The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases

Rosales, Francisco Espinosa; Peylan‐Ramu, Nili; Cividalli, Gabriel; Váradi, Gábor; Or, R.; Naparstek, E; Slavin, Shimon; Nagler, Arnon

doi:10.1038/sj.bmt.1701758

Cited by 21 publications

(13 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thiotepa is a potent immunosuppressive and myelosuppressive drug and has been successfully used with melphalan (49–51). It has promoted engraftment in murine transplant models (52, 53) as well as in clinical studies of T cell depleted HSCT and UCBT (54–56). Hydroxyurea can induce cycling of the stem cell pool potentially sensitizing them to melphalan and thiotepa (57).…”

Section: Discussionmentioning

confidence: 99%

A Novel Reduced-Intensity Conditioning Regimen for Unrelated Umbilical Cord Blood Transplantation in Children with Nonmalignant Diseases

Parikh

Mendizabal

Benjamin

et al. 2014

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Reduced intensity conditioning (RIC) regimens have the potential to decrease transplant-related morbidity and mortality. However, engraftment failure has been prohibitively high after RIC unrelated umbilical cord blood transplantation (UCBT) in chemotherapy-naïve children with non-malignant diseases (NMD). Twenty-two children with a median age of 2.8 years, many with severe comorbidities and prior viral infections were enrolled in a novel RIC protocol consisting of hydroxyurea, alemtuzumab, fludarabine, melphalan and thiotepa followed by single UCBT. Patients were transplanted for inherited metabolic disorders (N=8), primary immunodeficiencies (N=9), hemoglobinopathies (N=4) and Diamond Blackfan anemia (N=1). Most UCB units were HLA-mismatched with median infused total nucleated cell dose of 7.9 × 107/kg. No serious organ toxicities were attributable to the regimen. The cumulative incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65%–100%) in a median of 20 days, with the majority sustaining >95% donor chimerism at 1 year. Cumulative incidence of acute graft-versus-host disease (GVHD) grades II–IV and III–IV by day 180 was 27.3% (95% CI, 8.7%–45.9%) and 13.6% (95 CI, 0%–27.6%), respectively. Cumulative incidence of extensive chronic GVHD was 9.1% (95% CI, 0%–20.8%). The primary causes of death were viral infections (N=3), acute GVHD (N=1) and transfusion reaction (N=1). One-year overall and event-free survivals were 77.3% (95% CI, 53.7%–89.8%) and 68.2% (95% CI, 44.6%–83.4%) with 31 months median follow-up. This is the first RIC protocol demonstrating durable UCB engraftment in children with NMD. Future risk-based modifications of this regimen could decrease the incidence of viral infections. (www.clinicaltrials.gov/NCT00744692)

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Reduced-Intensity Conditioning Regimen for Unrelated Umbilical Cord Blood Transplantation in Children with Nonmalignant Diseases

Parikh

Mendizabal

Benjamin

et al. 2014

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…It was necessary to modify the regimen to achieve more effective eradication of the patients' stem cells and reduce disease recurrence without increasing regimen-related toxicity. Rosales et al [8] reported that the thiotepa in BMT for genetic diseases might provide a prospective conditioning followed by T-cell depletion. In our patients, PBSC was infused without manipulation.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Peripheral Blood Stem Cell Transplantation in Β -Thalassemia

Fang

Huang

Chen

et al. 2002

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

Six transfusion-dependent beta-thalassemia major patients were treated with allogeneic peripheral blood stem cell (PBSC) transplant. The donors were HLA identical siblings except one donor who was a father with one-antigen mismatch of HLA-B loci. The donors were mobilized with G-CSF and PBSC was infused without manipulation. Engraftment was documented in all patients. Acute graft versus host disease (GvHD) was present in 4 patients but could be controlled with steroid or/and ATG. One patient died of hepatic veno-occlusive disease (HVOD) and survivors were all transfusion independent (ex-thalassemia). Chronic GvHD occurred in one patient. Allogeneic PBSC transplantation could achieve disease-free survival in beta-thalassemia major patients.

show abstract

“…Between the years 2003 and 2008, 16 patients who had thalassemia recurrence following graft failure after the first graft were prospectively enrolled in this study. The median patient age was 9 years (range, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and the median donor age was 16 years (range, 2-29). Patient characteristics at the time of second transplantation are summarized in Table 1.…”

Section: Characteristics Of the Patientsmentioning

confidence: 99%

Second hematopoietic SCT in patients with thalassemia recurrence following rejection of the first graft

Gaziev

Sodani

Lucarelli

et al. 2008

Bone Marrow Transplant

View full text Add to dashboard Cite

There is a substantial incidence of graft failure in patients with thalassemia after myeloablative conditioning regimens especially in class 3 patients in whom its incidence could be as high as 8-38.5%. Most patients with graft failure have recurrence of thalassemic marrow. Historically, results of second transplants for thalassemia were poor because of a high rejection rate and/or increased TRM. Sixteen patients with thalassemia recurrence following rejection of the first graft and with a median age of 9 years (range, 4-20) were given second transplants using BM (n=7) or PBSC (n=9) after preparation with a new treatment protocol. All but two patients received stem cells from the same donor. The median interval between two transplants was 28 months (range, 8-204). The sustained engraftment rate was high (94%) with only one patient having primary graft failure. The probability of overall survival, event-free survival, TRM and graft failure were 79, 79, 16 and 6%, respectively. There were three transplant-related deaths. Thirteen patients are alive with Lansky/Karnofsky score of 100. This intensified treatment protocol was well tolerated with no significant increase in toxicity. The excellent results obtained with this new preparative regimen allow us to recommend it for second transplantation for patients with thalassemia recurrence.

show abstract

The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases

Cited by 21 publications

References 31 publications

A Novel Reduced-Intensity Conditioning Regimen for Unrelated Umbilical Cord Blood Transplantation in Children with Nonmalignant Diseases

A Novel Reduced-Intensity Conditioning Regimen for Unrelated Umbilical Cord Blood Transplantation in Children with Nonmalignant Diseases

Allogeneic Peripheral Blood Stem Cell Transplantation in Β -Thalassemia

Second hematopoietic SCT in patients with thalassemia recurrence following rejection of the first graft

Contact Info

Product

Resources

About