haematopoietic stem cells (HSCs), in which lentiviruses transferred normal and functional β-globin [28].”
BackgroundSoleimani, M., & Naghani, A. S. (2023) · Tissue and Cell · doi:10.1016/j.tice.2023.102044 · Cited by 1
Charoenkwan, P., Komwilaisak, P., Thepsuthummarat, K., et al. (2024) · Thalassemia Reports · doi:10.3390/thalassrep14010002 · Cited by 1
“Gene therapy has emerged as a curative treatment for thalassemia [4–6].”
BackgroundRavichandran, S., Hoffmann, M. H., Petersen, J., Sjø, L. D., Rasmussen, A. Ø., Eidesgaard, A., & Glenthøj, A. B. (2024) · Hemoglobin · doi:10.1080/03630269.2024.2335919 · Cited by 1
“Promising results are emerging from ongoing gene therapy trials involving patients with typical β-thalassemia [22,23].”
Review of Existing Method for Brain Delivery
Wang, Y., Li, Y., Li, W., & Yang, Y. (2025) · Theoretical and Natural Science · doi:10.54254/2753-8818/2024.19393 · Cited by 1
Novel Therapeutic Advances in β-Thalassemia
Srichairatanakool, S., & Tantiworawit, A. (2025) · Journal of Hematology and Transfusion Medicine (วารสารโลหิตวิทยาและเวชศาสตร์บริการโลหิต) · doi:10.69898/jhtm.35.2025.275741 · Cited by 1
Bhatt, N. S., Richards, A., Beebe, K. L., & Khera, N. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-84988-6_12 · Cited by 2
Athanassiadou, A., Athanassiadou, A., Sgourou, A., et al. (2025) · Human Gene Therapy · doi:10.1089/hum.2025.034 · Cited by 1
“Len-tiviral vectors used were the GLOBE), 54 carrying the elements HS2 and HS3 of the LCR; the BB305 vectors, 55,56 carrying the LCR elements HS2, HS3, and HS4; and the lentiviral vector TNS9.”
InfluentialGao, Z.-Y., Yang, Z.-X., Deng, D.-H., Zhang, F., Yu, B., Zhang, Y., Lv, X., Nakamura, Y., Gong, A., Cheng, T., et al. (2025) · Blood Science · doi:10.1097/bs9.0000000000000253 · Cited by 1
“The T87Q substitution, retained from the clinical BB305 design, 24,26 abrogates HbS polymerization and enables allele-specific RT-qPCR.”
InfluentialThe development of an advanced lentiviral gene therapy for beta-thalassemia
Liu, H., Wang, Y., Zhang, R., & Chang, L. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152963 · Cited by 1
Stimulus-Responsive Delivery Systems for Gene Therapy Products
Sakhno, N. G., & Gunar, O. V. (2025) · Applied Biochemistry and Microbiology · doi:10.1134/s0003683825700334 · Cited by 1
Emerging Considerations in Transfusion Medicine
Gibson, N. M., Kwiatkowski, J. L., & Chou, S. T. (2025) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2025.10.006 · Cited by 1
Self-citationClinical pharmacology insights from recent cell and gene therapy approvals relevant to pediatrics
Kunanayagam, S., Wang, M. C., Loucks, C. M., García‐Bournissen, F., Verstegen, R. H. J., & Lewis, T. R. (2026) · Pediatric Research · doi:10.1038/s41390-026-05138-6 · Cited by 1
The expanding therapeutic landscape of β-thalassaemia
Musallam, K. M., Sheth, S., Locatelli, F., Shah, F., Rivella, S., Kuo, K. H. M., Forni, G. L., Kattamis, A., Aydınok, Y., Glenthøj, A. B., et al. (2026) · The Lancet Haematology · doi:10.1016/s2352-3026(26)00173-0 · Cited by 2
Self-citationRecent progress in gene therapies for mucopolysaccharidoses
Ginocchio, V. M., & Brunetti‐Pierri, N. (2018) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2018.1529564 · Cited by 1
Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento.
Carvajal-Alzate, M. (2019) · Archivos de Medicina (Manizales) · doi:10.30554/archmed.19.1.2732.2019 · Cited by 1
Cellules humaines à usage thérapeutique : état de la question
Guilhot, F. (2020) · Bulletin de l Académie Nationale de Médecine · doi:10.1016/j.banm.2020.07.051 · Cited by 3
The Erythrocyte - A Unique Cell
Rajashekaraiah, V. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.101007 · Cited by 1
Therapeutic targeting non-coding RNAs
Ray, R. M., Lazăr, A. D., Balahura, L.-R., Dobranici, A., Costache, M., & Dinescu, S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-90406-3.00006-3 · Cited by 1
Wang, X., McKillop, W. M., Dlugi, T. A., Faber, M. L., Argote, J. A., Chambers, C. B., Wilber, A. C., & Medin, J. A. (2023) · The Journal of Gene Medicine · doi:10.1002/jgm.3567 · Cited by 1
“63 In clinical studies using LentiGlobin to treat SCD, acute myeloid leukemia (AML) developed in two of the 44 patients treated but neither event was deemed the result of LV-related insertional oncogenesis.”
BackgroundHaematopoietic Stem Cell Transplantation in Thalassaemia Major: A Narrative Review
Yousuf, R., Jahan, D., Sinha, S., & Haque, M. (2023) · Advances in Human Biology · doi:10.4103/aihb.aihb_104_23 · Cited by 1
When should gene therapy be considered for transfusion-dependent β-thalassemia patients?
Mensah, C., & Sheth, S. (2023) · Hematology · doi:10.1182/hematology.2023000513 · Cited by 1
Steinberg, M. H. (2023) · touchREVIEWS in Oncology & Haematology · doi:10.17925/ohr.2023.19.2.29 · Cited by 1
Gene Editing in Hematopoietic Stem Cells
Liao, J., & Wu, Y. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-99-7471-9_11 · Cited by 2
Chabannon, C., Visentin, S., Granata, A., & Thuret, I. (2024) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2024.103926 · Cited by 1
Exagamglogene autotemcel: a beacon of hope for severe sickle cell disease and thalassemia management
Anand, A., Singh, M. P., Sharma, R. K., et al. (2024) · International Journal of Surgery Open · doi:10.1097/io9.0000000000000146 · Cited by 1
Hotspots and status of Fetal Alpha-Thalassemia from 2009 to 2023: a bibliometric analysis
Li, Q., Li, X., he, S. T., & Li, J. (2024) · Frontiers in Pediatrics · doi:10.3389/fped.2024.1467760 · Cited by 1
WGCNA and LASSO regression-based selection and validation of microRNA biomarkers of β-thalassemia
Yang, F., Shi, L., Su, S., Li, Y., Cheng, H., Liang, Z., Pang, L., & Lai, K. (2025) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2025.102957 · Cited by 1
The inborn errors of metabolism: General aspects
Cox, T. M., & Watts, R. W. E. (2020) · doi:10.1093/med/9780198746690.003.0225 · Cited by 2
Fertility Preservation in a Female Adolescent with a Hemoglobinopathy
Pavone, M. E., Manuel, S., & Thompson, A. A. (2019) · Springer eBooks · doi:10.1007/978-3-030-02868-8_61 · Cited by 1
Self-citationGentherapie von Hämoglobinkrankheiten – aktuelle Konzepte und Herausforderungen
Kulozik, A. E., & Kunz, J. B. (2019) · Transfusionsmedizin · doi:10.1055/a-0825-9666 · Cited by 2
Girelli, D., & Busti, F. (2020) · Haematologica · doi:10.3324/haematol.2020.253393 · Cited by 2
Haematology in the UK: A 60‐year personal perspective
Hoffbrand, A. V. (2021) · eJHaem · doi:10.1002/jha2.213
Maggio, A. (2021) · British Journal of Haematology · doi:10.1111/bjh.17948 · Cited by 1
“The possibility of curing a severe haemoglobin (Hb) disorder in a murine thalassaemia intermedia model using a lentivirus vector was shown by May et al.2 Thompson et al.3 suggested as gene therapy with autologous CD34+ transduced cells with the lentivirus BB305 vector, which eliminated the need for long-term red-cell…”
BackgroundCohn, C. S., Allen, E. S., Cushing, M. M., Dunbar, N. M., Friedman, D. F., Goel, R., Harm, S. K., Heddle, N. M., Hopkins, C. K., Klapper, E. B., et al. (2019) · Transfusion · doi:10.1111/trf.15348 · Cited by 1
“reported a phase 1/2 study in which mobilized autologous CD34+ cells from 22 subjects were transduced ex vivo with LentiGlobin BB305 vector encoding hemoglobin A, then reinfused after myeloablative busulfan conditioning.(49) In all patients after 15 to 42 months of follow-up, the gene therapy reduced or eliminated the…”
MethodKunz, J. B., & Kulozik, A. E. (2020) · Springer Reference Medizin · doi:10.1007/978-3-662-60300-0_216 · Cited by 1
Bari, S., Chong, P., & Hwang, W. Y. K. (2019) · BLOOD CELL THERAPY / The official journal of APBMT · doi:10.31547/bct-2019-004 · Cited by 1
Gene Therapy for Inherited Metabolic Diseases
Longo, N., & Lai, K. (2022) · Springer eBooks · doi:10.1007/978-3-030-94510-7_8 · Cited by 1
Retroviral Vectors for Gene Therapy of Monogenic Diseases
Yoder, K. E., Rabe, A. J., & Larue, R. C. (2022) · Springer eBooks · doi:10.1007/978-3-030-93333-3_7 · Cited by 1
Gene Therapy for Human Diseases: Recent Achievements and Near-Term Development Prospects
Айтбаев, К. А., Murkamilov, I. T., Абдилалимовна, М. Ж., & Yusupov, F. A. (2022) · The Russian Archives of Internal Medicine · doi:10.20514/2226-6704-2022-12-5-363-369 · Cited by 2
Corrons, J. V., & Krishnevskaya, E. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.109637 · Cited by 1
Pediatric Bone Marrow Transplantation
Yadav, S. P., Sharma, A., Shah, R. M., & Satwani, P. (2020) · Organ and tissue transplantation · doi:10.1007/978-3-319-64938-2_11-1 · Cited by 1
Westin, E. R., Tsao, D., Atay, O., Landry, B. P., Ye, P. P., Chandler-Brown, D. B., Alford, B. D., Hoskovec, J. M., Subramaniam, A., Pawlik, K. M., et al. (2021) · medRxiv · doi:10.1101/2021.09.02.21262837 · Cited by 2
Hematology of childhood and adolescence
Bellantoni, A. J., Mangoli, A., & Deel, M. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818872-9.00038-8 · Cited by 1
Genetically engineered microglia-like cells have therapeutic potential for neurodegenerative diseasePreprint
Plasschaert, R. N., DeAndrade, M. P., Hull, F., Nguyen, Q., Peterson, T., Yan, A., Loperfido, M., Baricordi, C., Barbarossa, L., Yoon, J. K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.16.460703 · Cited by 1
Stochastic modelling of cell differentiation networks from partially-observed clonal tracking dataPreprint
Core, L. D., Pellin, D., Grzegorczyk, M. A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.08.499353 · Cited by 1
Han, N., Li, Y., Ouyang, W., Dong, G., Guo, H., Chen, Y., Huang, Y., Zeng, X., Zou, H., He, J., et al. (2023) · medRxiv · doi:10.1101/2023.03.21.23287513 · Cited by 1
Anämien bei Kindern und Jugendlichen
Kunz, J. B., & Kulozik, A. E. (2019) · Springer Reference Medizin · doi:10.1007/978-3-642-54671-6_216-2
Gene transfer delivers (β-globin)
Hinrichs, C. S. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat8522
Prospects for Cure in Wilson Disease
Camarata, M. A., To, U. K., & Schilsky, M. L. (2018) · OBM Genetics · doi:10.21926/obm.genet.1803030
Gene and Cell Therapy: Tearing Down Walls
VandenDriessche, T. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.29074.tva
Most Recent Clinical Advances in CAR T Cell and Gene Therapy 2017/2018
Abutalib, S. A., & Gill, S. I. (2018) · Advances and controversies in hematopoietic transplantation and cell therapy · doi:10.1007/978-3-319-54368-0_2
21st Century FOX: Toward Gene Therapy for the Regulatory T Cell Deficiency Syndrome IPEX
Petty, N. E., & Gill, S. I. (2019) · Cell stem cell · doi:10.1016/j.stem.2018.12.016
Was ist neu in der Diagnostik und Therapie der Hämoglobinopathien?
Cario, H., & Lobitz, S. (2019) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-0601-4921
Stem cell transplantation in sickle-cell disease
Sheth, S. (2019) · The Lancet Haematology · doi:10.1016/s2352-3026(19)30150-4
Present and Future Strategies with Curative Intent for Hereditary Hemoglobinopathies
Oliveira, V. G., Saraiva, A. F., Costa, F., & de Sousa, A. B. (2019) · OBM Transplantation · doi:10.21926/obm.transplant.1903086
Pharmacodynamic Evaluation: Gene Therapy
Grandchamp, N. (2020) · Springer eBooks · doi:10.1007/978-3-319-68864-0_51 · Cited by 1
Production of foetal globin in adult monkeys
Bauer, D. E. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0475-3
Gene Therapy: Principles and Clinical Potential
Buckley, S. M. K., & David, A. L. (2019) · Cambridge University Press eBooks · doi:10.1017/9781108564434.053
Aktuelle Entwicklung der Gentherapie bei pädiatrischen Erkrankungen
Rosenecker, J. (2020) · Monatsschrift Kinderheilkunde · doi:10.1007/s00112-019-00816-8
Klump, H. (2020) · Learning materials in biosciences · doi:10.1007/978-3-030-33923-4_1 · Cited by 1
Chan, D. C. H. (2020) · MacSphere (McMaster University) · doi:10.71548/16397
T Cell Engineering and the Rise of CAR-T Cell Therapies
Philipson, B. I., & Milone, M. C. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-812034-7.00004-2
Gene Therapy of the β Hemoglobinopathies: Success and Challenges
Payen, E., & Leboulch, P. (2019) · Hemoglobin · doi:10.1080/03630269.2020.1715572
Self-citationCurrent standards and the latest developments in the treatment of thalassaemia
Teawtrakul, N. (2020) · ISBT Science Series · doi:10.1111/voxs.12556
Dorgaleleh, S., Barahouie, A., Dastaviz, F., Ghodsalavi, Z., & Oladnabi, M. (2020) · International Journal of Pediatrics · doi:10.22038/ijp.2020.47309.3839 · Cited by 1
“In addition, lentivirus vectors were confirmed to be safe, safe and low in toxic effects (23, 24).”
BackgroundGenetic Correction of Thalassemia: Development of a Transformative Is Delivered
Moss, P. A. H. (2018) · The Hematologist · doi:10.1182/hem.v15.4.8755
Lentiglobin Gene Therapy Looks Promising in Patients With Transfusion-Dependent β-thalassemia
Keel, S. (2018) · The Hematologist · doi:10.1182/hem.v16.1.9290
The Promise of Novel Therapies for β Thalassemia Syndromes
Sheth, S. (2018) · The Hematologist · doi:10.1182/hem.v15.5.8894
Assessing and reconditioning kidneys using normothermic machine perfusion
Georgiades, F., Hosgood, S. A., & Nicholson, M. L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819451-5.00011-1
Gracia Quejereta: Una madrileña en Oxford
Rioyo, J. (1996) · Cinemanía
In UteroStem Cell Transplantation, Enzyme Replacement, and Gene Therapy
MacKenzie, T. C., & Schwab, M. E. (2021) · Wiley eBooks · doi:10.1002/9781119676980.ch30
Gene Therapy in Global Health: Meeting the Needs of Chinese Patients with Beta-Thalassemia
Flotte, T. R. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.29162.trf
Freij, J. B. (2021) · Clinical Research in Practice The Journal of Team Hippocrates · doi:10.22237/crp/1622160060
“consists of two phase 1/2 non-randomized, open-label, single dose clinical trials examining the efficacy and safety of gene therapy in treating patients with transfusion-dependent β-thalassemia.(7) The trial enrolled 22 patients in total.”
BackgroundPattabhi, S., Lotti, S. N., Berger, M. P., Singh, S., & Rawlings, D. J. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.30.450644
Lifting the lid on perioperative goal-directed therapy
Martín, D. (2021) · British Journal of Anaesthesia · doi:10.1016/j.bja.2021.07.009
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
