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
60 Own result · 11 No basis given · 9 Own interpretation · 7 No full text of the sources · 5 Partly supported · 4 Own method · 2 Supported so far · 2 Sources not found · 1 Couldn’t confirm · 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
plain- Asserted: passes — The authors put it forward as true.
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- 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)
plain- Asserted: passes — The authors put it forward as true.
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- Could not verify
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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.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- 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.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
boosteddirectSingle case- Asserted: passes — The authors put it forward as true.
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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
plainSingle case- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- 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
plainn = 3- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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 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.
plainn = 22- Asserted: passes — The authors put it forward as true.
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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.
plainn = 22- Asserted: passes — The authors put it forward as true.
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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
“and red-cell transfusions were discontinued in 3 patients.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > RESULTS
plainn = 9- Asserted: passes — The authors put it forward as true.
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- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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
plainn = 13- Asserted: passes — The authors put it forward as true.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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It 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
plainSingle case- Asserted: passes — The authors put it forward as true.
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It 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
plainSingle case- Asserted: passes — The authors put it forward as true.
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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
plainSingle case- Asserted: passes — The authors put it forward as true.
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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
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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It 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.
plainn = 50- Asserted: passes — The authors put it forward as true.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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It 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.
plainn = 12- Asserted: passes — The authors put it forward as true.
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It 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.
plainn = 22- Asserted: passes — The authors put it forward as true.
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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
plainSingle case- Asserted: passes — The authors put it forward as true.
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Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
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It 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
plainn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
“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.
“1103 β 0 /β 0 24 8.7 9.8 Yes NA”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
“* Listed are the values a median of 26 months (range, 15 to 42) after drug product infusion.”
§ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia > Figure 4 (facing page). Changes in Transfusion Requirements after Gene Therapy.
“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
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Position-independent, high-level expression of the human β-globin gene in transgenic mice
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Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
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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
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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.
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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
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Self-citation
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 601–681 of 681
Place de la thérapie génique dans la bêta-thalassémie
Thuret, I. (2021) · Transfusion Clinique et Biologique · doi:10.1016/j.tracli.2021.09.001
The 2020 Joseph W. St Geme, Jr. Leadership Award Address: On Leadership and the Joy of Pediatrics
Geme, J. W. S. (2021) · PEDIATRICS · doi:10.1542/peds.2021-053872
Current Trends in the Gene Therapy of Hematologic Disorders
Nikolova, D. N. (2021) · Acta Medica Bulgarica · doi:10.2478/amb-2021-0048
Luzzatto, L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00143-2 · Cited by 3
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_11-2
Aktuelle gentherapeutische Behandlungsansätze bei Hämoglobinopathien
Meisel, R. (2022) · Kinder- und Jugendmedizin · doi:10.1055/a-1683-2186
Völkl, A., & Oduncu, F. S. (2022) · Elsevier eBooks · doi:10.1016/b978-3-437-23337-1.00004-7
Cavazzana, M., & Diana, J. (2020) · Elsevier eBooks · doi:10.1016/b978-2-294-76049-5.00029-1
Self-citationGene therapy for primary immune deficiencies
Kohn, D. B. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816768-7.00058-2
Unlocking effective transgene expression potential in gene therapy with viral vectors
Halim, N. S. S. A., Halim, N. H. A., Vengidasan, L., Zakaria, N., Ismail, I. S., & Yahaya, B. H. (2021) · Biomedical Research and Therapy · doi:10.15419/bmrat.v8i9.695
Pharmacodynamic Evaluation: Gene Therapy
Grandchamp, N. (2019) · Springer eBooks · doi:10.1007/978-3-319-56637-5_51-1
Formulary Drug Reviews: Betibeglogene Autotemcel
Levien, T. L., & Baker, D. E. (2022) · Hospital Pharmacy · doi:10.1177/00185787221142462
New Insights in β-Thalassaemia
Paubelle, É., & Thomas, X. (2019) · EMJ Hematology · doi:10.33590/emjhematol/10314844
Gene and Cell Therapy: How to Build a BioDrug
Baumeister, S. H. C., & Woolfrey, A. E. (2022) · Pediatric oncology · doi:10.1007/978-3-031-06357-2_6
Thalassemia enters a new age … And more lies ahead
Cohen, A. R. (2023) · American Journal of Hematology · doi:10.1002/ajh.26844
Development of in vitro gene editing therapy in disease treatment
Han, Y., Wenbin, S., Yan, Y., & Zhao, J. (2023) · Highlights in Science Engineering and Technology · doi:10.54097/hset.v36i.5651
A Journey from Blood Cells to Genes and Back
Luzzatto, L. (2023) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-101022-105018 · Cited by 1
Albahout, K. S., Yunus, M., Mohammad, Y. G., et al. (2023) · Cureus · doi:10.7759/cureus.42151
“overload and other serious complications [10,11].”
Stem Cell Transplant for Hemoglobinopathies
Sharma, S. K. (2023) · Springer eBooks · doi:10.1007/978-981-19-5802-1_28
Terzi, Ö. (2023) · Medical Science and Discovery · doi:10.36472/msd.v10i8.990
“519 Medical Science and Discovery, 2023; 10(8):517-520 DISCUSSION”
BackgroundInfluentialHaemoglobinopathies: Prevention, Diagnosis, Treatment and Management in Sub-Saharan Africa
Yeldu, M. M., Erhabor, O., Abdurrahman, Y., Bagudo, A. I., & Waziri, G. (2023) · International Journal of Pharmaceutical and Bio-Medical Science · doi:10.47191/ijpbms/v3-i8-08
Global Trends on β-thalassemia Research over 10 Years: A Bibliometric AnalysisPreprint
Lv, A., li, J., Chen, M., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3350136/v1
Un enjeu de recherche fondamentale et clinique
Lethimonnier, F., & Samuel, D. (2023) · Annales des Mines - Réalités industrielles · doi:10.3917/rindu1.234.0033
Reducing the transcriptional read‐through rate of a lentiviral vector for β‐thalassemia gene therapy
Wu, J., Chen, Y., Shen, W., Zhang, J., & Zeng, F. (2023) · The Journal of Gene Medicine · doi:10.1002/jgm.3640
Optimizing lentiviral genomic integrations to cure beta-thalassemia: The least required for success?
Rivella, S. (2024) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2024.101222
Валерьевна, Г. Е., Kulikova, E. A., Paveliev, I. A., Kuznetsova, O. S., Senina, A. S., & Gusev, A. B. (2024) · Genes and Cells · doi:10.17816/gc601855
Vector-Mediated Genotoxicity and Mutagenicity in Hematopoietic Stem Cell Gene Therapy
YILMAZ, S., & Kartal, Y. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15717-2.00100-1
ПРОБЛЕМА ГЕМОГЛОБИНОПАТИЙ В МИРЕ И СОВРЕМЕННЫЕ МЕТОДЫ БОРЬБЫ С НИМИ
Меджнун, Ш. О. Б., & Рена, Ф. К. М. (2024) · Международная научно-практическая конференция «Актуальные проблемы науки и образования в условиях современных вызовов» · doi:10.58351/240307.2024.98.86.002
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) · SSRN Electronic Journal · doi:10.2139/ssrn.4805812
Self-citationLiu, J., Li, Y., Zhou, K., Zhang, S., Wang, Y., Wang, X., Lan, X., Chen, Q., & Zhao, Y. (2024) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.4c00319
Abuhelwa, Z., Cheng, J. H., & Li, J. Y. (2024) · Springer eBooks · doi:10.1007/978-3-031-62373-8_12
Clinical applications of gene editing and therapy
Badat, M., & Davies, J. O. J. (2025) · Wiley eBooks · doi:10.1002/9781119706687.ch7
Sola, D., Daniele, M. S. B. L., Danesi, L., et al. (2025) · Pituitary · doi:10.1007/s11102-025-01540-1
“Additionally, gene therapy has been proposed as a potential approach to correct the genetic mutations that underlie this disease [4].”
Hematopoietic cell transplantation and cellular therapy
Khan, I., Shah, N. N., & Ulrickson, M. L. (2022) · doi:10.1182/ashsap8.chapter14
Thomas, S., Okodaso, H., Kanjia, K., Khatu, V., Michaud, D. S., Singh, K., Jones, K., Taylor, C., Ikolo, B. T., & Ikolo, F. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1010722
Lundstrom, K. H. (2025) · Springer eBooks · doi:10.1007/978-3-031-77911-4_16
Balusu, R., Soder, R. P., Dudley, N. R., McGuirk, J. P., & Abhyankar, S. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.07.027
Khuzae, Z. H. A., Aseery, A. A., Asiri, H. A., Faqihi, N. H., Dawmari, M. A., & Alyami, N. B. S. (2025) · Cuestiones de Fisioterapia · doi:10.48047/tw5tza77
Damavandi, S. A., Rezaeizadeh, H., Rahimi, R., et al. (2025) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000003565
New therapeutic options for the treatment of transfusion-dependent Diamond-Blackfan anemia
Bataev, A., Klyukhin, V. V., & Smetanina, N. S. (2025) · Pediatric Hematology/Oncology and Immunopathology · doi:10.24287/1726-1708-2025-24-2-140-146
Congenital dyserythropoietic anemias
Klyukhin, V. V., & Smetanina, N. S. (2025) · Pediatric Hematology/Oncology and Immunopathology · doi:10.24287/1726-1708-2025-24-2-130-139
Aswad, H. A., Haleem, A. A., & Eissa, A. A. (2025) · International Journal of Hematology · doi:10.1007/s12185-025-04067-0
“Over the past 30 years, HSCT has been accomplished with success [10, 11].”
Novel strategies to expand and engineer hematopoietic stem cells
Klein, B. R., Blake, A., Rashmil, R., & Desai, A. B. (2025) · Stem Cells · doi:10.1093/stmcls/sxaf065
Samanta, A., Pan, P., Payra, S. K., & Bhattacharyya, N. (2025) · Biosciences Biotechnology Research Asia · doi:10.13005/bbra/3424
Unraveling hematopoietic stem cell ontogeny through single-cell multi-omics approaches
Jia, Y., Huo, S., Wu, F., Song, N., & Li, M. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1704887 · Cited by 2
Xu, F., Wei, S., Yi, J., et al. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1640625
Role of gene therapy and immunotherapy in precision medicine
Khan, I. A., Khatun, H., & Viswa, P. D. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33302-6.00011-1
Development and Application of Respiratory Pseudovirus Packaging System
Fu, J., Chen, R., Zhong, S., Jiang, H., Yang, J., Ma, X., & Lu, C. (2025) · Aerosol Science and Engineering · doi:10.1007/s41810-025-00363-8
Modern therapeutic approaches for β-thalassemia: from blood transfusion to gene therapy
Dolgushina, E. N., Коптева, О. С., Shakirova, A. L., Lepik, K. V., Bykova, T. A., Zubarovskaya, L. S., & Kulagin, A. (2026) · Russian Journal of Pediatric Hematology and Oncology · doi:10.21682/2311-1267-2025-12-3-56-67
Release-Independent Transcription from Covalently Cross-Linked Hierarchically Folded DNA Condensates
Wang, Y., Chen, X., He, J., Zhao, Y., & Chen, Q. (2026) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.5c04105
Joarder, D. N., Afrida, N., Rahman, M., et al. (2026) · International Journal of Research in Medical Sciences · doi:10.18203/2320-6012.ijrms20260601
Brousse, V. A. M. (2018) · theses.fr (ABES) · doi:10.70675/25847085z217dz4270z9ae1za20faba3e022
Self-citationThérapie génique translationnelle des surdités et troubles vestibulaires d'origine génétique
Lahlou, G. (2020) · theses.fr (ABES) · doi:10.70675/d992d926z590ez4d57zbb4fza9922aca932f
Ex vivo gene therapy for β-hemoglobinpathies and metabolic disorders
Laurent, M. (2023) · theses.fr (ABES) · doi:10.70675/ba5c585dzaa79z48d2z9f40zfee1cdd49d32
CRISPR-Cas9-based strategies for enhanced targeted integration
Lacombe, L. (2024) · theses.fr (ABES) · doi:10.70675/9c9d279dz512az4b72z8322zea205cef9b67
Immune Effector Cell and Gene Therapies in Pediatric Critical Care
Ragoonanan, D. S., & Mahadeo, K. M. (2026) · Springer eBooks · doi:10.1007/978-3-319-74698-2_200-2
New Gene Therapy Strategy for β-Thalassemia
Liang, D., Schmidt‐Wolf, I. G. H., & Pu, J. (2026) · Stem Cell Reviews and Reports · doi:10.1007/s12015-026-11132-6 · Cited by 1
“The LentiGlobin BB305 vector has been dem - onstrated in Phase 1 and 2 studies to led to the discontinuation of blood transfusions for 68% of patients with TDT and for the remaining part who continued transfusions, annual-ized transfusion requirements were decreased by 73% [94 ].”
Recent Advancements in Gene Therapy
Kumar, S. (2026) · Springer eBooks · doi:10.1007/978-981-95-7688-3_11
Histoire de l’hématologie pédiatrique
Sirvent, N. (2026) · Perfectionnement en Pédiatrie · doi:10.1016/j.perped.2026.04.005
Soliman, A. T., Kardousha, A., Elkalaf, M. M. I. R., et al. (2026) · Indian Journal of Hematology and Blood Transfusion · doi:10.1007/s12288-026-02453-0
Thalassemia in Guangxi: current situation and future prospects
Liang, L., & He, S. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1842288
Human CD34 as a biomarker and functional tool in progenitor cell isolation: A comprehensive review
Woodard, G. E. (2026) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2026.104454
Rapid cell culture-based assay for the detection of infectious viruses and viral vectors
Khaloian, S., Heinz, S., Guertler, P., et al. (2026) · Journal of Virological Methods · doi:10.1016/j.jviromet.2026.115412
Sharma, A., & Corbacioglu, S. (2026) · Blood Advances · doi:10.1182/bloodadvances.2026019856
“8,36,37 Treosulfan has shown a favorable profile in high-risk patients, such as those with hemophagocytic lympho-histiocytosis or infantile malignant osteopetrosis, in whom historical incidences of VOD/SOS have ranged from 30% to 60%, 38,39 with reductions in the incidence to 0% to 10% in some case…”
Franceschi, L. D., Aljurf, M. D., BARONCIANI, D., Bento, C., Chabannon, C., Corbacioglu, S., de la Fuente, J., Forni, G. L., Kattamis, A., Locatelli, F., et al. (2026) · Bone Marrow Transplantation · doi:10.1038/s41409-026-02947-5
Beyond innovation: why rare disease gene therapy needs a reset
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“The approval of onasemnogene abeparvovec for SMA type 1, voretigene neparvovec for RPE65 -associated retinal dystrophy, and betibeglogene autotemcel for transfusion-dependent beta-thalassemia demonstrates what is achievable [1,20,21].”
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Perspective Chapter: Fetal Hemoglobin Modulators
Walke, V. A. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1017037
Heider, C., Donovan, M. L., Walpole, C., Murphy, P. R., Alim, L., Buckle, I., O’Brien, L., Nakayama, M., Barry, S. C., Mannering, S. I., et al. (2026) · Human Gene Therapy · doi:10.1177/10430342261478743
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“In phase 1/2 clinical studies, gene therapy with modified CD34+ cells safely reduced or eliminated the need for long-term transfusions in patients with severe β -thalassemia [149].”
Samaga, R., Singh, U., & Pawar, S. D. (2026) · Biotechnology and Bioengineering · doi:10.1002/bit.70361
Genetherapy in neurological disorders
Bushlyar, V., Roy, B., & Chatterjee, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44631-3.00001-9
Making space for cures: Conditioning for autologous hematopoietic stem cell gene therapies
Crees, Z. D., DiPersio, J. F., & Persaud, S. P. (2026) · Seminars in Hematology · doi:10.1053/j.seminhematol.2026.09.001
2026 Update on Clinical Trials in β‐Thalassemia
Musallam, K. M., Locatelli, F., Algeri, M., Cappellini, M. D., & Taher, A. T. (2026) · American Journal of Hematology · doi:10.1002/ajh.70472
Autophagy Defects and Mitochondrial Retention in Erythroid Diseases
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Precision reactivation of fetal hemoglobin: expanding the gene-editing landscape for β-thalassemia
Xie, S., & Ye, Y. (2026) · Journal of Translational Genetics and Genomics · doi:10.20517/jtgg.2026.88
Lü, D., Gong, X., Guo, X., Qin, C., Li, W., Chen, Y., Li, D., & Zeng, F. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00589-z
Evolution of Gene Therapy in Hematology
Loves, R. H., & Kohn, D. B. (2026) · Seminars in Hematology · doi:10.1053/j.seminhematol.2026.09.005
Gene Therapy for Hemoglobinopathies
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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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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.
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